Unified Language for Knowledge Dissemination: The Vascular Ageing Glossary, an Initiative by VascAgeNet.

Objectives: In general, a terminology shared and agreed by different stakeholders is important to facilitate communication and cooperation. This holds true in the field of vascular ageing for the benefit of global cardiovascular health. The need to promote a common language and understanding across this area was recognised by VascAgeNet, a collaborative network with relevant and diverse expertise in the vascular ageing field, supported by the European Cooperation in Science and Technology. To contribute to the spread of unified terms in the vascular ageing field, a glossary was created by VascAgeNet and this paper describes the systematic process used for its development. Methods: An initial list of terms and preliminary definitions were collated from the network. A dedicated team was created to design the glossary development process, to facilitate its implementation and to maximise outreach and dissemination. The key steps of the process were to determine: (1) the target audience; (2) a list of priority terms; (3) a template structure for definitions; (4) methods for collecting feedback and (5) the dissemination plan. Results: An implementation strategy was provided for each key step and shared within the network; main decisions were agreed by all members of the glossary team. Small groups of definitions were released on a regular basis within a pilot phase including 19 terms (status: 05.09.2023) that were published openly at https://vascagenet.eu/official-glossary. Conclusions: The strategy for creating the first Vascular Ageing Glossary has been successfully designed and developed within VascAgeNet. A pilot phase covering the first publicly available terms was completed. The glossary is a living document, available to the scientific community, which aims to unify the vascular ageing language. Supplementary Information: The online version contains supplementary material available at 10.1007/s44200-023-00041-5.

Anti-tumor effect of antibody-drug conjugate targeting cell adhesion molecule 1 on GIST cells representing small intestinal GIST.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the alimentary tract. The prognosis depends on the primary site, and small intestinal GISTs have a worse prognosis than gastric GISTs. Molecularly targeted drugs to inhibit tyrosine kinase activity of KIT were used for unresectable or recurrent GISTs. However, secondary resistance to the drugs is often acquired, and treatments based on other mechanisms are needed. Previously, we reported that cell adhesion molecule 1 (CADM1) was highly expressed in most of small intestinal GISTs but not in most of gastric GISTs. In the present study, we examined whether the antibody-drug conjugate (ADC) with anti-CADM1 antibody and monomethyl auristatin E (anti-CAD-ADC) shows anti-tumor effect on CADM1-expressing human GIST cells. The ADC adhibited in this study was previously used for CADM1-expressing human mesothelioma cells and showed anti-tumor effect for them in vitro. GIST-T1 cell line of gastric origin which scarcely expresses CADM1 and GIST-T1 cells transfected with CADM1 cDNA (GIST-T1-CAD cells) which highly expresses CADM1 and represents small intestinal GIST were used. In vitro, anti-CAD-ADC showed remarkable cytotoxic activity on GIST-T1-CAD cells, but control ADC did not. Both anti-CAD-ADC and control ADC did not show anti-tumor effect on original GIST-T1 cells. When GIST-T1-CAD cells were subcutaneously injected to the nude mice, intravenous administration of anti-CAD-ADC showed inhibitory effect for tumor enlargement. Tumor of GIST-T1 cells grew even after anti-CAD-ADC injection. When GIST-T1-CAD cells were injected into peritoneal cavity of the SCID mice, intraperitoneal administration of anti-CAD-ADC showed reduction of the peritoneal tumor. On the other hand, peritoneal tumor grew after control ADC administration. Tissue and organ damage due to administration of anti-CAD-ADC was not apparent by macroscopic and histological examinations in mice. These results indicate that anti-CAD-ADC could have apparent anti-tumor effect on CADM1-expressing human GIST cells both in in vitro and in vivo mouse models.

An extremely rare case of primary alveolar rhabdomyosarcoma in the central nervous system.

Background: Alveolar rhabdomyosarcoma (ARMS) shows a predilection for the peripheral extremities and is very rarely identified as a primary in the brain. Here, we report a case of ARMS with multiple lesions exclusively within the central nervous system (CNS). Case Description: A 20-year-old man presented to our hospital with a gradually increasing headache and disturbance of consciousness. Neuroimaging showed hydrocephalus and multiple tumor lesions, including in the brainstem and cerebellum, with uniform gadolinium enhancement on T1-weighted magnetic resonance imaging, as well as spinal cord seeding. Cerebrospinal fluid (CSF) analysis showed a slightly elevated cell count (6/µL; normal, <5/µL) and highly elevated protein (153 mg/dL). In addition, atypical cells were cytologically identified in the CSF. No other laboratory findings were abnormal. Emergency ventricular drainage was performed to control cerebral pressure, followed by a biopsy to confirm the diagnosis. Histological examination revealed a fascicular arrangement of oval cells with eosinophilic cytoplasm and tumor cells with pleomorphic nuclei and prominent nucleoli. Immunohistochemical studies showed negative results for glial fibrillary acidic protein and positive results for desmin and myogenin. In addition, molecular analysis revealed that this tumor had the H3F3A p.Lys28Met mutation and no paired box (PAX)3-forkhead box O1 (FOXO1) or PAX7-FOXO1 fusion genes. ARMS was, therefore, diagnosed. Chemotherapy and radiotherapy were subsequently initiated, but tumor growth could not be controlled, and the patient died 6 months after surgery. Conclusion: This report describes an extremely rare case of ARMS arising exclusively within the CNS.

Beyond "business as usual": lessons from FIFA for fair benefit-sharing in global health.

While researchers and agencies from low- and middle-income countries often contribute significantly to public health surveillance data, which is crucial for effective pandemic prevention, preparedness, and response activities, they often do not receive adequate compensation for their contributions. Incentivizing data sharing is important for informing public health responses to pathogens with pandemic potential. However, existing data-sharing legal frameworks have limitations. In this context, we looked beyond "business as usual" candidates to explore the applicability of a benefit-sharing model developed and implemented by the Fédération Internationale de Football Association (International Federation of Association Football; FIFA) in international association football. This model rewards grassroots contributions and redistributes benefits, promoting a fair balance of interests across diverse economic contexts. We discuss adapting FIFA's mechanisms, including training compensation and solidarity payments, to create a novel benefit-sharing framework in global health. Given the complexity of global health, we note ways in which components of the FIFA model would need to be adapted for global health. Challenges such as integrating into existing legal frameworks, ensuring broad international buy-in, and accommodating different pandemic periods are examined. While adapting the FIFA model presents challenges, it offers a promising approach to achieving more equitable data sharing and benefit distribution in global health.

Expanding Public Health Initiatives Through Community Pharmacies and Student Pharmacists: A Programmatic Case Study.

BACKGROUND: Community pharmacies are critical to the public health infrastructure in the United States and provide reliable information for public health concerns. Public health agencies curate educational materials that community pharmacy teams can disseminate. Student pharmacists participate in experiential learning at community pharmacies which could be utilized for dissemination of these resources. OBJECTIVES: The objectives of this project were to: (1) design a model for dissemination of public health information at community pharmacies; and (2) evaluate both the dissemination model's reach within communities and student pharmacist learnings from engagement in the model. METHODS: We engaged student pharmacists in a model to disseminate information at community pharmacies for two Centers for Disease Control and Prevention initiatives about Opioid Use Disorder Anti-Stigma and Antibiotic Stewardship Education. The number of pharmacies and student pharmacists who participated from 2021-2023 were retrospectively reviewed to demonstrate programmatic reach. A retrospective text mining of student assignments was conducted to evaluate student experiences. Descriptive statistics were used to report quantitative data. An inductive, rapid content analysis was completed for qualitative data. RESULTS: Across three years, 333 student pharmacists participated. Students reached 121 community pharmacies, 139 practicing pharmacist preceptors, and over 2000 patients with education and resources. Eleven student learning points emerged from the qualitative analysis. These included learnings around opioid use disorder and antibiotic stewardship. Students also acknowledged that there are public health needs present in communities and that community pharmacy teams are well-positioned to address these needs. CONCLUSION: Engaging student pharmacists to distribute curated information from public health authorities, to both pharmacist preceptors and patients at community pharmacies, is one way to educate future pharmacists, pharmacy teams, and communities on public health priorities. Pharmacies can serve as key venues in communities for dissemination of reliable public health information.

Coexistence of multidrug resistance and ESBL encoding genes - blaTEM, blaSHV, and blaCTX-M; its amplification and dispersion in the environment via municipal wastewater treatment plant.

Municipal wastewater treatment plants (MWWTPs) are a global source of antibiotic resistance genes (ARGs), collecting wastewater from a variety of sources, including hospital wastewater, domestic wastewater, runoff from agricultural and livestock farms, etc. These sources are contaminated with organic and inorganic pollutants, ARGs and antibiotic-resistant bacteria (ARB). Such pollutants aided eutrophication and encouraged bacterial growth. During bacterial growth horizontal gene transfer (HGT) and vertical gene transfer (VGT) of ARGs and extended-spectrum ß-lactamase (ESBL) encoding genes may facilitate, resulting in the spread of antibiotic resistance exponentially. The current study investigated the prevalence of multidrug resistance (MDR) and ESBL encoding genes in various treatment units of MWWTP and their spread in the environment. A total of three sampling sites (BUT, BRO, and BFB) were chosen, and 33 morphologically distinct bacterial colonies were isolated. 14 of the 33 isolates tested positive for antibiotic resistance and were further tested for the coexistence of MDR and ESBL production. The selected 14 isolates showed the highest resistance to trimethoprim (85.71%), followed by ciprofloxacin, azithromycin, and ampicillin (71.42%), tetracycline (57.14%), and vancomycin, gentamicin, and colistin sulphate (50%). A total of 9 isolates (64.28%) were phenotypically positive for ESBL production (BUT2, BUT3, BUT5, BRO1, BRO2, BRO3, BRO4, BRO5 and BFB1). The molecular detection of ESBL encoding genes, i.e. blaTEM, blaSHV, and blaCTX-M was carried out. The most prevalent gene was blaTEM (69.23%), followed by blaSHV (46.15%), and blaCTX-M (23.07%). In this study, 9 isolates (64.28%) out of 14 showed the coexistence of MDR and ESBL encoding genes, namely BUT3, BUT4, BUT5, BUT6, BUT7, BRO1, BRO2, BRO4, and BFB1. The coexistence of ESBL encoding genes and resistance to other antibiotic classes exacerbates human health and the environment.

Relating caregiver experiences to personalized "push" content in mobile applications among caregivers of pediatric patients with oncology conditions.

OBJECTIVE: With the evolution of data algorithms and personalized push systems in mobile applications, patients who have searched for disease-related information may repeatedly receive similar content on app homepages or through notifications. This study aims to assess the influence of health-related content delivered through mobile applications on the anxiety and depression levels of caregivers of pediatric oncology patients. METHODS: A survey consisting of 16 questions was conducted among 91 caregivers of pediatric oncology patients at the Children's Hospital affiliated with Chongqing Medical University. The questionnaire was designed by oncologists and the Hospital Anxiety and Depression Scale was used to assess the caregivers' psychological states. RESULTS: The study found that 31.5% of caregivers exhibited borderline anxiety symptoms, while 20.2% displayed borderline depression symptoms. Caregivers who noticed changes in homepage recommendations reported higher levels of anxiety (p = .004) and depression (p = .034). Additionally, 50.6% occasionally felt anxious or uneasy due to personalized notifications and 19.1% frequently felt this way. Moreover, 53.9% of the caregivers reported a negative impact on their emotions or daily life. SIGNIFICANCE: Personalized push notifications related to disease information in mobile applications can impose a significant psychological burden on patients and their caregivers. Mobile application developers and healthcare providers must strengthen their support in the digital health domain to enhance the emotional well-being of cancer patients and their caregivers.

The Toxoplasma secreted effector TgWIP modulates dendritic cell motility by activating host tyrosine phosphatases Shp1 and Shp2.

The obligate intracellular parasite Toxoplasma gondii causes life-threatening toxoplasmosis to immunocompromised individuals. The pathogenesis of Toxoplasma relies on its swift dissemination to the central nervous system through a 'Trojan Horse' mechanism using infected leukocytes as carriers. Previous work found TgWIP, a protein secreted from Toxoplasma, played a role in altering the actin cytoskeleton and promoting cell migration in infected dendritic cells (DCs). However, the mechanism behind these changes was unknown. Here, we report that TgWIP harbors two SH2-binding motifs that interact with tyrosine phosphatases Shp1 and Shp2, leading to phosphatase activation. DCs infected with Toxoplasma exhibited hypermigration, accompanying enhanced F-actin stress fibers and increased membrane protrusions such as filopodia and pseudopodia. By contrast, these phenotypes were abrogated in DCs infected with Toxoplasma expressing a mutant TgWIP lacking the SH2-binding motifs. We further demonstrated that the Rho-associated kinase (Rock) is involved in the induction of these phenotypes, in a TgWIP-Shp1/2 dependent manner. Collectively, the data uncover a molecular mechanism by which TgWIP modulates the migration dynamics of infected DCs in vitro.

Health professionals' counselling on the use of infant formula: A scoping review.

OBJECTIVE: Many parents experience lack of support and access to resources on how to prepare, handle, and provide formula milk to their infants. The purpose of this scoping review was to map and describe key information in existing research about how healthcare professionals receive information and how they inform and counsel parents about formula milk. DESIGN: A scoping review fulfilling the PRISMA-ScR checklist criteria used systematic searches targeting the study objective in the databases Embase, MEDLINE, and CINAHL on February 8th and 9th, 2022. RESULTS: Six studies with 959 participants in total were included. The research designs were focus group studies with and without combining individual interviews, an individual interview study, a study consisting of individual interviews and ethnographic observations, a survey, and a two-phase study consisting of a qualitative interview and a quantitative survey. Findings indicate lack of evidence-based information provided about infant formula by health care professionals when they counsel parents on formula feeding. CONCLUSIONS: Few studies focus on how healthcare professionals inform and counsel parents about formula milk. Health authorities should provide more evidence-based information to make formula feeding more feasible. Due to conflicting and omitted information, mothers often receive poor counselling on formula feeding.

A deep cut into early cryptococcal pathogenesis.

Dissemination from one organ system to another is common to many pathogens and often the key process separating simple illness from fatal infection. The pathogenic Cryptococcus species offer a prime example. Cryptococcal infection is thought to begin in the lungs, as a mild or asymptomatic pneumonia. However, bloodborne dissemination from the lungs to the brain is responsible for the most devastating forms of infection. As with other disseminating infections, the transition likely depends on rare but crucial events, such as the crossing of a tissue barrier. By their nature, these events are difficult to study. Francis et al. (mBio 15:e03078-23, 2024, https://doi.org/10.1128/mbio.03078-23) have addressed this difficulty by developing a powerful imaging pipeline to scan through unprecedented volumes of tissue from mice infected with Cryptococcus at multiple stages of infection. Their observations challenge some of our basic assumptions about cryptococcal pathogenesis, including when and how the organism reaches the bloodstream and the central nervous system.

Implementation of a Parent Training Program During Community-Based Dissemination (From In-Person to Hybrid): Mixed Methods Evaluation.

BACKGROUND: Parent training interventions support and strengthen parenting practices and parent-child relationships and improve child behavior. Between March 2018 and February 2020, a community-based parenting program conducted 38 in-person Chicago Parent Program (CPP) groups. In response to the COVID-19 pandemic, we modified the delivery of the in-person CPP to hybrid delivery using the self-administered, web-based version of the CPP (ezParent) paired with web-based, videoconferenced group sessions. OBJECTIVE: This study aims to describe the delivery transition and implementation outcomes of the hybrid delivery of the CPP (ezParent+group) during community-based dissemination. METHODS: This single-group, mixed methods retrospective evaluation examined the implementation outcomes using the RE-AIM (Reach, Efficacy, Adoption, Implementation, and Maintenance) framework. We report on data from hybrid ezParent delivery between September 2020 and August 2022. Parents completed pre- and postprogram surveys that included motivation to participate and perceived changes in parent-child behavior. Digital analytics captured ezParent completion. Facilitators completed fidelity assessments and participated in postintervention interviews. RESULTS: In total, 24 hybrid ezParent groups (n=240 parents) were delivered by 13 CPP-trained facilitators. Parents reported high levels of satisfaction with the program and improvements in their feelings of parenting self-efficacy and their child's behavior following their participation in hybrid ezParent. On average, parents completed 4.58 (SD 2.43) 6 ezParent modules. The average group attendance across the 4 sessions was 71.2%. Facilitators found the hybrid delivery easy to implement and reported high parent engagement and understanding of CPP strategies. CONCLUSIONS: Using the hybrid ezParent intervention is a feasible and effective way to engage parents. Lessons learned included the importance of academic and community-based organization partnerships for delivering and evaluating robust programs. Implementation facilitators and barriers and future research recommendations are discussed.

Engaging With Health Consumers in Scientific Conferences-As Partners not Bystanders.

INTRODUCTION: It is now widely recognised that engaging consumers in research activities can enhance the quality, equity and relevance of the research. Much of the commentary about consumer engagement in research focuses on research processes and implementation, rather than dissemination in conference settings. This article offers reflections and learnings from consumers, researchers and conference organisers on the 12th Health Services Research Conference, a biennial conference hosted by the Health Services Research Association of Australia and New Zealand (HSRAANZ). METHOD: We were awarded funds via a competitive application process by Bellberry Limited, a national not-for-profit agency with a focus on improving research quality, to incorporate consumer engagement strategies in conference processes and evaluate their impact. FINDINGS: Strategies included consumer scholarships, a buddy system, designated quiet space and consumer session co-chairs; the reflections explored in this paper were collected in the funded, independent evaluation. Our insights suggest a need for more structured consumer involvement in conference planning and design, as well as the development of specific engagement strategies. CONCLUSION: To move toward active partnership in scientific conference settings, our experience reinforces the need to engage consumers as members in designing and conducting research and in presenting research and planning conference content and processes. PUBLIC CONTRIBUTION: Consumer engagement in research dissemination at conferences is the focus of this viewpoint article. Consumers were involved in the conception of this article and have contributed to authorship at all stages of revisions and edits.

Strengthening a culture of research dissemination: A narrative report of research day at King Faisal Hospital Rwanda, a tertiary-level teaching hospital in Rwanda.

BACKGROUND: There are significant gaps in research output and authorship in low- and middle-income countries. Research dissemination events have the potential to help bridge this gap through knowledge transfer, institutional collaboration, and stakeholder engagement. These events may also have an impact on both clinical service delivery and policy development. King Faisal Hospital Rwanda (KFH) is a tertiary-level teaching hospital located in Kigali, Rwanda. To strengthen its research dissemination, KFH conducted an inaugural Research Day (RD) to disseminate its research activities, recognize staff and student researchers at KFH, define a research agenda for the hospital, and promote a culture of research both at KFH and in Rwanda. METHODS: RD was coordinated by an interdisciplinary committee of clinical and non-clinical staff at KFH. Researchers were encouraged to disseminate their research across all disciplines. Abstracts were blind reviewed using a weighted rubric and ranked by overall score. Top researchers were also awarded and recognized for their work, and equity and inclusion was at the forefront of RD programming. RESULTS: RD had over 100 attendees from KFH and other public, private, and academic institutions. Forty-seven abstracts were submitted from the call for abstracts, with the highest proportion studying cancer (17.02%) and sexual and reproductive health (10.64%). Thirty-seven researchers submitted abstracts, and most of the principal investigators were medical doctors (35.14%), allied health professionals (27.03%), and nurses and midwives (16.22%). Furthermore, 30% of principal investigators were female, with the highest proportion of them being nurses and midwives (36.36%). CONCLUSION: RD is an effective way to disseminate research in a hospital setting. RD has the potential to strengthen the institution's research agenda, engage the community in ongoing projects, and provide content-area support to researchers. Equity and inclusion should be at the forefront of research dissemination, including gender equity, authorship representation, and the inclusion of interdisciplinary health professionals. Stakeholder engagement can also be utilized to strengthen institutional research collaboration for greater impact.

Co-existence of two plasmids harboring transferable resistance-nodulation-division pump gene cluster, tmexCD1-toprJ1, and colistin resistance gene mcr-8 in Klebsiella pneumoniae.

BACKGROUND: The emergence of plasmid-mediated mobile colistin resistance (mcr) gene poses a great challenge to the clinical application of polymyxins. To date, mcr-1 to mcr-10 have been found in animals, humans, and the environment. Among them, mcr-8 was first identified in Klebsiella pneumoniae (K. pneumoniae) of swine origin, and then mcr-8.1 to mcr-8.5 were successively identified. Notably, K. pneumoniae is the major host of the mcr-8 gene in both animals and humans. This study aims to explore the characteristics of K. pneumoniae strains carrying the mcr-8 gene and tmexCD1-toprJ1 gene cluster and investigate the correlation between these two antibiotic resistance genes. METHODS: The isolates from the poultry farms and the surrounding villages were identified by mass spectrometer, and the strains positive for mcr-1 to mcr-10 were screened by polymerase chain reaction (PCR). The size of the plasmid and the antimicrobial resistance genes carried were confirmed by S1-nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern hybridization, and the transferability of the plasmid was verified by conjugation experiments. Antimicrobial susceptibility testing (AST) and whole genome sequencing (WGS) were used to characterize the strains. RESULTS: Two K. pneumoniae isolates (KP26 and KP29) displaying polymyxin resistance were identified as mcr-8 gene carriers. Besides that, tigecycline-resistant gene cluster tmexCD1-toprJ1 was also found on the other plasmid which conferred strain resistance to tigecycline. Through epidemiological analysis, we found that the mcr-8 gene has dispersed globally, circulating in the human, animals, and the environment. Furthermore, our analysis suggests that the coexistence of mcr-8 and tmexCD1-toprJ1 on a single plasmid might evolved through plasmid recombination. CONCLUSIONS: Although the mcr-8 and tmexCD1-toprJ1 gene clusters in the two strains of K. pneumoniae in this study were on two different plasmids, they still pose a potential threat to public health, requiring close monitoring and further study.

Genetic Algorithm-Based Cooperative Coding and Caching Data Dissemination Scheme in Multi-UAV-Enabled Internet of Vehicles.

Unmanned Aerial Vehicles (UAVs) have emerged as efficient tools in disaster-stricken areas, facilitating efficient data dissemination for post-disaster rescue operations. However, the limited onboard energy of UAVs imposes significant constraints on their operational lifespan, thereby presenting substantial challenges for efficient data dissemination. Therefore, this work investigates a data dissemination scheme to enhance the UAVs' bandwidth efficiency in multi-UAV-enabled Internet of Vehicles, thereby reducing UAVs' energy consumption and improving overall system performance when UAVs hover along designated flight trajectories for data dissemination. Specifically, first, we present a software-defined network-based framework for data dissemination in multi-UAV-enabled IoV. According to this framework, we formulate a problem called C2BS (Coding-based Cooperative Broadcast Scheduling) that focuses on optimizing the UAVs' bandwidth efficiency by leveraging the combined benefits of coding and caching. Furthermore, we demonstrate the NP-hardness of the C2BS problem by employing a polynomial time reduction technique on the simultaneous matrix completion problem. Then, inspired by the benefits offered by genetic algorithms, we propose a novel approach called the Genetic algorithm-based Cooperative Scheduling (GCS) algorithm to address the C2BS problem. This approach encompasses a coding scheme for representing individuals, a fitness function for assessing individuals, operators (i.e., crossover and mutation) for generating offspring, a local search technique to enhance search performance, and a repair operator employed to rectify infeasible solutions. Additionally, we present an analysis of the time complexity for the GCS algorithm. Finally, we present a simulation model to evaluate the performance. Experimental findings provide evidence of the excellence of the proposed scheme.

TikTok and teen mental health: an analysis of user-generated content and engagement.

BACKGROUND: TikTok is a social media mobile application that is widely used by adolescents, and has the potential to serve as a revolutionary platform for public and mental health discourse, education, and intervention. OBJECTIVE: Our study aimed to describe the content and engagement metrics of the hashtag #teenmentalhealth on TikTok. METHODS: In this study, we: (a) conducted a directed content analysis of the Top 100 TikTok videos tagged with #teenmentalhealth, and (b) collected data on video engagements (views, likes, saves, and shares) and computed view-based engagement rates. RESULTS: The videos collectively garnered 144,320,591 views; 28,289,655 likes; 219,780 comments; 1,971,492 saves; and 478,696 shares. Most of the generated content were from teens and therapists. Engagement metrics revealed strong user engagement rates across user types. The most prevalent content categories represented across videos were personal experience, coping techniques or treatment, humor, interpersonal relationships, and health campaign. The content categories with the highest engagement rates were relatable media representation, health campaign, social isolation, and humor. Only a single video incorporated evidence-based treatment content. CONCLUSION: TikTok facilitates communication and information dissemination on teen mental health. Future research should focus on improving the quality and credibility of digital content while maintaining engagement through creativity, self-expression, and relatability. Use of popular social media platforms and community-engaged research to disseminate evidence-based content may help bridge the translational research gap.

The Toxoplasma secreted effector TgWIP modulates dendritic cell motility by activating host tyrosine phosphatases Shp1 and Shp2.

The obligate intracellular parasite Toxoplasma gondii causes life-threatening toxoplasmosis to immunocompromised individuals. The pathogenesis of Toxoplasma relies on its swift dissemination to the central nervous system through a 'Trojan Horse' mechanism using infected leukocytes as carriers. Previous work found TgWIP, a protein secreted from Toxoplasma, played a role in altering the actin cytoskeleton and promoting cell migration in infected dendritic cells (DCs). However, the mechanism behind these changes was unknown. Here, we report that TgWIP harbors two SH2-binding motifs that interact with tyrosine phosphatases Shp1 and Shp2, leading to phosphatase activation. DCs infected with Toxoplasma exhibited hypermigration, accompanying enhanced F-actin stress fibers and increased membrane protrusions such as filopodia and pseudopodia. By contrast, these phenotypes were abrogated in DCs infected with Toxoplasma expressing a mutant TgWIP lacking the SH2-binding motifs. We further demonstrated that the Rho-associated kinase (Rock) is involved in the induction of these phenotypes, in a TgWIP-Shp1/2 dependent manner. Collectively, the data uncover a molecular mechanism by which TgWIP modulates the migration dynamics of infected DCs in vitro.

Diflubenzuron larvicide auto-dissemination: A modeling study.

Proposing substitutes for Pyriproxyfen (PPF) in the auto-dissemination strategy is essential to ensure the continuity of the strategy in the field, especially in the case of the emergence of populations resistant to this larvicide. One possible substitute among the compounds already in use in Brazil is the larvicide Diflubenzuron (DFB). The equation that defines the proportion of oviposition sites (habitats) contaminated by the auto-dissemination strategy was modified to account for the number of visits required to reach the necessary concentration of DFB for contamination, considering scenarios with varying numbers of oviposition sites and mosquito densities. The dissemination was evaluated in oviposition sites of 2 L, 1.5 L, 1 L, 0.5 L, 0.2 L, and 0.1 L. The minimum concentration of active ingredient (a.i) of DFB required for a commercial product to contaminate at least 50% of oviposition sites was also investigated, along with the impact of other vector control methods, such as the removal/destruction of oviposition sites and the use of insecticides to kill adult 'females, on the auto-dissemination approach. The use of pure DFB compounds enabled contamination efficiency of more than 50% in oviposition sites with a volume of less than 2 L in scenarios with fewer oviposition sites. On the other hand, with the use of the commonly used concentration of the product, similar efficacy was only achieved in oviposition sites of 0.1 L and 0.2 L in medium and high infestation scenarios. Strategies that reduce the number of available oviposition sites work synergistically with the auto-dissemination strategy, making it possible to use less concentrated products and contaminated sites of larger volume. The strategy proved to be resilient in situations of insecticide application according to the concentration of DFB used, abundance of females, and low number of oviposition sites. Increasing the number of dissemination traps on the field also contributes to better results, especially for oviposition sites of 0.5 L and 1 L. The results of the model obtained under the stipulated conditions provide further support for the potential use of DFB as a substitute for PPF in the auto-dissemination strategy.

G-CSF Induces Neutrophil Extracellular Traps Formation and Promotes Ovarian Cancer Peritoneal Dissemination.

Epithelial ovarian cancer is characterized by aggressive peritoneal dissemination. Neutrophils are mobilized to peritoneal cavity in some patients with ovarian cancer dissemination, however, its pathological significance remains unknown. This study aimed to investigate the role of neutrophil extracellular traps (NETs) in ovarian cancer dissemination. We conducted a retrospective analysis of clinical data and samples from 340 patients with ovarian cancer who underwent primary surgery between 2007 and 2016 at the Osaka University Hospital. In vitro, NETs formation was induced by stimulating human peripheral neutrophils. The human ovarian cancer cell line, OVCAR8, was co-cultured with NETs. For an ovarian cancer dissemination mouse model, we performed an intraperitoneal injection of OVCAR8 cells into nude mice. The association between NETs and peritoneal dissemination was explored, and model mice were treated with the peptidylarginine deiminase 4 (PAD4) inhibitor GSK484 to assess antitumor efficacy. Neutrophilia (neutrophil count >7000/mm3) correlated with shorter survival, advanced peritoneal dissemination, elevated granulocyte colony-stimulating factor (G-CSF) levels, increased neutrophil count in ascites, and augmented NETs foci in peritoneal dissemination sites. In vitro assays revealed that G-CSF stimulated neutrophils to form NETs, promoting cancer cell adhesion. In vivo investigations revealed that G-CSF-producing tumor-bearing mice had accelerated peritoneal dissemination and poor prognosis. NETs formation was pathologically observed at the peritoneal dissemination sites. Inhibition of NETs formation by GSK484 significantly delayed peritoneal dissemination in vivo. In conclusion, G-CSF was associated with intra-abdominal NETs formation and increased peritoneal dissemination. NETs represent potential therapeutic targets for ovarian cancer, particularly in patients with neutrophilia.

Do Human Assertions Really Adhere Strictly to Norms? The Effect of Threatening Content in Information on Personalized Norm Perception.

Assertion is the use of declarative sentences to convey information, which necessitates meeting the "justified-belief norm" as a prerequisite. However, a significant amount of misinformation that did not meet these conditions was spread during COVID-19, leading to a reintroduction of the assertion norm. One possible hypothesis is that the threatening content of the misinformation influenced the perception of the norm. However, this remains unclear to researchers. Therefore, we conducted two experiments to investigate the effect of threatening content in information on individuals' perceptions of norms. In all the experiments, participants read backstories with and without threatening content, followed by answering assertion questions. It was observed that people do follow a looser assertion norm for information that contains threatening content. Additionally, further exploration revealed that threatening factors also lead individuals to more easily perceive the related content as truth and reduce the probability of being blamed. These two outcomes provide some explanation for the underlying mechanism of threatening factors' influence. The research results further refined the theory of assertion norms, offering a certain basis for information management.