Dissemination Rates Research Articles

Clinical Benefits of Photodynamic Therapy Using Talaporfin Sodium in Patients With Isocitrate Dehydrogenase-Wildtype Diagnosed Glioblastoma: A Retrospective Study of 100 Cases.

Photodynamic therapy (PDT) with talaporfin sodium is an intraoperative local therapy administered after the surgical removal of malignant gliomas. However, its clinical efficacy in a large patient population has not been determined. To analyze the clinical outcomes and prognosis in isocitrate dehydrogenase (IDH)-wildtype glioblastoma patients treated with PDT. This retrospective study included patients with newly diagnosed IDH-wildtype glioblastoma treated at Kobe University Hospital between January 2013 and December 2022. PDT involves irradiation of the resection cavity with a 664-nm semiconductor laser after an intravenous infusion of talaporfin sodium. The main outcome measures were the recurrence patterns and survival times, which were compared between the PDT and non-PDT groups. Univariate and multivariate analyses were used to determine the prognostic factors. In addition, adverse events and prognostic factors in the PDT group were analyzed. A total of 44 and 56 patients were included in the PDT and non-PDT groups, respectively. The local recurrence rate was significantly lower in the PDT group than in the non-PDT group (51.3% vs 83.9%), whereas the distant recurrence and dissemination rates were significantly higher in the PDT group than in the non-PDT group (48.7% vs 16.1%). Two grade 3 adverse events were observed in the PDT group. The median progression-free survival and overall survival times were significantly longer in the PDT group than in the non-PDT group (progression-free survival: 10.8 vs 9.3 months, respectively, and overall survival: 24.6 vs 17.6 months, respectively). Multivariate analysis of the PDT groups revealed that younger age was an independent prognostic factor. PDT with talaporfin sodium provided effective local control with minimal adverse effects. The survival time of the patients treated with PDT was significantly longer than that of the patients who did not receive PDT. Therefore, a randomized controlled clinical trial on PDT is warranted.

WNV and SLEV coinfection in avian and mosquito hosts: impact on viremia, antibody responses, and vector competence.

West Nile virus (WNV) and St. Louis encephalitis virus (SLEV) are closely related flaviviruses that can cause encephalitis in humans and related diseases in animals. In nature, both are transmitted by Culex, with wild birds, including jays, sparrows, and robins, serving as vertebrate hosts. WNV and SLEV circulate in the same environments and have recently caused concurrent disease outbreaks in humans. The extent that coinfection of mosquitoes or birds may alter transmission dynamics, however, is not well characterized. We therefore sought to determine if coinfection alters infection kinetics and virus levels in birds and infection rates in mosquitoes. Accordingly, American robins (Turdus migratorius), two species of mosquitoes, and vertebrate and invertebrate cells were infected with WNV and/or SLEV to assess how simultaneous exposure may alter infection outcomes. There was variable impact of coinfection in vertebrate cells, with some evidence that SLEV can suppress WNV replication. However, robins had comparable viremia and antibody responses regardless of coinfection. Conversely, in Culex cells and mosquitoes, we saw a minimal impact of simultaneous exposure to both viruses on replication, with comparable infection, dissemination, and transmission rates in singly infected and coinfected mosquitoes. Importantly, while WNV and SLEV levels in coinfected mosquito midguts were positively correlated, we saw no correlation between them in salivary glands and saliva. These results reveal that while coinfection can occur in both avian and mosquito hosts, the viruses minimally impact one another. The potential for coinfection to alter virus population structure or the likelihood of rare genotypes emerging remains unknown.IMPORTANCEWest Nile virus (WNV) and St. Louis encephalitis virus (SLEV) are closely related viruses that are transmitted by the same mosquitoes and infect the same birds in nature. Both viruses circulate in the same regions and have caused concurrent outbreaks in humans. It is possible that mosquitoes, birds, and/or humans could be infected with both WNV and SLEV simultaneously, as has been observed with Zika, chikungunya, and dengue viruses. To study the impact of coinfection, we experimentally infected vertebrate and invertebrate cells, American robins, and two Culex species with WNV and/or SLEV. Robins were efficiently coinfected, with no impact of coinfection on virus levels or immune response. Similarly, in mosquitoes, coinfection did not impact infection rates, and mosquitoes could transmit both WNV and SLEV together. These results reveal that WNV and SLEV coinfection in birds and mosquitoes can occur in nature, which may impact public health and human disease risk.

Vector Competence of Aedes aegypti from São Tomé and Príncipe for West Nile Virus Transmission.

The global distribution of Aedes aegypti mosquitoes, particularly in tropical regions, poses a significant public health risk due to their apparent ability to transmit arboviruses such as West Nile virus (WNV). This study aimed to evaluate the vector competence of Ae. aegypti from São Tomé and Príncipe (STP) for the transmission of the WNV PT6.39 strain, considering its potential role as a bridge vector in a region where Culex quinquefasciatus would be the main vector. Aedes aegypti mosquitoes were collected, reared, and experimentally infected with WNV, with viral dissemination and transmission potential assessed 7, 14, and 21 days post infection (dpi). The results showed an increasing trend in infection rates, from 5% at 7 dpi to 35% at 21 dpi, with corresponding dissemination rates of 0%, 100%, and 43%. The transmission rates also increased from 0% at 7 dpi to 67% at 21 dpi, with a maximum transmission efficiency of 10% observed at the final time point. Although Ae. aegypti from STP demonstrated the potential to transmit WNV, the overall transmission efficiency remained relatively low. These findings provide necessary insights into the vector competence of Ae. aegypti in this region, highlighting the importance of continued monitoring and targeted vector control measures to mitigate the risk of potential WNV outbreaks.

Vulvar Paget’s Disease with Inguinal Lymph Node Metastasis: A Case Report

Vulvar Paget's disease is a clinical condition with an invariable course affecting women of advanced age, and is associated with a significant rate of recurrence and dissemination, especially in its invasive form, which has a high metastatic potential. Here we present details of a unique case involving a 77-year-old woman with a history of disease progression over more than a decade. She initially presented with an erythematous lesion in the vulvar region, which was later diagnosed as adenocarcinoma in situ. During follow-up, the affected area extended to the perineal and gluteal regions, indicating an invasive aspect of the tumor. Due to surgical oncology recommendations, tissue resection was not feasible. The pacient experienced a significant worsening of symptoms, including local peeling of the affected region, and a biopsy confirmed Paget's disease in the vulvar region. Subsequently, imaging tests indicated changes in the volume of the inguinal lymph nodes. The patient underwent lymphadenectomy for histological analysis and to prevent systemic dissemination. Indicators of lymph node metastasis, suggestive of a gynecological primary site, were observed. Our case provides valuable insights for pathologists to consider the differential diagnosis of vulvar lesions.

Bifurcation Analysis and Optimal Control of an SEIR Model with Limited Medical Resources and Media Impact on Heterogeneous Networks

The spread of epidemic diseases is often considered to be bound up with human behavior. Both treatment and awareness-raising are seen as important preventive measures during an outbreak. In this paper, an SEIR model on heterogeneous network containing saturated treatment function with media information variable is constructed. Through mathematical analysis, the basic reproduction number and equilibriums of the system are derived. The global stability of disease-free equilibrium is further proved based on LaSalle’s invariant principle. It is also found that with a gradual increase of the delayed treatment parameter, the system exhibits a transition from forward bifurcation to backward bifurcation with the variation of the basic reproduction number. Finally, an optimal control problem is formulated with both treatment rate and media information dissemination rate as control variables and solved using the Pontryagin’s maximum principle. All the above results are verified by numerical experiments.

Central nervous system dissemination in spinal cord astrocytomas: association with H3 K27M mutation

OBJECTIVE Patients with spinal cord astrocytomas (SCAs) are at high risk for CNS dissemination, yet comprehensive data on characteristics of dissemination are lacking. This study depicts the exact incidence and patterns of dissemination by analyzing data from a large-scale dataset of SCA. METHODS The authors included 94 patients with SCA based on the 2021 WHO classification from 2011 to 2022, retrospectively collected their clinical and pathological characteristics, and analyzed factors influencing SCA dissemination. RESULTS CNS dissemination, encompassing leptomeningeal spreading and/or subarachnoid seeding, was evaluated in 94 patients with and without H3 K27 alterations, with an overall dissemination rate reaching 85.0% at 5-year follow-up. Patients with altered H3 K27 had a significantly higher 5-year CNS dissemination rate than patients with H3 K27 wildtype status (95.2% vs 68.0%, p = 0.002). The median dissemination-free survival in H3 K27–altered patients was 14.37 (95% CI 2.84–25.89) months, significantly shorter than those with H3 K27 wildtype (statistics not calculated; p < 0.001). Based on univariate Cox regression analysis, H3 K27M alteration, higher histopathological grade, Ki-67 index (≥ 10%), and tumor length (≥ 4 segments) were identified as potential factors associated with CNS dissemination in SCAs. Multivariate Cox regression analysis revealed that H3 K27M alteration appeared to be a risk factor for this phenomenon (HR 2.089, 95% CI 0.940–4.642, p = 0.070). Following dissemination, H3 K27–altered patients had a median postdissemination survival of 8.83 (95% CI 7.13–10.54) months, which was significantly shorter than the 13.40 (95% CI 3.98–34.26) months in those with H3 K27 wildtype (p = 0.008). CONCLUSIONS Factors indicative of higher SCA malignancy, such as H3 K27M alteration, higher histopathological grade, Ki-67 index (≥ 10%), and tumor length (≥ 4 segments), were similarly suggestive of higher rates of dissemination. The occurrence of dissemination is closely associated with the outcome events in patients with SCA.

Future worldwide coronavirus disease 2019 epidemic predictions by Gaidai multivariate risk evaluation method.

Accurate estimation of pandemic likelihood in every US state of interest and at any time. Coronavirus disease 2019 (COVID-19) is an infectious illness with a high potential for global dissemination and low rates of fatality and morbidity, placing some strains on national public health systems. This research intends to benchmark a novel technique, that enables hazard assessment, based on available clinical data, and dynamically observed patient numbers while taking into account pertinent territorial and temporal mapping. Multicentre, population-based, and biostatistical strategies have been utilized to process raw/unfiltered medical survey data. The expansion of extreme value statistics from the univariate to the bivariate situation meets with numerous challenges. First, the univariate extreme value types theorem cannot be directly extended to the bivariate (2D) case,-not to mention challenges with system dimensionality higher than 2D. Assessing outbreak risks of future outbreaks in any nation/region of interest. Existing bio-statistical approaches do not always have the benefits of effectively handling large regional dimensionality and cross-correlation between various regional observations. These methods deal with temporal observations of multi-regional phenomena. Apply contemporary, novel statistical/reliability techniques directly to raw/unfiltered clinical data. The current study outlines a novel bio-system hazard assessment technique that is particularly suited for multi-regional environmental, bio, and public health systems, observed over a representative period. With the use of the Gaidai multivariate hazard assessment approach, epidemic outbreak spatiotemporal risks may be properly assessed. Based on raw/unfiltered clinical survey data, the Gaidai multivariate hazard assessment approach may be applied to a variety of public health applications. The study's primary finding was an assessment of the risks of epidemic outbreaks, along with a matching confidence range. Future global COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-COV2) epidemic risks have been examined in the current study; however, COVID-19/SARS-COV2 infection transmission mechanisms have not been discussed.

Clinical immunological characteristics of anti-interferon-γ autoantibodies syndrome: a 3 year prospective cohort study

ABSTRACT Anti-interferon-γ autoantibodies (AIGAs) syndrome is susceptible to disseminated opportunistic infections due to increased AIGAs, but its clinical immunological characteristics remain unrecognized. We conducted a prospective cohort study between January 2021 and December 2023, recruiting patients with opportunistic infections who were categorized into AIGAs-positive and AIGAs-negative groups. Clinical immunological data and outcomes were documented. A subset of AIGAs-positive patients received glucocorticoid treatment, and its effectiveness was evaluated. A total of 238 patients were enrolled, with 135 AIGAs-positive and 103 AIGAs-negative patients. AIGAs-positive patients showed higher rates of multiple pathogen dissemination, shorter progression-free survival (PFS), and increased exacerbation frequency. They also showed elevated erythrocyte sedimentation rate (ESR), globulin (GLB), immunoglobulin (Ig)G, IgE, and IgG4 levels. Among the 70 AIGAs-positive patients monitored for at least six months, three subtypes were identified: high AIGAs titer with immune damage, high AIGAs titer without immune damage, and low AIGAs titer without immune damage. Of the 55 patients followed for 1 year, decreasing AIGAs titer and immune indices (GLB, IgG, IgE, IgG4) were observed. Among the 31 patients with high AIGAs titer and immune damage treated with low-dose glucocorticoids at the stable phase, reductions were observed in immune indices and AIGAs titer in 67.74% of cases. In summary, AIGAs-positive patients exhibit infectious and immunological characteristics. Elevated AIGAs, IgG, IgG4, and IgE indicate abnormal immune damages. AIGAs titer generally decrease over time. Stable-phase AIGAs-positive patients can be categorized into three subtypes, with those having high AIGAs titer and increased immune indices potentially benefitting from glucocorticoid treatment.

Insights of infected Schwann cells extinction and inherited randomness in a stochastic model of leprosy

Investigating disease progression, transmission of infection and impacts of Multidrug Therapy (MDT) to inhibit demyelination in leprosy involves a certain amount of difficulty in terms of the in-built uncertain complicated and complex intracellular cell dynamical interactions. To tackle this scenario and to elucidate a more realistic, rationalistic approach of examining the infection mechanism and associated drug therapeutic interventions, we propose a four-dimensional ordinary differential equation-based model. Stochastic processes has been employed on this deterministic system by formulating the Kolmogorov forward equation introducing a transition state and the quasi-stationary distribution, exact distribution analysis have been investigated which allow us to estimate an expected time to extinction of the infected Schwann cells into the human body more prominently. Additionally, to explore the impact of uncertainty in the key intracellular factors, the stochastic system is investigated incorporating random perturbations and environmental noises in the disease dissemination, proliferation and reinfection rates. Rigorous numerical simulations validating the analytical outcomes provide us significant novel insights on the progression of leprosy and unravelling the existing major treatment complexities. Analytical experiments along with the simulations utilizing Monte-Carlo method and Euler–Maruyama scheme involving stochasticity predicts that the bacterial density is underestimated due to the recurrence of infection and suggests that maintaining a drug-efficacy rate in the range 0.6−0.8 would be substantially efficacious in eradicating leprosy.

Gamma-Irradiated Female Aedes aegypti Mosquitoes Exhibit Greater Susceptibility to Mayaro Virus.

Mayaro virus (MAYV) is an alphavirus endemic in many parts of Central and South America transmitted to humans by Aedes aegypti. Currently, there is no vaccine or treatment of Mayaro infection, and therefore it is essential to control transmission by reducing populations of Ae. aegypti. Unfortunately, Ae. aegypti are extremely difficult to control with traditional integrated vector management (IVM) because of factors such as growing resistance to a dwindling list of registered insecticides and cryptic immature and adult habitats. The sterile insect technique (SIT) by irradiation is gaining traction as a novel supplemental tool to IVM. The SIT is being used operationally to release large numbers of sterilized colony-reared male mosquitoes in an intervention area to overwhelm females in the natural population, eventually causing population decline because of high frequencies of unfertilized eggs. However, little is known about the effect of irradiation on vector competence for mosquito-borne viruses such as MAYV in females that may be accidentally reared, irradiated, and released alongside males. In this investigation, we exposed female Ae. aegypti pupae to radiation and evaluated vector competence after inoculation with MAYV. Infection and dissemination rates of irradiated (10 and 40 Gy) Ae. aegypti were higher than those of non-irradiated cohorts at 7 and 14 days after infection. Although these results indicate a need to maintain effective sex sorting prior to irradiation and release of Ae. aegypti, our results are consistent with several previous observations that vectorial capacity and vector competence are likely lower in irradiated than in nonirradiated females.

An innovative fractional-order evolutionary game theoretical study of personal protection, quarantine, and isolation policies for combating epidemic diseases

This study uses imposed control techniques and vaccination game theory to study disease dynamics with transitory or diminishing immunity. Our model uses the ABC fractional-order derivative mechanism to show the effect of non-pharmaceutical interventions such as personal protection or awareness, quarantine, and isolation to simulate the essential control strategies against an infectious disease spread in an infinite and uniformly distributed population. A comprehensive evolutionary game theory study quantified the significant influence of people’s vaccination choices, with government forces participating in vaccination programs to improve obligatory control measures to reduce epidemic spread. This model uses the intervention options described above as a control strategy to reduce disease prevalence in human societies. Again, our simulated results show that a combined control strategy works exquisitely when the disease spreads even faster. A sluggish dissemination rate slows an epidemic outbreak, but modest control techniques can reestablish a disease-free equilibrium. Preventive vaccination regulates the border between the three phases, while personal protection, quarantine, and isolation methods reduce disease transmission in existing places. Thus, successfully combining these three intervention measures reduces epidemic or pandemic size, as represented by line graphs and 3D surface diagrams. For the first time, we use a fractional-order derivate to display the phase-portrayed trajectory graph to show the model’s dynamics if immunity wanes at a specific pace, considering various vaccination cost and effectiveness settings.

Energy efficient clustering and sink mobility protocol using Improved Dingo and Boosted Beluga Whale Optimization Algorithm for extending network lifetime in WSNs

In Wireless Sensor Networks (WSNs), the potential design challenge of energy efficiency is determined to be handled through the strategies of clustering and routing. The approaches of clustering and routing in WSNs pertain to the problems of Non-deterministic Polynomial (NP)-hard optimization. In this context, swarm intelligence-based algorithms are identified to be suitable and ideal for determining near-optimal and optimal solutions in the search space. On the other hand, APTEEN routing protocol possesses the issues that are related to unnecessary energy drain, ineffective overall network coverage and premature death of certain nodes. To address these issues, an attempt to optimize the APTEEN routing protocol using Dingo Optimization Algorithm (DOA) and Beluga Whale Optimization Algorithm (BWOA) is made in this proposed clustering protocol. With this motivation, Improved Dingo and Boosted Beluga Whale Optimization Algorithm (IDBBWOA) is proposed for determining the optimal cluster head and perform energy-efficient routing to minimized the energy consumption and maximize the lifetime of the network. It specifically used Improved Dingo Optimization Algorithm (IDOA) for attaining cluster head (CH) selection and energy efficient routing through the adoption fitness parameters of Residual Energy, Distance within and between Clusters, Network coverage, Node Degree for maximizing the rate of reliable data dissemination. It also incorporated Boosted Beluga Whale Optimization Algorithm (BBWOA) for determining the optimal points over the sink node can be moved to prevent multi-hop between CHs and the sink nodes, since it is essential for addressing the issue of hot-spot and extends the network lifetime. The simulation results of the proposed IDBBWOA approach revealed its efficacy in improving the mean throughput by 18.92 %, sustaining alive nodes by 34.28 %, and maintaining residual energy by 29.34 %, compared to the benchmarked approaches used for evaluation.

Research on the Challenges and Countermeasures of Online Public Opinion under Generative Artificial Intelligence

With the widespread application and sustained impact of AIGC (Artificial Intelligence Generated Content) technology, exemplified by Chat GPT, the ecology of online public opinion in the field of news communication is undergoing profound changes. The new characteristics of online public opinion, such as massive data, multimodal information, precise dissemination, content confusion, and efficient rate, present challenges including more complex information, emotional dissemination, intricate fields, and difficult judgment and analysis. To address these, responses can be formulated from macro, meso, and micro levels, including accelerating legislative standardization, identifying responsible entities, and enhancing personal literacy, thereby improving the governance capacity of public opinion.

Assessing the Content and Effect of Web-Based Decision Aids for Postmastectomy Breast Reconstruction: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Web-based decision aids have been shown to have a positive effect when used to improve the quality of decision-making for women facing postmastectomy breast reconstruction (PMBR). However, the existing findings regarding these interventions are still incongruent, and the overall effect is unclear. We aimed to assess the content of web-based decision aids and its impact on decision-related outcomes (ie, decision conflict, decision regret, informed choice, and knowledge), psychological-related outcomes (ie, satisfaction and anxiety), and surgical decision-making in women facing PMBR. This systematic review and meta-analysis followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 6 databases, PubMed, Embase, Cochrane Library, CINAHL, PsycINFO, and Web of Science Core Collection, were searched starting at the time of establishment of the databases to May 2023, and an updated search was conducted on April 1, 2024. MeSH (Medical Subject Headings) terms and text words were used. The Cochrane Risk of Bias Tool for randomized controlled trials was used to assess the risk of bias. The certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. In total, 7 studies included 579 women and were published between 2008 and 2023, and the sample size in each study ranged from 26 to 222. The results showed that web-based decision aids used audio and video to present the pros and cons of PMBR versus no PMBR, implants versus flaps, and immediate versus delayed PMBR and the appearance and feel of the PMBR results and the expected recovery time with photographs of actual patients. Web-based decision aids help improve PMBR knowledge, decisional conflict (mean difference [MD]=-5.43, 95% CI -8.87 to -1.99; P=.002), and satisfaction (standardized MD=0.48, 95% CI 0.00 to 0.95; P=.05) but have no effect on informed choice (MD=-2.80, 95% CI -8.54 to 2.94; P=.34), decision regret (MD=-1.55, 95% CI -6.00 to 2.90 P=.49), or anxiety (standardized MD=0.04, 95% CI -0.50 to 0.58; P=.88). The overall Grading of Recommendations, Assessment, Development, and Evaluation quality of the evidence was low. The findings suggest that the web-based decision aids provide a modern, low-cost, and high dissemination rate effective method to promote the improved quality of decision-making in women undergoing PMBR. PROSPERO CRD42023450496; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=450496.

Forced convective tangent hyperbolic nanofluid flow subject to heat source/sink and Lorentz force over a permeable wedge: Numerical exploration

Abstract The magnetohydrodynamics tangent hyperbolic nanofluid (THNF) flow with the mutual impact of melting heat transfer and wedge angle over a permeable wedge is investigated numerically in the present study. Electronic devices generate excessive heat during operations, so THNF is often employed to regulate them. THNF has the ability to neutralize heat with greater efficacy, thereby reducing the probability of overheating. The influence of thermal radiation, Soret and Dufour, and heat source/sink is also observed on the fluid flow. The modeled equations are simplified to the lowest order through the similarity conversion. The obtained set of dimensionless equations is further calculated numerically by employing the parametric continuation method. The computational findings of the present study are compared to the published results for accuracy purposes. It has been detected that the results are precise and reputable. Moreover, from the graphical results, it has been perceived that the effect of permeability factor (K p) reduces the fluid flow. The rising effect of wedge angle factor enhances the energy dissemination rate and shearing stress; however the augmentation of Weissenberg number drops skin friction and energy transference rate.

Vector competence of Swedish Culex pipiens mosquitoes for Japanese encephalitis virus

BackgroundJapanese encephalitis virus (JEV) is an emerging mosquito-borne Orthoflavivirus that poses a significant public health risk in many temperate and tropical regions in Asia. Since the climate in some endemic countries is similar to temperate climates observed in Europe, understanding the role of specific mosquito species in the transmission of JEV is essential for predicting and effectively controlling the potential for the introduction and establishment of JEV in Europe.MethodsThis study aimed to investigate the vector competence of colonized Culex pipiens biotype molestus mosquitoes for JEV. The mosquitoes were initially collected from the field in southern Sweden. The mosquitoes were offered a blood meal containing the Nakayama strain of JEV (genotype III), and infection rates, dissemination rates, and transmission rates were evaluated at 14, 21, and 28 days post-feeding.ResultsThe study revealed that colonized Swedish Cx. pipiens are susceptible to JEV infection, with a stable infection rate of around 10% at all timepoints. However, the virus was only detected in the legs of one mosquito at 21 days post-feeding, and no mosquito saliva contained JEV.Conclusions Overall, this research shows that Swedish Cx. pipiens can become infected with JEV, and emphasizes the importance of further understanding of the thresholds and barriers for JEV dissemination in mosquitoes.Graphical

Evaluating the mosquito vector range for two orthobunyaviruses: Oya virus and Ebinur Lake virus

BackgroundMosquito-borne viruses cause various infectious diseases in humans and animals. Oya virus (OYAV) and Ebinur Lake virus (EBIV), belonging to the genus Orthobunyavirus within the family Peribunyaviridae, are recognized as neglected viruses with the potential to pose threats to animal or public health. The evaluation of vector competence is essential for predicting the arbovirus transmission risk.MethodsTo investigate the range of mosquito vectors for OYAV (strain SZC50) and EBIV (strain Cu20-XJ), the susceptibility of four mosquito species (Culex pipiens pallens, Cx. quinquefasciatus, Aedes albopictus, and Ae. aegypti) was measured through artificial oral infection. Then, mosquito species with a high infection rate (IR) were chosen to further evaluate the dissemination rate (DR), transmission rate (TR), and transmission efficiency. The viral RNA in each mosquito sample was determined by RT-qPCR.ResultsThe results revealed that for OYAV, Cx. pipiens pallens had the highest IR (up to 40.0%) among the four species, but the DR and TR were 4.8% and 0.0%, respectively. For EBIV, Cx. pipiens pallens and Cx. quinquefasciatus had higher IR compared to Ae. albopictus (1.7%). However, the EBIV RNA and infectious virus were detected in Cx. pipiens pallens, with a TR of up to 15.4% and a transmission efficiency of 3.3%.ConclusionsThe findings indicate that Cx. pipiens pallens was susceptible to OYAV but had an extremely low risk of transmitting the virus. Culex pipiens pallens and Cx. quinquefasciatus were susceptible to EBIV, and Cx. pipiens pallens had a higher transmission risk to EBIV than Cx. quinquefasciatus.Graphical

Mayaro virus, a potential threat for Europe: vector competence of autochthonous vector species

BackgroundMayaro virus (MAYV) is an emerging alphavirus, primarily transmitted by the mosquito Haemagogus janthinomys in Central and South America. However, recent studies have shown that Aedesaegypti, Aedesalbopictus and various Anopheles mosquitoes can also transmit the virus under laboratory conditions. MAYV causes sporadic outbreaks across the South American region, particularly in areas near forests. Recently, cases have been reported in European and North American travelers returning from endemic areas, raising concerns about potential introductions into new regions. This study aims to assess the vector competence of three potential vectors for MAYV present in Europe.MethodsAedesalbopictus from Italy, Anophelesatroparvus from Spain and Culexpipiens biotype molestus from Belgium were exposed to MAYV and maintained under controlled environmental conditions. Saliva was collected through a salivation assay at 7 and 14 days post-infection (dpi), followed by vector dissection. Viral titers were determined using focus forming assays, and infection rates, dissemination rates, and transmission efficiency were calculated.ResultsResults indicate that Ae.albopictus and An.atroparvus from Italy and Spain, respectively, are competent vectors for MAYV, with transmission possible starting from 7 dpi under laboratory conditions. In contrast, Cx.pipiens bioform molestus was unable to support MAYV infection, indicating its inability to contribute to the transmission cycle.ConclusionsIn the event of accidental MAYV introduction in European territories, autochthonous outbreaks could potentially be sustained by two European species: Ae.albopictus and An.atroparvus. Entomological surveillance should also consider certain Anopheles species when monitoring MAYV transmission.Graphical abstract

Abstract PO4-13-08: Mechanical conditioning (MeCo) score is higher in circulating tumor cells (CTCs) compared to primary tumors in early-stage breast cancer and even higher in metastases compared to CTCs in metastatic breast cancer

Abstract Background: The mechanical conditioning (MeCo) score is a gene expression signature that is acquired early by cancer cells in the primary breast tumor and is reflective of their responsiveness to matrix stiffness (fibrotic-like matrix rigidity). Further, chromatin remodeling in response to stiffness allows cancer cells to retain their aggressive features even in the absence of mechanical stimulation by the primary tumor microenvironment, for instance, during their dissemination through the circulation in metastasis. Importantly, patients who have high MeCo score tumors are at higher risk of developing metastatic breast cancer, compared to low MeCo scores (p< 0.0001; HR=2.2, 95%CI 1.7-2.7; Watson et al 2021, PMID: 34192535). Moreover, circulating tumor cells (CTCs) are associated with higher rate of metastatic dissemination, making CTC detection in the circulation of breast cancer patients a significant prognostic biomarker for breast cancer metastasis. Beyond their enumeration per blood volume units, specific prognostic features of CTCs are not fully explored. We sought to determine whether, compared to primary tumors, CTCs retain high MeCo scores and whether these scores are maintained during late-stage breast cancer in the metastatic sites. Methods: CTCs were isolated from peripheral blood of two patient cohorts: stage II-III breast cancer patients using immunomagnetic enrichment/FACS methodology (Lang et al 2018, PMID: 29868978) and of metastatic breast cancer patients using ANGLE Parsortix microfluidics system (Ring et al 2022, PMID: 35000083). Gene expression profiling using RNA-seq was performed in CTCs and in matching primary tumors (PT) and metastases (MET) for the early-stage and late-stage cohorts, respectively. A quantile normalization approach was used to allow comparison across cohorts. MeCo scores were computed for all samples as per Watson et al 2021. Wilcoxon matched-pairs signed rank test was performed for comparison of MeCo scores from matching samples within each cohort; Mann-Whitney unpaired test was used to compared MeCo scores of CTCs across cohorts. Results: In 12 pairs of early-stage breast cancer patient CTCs and PT, MeCo scores of CTCs were significantly higher than their matched PTs (p=0.026). Furthermore, in 26 pairs of metastatic patient’s CTCs and MET, MeCo scores of METs were significantly higher than matching CTCs (p=0.0004). MeCo scores of CTCs were similar between early- and late-stage breast cancer despite differing CTC isolation strategies (epitope-dependent and microfluidics size gradient). 98% of genes in the MeCo score were present in the evaluable CTC, MET and PT samples. Conclusions: Our results show that the MeCo score is higher in CTCs compared to PTs and in METs compared to CTCs in early- and late-stage breast cancer, respectively. Therefore, the MeCo score is progressively higher throughout the metastatic cascade in breast cancer. These findings demonstrate that mechanical conditioning is retained during metastatic progression, even as cancer cells transition through the circulation where the initial induction by matrix stiffness is lost. Further, these findings support that cancer cells with higher MeCo scores are more competent with–and potentially selected for by–metastatic progression. Importantly, these findings provide a novel feature of CTCs, mechanical conditioning (MeCo), which is associated with higher capacity for metastasis. Further, since the CTC MeCo score is elevated even in early-stage breast cancer, it could provide, in addition to CTC enumeration, a potential prognostic tool to predict metastatic risk in breast cancer patients. Citation Format: Gus Mouneimne, Adam Watson, Adam Grant, Daniel Campo, Alexander Ring, Pushpinder Bains, Julie Lang. Mechanical conditioning (MeCo) score is higher in circulating tumor cells (CTCs) compared to primary tumors in early-stage breast cancer and even higher in metastases compared to CTCs in metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-13-08.

Infection, dissemination, and transmission of lumpy skin disease virus in Aedes aegypti (Linnaeus), Culex tritaeniorhynchus (Giles), and Culex quinquefasciatus (Say) mosquitoes

Lumpy skin disease virus (LSDV) is a transboundary viral disease in cattle and water buffaloes. Although this Poxvirus is supposedly transmitted by mechanical vectors, only a few studies have investigated the role of local vectors in the transmission of LSDV. This study examined the infection, dissemination, and transmission rates of LSDV in Aedes aegypti, Culex tritaeniorhynchus, and Culex quinquefasciatus following artificial membrane feeding of 102.7, 103.7, 104.7 TCID50/mL LSDV in sheep blood. The results demonstrated that these mosquito species were susceptible to LSDV, with Cx tritaeniorhynchus exhibiting significantly different characteristics from Ae. aegypti and Cx. quinquefasciatus. These three mosquito species were susceptible to LSDV. Ae. aegypti showed it as early as 2 days post-infection (dpi), indicating swift dissemination in this particular species. The extrinsic incubation period (EIP) of LSDV in Cx. tritaeniorhynchus and Cx. quinquefasciatus was 8 and 14 dpi, respectively. Ingestion of different viral titers in blood did not affect the infection, dissemination, or transmission rates of Cx. tritaeniorhynchus and Cx. quinquefasciatus. All rates remained consistently high at 8–14 dpi for Cx. tritaeniorhynchus. In all three species, LSDV remained detectable until 14 dpi. The present findings indicate that, Ae. aegypti, Cx. tritaeniorhynchus, and Cx. quinquefasciatus may act as vectors during the LSDV outbreak; their involvement may extend beyond being solely mechanical vectors.