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Editorial Note: The excitotoxin quinolinic acid induces tau phosphorylation in human neurons

Impact of health insurance coverage on Chuna Manual Therapy utilization: A cross-sectional analysis using data from the 2017 and 2020 Korean Medicine Utilization and Herbal Medicine Consumption Survey

Chuna Manual Therapy (CMT) is a component of traditional Korean Medicine that was integrated into national health insurance coverage of the Republic of Korea in 2019 to improve accessibility. This study investigates the impact of this policy change on CMT utilization patterns using data from the Korean Medicine Utilization and Herbal Medicine Consumption Survey, comparing pre-insurance (2017) and post-insurance (2020) periods. A descriptive cross-sectional analysis was conducted with a nationally representative sample, and logistic regression analysis was used to identify key determinants of CMT utilization. The results show a significant increase in CMT utilization, particularly among outpatients. Notable demographic shifts included an increased utilization among males, individuals with higher education levels, and those employed in professional, service, and skilled labor occupations. While insurance coverage improved accessibility, overall satisfaction with treatment results and costs slightly declined. Musculoskeletal disorders remained the primary conditions treated with CMT. The findings highlight that while insurance coverage expanded access to CMT, its effects on patient satisfaction and healthcare costs require further investigation. Further studies should assess the long-term implications of insurance coverage on both patient outcomes and healthcare provider practices.

Author Correction: Global influence of soil texture on ecosystem water limitation

Expression of Concern: Hybrid feature selection and classification technique for early prediction and severity of diabetes type 2

Analysis of alterations in the composition of the intestinal microbiota in frail older individuals

Background Frailty is an ageing-associated geriatric syndrome that severely affects the functional status, quality of life and life expectancy of older adults. Immune dysfunction and chronic inflammation play crucial roles in frailty, and this study aimed to explore the correlation between the intestinal microbiota and frailty. Methods A cross-sectional survey was conducted using a comprehensive geriatric assessment of older individuals who underwent medical checkups at the Health Management Center from April 2023 to May 2024. A total of 672 older individuals who met the inclusion criteria were included and divided into a healthy control group and a frail case group. Clinical data, as well as blood and stool samples, were collected. The data from the two groups were analysed with 16S rRNA sequencing in 20 and 30 cases, respectively. SPSS 25.0 was used for statistical analysis. Results There were significant differences in income, smoking, and globulin levels between the two groups, while there were no differences in age or sex. There was no significant difference in the abundance or species evenness of intestinal bacteria between the two groups. However, the abundance of accessory bacteria, bifidobacteria, and Escherichia coli in the frail group was greater than that in the control group. Specifically, Escherichia-Shigella was significantly upregulated and fit well into the prediction model of frailty. Conclusion The gut microbiota of frail older individuals underwent significant changes in structural composition, and the presence of Escherichia-Shigella may be a diagnostic marker for debilitating diseases. These findings provide an essential clinical reference value for developing methods for preventing or alleviating frailty based on specific microbial communities.

Societal cost of day-care approach (DCA): A low-cost approach in urban and rural settings for management of childhood severe pneumonia in Bangladesh

Objective Childhood severe pneumonia is the leading cause of under-five deaths in Bangladesh. A new day-care management approach (DCA) was implemented in primary-level healthcare facilities in urban and rural areas of Bangladesh. Reliable cost estimates are important to determine the economic viability of the new management approach. The objective of this study were to estimate the mean societal cost per patient for a new Day-care approach (DCA) in managing childhood severe pneumonia, to assess cost variation in urban and rural healthcare settings, and to determine important cost predictors. Study design This study was conducted alongside a cluster randomized trial conducted in Bangladesh Children diagnosed with severe pneumonia were enrolled between November 2015 and March 2019. Employing a bottom-up micro-costing approach from a societal perspective, detailed household and provider cost data were collected from sixteen intervention facilities (n = 16). Data collection involved structured questionnaires administered face-to-face with facility staff, interviews with parents/caregivers, and patient record reviews. Analysis measured mean cost and cost variation across socio-economic groups, facility location, clinical variables, and determined cost-sensitive parameters. A p-value of < 0.05 was considered as statistically significant level. Results 1,745 children were enrolled, 63% were male, and 57% were less than a year old. The mean societal cost per patient was US$94.2 (95% CI: US$92.2, US$96.3) with a mean length-of-stay (LoS) of 4.1 days (SD ± 3.0). Costs of medical personnel (US$32.6), caregiver’s productivity loss (US$26) and medicines (US$22) were the major cost contributors. Mean cost was significantly higher for urban-located facilities compared to rural (difference US$17, 95% CI: US$12.6, US$20.8). No cost variation was found by age, sex, and clinical variables. Conclusion Findings suggest that this novel DCA management approach is a low-cost management option, and particularly beneficial for rural residences and therefore has the potential to reduce the overall cost burden for childhood severe pneumonia management. These findings have implications for policy-making decisions in resource-poor settings for childhood pneumonia management.

Leveraging detection uncertainty to estimate Renibacterium salmoninarum infection status among multiple tissues and assays

Effective disease surveillance relies on accurate pathogen testing and robust prevalence estimates. Diagnostic specificity (DSp), the probability that an uninfected animal tests negative, is high when false positives are low. Diagnostic sensitivity (DSe) is the probability an infected animal tests positive; higher DSe means fewer false negatives. However, sensitivity and false negatives are harder to estimate without a “gold standard”, an assay that can detect between 90 − 100% of true positive infections. Occupancy estimation of infection prevalence offers one solution by allowing for imperfect detection of the pathogen. Testing potentially infected tissues multiple times allows for the use of a Bayesian multistate occupancy model to estimate the probability of pathogen infection in tissues (Ψk) and detection probabilities (p) for different assays. Using Ψk and p from the posterior distribution, the conditional probability of detecting the pathogen can be modeled, allowing for the calculation of DSe. Renibacterium salmoninarum is a bacterial pathogen causing bacterial kidney disease among salmonid species and was the model pathogen we used to train our model. The current testing standard for salmonids combines initial screening for antibodies using direct fluorescent antibody test (DFAT) with polymerase chain reaction (PCR) confirmation to detect R. salmoninarum. However, detection of R. salmoninarum still varies between species, tissues, and assays. Here, a multi-state occupancy model was used to estimate detection probability among individual and dual kidney/liver infections with DFAT and qPCR in fish with an unknown infection status. Both assays produced false negatives, but qPCR had fewer than DFAT and a higher DSe. Infection state was often misclassified, but multiple surveys per individual or combining tissues for testing improved DSe for both assays.

MHF: A multi-task hybrid fusion method for underwater image enhancement based on biological vision

Enhancement of underwater images is a new challenge in image research because low image visibility and contrast due to wavelength attenuation of underwater light and the effect of suspended particles in the water are most obvious. These problems can lead to difficulties in underwater information extraction and affect the development of underwater research, so we propose a multi-task hybrid fusion method (MHF) for underwater image enhancement based on biological vision. In terms of technological innovation, we designed an improved type II fuzzy set computation module based on the foundation of biological vision to improve the visibility of images. Meanwhile, we designed an adjustable contrast stretching module to improve image visibility. In addition, inspired by the fusion approach, we introduce a visual fusion module which fuses the results of the above two modules with a weight ratio. Therefore, this method focusing on multi-task synchronization can overcome the limitations of previous methods and effectively solve the problems of white balance distortion, color shift, low visibility, and low contrast in underwater images, and achieve the best results in the application tests of geometric rotation estimation, feature point matching, and edge detection. The experimental results demonstrate that the application results of this research method on 2 datasets outperform the top 14 existing algorithms. The wide applicability and excellent performance of the method are verified through application tests on various underwater vision tasks. By explicitly addressing the limitations of existing methods, the method becomes an advantageous solution in underwater image processing, providing enhancements in image quality and task-specific applications in a concise and efficient manner.

Association between radiographic severity with health-related quality of life in elderly women with knee osteoarthritis: A cross-sectional study

Background and aims Knee osteoarthritis (OA) is a common chronic condition among the elderly, leading to a decline in OA patients’ quality of life. This study aimed to investigate the relationship between radiographic severity and health-related quality of life (HRQoL) in elderly women with knee OA. Methods A total of 80 elderly women with knee OA were enrolled in this study. Radiographic severity was assessed with the Kellgren-Lawrence (K/L) scale, we divided the subjects into early (1–2) and late (3–4) according to the K/L stage. HRQoL assessment was conducted using the MOS item Short-Form 36 (SF-36). The association of HRQoL with knee OA severity was estimated using logistic regression. Applied a random forest model to assess the importance and accuracy of relevant variables in the occurrence of OA. The LASSO (Least Absolute Shrinkage and Selection Operator) regression was then used to identify key factors associated with OA, which were incorporated into the development of a risk prediction nomogram model. Furthermore, a receiver operating characteristic (ROC) curve was constructed to evaluate the model’s discriminative ability for OA. Result The mean age of the patients was 64.7 ± 6.74 years, and the mean course of disease was 5.01 ± 2.12 years. HRQoL score (SF-36 PCS and MCS) was significantly worse in the late-stage group compared to the early group (p < 0.05). The late group K/L scale has a negative correlation with SF-36 PCS (r = -0.598) and MCS (r = -0.625) and a strong positive correlation. In logistic regression analysis, the K/L scale were significantly associated with SF-36MCS (OR = 0.86, p = 0.041), SF-36 PCS (OR = 0.85, p = 0.025) and TUG (OR = 1.80, p = 0.001). The nomogram model based on key OA risk factors identified by LASSO regression demonstrated substantial predictive value for OA, with an area under the curve (AUC) of 72.2%. Conclusion The radiographic severity of knee OA was correlated with health-related quality of life. The HRQoL is an important predictive indicator of the severity of knee OA severity, which might provide beneficial management and treatment for patients with knee OA.

A conceptual and computational framework for modeling the complex, adaptive dynamics of epidemics: The case of the SARS-CoV-2 pandemic in Mexico

In the quest to ensure adequate preparedness for health emergencies caused by infectious disease pandemics, there is a need for tools that can address the myriad relevant questions related to the spread and trajectory of pandemics. A hybrid intelligence model that combines human and artificial intelligence may provide a viable solution, as it can process data from models that comprehensively integrate contextual and direct factors, effectively mimicking the social processes surrounding transmission while incorporating human interpretation to enhance our understanding of pandemics. Using data from the COVID-19 pandemic, we demonstrate the implementation of this approach with the publically available EpI-PUMA (Epidemiological Intelligence Platform for the Universidad Nacional Autónoma de México (“PUMA”)) project and platforms, where a user may create their own hybrid intelligence Bayesian classifier models for a range of epidemiological indicators of interest. EPI-Puma integrates data from various public sources (including the national registry of SARS-CoV-2 cases, census data, poverty indicators, climate data and data related to atmospheric contaminants), enabling the deployment of models that predict a range of relevant outcomes. The main criteria for the data included was its coverage (at least at the municipality level) and availability (public data). EPI-Puma was able to identify both the differential predictive value of the different sets of factors related to the epidemic path and well as anticipate with a high probability the path of the pandemic (typical areas under the ROC curve for the associated classifiers being 0.8–0.9).

Flight route EDR estimation using MHE to fuse three-dimensional wind information in the QAR data analysis

To address the problem that vertical wind data can provide information only on turbulence fluctuations in the vertical direction, meaning that the consideration of insufficiently compre-hensive turbulence information leads to low accuracy in eddy dissipation rate(EDR) estimation based on vertical wind (VWE), the paper proposes a flight route EDR estimation using MHE to fuse three-dimensional wind information in the Quick Access Recorder(QAR) data analysis. Quality control is performed on QAR data to eliminate irrelevant features for computing vertical wind and the two horizontal wind components. The corresponding formulas are then applied to obtain three-dimensional wind data information. Subsequently, a multi-head attention mechanism is employed to quantify the relationship between three-dimensional wind characteristics and the feature matrix (vertical acceleration). This process generates feature fusion weights, which are mapped onto the three-dimensional wind matrix and used to convert the three-dimensional wind data into one-dimensional wind data, thereby achieving the fusion of three-dimensional wind features. Finally, through maximum likelihood estimation(MLE) combine the new wind data in the frequency domain, the estimation of the flight route EDR is realized. Experimental results confirmed that the proposed estimation algorithm exhibits optimal performance compared to EDR estimations based on PCE and VWE, and the estimated values have smaller errors relative to the true EDR values. The proposed algorithm provides highly accurate EDR estimations for flight paths and demonstrates good practical applicability for assessing turbulence intensity along flight routes, thereby enhancing the safety of aircraft during flight.

Anti-cancer activity elucidation of geissolosimine as an MDM2-p53 interaction inhibitor: An in-silico study

For cancer treatment, Inhibition of murine double minute (MDM2) & p53 interaction is considered an attractive therapeutic approach. In this study, we performed an integrated virtual screening (i.e., QSAR, structural similarity, molecular docking, and molecular dynamic simulation) on the in-house building alkaloids library. Geissolosimine (i.e., an indole alkaloid) was predicted as a potential inhibitor for MDM2-p53 interaction. The predicted pIC50 value of Geissolosimine, was 7.013 M. Moreover, Geissolosimine showed 0.62% structural similarity to ‘SAR405838’ (i.e., a clinical trial inhibitor for MDM2-p53 interaction inhibition); and a docking score of -10.9 kcal/mol that was higher than the ‘SAR405838’.100 ns molecular dynamics simulation (MDS) was performed to validate the docking result and it exhibited better binding stability to MDM2. The pharmacokinetic & drug-likeness analysis suggested that Geissolosimine had potential to be a drug-like compound. However, in vitro & in vivo assays will be required to validate this study.

The innovation of traditional handicrafts and cultural identity: A multidimensional value analysis using the DEMATEL-ISM method

This study aims to explore how cultural identity influences the protection and innovation of traditional crafts through multidimensional pathways. Using the examples of macau shipbuilding and portuguese tile painting, 14 influencing factors were extracted from three dimensions—culture and expression, aesthetics and creation, and cognition and emotion—through the Delphi method and expert feedback. The decision-making trial and evaluation laboratory (DEMATEL) method was used to analyze causal relationships, and interpretive structural modelling (ISM) was employed to construct a hierarchical model consisting of core, direct, and indirect factors. The results indicate that historical continuity, knowledge transmission, and the integration of tradition and modernity are core factors, forming the cultural foundation for traditional craft innovation. Direct factors, such as creative expression, local culture, and emotional communication, play a pivotal role in connecting the core and indirect layers, while indirect factors like visual appeal, design originality, and craft education reflect the multidimensional value of traditional crafts. The study provides a clear, hierarchical pathway that explains the systematic process from cultural identity to innovation practice, offering valuable insights for sustainable craft innovation in the context of globalization.

Publisher Correction: Oncolytic virus VG161 in refractory hepatocellular carcinoma

Prevalence and factors associated with Tungiasis among school age children in Sub Saharan Africa: A systematic review and meta-analysis

Introduction Tungiasis is an overlooked tropical disease resulting from the penetration of the skin by sand fleas. It leads to significant suffering and can be fatal, particularly affecting school age children and elders, primarily above 60 years old, in rural and urban slums across Sub-Saharan Africa. Despite its great public health consequences, the condition remains largely under reported by the scientific communities mainly in Sub Saharan African countries. Objective To assess the prevalence of Tungiasis and associated factors among school-age children in Sub-Saharan Africa. Methods and materials This systematic review and meta-analysis was done based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA 2020). Literatures were searched from a variety of databases, including PubMed, Science-Direct, Google Scholar, Hinari, and Google. The eligible studies data were extracted using Microsoft Excel and exported to statistical software, STATA version 14 for further analysis. A random-effect model was considered to estimate the prevalence of Tungiasis. The Egger test and funnel plot were used to evaluate publication bias, whereas I2 statistic was used to measure heterogeneity. The finding of this SRMA was done using 23 selected studies with 9781 study participants. Results This review revealed that the pooled prevalence of Tungiasis was 37.86%% (95% CI: 30.95–44.77; I2 = 98.3%, P < 0.000). In terms of risk factors of Tungiasis, school children who lived with domestic animals (cat or dog) in their home were 2.73 times more likely to affected by Tungiasis compared to those without these pets in their home (OR: 2.73, 95% CI: 1.53–3.94). Additionally, school age children who did not wear shoes at all and wear occasionally were 11.26 (AOR: 11.26, 95% CI: 4.04, 18.49) and 7.61 (OR: 7.61, 95% CI: 3.39, 11.83) more likely to affected by Tungiasis compared to those who were regularly. Finally, school-age children who lived in mud-plastered walls were 4.97 times more likely to be affected by Tungiasis compared to those who lived in cemented wall homes (OR: 4.97, 95% CI: 2.61, 4.61). Conclusion Generally, this systematic review and meta-analysis disclosed that a third of school age children were affected by Tungiasis. Additionally, housing conditions, shoe-wearing practices, and the condition of living with domestic animals were factors significantly associated with Tungiasis. Hence, concerned governmental and non-governmental organizations should work to enhance behavioral modification towards prevention and control of Tungiasis. One-third of the school-aged children were affected by Tungiasis. Contributing factors included inadequate housing conditions, footwear habits, and the presence of domestic animals. Therefore, relevant governmental and non-governmental organizations should promote behavioral changes to prevent and control Tungiasis.

Fatty acid metabolism suppresses neonatal cardiomyocyte proliferation by increasing PDK4 and HMGCS2 expression through PPARδ

Cardiomyocytes lose their capacity to regenerate immediately after birth. Simultaneously, cardiomyocytes change energy metabolism from glycolysis to oxidative phosphorylation, especially using fatty acids. Accumulating evidence has revealed that fatty acid metabolism weakens the proliferative ability of cardiomyocytes. However, its underlying molecular mechanism remains unclear. In this study, we investigated how fatty acid metabolism contributes to cell cycle regulation in neonatal cardiomyocytes. Cultured neonatal rat cardiomyocytes (NRCMs) were treated with a fatty acid mixture (FA) consisting of palmitic and oleic acids containing L-carnitine. The FA treatment increased not only β-oxidation-related enzymes but also pyruvate dehydrogenase kinase 4 (PDK4), a fatty acid metabolism regulator, and HMG-CoA synthase 2 (HMGCS2), a ketogenic factor. Moreover, Ki67-positive proliferative NRCMs were reduced by the FA, indicating that fatty acids suppress the NRCM cell cycle. GW501516, a peroxisome proliferator-activated receptor δ (PPARδ) activator, also upregulated fatty acid metabolism genes and disturbed NRCM proliferation, whereas GSK3787, a PPARδ inhibitor, recovered FA-induced the cell cycle arrest. Furthermore, overexpression of PDK4 or HMGCS2 using a lentiviral vector suppressed cell cycle activity in NRCMs, and silencing either gene regained cell cycle even in FA-rich condition. In conclusion, fatty acid metabolism increased PDK4 and HMGCS2 via PPARδ activation and suppressed NRCM proliferation.

Anatomically distinct cortical tracking of music and speech by slow (1–8Hz) and fast (70–120Hz) oscillatory activity

Music and speech encode hierarchically organized structural complexity at the service of human expressiveness and communication. Previous research has shown that populations of neurons in auditory regions track the envelope of acoustic signals within the range of slow and fast oscillatory activity. However, the extent to which cortical tracking is influenced by the interplay between stimulus type, frequency band, and brain anatomy remains an open question. In this study, we reanalyzed intracranial recordings from thirty subjects implanted with electrocorticography (ECoG) grids in the left cerebral hemisphere, drawn from an existing open-access ECoG database. Participants passively watched a movie where visual scenes were accompanied by either music or speech stimuli. Cross-correlation between brain activity and the envelope of music and speech signals, along with density-based clustering analyses and linear mixed-effects modeling, revealed both anatomically overlapping and functionally distinct mapping of the tracking effect as a function of stimulus type and frequency band. We observed widespread left-hemisphere tracking of music and speech signals in the Slow Frequency Band (SFB, band-passed filtered low-frequency signal between 1–8Hz), with near zero temporal lags. In contrast, cortical tracking in the High Frequency Band (HFB, envelope of the 70–120Hz band-passed filtered signal) was higher during speech perception, was more densely concentrated in classical language processing areas, and showed a frontal-to-temporal gradient in lag values that was not observed during perception of musical stimuli. Our results highlight a complex interaction between cortical region and frequency band that shapes temporal dynamics during processing of naturalistic music and speech signals.

Exploring the impact of surgical treatment for lung cancer in patients with Airway Obstruction from a Lung Cancer Screening Program

Introduction Little information is available on the surgical treatment options for patients with Airway Obstruction (AO) and early-stage non-small cell lung cancer (NSCLC) followed in lung cancer screening programs (LCS). This study aims to compare the potential impact of anatomical sub lobar resections vs. lobectomies in these patients. Methods This is a retrospective analysis of participants who underwent surgical resections within a Lung Cancer Screening Program, including those with AO (post bronchodilator FEV1/FVC < 0.70). The short-term survival, locoregional recurrence, perioperative complications, and difference between pre and postoperative pulmonary function tests were compared between the surgical groups in those with AO. Results Anatomical sub lobar resections or lobectomies for Stages IA and IB NSCLC were performed in 133 patients. Out of these, 57 had AO. Anatomical sub lobar resections were non-inferior to lobectomies for short-term survival in patients with AO (3-year survival rate: 95.8% vs. 97%, p = 0.83). In these patients, sub lobar resections had a higher recurrence rate (12.5% vs 0%, p < 0.01). No significant differences were found in postoperative complications between surgical techniques (sub lobar 33% vs lobectomy 24%, p = 0.44). Lastly, no significant difference was found on the change between pre and postoperative FEV1 and DLCO (p = 0.96 and 0.79 for FEV1 and DLCO, respectively). Conclusions The present retrospective analysis suggests that sub lobar resection might be the best surgical option for treating early-stage NSCLC in patients with AO, where lung function preservation techniques are desired, but requires closer follow up to detect recurrence. Further studies in larger samples should confirm our findings.

A qualitative exploration of the therapeutic characteristics of the art of therapy: Perspectives on Ayres Sensory Integration

Since Dr. Jean Ayres first ignited the spark that became Ayres Sensory Integration® others have followed, inspired by her legacy to continue her dedicated life’s work. This theoretical approach continues to evolve, yet its fundamental core principles remain true to Dr Ayres’s original ideal. Empowering practitioners to set the just right challenge, an inviting therapeutic relationship, and to entice engagement through play was conceptualized as the art of therapy. This qualitative phenomenological study explores the therapeutic characteristics of the art of therapy, emphasizing the just right challenge, the therapeutic relationship and the experience of flow from the occupational therapist’s viewpoint. Eight participants kept reflective journals and engaged in semi-structured interviews which were analyzed using reflective thematic analysis. Three overarching themes were developed; 1) “The Human Connection” exploring components of the therapeutic relationship; 2) “Setting the Scene” investigating how the just right challenge is set, including the preparation and external factors involved; 3) “Magic Happens! The Optimal Experience” exploring a sense of achievement, how flow feels and how it is learned. Participants shared their unique therapeutic observations and provided clear insight into their understanding of the art of therapy. The findings demonstrated that this concept is complex and multifaceted with learning enhanced through mentorship and hands-on experiences. This highlighted the significant implications for the education and ongoing mentoring of both practicing and new clinicians. This study provided novel insight into the field of occupational therapy using Ayres Sensory Integration® by developing a deeper understanding of therapists’ experiences of the art of therapy.

Epidemiology of patients treated for multiple myeloma using a new algorithm in the French national health insurance database (SNDS): Results from the MYLORD study

Background Management of multiple myeloma (MM) has evolved in the last decade, impacting epidemiology and creating the need for a revised algorithm for patient identification in the French National Health Insurance database (SNDS). The objective of the MYLORD study was to provide up-to-date epidemiological indicators for MM using the SNDS. Methods Adults treated for MM between 2014 and 2020 were identified using hospital stays (ICD-10 code C90*) and/or Long-Term Disease status for MM (ICD-10 C90*) and treatment dispensation (MM specific treatments), or lenalidomide or thalidomide with 2 conditions: at least 2 Serum or Urine-Protein Electrophoresis performed within 4 months after the first drug dispensing and no hospital stays for other indications than MM. Results In 2020 in France, the number of new patients treated for MM was estimated at 5,608, corresponding to a world age-standardized incidence rate (ASIR) of 3.67 (3.55–3.78) per 100,000 patients. The total number of patients treated for MM was estimated at 33,675 corresponding to a world age-standardized prevalence rate (ASPR) of 22.34 (22.06–22.63) per 100,000 patients. The world ASIR slightly increased from 2014 to 2018, then slightly decreased until 2020. There is a regular increase of the ASPR every year in both men and women. Conclusions The algorithm developed for the MYLORD study considerably improves the identification of patients treated for MM in the SNDS compared to the current French references and allows to generate robust epidemiological indicators. The stable incidence and the increase in prevalence from 2014 to 2020 reflect the improvement in therapeutic management over the years.