Dual-Site Chemosensor for Visualizing •OH-GSH Redox and Tracking Ferroptosis-Inducing Pathways In Vivo.

Oxidative stress, characterized by an imbalance between oxidative and antioxidant processes, results in excessive accumulation of intracellular reactive oxygen species. Among these responses, the regulation of intracellular hydroxyl radicals (•OH) and glutathione (GSH) is vital for physiological processes. Real-time in situ monitoring these two opposing bioactive species and their redox interactions is essential for understanding physiological balance and imbalance. In this study, we developed a dual-site fluorescence chemosensor OG-3, which can independently image both exogenous and endogenous •OH and GSH in separate channels both within cells and in vivo, eliminating issues of spatiotemporal inhomogeneous distribution and cross-interference. With its imaging capabilities of monitoring •OH-GSH redox, OG-3 elucidated two different pathways for ferroptosis induction: (i) inhibition of system xc- to block cystine uptake (extrinsic pathway) and (ii) GPX4 inactivation, leading to the loss of antioxidant defense (intrinsic pathway). Moreover, we assessed the antiferroptotic function and effects of ferroptosis inhibitors by monitoring •OH and GSH fluctuations during ferroptosis. This method provides a reliable platform for identifying potential ferroptosis inhibitors, contributing to our understanding of relevant metabolic and physiological mechanisms. It shows potential for elucidating the regulation of ferroptosis mechanisms and investigating further strategies for therapeutic applications.

Liquid Metal-Doped Conductive Hydrogel for Construction of Multifunctional Sensors.

Interest in wearable and stretchable multifunctional sensors has grown rapidly in recent years. The sensing elements must accurately detect external stimuli to expand their applicability as sensors. However, the sensor's self-healing and adhesion to a target object have been major challenges in developing such practical and versatile devices. In this study, we prepared a hydrogel (LM-SA-PAA) composed of liquid metal (LM), sodium alginate (SA), and poly(acrylic acid) (PAA) with ultrastretchable, excellent self-healing, self-adhesive, and high-sensitivity sensing capabilities that enable the conformal contact between the sensor and skin even during dynamic movements. The excellent self-healing performance of the hydrogel stems from its double cross-linked networks, including physical and chemical cross-linked networks. The physical cross-link formed by the ionic interaction between the carboxyl groups of PAA and gallium ions provide the hydrogel with reversible autonomous repair properties, whereas the covalent bond provides the hydrogel with a stable and strong chemical network. Alginate forms a microgel shell around LM nanoparticles via the coordination of its carboxyl groups with Ga ions. In addition to offering exceptional colloidal stability, the alginate shell has sufficient polar groups, ensuring that the hydrogel adheres to diverse substrates. Based on the efficient electrical pathway provided by the LM, the hydrogel exhibited strain sensitivity and enabled the detection of various human motions and electrocardiographic monitoring. The preparation method is simple and versatile and can be used for the low-cost fabrication of multifunctional sensors, which have broad application prospects in human-machine interface compatibility and medical monitoring.

Mathematical and statistical models for the control of mosquito-borne diseases: the experience of Costa Rica.

Objective: To summarize the results of research conducted in Costa Rica in which mathematical and statistical methods were implemented to study the transmission dynamics of mosquito-borne diseases. Methods: Three articles with mathematical and statistical analysis on vector-borne diseases in Costa Rica were selected and reviewed. These papers show the value and relevance of using different quantitative methods to understand disease dynamics and support decision-making. Results: The results of these investigations: 1) show the impact on dengue case reports when a second pathogen emerges, such as chikungunya; 2) recover key parameters in Zika dynamics using Bayesian inference; and 3) show the use of machine learning algorithms and climatic variables to forecast the dengue relative risk in five different locations. Conclusions: Mathematical and statistical modeling enables the description of mosquito-borne disease transmission dynamics, providing quantitative information to support prevention/control methods and resource allocation planning.

Molecular Characterization and Functional Analysis of Two Steroidogenic Genes TSPO and SMAD4 in Yellow Catfish.

The steroid hormones are required for gonadal development in fish. The present study was undertaken to characterize the cDNA and promoter sequences of TSPO and SMAD4 genes in yellow catfish Pelteobagrus fulvidraco, explored the mRNA tissue expression and deciphered their promoter regions. Yellow catfish TSPO and SMAD4 shared the similar domains to the corresponding genes from other vertebrates. The TSPO and SMAD4 mRNAs were widely expressed in the detected tissues, but at different levels. Several transcription factors were predicted, such as Sp, GATA, AP1, SOX1, SRY, STAT, HNF4α, PPARγ, Pu.1 and FOXL2. PPARγ overexpression increased but STAT3 overexpression reduced TSPO promoter activity, and FOXL2 overexpression inhibited the promoter activity of TSPO and SMAD4. The site mutation and EMSA analysis indicated that TSPO promoter possessed STAT3 and FOXL2 sites. Overall, our provided the novel understanding into the transcriptionally regulatory mechanisms of TSPO and SMAD4 in fish.

Dietary Nano-ZnO Is Absorbed via Endocytosis and ZIP Pathways, Upregulates Lipogenesis, and Induces Lipotoxicity in the Intestine of Yellow Catfish.

Nano-sized zinc oxide (nano-ZnO) affects lipid deposition, but its absorption patterns and mechanisms affecting lipid metabolism are still unclear. This study was undertaken to investigate the molecular mechanism of nano-ZnO absorption and its effects on lipid metabolism in the intestinal tissues of a widely distributed freshwater teleost yellow catfish Pelteobagrus fulvidraco. We found that 100 mg/kg dietary nano-ZnO (H-Zn group) significantly increased intestinal Zn contents. The zip6 and zip10 mRNA expression levels were higher in the H-Zn group than those in the control (0 mg/kg nano-ZnO), and zip4 mRNA abundances were higher in the control than those in the L-Zn (50 mg/kg nano-ZnO) and H-Zn groups. Eps15, dynamin1, dynamin2, caveolin1, and caveolin2 mRNA expression levels tended to reduce with dietary nano-ZnO addition. Dietary nano-ZnO increased triglyceride (TG) content and the activities of the lipogenic enzymes glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), and isocitrate dehydrogenase (ICDH), upregulated the mRNA abundances of lipogenic genes 6pgd, fatty acid synthase (fas), and sterol regulatory element binding protein 1 (srebp1), and reduced the mRNA expression of farnesoid X receptor (fxr) and small heterodimer partner (shp). The SHP protein level in the H-Zn group was lower than that in the control and the L-Zn group markedly. Our in vitro study indicated that the intestinal epithelial cells (IECs) absorbed nano-ZnO via endocytosis, and nano-Zn-induced TG deposition and lipogenesis were partially attributable to the endocytosis of nano-ZnO in IECs. Mechanistically, nano-ZnO-induced TG deposition was closely related to the metal responsive transcription factor 1 (MTF-1)-SHP pathway. Thus, for the first time, we found that the lipogenesis effects of nano-ZnO probably depended on the key gene shp, which is potentially regulated by MTF1 and/or FXR. This novel signaling pathway of MTF-1 through SHP may be relevant to explain the toxic effects and lipotoxicity ascribed to dietary nano-ZnO addition.

Construction of genome-wide protein tagging cell and mouse libraries.

Mice are the most widely used model organism for the study of gene functions and disease mechanisms through the generation of gene-modified mice. Since the 1980s, different genetic manipulation technologies have been developed to reveal gene functions in vivo, including homologous recombination strategies mediated by embryonic stem cells, transgenic strategies mediated by gametes, and the latest genetic modification strategies based on CRISPR/Cas9 technology. Semi-cloning technology mediated by "artificial spermatids" (androgenetic haploid embryonic stem cells, also termed sperm-like stem cells) is developed by Chinese scientists in 2012. In combination with CRISPR/Cas9, semi-cloning technology enables one-step generation of gene-modified mice through injection of "artificial spermatids" with specific gene modifications into oocytes. It has the characteristics of short construction cycle, high efficiency, low cost, and high application compatibility. In 2017, the Center for Excellence in Molecular Cell Science (CEMCS) of CAS has launched the genome tagging project (GTP) based on "artificial spermatid"-mediated semi-cloning technology. The ambitious goal of GTP is to tag every protein in mice and construct a unique mouse library that maintains the genome-wide protein-tagging mouse models. Subsequently, the GTP center was established at CEMCS to pursue the project. GTP center developed strategies to generate protein-tagging cells and mice. Briefly, a tag sequence is precisely inserted in a specific protein- coding gene endogenously in cultured "artificial spermatids"in vitro to build a cell library, in which, each cell line carrying a specific protein tag. The tagged cells could be further used as a sperm replacement to produce tagged mice in one step upon injection into oocytes. The tagged mouse library enables global analysis of protein expression, localization, and complexes using standard tag-based assays in vivo. By April 2021, the GTP center has generated 1532 tagged cell lines, 277 of which have been successfully used to produce tagged mice through oocyte injection. A total of 242 tagged mouse strains have been distributed to 66 research teams in 32 research institutions of 15 districts in 3 countries. The database of tagging product resources has been established and released regularly on the GTP website for scientists to inquire and order. Later, more information about GTP products, such as mouse breeding, protein tissue expression map, published literature, etc., will also be successively published on the GTP website. The GTP center will provide a standardized platform for protein function research, which may dramatically promote the development of life science and clinical transformation.

Highly luminescent N-doped carbon dots as a fluorescence detecting platform for Fe3+ in solutions and living cells.

Iron (Fe3+) is one of the most essential elements in the human body; deficiency or overdose of Fe3+ may have adverse effects on human health and immunity. Hence, it is essential to establish a sensitive and selective method for ion detection. In this study, novel green fluorescent N-doped carbon dots (N-CDs) were prepared with caffeic acid as the carbon source via a simple hydrothermal method. The solution of the as-prepared N-CDs exhibits 21.5% quantum yield, good salt stability, excellent water solubility, low cytotoxicity and good photobleaching resistance. The N-CDs can be used as a fluorescent probe for the detection of Fe3+ ions in aqueous solutions and bioimaging in living cells.

Functional Analysis of Two Zinc (Zn) Transporters (ZIP3 and ZIP8) Promoters and Their Distinct Response to MTF1 and RREB1 in the Regulation of Zn Metabolism.

ZIP (zinc-regulated transporters, iron-regulated transporter-like protein) family plays an important role in organism Zn balance. This research identified the promoter regions of ZIP3 and ZIP8, two members of ZIP family, from a freshwater teleost yellow catfish Pelteobagrus fulvidraco, characterized the binding sequences of the metal-responsive transcription factor-1 (MTF-1) and Ras responsive element binding protein 1 (RREB1) on their promoter regions. The present study cloned and obtained the 2027 bp of ZIP3 promoter and 1664 bp of ZIP8 promoter, and predicted several key elements on their promoters, such as the binding sites of CREB (cAMP-response element binding protein), KLF4 (Kruppel like factor 4), MTF-1 and RREB1. The sequence deletion from -361 bp to -895 bp down-regulated the luciferase activity of ZIP3 promoter, and the deletion from -897 bp to -1664 bp down-regulated the luciferase activity of ZIP8 promoter. Within different deletion plasmids, the relative luciferase activities of ZIP3 and ZIP8 promoters changes to Zn incubation in a Zn concentration-dependent manner. The site mutagenesis and EMSA (electrophoretic mobility shift assay) found that the -1327 bp/-1343 bp MTF-1 binding site and the -248 bp/-267 bp RREB1 binding site on the ZIP3 promoter, and the -1543 bp/-1557 bp MTF-1 binding site on the ZIP8 promoter are functional sites. Low Zn increased the binding capability between MTF-1 and its responsive site on the ZIP3 promoter, and high Zn increased the transcriptional activation ZIP3 by RREB1; Zn also promoted the binding ability between MTF-1 and its responsive element on the ZIP8 promoter. This study provides the first direct evidence for the response elements of MTF-1 and RREB1 on ZIP3 and MTF-1 on ZIP8 to Zn, which are very important for the evaluation of Zn nutrition and toxicity in vertebrates.

Graphene Aerogel-Metal-Organic Framework-Based Electrochemical Method for Simultaneous Detection of Multiple Heavy-Metal Ions.

The development of an effective method for detecting heavy-metal ions remains a serious task because of their high toxicity to public health and environments. Herein, a new electrochemical method based on a graphene aerogel (GA) and metal-organic framework (MOF) composites was developed for simultaneous detection of multiple heavy-metal ions in aqueous solutions. The GA-MOF composites were synthesized via the in situ growth of the MOF UiO-66-NH2 crystal on the GA matrix. GA not only serves as the backbone for UiO-66-NH2 but also enhances the conductivity of the composites by accelerating the electron transfer in the matrix. UiO-66-NH2 worked as a binding site for heavy-metal ions because of the interaction between hydrophilic groups and metal cations. The detection performance of the GA-UiO-66-NH2 composite-modified electrodes was determined. The developed electrochemical method can be successfully applied for individual and simultaneous detection of heavy-metal ions, namely, Cd2+, Pb2+, Cu2+,and Hg2+, in aqueous solutions with high sensitivity and selectivity. The method can also be used for simultaneous detection of Cd2+, Pb2+, Cu2+, and Hg2+ in river water and the leaching solutions of soil and vegetable with high accuracy and reliability. This work provides a new approach for simultaneous detection of multiple heavy-metal ions in practical applications.

GaCl3-Catalyzed C-H Cyanation of Indoles with N-Cyanosuccinimide.

An efficient GaCl3-catalyzed direct cyanation of indoles and pyrroles using bench-stable electrophilic cyanating agent N-cyanosuccinimide was achieved and afforded 3-cyanoindoles and 2-cyanopyrroles in good yields and excellent regioselectivities. Notably, this protocol exhibited high reactivity for unprotected indoles and was applicable to a broad range of indole and pyrrole substrates.

Cancer-associated fibroblasts provide a suitable microenvironment for tumor development and progression in oral tongue squamous cancer.

BACKGROUND: Oral tongue squamous cell carcinoma (OTSCC) is still associated with a poor prognosis due to local recurrence and metastasis. Cancer-associated fibroblasts (CAFs) play an important role in the complex processes of cancer stroma interaction and tumorigenesis. This study aims to determine the role of CAFs in the development and progression of OTSCC. METHODS: Immunohistochemistry was performed to evaluate the frequency and distribution of CAFs in 178 paraffin specimens from patients with OTSCC. Immunofluorescence, a cell proliferation assay, flow cytometry, migration and invasion assays and western blot analysis were used to study the effects of CAFs and the corresponding conditioned medium (CM) on the proliferation and invasion of OTSCC cell lines. RESULTS: Statistical analysis showed a strong correlation between the frequency and distribution of CAFs and the clinicopathological characteristics of patients with cN0 OTSCC, including pathological stage (P = 0.001), T classification (P = 0.001), and N classification (P = 0.009). Survival analysis demonstrated a negative correlation of the frequency and distribution of CAFs with the overall survival and disease-free survival of patients with cN0 tongue squamous cell cancer (P = 0.009, 0.002, respectively); Cox regression analysis showed that the presence of CAFs (relative risk: 2.113, CI 1.461-3.015, P = 0.023) is an independent prognostic factor. A functional study demonstrated that CAFs and CM from CAFs could promote the growth, proliferation, mobility, invasion and even Epithelial Mesenchymal Transition (EMT) of OTSCC cells compared with NFs and CM from NFs. CONCLUSIONS: CAFs were an independent prognostic factor for patients with OTSCC. Compared with NFs, CAFs and their CM have the ability to promote the growth, proliferation, metastasis and even EMT of OTSCC cells.

Synthesis and antifungal activity of ethers, alcohols, and iodohydrin derivatives of sclareol against phytopathogenic fungi in vitro.

This study synthesized 20 sclareol derivatives. The antifungal activities of these derivatives were evaluated in vitro against five phytopathogenic fungi using the mycelium growth rate method. Among all the tested compounds, compound 16 with one iodine atom and three hydroxyl groups displayed higher fungicidal activities against all the tested phytopathogenic fungi than precursor sclareol. Compound 16 also showed more pronounced antifungal activities against Curvularia lunata (IC50=12.09 µg/mL) and Alternaria brassicae (IC50=14.47 µg/mL) than the positive control, a commercial agricultural fungicide thiabendazole.

Direct carotid-cavernous fistula after functional endoscopic sinus surgery - A case report.

INTRODUCTION AND IMPORTANCE: Direct carotid-cavernous fistulas (CCF) are primarily caused by head trauma. Some cases have also been attributed to iatrogenic injuries during endovascular procedures. However, the reports of functional endoscopic sinus surgery (FESS) associated with direct CCFs are extremely rare. PRESENTATION OF CASE: A 52-year-old male worker, who suffered from chronic sinusitis and underwent functional endoscopic sinus surgery (FESS) performed by an otolaryngologist. Intra-operative finding indicated a left sphenoid sinus wall injury without internal carotid artery bleeding, which was repaired using mucosa and tissue glue. One month after discharge, he began experiencing tinnitus, headache and swelling in his left eye. Cerebral angiography revealed a direct carotid-cavernous fistula (CCF) on the left side. The patient underwent transarterial and transvenous stent-assisted coiling using detachable coils and Onyx, which alleviated his symptoms. CLINICAL DISCUSSION: A cavernous-carotid fistula following FESS is an exceedingly rare occurrence first reported by Karaman et al. in 2009. The incidence of internal carotid artery injury during FESS or endonasal endoscopic surgery (EES) is estimated to be between 0 and 0.1 %. Currently, there is no definitive explanation for the development of a carotid-cavernous fistula (CCF) post-FESS. Previous studies suggest that procedures like transsphenoidal surgery and EES can induce pseudoaneurysms in the internal carotid artery. If the cavernous pseudoaneurysm ruptures, it could lead to the formation of a CCF. CONCLUSION: A direct cavernous-carotid fistula following functional endoscopic sinus surgery is a very rare. Consequently, when encountering patients with a carotid-cavernous fistula, relevant procedure history should be considered.

Does Deep Squat Quality Affect the Propulsion of Baseball Throwing?

This study investigates the influence of the quality of the "deep squat" movement, adapted from the Functional Movement Screen (FMS) system, on the lower extremity movement pattern during baseball throwing, and its potential impact on throwing performance and propulsion efficiency. Twenty-two baseball players were recruited and categorized into two groups: 13 in the high-score squat group (HSS) and 9 in the low-score squat group (LSS), based on their deep squat screening results. This research explored disparities in ball velocity, propulsion efficiency, propulsion ground reaction force (GRF) characteristics, and throwing kinematics between these two groups. The findings revealed no significant difference in ball velocity between the groups. However, the LSS group demonstrated a lower propulsion GRF efficiency (p < 0.030, ES = 0.46), along with a higher vertical peak GRF (p < 0.002, ES = 0.66). In the pivot leg, the HSS group exhibited significantly lower impulse forces in the Impulse Fresultant (p < 0.035, ES = 0.45), throwing direction (p < 0.049, ES = 0.42), and vertical direction (p < 0.048, ES = 0.42). Additionally, the contribution to the ball velocity of the pivot leg was significantly greater in the HSS group, along with significantly better efficiency in Impulse Fresultant (p < 0.035, ES = 0.45), throwing direction (p < 0.053, ES = 0.41), and vertical direction (p < 0.032, ES = 0.46). In the leading leg, the HSS group demonstrated significantly lower impulse forces in the Impulse Fresultant (p < 0.001, ES = 0.69), throwing direction (p < 0.007, ES = 0.58), and vertical direction (p < 0.001, ES = 0.70). Moreover, the contribution to the ball velocity of the leading leg was significantly greater in the HSS group, accompanied by significantly better efficiency in Impulse Fresultant (p < 0.003, ES = 0.63), throwing direction (p < 0.005, ES = 0.60), and vertical direction (p < 0.021, ES = 0.49). In conclusion, this study suggests that squat screening is a valuable tool for assessing propulsion efficiency. Coaches and trainers should be mindful of players with low squat quality but high throwing performance, as they may face increased impact and injury risks in the future.

Correction: Polydiacetylene-based colorimetric and fluorometric sensors for lead ion recognition.

[This corrects the article DOI: 10.1039/D2RA03435B.].

Comparison of ground reaction force among stride types in baseball pitching.

This study aims to investigate the different ground reaction force (GRF) characteristics from different stride types. This study included 30 Taiwanese elite college and professional baseball pitchers. Each pitcher was classified into one of the following stride types: tall and fall (TF), dip and drive (DD), or mixed (MX). Our findings indicated that DD pitchers pressed their bodies forward earlier than TF pitchers. In contrast, the GRF of the pivot leg of TF pitchers increased slowly in the first half of the stride phase and continued to increase even after the stride leg touched the ground. This type of continuous pressing in TF was different from that in DD and MX pitchers, which decreased rapidly into the arm-cocking & acceleration phases. We conclude that the lower extremities were used differently by TF, DD and MX pitchers. This information could serve as a training guideline for coaches and pitchers to enhance training effectiveness, while simultaneously lowering injury risks.

Time to Local Recurrence as a Predictor of Survival in Adult Head and Neck Soft Tissue Sarcoma.

OBJECTIVES: We sought to evaluate the impact of the time interval from surgical resection to local recurrence (TTLR) on clinical outcomes in head and neck soft tissue sarcoma (HNSTS). METHODS: A total of 401 patients who underwent R0 resection for primary HNSTS were included in this study. Patients with local recurrence as the first event after their initial resection were divided into early local recurrence (ELR) or late local recurrence (LLR) groups according to TTLR. Multiple survival analyses were performed to identify the independent prognostic predictors of overall survival (OS) and survival after local recurrence (SAR). RESULTS: Two hundred and nine of the 401 patients (52.1%) developed local recurrence during a median follow-up period of 134.6 months. Patients in the ELR group had a shorter median OS time (35.0 vs. 120.6, p < 0.001) and lower 5-year OS rate (47.7% vs. 80.9%, p < 0.001) than those in the LLR group. Moreover, the ELR group exhibited worse SAR (p = 0.001) than the LLR group, and multivariate analyses demonstrated TTLR as an independent prognostic factor for SAR (p = 0.048) and OS (p = 0.004). Additionally, re-resection significantly prolonged SAR than other salvage interventions or no treatment (p < 0.001). CONCLUSION: In patients with HNSTS, ELR after R0 resection presents adverse effects on OS and SAR than those with LLR, and TTLR could serve as a promising predictor for survival. Salvage therapies, especially the re-resection could improve SAR and should be recommended when there are surgical indications after recurrence. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2174-2182, 2023.

Treatment outcomes of mucosal melanoma of the head and neck: Analysis of 190 cases from a single institution.

Objectives: To analyze the treatment outcomes and prognostic factors of mucosal melanoma of the head and neck (MMHN) from a single institution. Methods: From December 1989 to November 2018, 190 patients diagnosed with MMHN were included. Survival analysis was performed using the Kaplan-Meier method for univariate analysis with a log-rank test for significance and Cox regression for multivariate analysis. Results: With a median follow-up time of 43.5 months, 126 (68.5%) patients died. The median DSS was 35 months. The 3- and 5-year disease-specific survival (DSS) rates were 48.1% and 33.7%, respectively. The median overall survival (OS) was 34 months. The 3- and 5-year OS rates were 47.0% and 32.9%, respectively. In univariate analysis, the T3 stage, received surgery, R0 resection, and combined therapy (surgery+biotherapy/biochemotherapy) were significantly associated with better survival. Multivariable Cox regression analysis revealed that the T4 stage (HR = 1.692; 95% CI, 1.175-2.438; p = .005) and the N1 stage (HR = 1.600; 95% CI, 1.023-2.504; p = .039) were strong prognostic factors for poor survival, and that combined therapy (surgery+biotherapy/biochemotherapy) was a strong prognostic factor for better survival outcome (HR = 0.563; 95% CI, 0.354-0.896; p = .015). Conclusion: The prognosis of MMHN remains poor. Systemic treatment is warranted to reduce MMHN progression. Surgery combined with biotherapy may improve survival.

Assessing dengue fever risk in Costa Rica by using climate variables and machine learning techniques.

Dengue fever is a vector-borne disease affecting millions yearly, mostly in tropical and subtropical countries. Driven mainly by social and environmental factors, dengue incidence and geographical expansion have increased in recent decades. Therefore, understanding how climate variables drive dengue outbreaks is challenging and a problem of interest for decision-makers that could aid in improving surveillance and resource allocation. Here, we explore the effect of climate variables on relative dengue risk in 32 cantons of interest for public health authorities in Costa Rica. Relative dengue risk is forecast using a Generalized Additive Model for location, scale, and shape and a Random Forest approach. Models use a training period from 2000 to 2020 and predicted climatic variables obtained with a vector auto-regressive model. Results show reliable projections, and climate variables predictions allow for a prospective instead of a retrospective study.

Common patterns between dengue cases, climate, and local environmental variables in Costa Rica: A wavelet approach.

Dengue transmission poses significant challenges for public health authorities worldwide due to its susceptibility to various factors, including environmental and climate variability, affecting its incidence and geographic spread. This study focuses on Costa Rica, a country characterized by diverse microclimates nearby, where dengue has been endemic since its introduction in 1993. Using wavelet coherence and clustering analysis, we performed a time-series analysis to uncover the intricate connections between climate, local environmental factors, and dengue occurrences. The findings indicate that multiannual dengue frequency (3 yr) is correlated with the Oceanic Niño Index and the Tropical North Atlantic Index. This association is particularly prominent in cantons located along the North and South Pacific Coast, as well as in the Central cantons of the country. Furthermore, the time series of these climate indices exhibit a leading phase of approximately nine months ahead of dengue cases. Additionally, the clustering analysis uncovers non-contiguous groups of cantons that exhibit similar correlation patterns, irrespective of their proximity or adjacency. This highlights the significance of climate factors in influencing dengue dynamics across diverse regions, regardless of spatial closeness or distance between them. On the other hand, the annual dengue frequency was correlated with local environmental indices. A persistent correlation between dengue cases and local environmental variables is observed over time in the North Pacific and the Central Region of the country's Northwest, with environmental factors leading by less than three months. These findings contribute to understanding dengue transmission's spatial and temporal dynamics in Costa Rica, highlighting the importance of climate and local environmental factors in dengue surveillance and control efforts.