Modifiable lifestyle factors and lifetime risk of atrial fibrillation: longitudinal data from the Korea NHIS-HealS and UK Biobank cohorts.

BACKGROUND: The reason for higher incidence of atrial fibrillation (AF) in Europe compared with East Asia is unclear. We aimed to investigate the association between modifiable lifestyle factors and lifetime risk of AF in Europe and East Asia, along with race/ethnic similarities and disparities. METHODS: 1:1 propensity score matched pairs of 242,763 East Asians and 242,763 White Europeans without AF were analyzed. Modifiable lifestyle factors considered were blood pressure, body mass index, cigarette smoking, diabetes, alcohol consumption, and physical activity, categorized as non-adverse or adverse levels. Lifetime risk of AF was estimated from the index age of 45 years to the attained age of 85 years, accounting for the competing risk of death. RESULTS: The overall lifetime risk of AF was higher in White Europeans than East Asians (20.9% vs 15.4%, p < 0.001). The lifetime risk of AF was similar between the two races in individuals with non-adverse lifestyle factor profiles (13.4% vs 12.9%, p = 0.575), whereas it was higher in White Europeans with adverse lifestyle factor profiles (22.1% vs 15.8%, p < 0.001). The difference in the lifetime risk of AF between the two races increased as the burden of adverse lifestyle factors worsened (1 adverse lifestyle factor; 4.3% to ≥ 3 adverse lifestyle factors; 11.2%). Compared with East Asians, the relative risk of AF in White Europeans was 23% and 62% higher for one (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.16-1.29) and ≥ 3 adverse lifestyle factors (HR 1.62, 95% CI 1.51-1.75), respectively. CONCLUSIONS: The overall higher lifetime risk of AF in White Europeans compared with East Asians might be attributable to adverse lifestyle factors. Adherence to healthy lifestyle factors was associated with the lifetime risk of AF of about 1 in 8 regardless of race/ethnicity.

Solving the 250-year-old mystery of the origin and global spread of the German cockroach, Blattella germanica.

The origin of the German cockroach, Blattella germanica, is enigmatic, in part because it is ubiquitous worldwide in human-built structures but absent from any natural habitats. The first historical records of this species are from ca. 250 years ago (ya) from central Europe (hence its name). However, recent research suggests that the center of diversity of the genus is Asian, where its closest relatives are found. To solve this paradox, we sampled genome-wide markers of 281 cockroaches from 17 countries across six continents. We confirm that B. germanica evolved from the Asian cockroach Blattella asahinai approximately 2,100 ya, probably by adapting to human settlements in India or Myanmar. Our genomic analyses reconstructed two primary global spread routes, one older, westward route to the Middle East coinciding with various Islamic dynasties (~1,200 ya), and another younger eastward route coinciding with the European colonial period (~390 ya). While Europe was not central to the early domestication and spread of the German cockroach, European advances in long-distance transportation and temperature-controlled housing were likely important for the more recent global spread, increasing chances of successful dispersal to and establishment in new regions. The global genetic structure of German cockroaches further supports our model, as it generally aligns with geopolitical boundaries, suggesting regional bridgehead populations established following the advent of international commerce.

Histopathologic image-based deep learning classifier for predicting platinum-based treatment responses in high-grade serous ovarian cancer.

Platinum-based chemotherapy is the cornerstone treatment for female high-grade serous ovarian carcinoma (HGSOC), but choosing an appropriate treatment for patients hinges on their responsiveness to it. Currently, no available biomarkers can promptly predict responses to platinum-based treatment. Therefore, we developed the Pathologic Risk Classifier for HGSOC (PathoRiCH), a histopathologic image-based classifier. PathoRiCH was trained on an in-house cohort (n = 394) and validated on two independent external cohorts (n = 284 and n = 136). The PathoRiCH-predicted favorable and poor response groups show significantly different platinum-free intervals in all three cohorts. Combining PathoRiCH with molecular biomarkers provides an even more powerful tool for the risk stratification of patients. The decisions of PathoRiCH are explained through visualization and a transcriptomic analysis, which bolster the reliability of our model's decisions. PathoRiCH exhibits better predictive performance than current molecular biomarkers. PathoRiCH will provide a solid foundation for developing an innovative tool to transform the current diagnostic pipeline for HGSOC.

Effects of rehabilitation exercise program types on dynamic balance in patients with stroke: a meta-analysis of randomized controlled trials.

PURPOSE: The purposes of meta-analysis are to evaluate evidence about the effects of Rehabilitation Exercise Program on the balance of post-stroke patients, evaluated by the Berg Balance Scale (BBS). METHODS: The search was conducted 'stroke,' 'rehabilitation,' 'dynamic balance,' 'Berg Balance Scale,' 'exercise' and 'randomized controlled trial'using MEDLINE (accessed by PubMed), Web of Science (WoS), ProQuest, and Google Scholar for journal studies published from January 2018 to October 2022. Two independent reviewers performed the article selection, data extraction, and methodological quality assessment. The main outcome was dynamic balance assessed by the Berg Balance scale. RESULTS: The review included 30 papers and a total of 540 patients. The overall effect size was 0.550, a medium effect size according to the Cohen's standard. It was observed that gender has moderate effect size in male (0.551), female (0.458) and higher in male. Exercise type results showed large effect sizes in balance training (0.966), and aquatic activities (0.830), moderate effect sizes in virtual reality (0.762), moderate effect sizes in physically active (0.581), gait training (0.541), dual-task (0.478), trunk control (0.284), and small effect sizes in resistance training (0.128). CONCLUSIONS: Exercise programs are effective in improving dynamic balance in stroke patients. Especially, the meta-analysis showed higher Effect Size for balance training and virtual reality than for other programs making this relevant interventions for future head to head superiority studies that compare different balance interventions in stroke.

The Effect of a Table Tennis Exercise Program With a Task-Oriented Approach on Visual Perception and Motor Performance of Adolescents With Developmental Coordination Disorder.

In this study we investigated the effects of an 8-week table tennis exercise program with a task-oriented approach on visual perception and motor performance of 31 adolescents with developmental coordination disorder (DCD). The participants were identified by their teachers as having greater difficulty than their peers (450 students from three Korean middle schools) in physical education (PE) classes. On the Bruininks-Oseretsky Test of Motor Proficiency-2, these adolescents scored below the 15th percentile and showed difficulties in performing daily life activities due to motor performance problems; they did not have physical defects, intellectual or neurological impairments, or Attention Deficit Hyperactivity Disorder. Of 98 prospective adolescents with PE difficulties, we obtained personal assent and parents' informed consent from 54, and 31 of these met screening criteria for DCD through the Developmental Coordination Disorder Questionnaire-Korean. This final group was divided in non-random fashion (based on the proximal geographic grouping of the children's schools) between an experimental group (n = 16) and a control group (n = 15). The experimental group participated in the 8-week task-oriented table tennis training program with three 90-minute sessions per week, while the control group only participated in regular PE classes twice per week. We measured participants' visual perception and motor performance in the same environment before and after the intervention program. Participants' visual perception was significantly more improved in the experimental group than the control group, with specific improved skills in visual-motor search, visual-motor speed, figure-ground, and visual closure; copying and perceptual constancy skills did not improve significantly. In addition, total motor performance and motor sub-skills, including fine manual control, manual coordination, body coordination, strength, and agility were significantly more improved in the experimental group than in the control group. Thus, our task-oriented table tennis exercise program was of greater assistance than general PE classes for improving visual perception and motor performance in adolescents at risk of DCD.

European and US Guideline-Based Statin Eligibility, Genetically Predicted Coronary Artery Disease, and the Risk of Major Coronary Events.

BACKGROUND: A study was designed to investigate whether the coronary artery disease polygenic risk score (CAD-PRS) may guide lipid-lowering treatment initiation as well as deferral in primary prevention beyond established clinical risk scores. METHODS AND RESULTS: Participants were 311 799 individuals from the UK Biobank free of atherosclerotic cardiovascular disease, diabetes, chronic kidney disease, and lipid-lowering treatment at baseline. Participants were categorized as statin indicated, statin indication unclear, or statin not indicated as defined by the European and US guidelines on statin use. For a median of 11.9 (11.2-12.6) years, 8196 major coronary events developed. CAD-PRS added to European-Systematic Coronary Risk Evaluation 2 (European-SCORE2) and US-Pooled Cohort Equation (US-PCE) identified 18% and 12% of statin-indication-unclear individuals whose risk of major coronary events were the same as or higher than the average risk of statin-indicated individuals and 16% and 12% of statin-indicated individuals whose major coronary event risks were the same as or lower than the average risk of statin-indication-unclear individuals. For major coronary and atherosclerotic cardiovascular disease events, CAD-PRS improved C-statistics greater among statin-indicated or statin-indication-unclear than statin-not-indicated individuals. For atherosclerotic cardiovascular disease events, CAD-PRS added to the European evaluation and US equation resulted in a net reclassification improvement of 13.6% (95% CI, 11.8-15.5) and 14.7% (95% CI, 13.1-16.3) among statin-indicated, 10.8% (95% CI, 9.6-12.0) and 15.3% (95% CI, 13.2-17.5) among statin-indication-unclear, and 0.9% (95% CI, 0.6-1.3) and 3.6% (95% CI, 3.0-4.2) among statin-not-indicated individuals. CONCLUSIONS: CAD-PRS may guide statin initiation as well as deferral among statin-indication-unclear or statin-indicated individuals as defined by the European and US guidelines. CAD-PRS had little clinical utility among statin-not-indicated individuals.

Rapid detection of West Nile and Dengue viruses from mosquito saliva by loop-mediated isothermal amplification and displaced probes.

Arthropod-borne viruses are major causes of human and animal disease, especially in endemic low- and middle-income countries. Mosquito-borne pathogen surveillance is essential for risk assessment and vector control responses. Sentinel chicken serosurveillance (antibody testing) and mosquito pool screening (by RT-qPCR or virus isolation) are currently used to monitor arbovirus transmission, however substantial time lags of seroconversion and/or laborious mosquito identification and RNA extraction steps sacrifice their early warning value. As a consequence, timely vector control responses are compromised. Here, we report on development of a rapid arbovirus detection system whereby adding sucrose to reagents of loop-mediated isothermal amplification with displaced probes (DP-LAMP) elicits infectious mosquitoes to feed directly upon the reagent mix and expectorate viruses into the reagents during feeding. We demonstrate that RNA from pathogenic arboviruses (West Nile and Dengue viruses) transmitted in the infectious mosquito saliva was detectable rapidly (within 45 minutes) without RNA extraction. Sucrose stabilized viral RNA at field temperatures for at least 48 hours, important for transition of this system to practical use. After thermal treatment, the DP-LAMP could be reliably visualized by a simple optical image sensor to distinguish between positive and negative samples based on fluorescence intensity. Field application of this technology could fundamentally change conventional arbovirus surveillance methods by eliminating laborious RNA extraction steps, permitting arbovirus monitoring from additional sites, and substantially reducing time needed to detect circulating pathogens.

Etiological agent and clinical characteristics of haemorrhagic fever with renal syndrome in the southern Republic of Korea: a genomic surveillance study.

OBJECTIVES: High incidences of haemorrhagic fever with renal syndrome (HFRS) have been reported in the southern Republic of Korea (ROK). A distinct southern genotype of Orthohantavirus hantanense (HTNV) was identified in Apodemus agrarius chejuensis on Jeju Island. However, its association with HFRS cases in southern ROK remains elusive. We investigated the potential of the southern HTNV genotype as an etiological agent of HFRS. METHODS: Samples from 22 patients with HFRS and 193 small mammals were collected in the southern ROK. The clinical characteristics of patients infected with the southern HTNV genotype were analysed. Amplicon-based MinION sequencing was employed for southern HTNV from patients and rodents, facilitating subsequent analyses involving phylogenetics and genetic reassortment. RESULTS: High-throughput sequencing of HTNV exhibited higher coverage with a cycle of threshold value below 32, acquiring nearly whole-genome sequences from six patients with HFRS and seven A. agrarius samples. The phylogenetic pattern of patient-derived HTNV demonstrated genetic clustering with HTNV from Apodemus species on Jeju Island and the southern Korean peninsula, revealing genetic reassortment in a single clinical sample between the M and S segments. DISCUSSION: These findings imply that the southern HTNV genotype has the potential to induce HFRS in humans. The phylogenetic inference demonstrates the diverse and dynamic characteristics of the southern HTNV tripartite genomes. Therefore, this study highlights the significance of active surveillance and amplicon sequencing for detecting orthohantavirus infections. It also raises awareness and caution for physicians regarding the emergence of a southern HTNV genotype as a cause of HFRS in the ROK.

Associations of combined polygenic risk score and glycemic status with atrial fibrillation, coronary artery disease and ischemic stroke.

BACKGROUND: It is unknown whether high hemoglobin A1c (HbA1c) is associated with increases in the risk of cardiovascular disease among individuals with elevated genetic susceptibility. We aimed to investigate the association between HbA1c and atrial fibrillation (AF), coronary artery disease (CAD), and ischemic stroke according to the polygenic risk score (PRS). METHODS: The UK Biobank cohort included 502,442 participants aged 40-70 years who were recruited from 22 assessment centers across the United Kingdom from 2006 to 2010. This study included 305,605 unrelated individuals with available PRS and assessed new-onset AF, CAD, and ischemic stroke. The participants were divided into tertiles based on the validated PRS for each outcome. Within each PRS tertiles, the risks of incident events associated with HbA1c levels were investigated and compared with HbA1c < 5.7% and low PRS. Data were analyzed from November 2022 to May 2023. RESULTS: Of 305,605 individuals, 161,605 (52.9%) were female, and the mean (SD) age was 56.6 (8.1) years. During a median follow-up of 11.9 (interquartile range 11.1-12.6) years, the incidences of AF, CAD, and ischemic stroke were 4.6, 2.9 and 1.1 per 100 person-years, respectively. Compared to individuals with HbA1c < 5.7% and low PRS, individuals with HbA1c ≥ 6.5% and high PRS had a 2.67-times higher risk for AF (hazard ratio [HR], 2.67; 95% confidence interval (CI), 2.43-2.94), 5.71-times higher risk for CAD (HR, 5.71; 95% CI, 5.14-6.33) and 2.94-times higher risk for ischemic stroke (HR, 2.94; 95% CI, 2.47-3.50). In the restricted cubic spline models, while a U-shaped trend was observed between HbA1c and the risk of AF, dose-dependent increases were observed between HbA1c and the risk of CAD and ischemic stroke regardless PRS tertile. CONCLUSIONS: Our results suggest that the nature of the dose-dependent relationship between HbA1c levels and cardiovascular disease in individuals with different PRS is outcome-specific. This adds to the evidence that PRS may play a role together with glycemic status in the development of cardiovascular disease.

Cyclohexylalanine-Containing α-Helical Amphipathic Peptide Targets Cardiolipin, Rescuing Mitochondrial Dysfunction in Kidney Injury.

Mitochondrial dysfunction is linked to degenerative diseases, resulting from cardiolipin (CL)-induced disruption of cristae structure in the inner mitochondrial membrane (IMM); therefore, preserving cristae and preventing CL remodeling offer effective strategies to maintain mitochondrial function. To identify reactive oxygen species (ROS)-blocking agents against mitochondrial dysfunction, a library of cyclohexylamine-containing cell-penetrating α-helical amphipathic "bundle" peptides were screened. Among these, CMP3013 is selectively bound to abnormal mitochondria, preserving the cristae structure impaired by mitochondria-damaging agents. With a stronger affinity for CL compared with other IMM lipid components, CMP3013 exhibited high selectivity. Consequently, it protected cristae, reduced ROS production, and enhanced adenosine triphosphate (ATP) generation. In mouse models of acute kidney injury, a 1 mg/kg dose of CMP3013 demonstrated remarkable efficacy, highlighting its potential as a therapeutic agent for mitochondrial dysfunction-related disorders. Overall, CMP3013 represents a promising agent for mitigating mitochondrial dysfunction and associated diseases.

Changes in mosquito species and blood meal composition associated with adulticide applications.

Although adulticide application is a pillar in the integrated management of nuisance and vector mosquitoes, non-target effects of adulticide applications within ecosystems are a substantial concern. However, the impacts of adulticide applications on non-target organisms are not necessarily detrimental, and in some cases, may provide benefits to certain organisms or wildlife. Here, we hypothesized that adulticide applications have beneficial non-target impacts on vertebrate wildlife through reduced biting pressure. To test this, we collected mosquitoes from ultra-low volume Permanone-treated (intervention) and untreated (reference) areas and assessed mosquito abundance and diversity, and abundance of blood-engorged female mosquitoes. We performed DNA barcoding analysis on mosquito blood meals to identify host species. Our results demonstrated a significant reduction in mosquito abundance by 58.9% in the intervention areas, taking into account the reduction in reference areas. Consequently, this decline led to a 64.5% reduction in the abundance of blood-engorged females. We also found a temporal dynamic of mosquito composition driven by mosquito control actions in which different mosquito species became dominant at treated sites while composition at reference areas remained similar during the same period. The present study suggests that the beneficial effects of mosquito control treatments for humans extend to other vertebrates, which represents an unstudied and rarely recognized non-target impact.

Enhancement of NbO2-based oscillator neuron device performance via cryogenic operation.

The Niobium Dioxide (NbO2) oscillator neuron has garnered significant interest because of its simple structure compared to conventional CMOS-based circuits. However, the limited on/off resistance ratio narrows the range of series resistances that satisfy the self-oscillation conditions and limits its use in large-scale synaptic arrays. In this study, we report the possibility of improving the performance of NbO2-based oscillator neuron devices through cryogenic operation. The study emphasizes two crucial parameters: the on/off resistance ratio and the oscillation amplitude, both of which are essential for accurate weighted sum classification. The data suggest that these parameters can be effectively enhanced under cryogenic conditions. In addition, we revealed that 120 K is the optimal temperature for cryogenic operation, as it represents the temperature where the on/off resistance ratio ceases to increase. As a result, we revealed that the series resistance range satisfying the self-oscillation condition in a single oscillator increases from 20 to 126 kΩ. The research also probes the maximum possible array size at each temperature. At 300 K, representation is only possible for a 5 × 5 array, but at 120 K, a 30 × 30 array can be represented as a frequency. The evidence implies that the 120 K conditions not only broaden the range of series resistors that can be connected to a single oscillator but also increases the array size, thereby representing different weighted sum currents as frequencies. The research indicates that using carefully optimized cryogenic operation could be a viable method to enhance the necessary NbO2properties for an oscillator neuron device.

Video Analysis of Small Bowel Capsule Endoscopy Using a Transformer Network.

Although wireless capsule endoscopy (WCE) detects small bowel diseases effectively, it has some limitations. For example, the reading process can be time consuming due to the numerous images generated per case and the lesion detection accuracy may rely on the operators' skills and experiences. Hence, many researchers have recently developed deep-learning-based methods to address these limitations. However, they tend to select only a portion of the images from a given WCE video and analyze each image individually. In this study, we note that more information can be extracted from the unused frames and the temporal relations of sequential frames. Specifically, to increase the accuracy of lesion detection without depending on experts' frame selection skills, we suggest using whole video frames as the input to the deep learning system. Thus, we propose a new Transformer-architecture-based neural encoder that takes the entire video as the input, exploiting the power of the Transformer architecture to extract long-term global correlation within and between the input frames. Subsequently, we can capture the temporal context of the input frames and the attentional features within a frame. Tests on benchmark datasets of four WCE videos showed 95.1% sensitivity and 83.4% specificity. These results may significantly advance automated lesion detection techniques for WCE images.

Deep-Learning-Based Automated Rotator Cuff Tear Screening in Three Planes of Shoulder MRI.

This study aimed to develop a screening model for rotator cuff tear detection in all three planes of routine shoulder MRI using a deep neural network. A total of 794 shoulder MRI scans (374 men and 420 women; aged 59 ± 11 years) were utilized. Three musculoskeletal radiologists labeled the rotator cuff tear. The YOLO v8 rotator cuff tear detection model was then trained; training was performed with all imaging planes simultaneously and with axial, coronal, and sagittal images separately. The performances of the models were evaluated and compared using receiver operating curves and the area under the curve (AUC). The AUC was the highest when using all imaging planes (0.94; p < 0.05). Among a single imaging plane, the axial plane showed the best performance (AUC: 0.71), followed by the sagittal (AUC: 0.70) and coronal (AUC: 0.68) imaging planes. The sensitivity and accuracy were also the highest in the model with all-plane training (0.98 and 0.96, respectively). Thus, deep-learning-based automatic rotator cuff tear detection can be useful for detecting torn areas in various regions of the rotator cuff in all three imaging planes.

Coinfection With Severe Fever With Thrombocytopenia Syndrome and Scrub Typhus in Korea.

Background: Scrub typhus and severe fever with thrombocytopenia syndrome (SFTS) are the 2 most common tick-borne infectious diseases in Korea. Every year, an increasing number of cases are reported, which is a public health concern. Therefore, we aimed to investigate the prevalence of SFTS-scrub typhus coinfection in patients with SFTS. Methods: Clinical samples were collected from 129 patients with SFTS. One-step reverse-transcription polymerase chain reaction (PCR) was performed to identify the SFTS virus (SFTSV), and real-time PCR followed by nested PCR was performed to detect the Orientia tsutsugamushi gene for scrub typhus. Phylogenetic analysis was conducted to confirm the evolutionary relationships among different species. Results: Among 129 SFTS cases, 2 patients with SFTSV were positive for O. tsutsugamushi with a prevalence of coinfection of 1.6% (95% confidence interval, .001-.06). Phylogenetic analysis confirmed these as O. tsutsugamushi strain Boryong. Conclusions: Our study found that 1.6% of patients were coinfected with SFTS and scrub typhus infection. We believe that this information will add a new dimension to clinical diagnosis, which should be considered for better public health management. Further research is needed to better understand the ecological transmission dynamics and geographical distribution of SFTSV and O. tsutsugamushi in endemic countries.

Coxiella burnetii infection in a patient with tick bite.

INTRODUCTION: We report the case of a 60-year-old male who was hospitalized with fever, headache, fatigue, nausea, and myalgia for six days. METHODOLOGY: Polymerase chain reactions (PCR) were performed on patient blood samples, and four ticks were collected from the area the patient mowed. Indirect immunofluorescence assays (IFAs) were performed on serum samples to detect specific antibodies. RESULTS: The collected ticks were identified as Haemaphysalis longicornis. Coxiella species-specific nested PCR (N-PCR) and sequencing confirmed the presence of Coxiella burnetii in the patient, and Coxiella-like bacteria were identified in three of the four ticks. IFA results showed ≥ 4-fold increases in both IgM and IgG antibody titers against Q fever. CONCLUSIONS: Despite positive PCR results for Coxiella species in both the patient and the ticks, different bacterial species were isolated, suggesting that the patient was not infected with C. burnetii through tick bites. Further investigation is required to identify the carriers or transmitters of the infection.

Closed-loop cathode recycling in solid-state batteries enabled by supramolecular electrolytes.

Deconstructing solid-state batteries (SSBs) to physically separated cathode and solid-electrolyte particles remains intensive, as does the remanufacturing of cathodes and separators from the recovered materials. To address this challenge, we designed supramolecular organo-ionic (ORION) electrolytes that are viscoelastic solids at battery operating temperatures (-40° to 45°C) yet are viscoelastic liquids above 100°C, which enables both the fabrication of high-quality SSBs and the recycling of their cathodes at end of life. SSBs implementing ORION electrolytes alongside Li metal anodes and either LFP or NMC cathodes were operated for hundreds of cycles at 45°C with less than 20% capacity fade. Using a low-temperature solvent process, we isolated the cathode from the electrolyte and demonstrated that refurbished cells recover 90% of their initial capacity and sustain it for an additional 100 cycles with 84% capacity retention in their second life.

Evaluation of humoral immune response in relation to COVID-19 severity over 1 year post-infection: critical cases higher humoral immune response than mild cases.

Introduction: Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2. We investigated the antibody response against SARS-CoV-2 until 1 year after symptom onset. Methods: We collected 314 serum samples from 97 patients with COVID-19. Antibody responses were tested using an indirect immunofluorescence assay (IFA), enzyme-linked immunosorbent assay (ELISA), and plaque reduction neutralization test (PRNT) to detect specific neutralizing antibodies. Results: The positivity rates for neutralizing antibodies at a 1:10 titer cutoff were 58.1% at 1 week, 97.8% at 4 weeks, and 78% at 1 year after symptom onset (53.8% in asymptomatic patients and 89.3% in symptomatic patients). The IFA and anti-S1 ELISA IgG results significantly correlated with neutralizing antibody titers. Critical/fatal cases showed significantly higher antibody titers than the asymptomatic or mild-to-moderate illness groups. Nonetheless, the median number of days to the seroconversion of neutralizing antibodies was 10 and 15 in asymptomatic and symptomatic patients, respectively. The asymptomatic group had a significantly higher neutralizing potency index than the mild-to-severe illness groups. Conclusions: Neutralizing antibodies corresponded to earlier seroconversion but had a shorter presence in the asymptomatic group than in the symptomatic group and were still present 1 year after symptom onset in critical/fatal cases.

Behavioral interplay between mosquito and mycolactone produced by Mycobacterium ulcerans and bacterial gene expression induced by mosquito proximity.

Mycolactone is a cytotoxic lipid metabolite produced by Mycobacterium ulcerans, the environmental pathogen responsible for Buruli ulcer, a neglected tropical disease. Mycobacterium ulcerans is prevalent in West Africa, particularly found in lentic environments, where mosquitoes also occur. Researchers hypothesize mosquitoes could serve as a transmission mechanism resulting in infection by M. ulcerans when mosquitoes pierce skin contaminated with M. ulcerans. The interplay between the pathogen, mycolactone, and mosquito is only just beginning to be explored. A triple-choice assay was conducted to determine the host-seeking preference of Aedes aegypti between M. ulcerans wildtype (MU, mycolactone active) and mutant (MUlac-, mycolactone inactive). Both qualitative and quantitative differences in volatile organic compounds' (VOCs) profiles of MU and MUlac- were determined by GC-MS. Additionally, we evaluated the interplay between Ae. aegypti proximity and M. ulcerans mRNA expression. The results showed that mosquito attraction was significantly greater (126.0%) to an artificial host treated with MU than MUlac-. We found that MU and MUlac produced differential profiles of VOCs associated with a wide range of biological importance from quorum sensing (QS) to human odor components. RT-qPCR assays showed that mycolactone upregulation was 24-fold greater for MU exposed to Ae. aegypti in direct proximity. Transcriptome data indicated significant induction of ten chromosomal genes of MU involved in stress responses and membrane protein, compared to MUlac- when directly having access to or in near mosquito proximity. Our study provides evidence of possible interkingdom interactions between unicellular and multicellular species that MU present on human skin is capable of interreacting with unrelated species (i.e., mosquitoes), altering its gene expression when mosquitoes are in direct contact or proximity, potentially impacting the production of its VOCs, and consequently leading to the stronger attraction of mosquitoes toward human hosts. This study elucidates interkingdom interactions between viable M. ulcerans bacteria and Ae. aegypti mosquitoes, which rarely have been explored in the past. Our finding opens new doors for future research in terms of disease ecology, prevalence, and pathogen dispersal outside of the M. ulcerans system.