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Aloe vera, renowned for its medicinal and food applications, offers a sustainable, scalable, and cost-effective scaffold material for cultured meat production. Our method repurposes Aloe vera parenchyma into a sustainable and innovative scaffold for CM production. These scaffolds, derived from agricultural byproducts, feature a porous structure that retains liquids and supports bovine mesenchymal stem cell (bMSC) adhesion, proliferation, and extracellular matrix formation. By incorporating oleic acid, the scaffolds enable the accumulation of fat-like tissue, creating "lipid chunks" that can enhance the texture and flavor profile of plant-based meat alternatives. Furthermore, scalability is addressed by culturing the scaffolds in a macrofluidic single-use bioreactor (MSUB), showcasing the potential for large-scale production. This work demonstrates Aloe vera scaffold's versatility as a cost-effective material and highlights its promise for sustainable protein solutions and tissue engineering applications., Competing Interests: Competing interests: The authors declare no competing interests. The funders had no role in the study’s design, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results. All authors of this publication have provided their consent for its publication. The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding authors., (© 2025. The Author(s).)

Liver cancer poses a global health challenge with limited therapeutic options. Notably, the limited success of current therapies in patients with primary liver cancers (PLCs) may be attributed to the high heterogeneity of both hepatocellular carcinoma (HCCs) and intrahepatic cholangiocarcinoma (iCCAs). This heterogeneity evolves over time as tumor-initiating stem cells, or cancer stem cells (CSCs), undergo (epi)genetic alterations or encounter microenvironmental changes within the tumor microenvironment. These modifications enable CSCs to exhibit plasticity, differentiating into various resistant tumor cell types. Addressing this challenge requires urgent efforts to develop personalized treatments guided by biomarkers, with a specific focus on targeting CSCs. The lack of effective precision treatments for PLCs is partly due to the scarcity of ex vivo preclinical models that accurately capture the complexity of CSC-related tumors and can predict therapeutic responses. Fortunately, recent advancements in the establishment of patient-derived liver cancer cell lines and organoids have opened new avenues for precision medicine research. Notably, patient-derived organoid (PDO) cultures have demonstrated self-assembly and self-renewal capabilities, retaining essential characteristics of their respective in vivo tissues, including both inter- and intratumoral heterogeneities. The emergence of PDOs derived from PLCs serves as patient avatars, enabling preclinical investigations for patient stratification, screening of anticancer drugs, efficacy testing, and thereby advancing the field of precision medicine. This review offers a comprehensive summary of the advancements in constructing PLC-derived PDO models. Emphasis is placed on the role of CSCs, which not only contribute significantly to the establishment of PDO cultures but also faithfully capture tumor heterogeneity and the ensuing development of therapy resistance. The exploration of PDOs' benefits in personalized medicine research is undertaken, including a discussion of their limitations, particularly in terms of culture conditions, reproducibility, and scalability., Competing Interests: Declarations. Funding: Open access funding provided by Université Paris-Saclay. This work is part of the PREMELICAN (Precision Medicine in Liver Cancer) project, supported by funding from AP-HP Carnot Institute. Conflict of interest: Julien Giron-Michel, Maël Padelli, Estelle Oberlin, Hind Guenou, and Jean-Charles Duclos-Vallée have no conflicts of interest that are directly relevant to the content of this article. Ethics approval: No ethics approval was required. Consent to participate: Not applicable. Consent for publication: Not applicable. Availability of data and materials: All data represented are available in the public domain. Code availability: Not applicable. Author contributions: J.G.M. wrote the manuscript and designed the figures; J.G.M., M.P., E.O., H.G., and J.C.D.V. edited the manuscript. All authors read and approved the final manuscript., (© 2025. The Author(s).)

Leishmania is responsible for a neglected tropical disease affecting millions of people around the world and could potentially spread more due to climate change. This disease not only leads to significant morbidity but also imposes substantial social and economic burdens on affected populations, often exacerbating poverty and health disparities. Despite the complexity and effectiveness of the immune response, the parasite has developed various strategies to evade detection and manipulates host cells in favor of its replication. These evasion strategies start at early stages of the infection by hijacking immune receptors to silence critical cellular response that would otherwise limit the pathogen's propagation. Among these receptors, Fc receptors have emerged as a significant player in the immune evasion strategies employed by microorganisms, as they could promote inhibitory pathways. This review explores the potential role of one of these immune receptors, the FcγRIIA, in leishmaniasis and how this parasite may use it and the signaling pathways downstream to evade the host immune response. By understanding the potential interactions between Leishmania and immune receptors such as FcγRIIA, we may identify novel targets for therapeutic intervention aimed to enhance the host immune response and reduce the burden of this disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Leishmania is the causal parasite of leishmaniasis, a neglected tropical disease affecting millions of individuals worldwide, and its dissemination is linked to climate change. Despite the complexity and effectiveness of the immune response, the parasite has developed many strategies to evade it and take control of the host cell to replicate. These evasion strategies start at early stages of infection by hijacking immune receptors to mitigate the cellular response. In this study, we examined whether Leishmania uses the Fc receptor FcγRIIA/CD32a and its downstream signaling pathways to evade the host immune response., Methods: Regarding in vivo studies, CD32a transgenic mice and the corresponding wild types were infected with Leishmania major Friedlin strain. For the in vitro experiments, BMDMs isolated from WT or CD32a transgenic mice and control or CD32a knockdown differentiated THP-1s were infected with two species of Leishmania, Leishmania major and L. tropica., Results: In vivo, expression of FcγRIIA/CD32a was found to accelerate the signs of inflammation while simultaneously preventing the formation of necrotic lesions after Leishmania infection. In infected macrophages, the presence of FcγRIIA/CD32a did not affect the secretion of proinflammatory cytokines, while the balance between ITAMa and ITAMi proteins was disturbed with improved Fyn and Lyn activation. Unexpectedly, infection with L. tropica but not L. major triggered an intracytoplasmic processing of FcγRIIA/CD32a., Conclusions: Our observations underscore the significance of FcγRIIA/CD32a in cutaneous leishmaniasis and its potential use as a therapeutic target., Competing Interests: Declarations. Consent for publication: All the authors agree and consent for publication of the results presented in this manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

There are currently 1.2 million people living with HIV (Human Immunodeficiency Virus) in the United States. Virally suppressed HIV patients commonly experience chronic inflammation which increases the risk for other chronic conditions. This inflammation can be quantified with a variety of biomarkers. Some current antiretroviral compounds bring about metabolic abnormalities and promote weight gain often associated with increases in visceral adipose tissue (VAT) and an increase in the risk of diabetes mellitus and cardiovascular disease. Sulforaphane, an isothiocyanate found in cruciferous vegetables, has shown efficacy in animal models by reducing lipid levels, lowering inflammatory markers, and decreasing fat mass. A double-blind randomized controlled pilot study with 14 virally suppressed HIV patients was conducted to evaluate the effects of 40 mg (225 μmol) of sulforaphane, once daily, over 12 weeks, followed by a 4-week washout period. There was a significant decrease in C-reactive protein compared to the control group ( p  = 0.019). Sulforaphane has been studied in a multitude of conditions and diseases, but this is the first study in a human population of patients living with HIV., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Giron, Smiarowski and Katz.)

Self-assembly of biological elements into biomimetic cargo carriers for targeting and delivery is a promising approach. However, it still holds practical challenges. We developed a functionalization approach of DNA origami (DO) nanostructures with neuronal growth factor (NGF) for manipulating neuronal systems. NGF bioactivity and its interactions with the neuronal system were demonstrated in vitro and in vivo models. The DO elements fabricated by molecular self-assembly have manipulated the surrounding environment through static spatially and temporally controlled presentation of ligands to the cell surface receptors. Our data showed effective bioactivity in differentiating PC12 cells in vitro. Furthermore, the DNA origami NGF (DON) affected the growth directionality and spatial capabilities of dorsal root ganglion neurons in culture by introducing a chemotaxis effect along a gradient of functionalized DO structures. Finally, we showed that these elements provide enhanced axonal regeneration in a rat sciatic nerve injury model in vivo. This study is a proof of principle for the functionality of DO in neuronal manipulation and regeneration. The approach proposed here, of an engineered platform formed out of programmable nanoscale elements constructed of DO, could be extended beyond the nervous system and revolutionize the fields of regenerative medicine, tissue engineering, and cell biology., (© 2024 The Authors. Biotechnology Journal published by Wiley‐VCH GmbH.)

Reducing production costs, known as scaling, is a significant obstacle in the advancement of cultivated meat. The cultivation process hinges on several key components, e.g., cells, media, scaffolds, and bioreactors. This study demonstrates an innovative approach, departing from traditional stainless steel or glass bioreactors, by integrating food-grade plant-based scaffolds and thermoplastic film bioreactors. While thermoplastic films are commonly used for constructing fluidic systems, conventional welding methods are cost-prohibitive and lack rapid prototyping capabilities, thus inflating research and development expenses. The developed laser welding technique facilitates contamination-free and leakproof sealing of polyethylene films, enabling the efficient fabrication of macrofluidic systems with various designs and dimensions. By incorporating food-grade plant-based scaffolds, such as rice seeded with bovine mesenchymal stem cells, into these bioreactors, this study demonstrates sterile cell proliferation on scaffolds within macrofluidic systems. This approach not only reduces bioreactor prototyping and construction costs but also addresses the need for scalable solutions in both research and industrial settings. Integrating single-use bioreactors with minimal shear forces and incorporating macro carriers such as puffed rice may further enhance biomass production in a scaled-out model. The use of food-grade plant-based scaffolds aligns with sustainable practices in tissue engineering and cultured-meat production, emphasizing its suitability for diverse applications.

The emergence of autonomous vehicles (AVs) marks a transformative leap in transportation technology. Central to the success of AVs is ensuring user safety, but this endeavor is accompanied by the challenge of establishing trust and acceptance of this novel technology. The traditional "one size fits all" approach to AVs may limit their broader societal, economic, and cultural impact. Here, we introduce the Persona-PhysioSync AV (PPS-AV). It adopts a comprehensive approach by combining personality traits with physiological and emotional indicators to personalize the AV experience to enhance trust and comfort. A significant aspect of the PPS-AV framework is its real-time monitoring of passenger engagement and comfort levels within AVs. It considers a passenger's personality traits and their interaction with physiological and emotional responses. The framework can alert passengers when their engagement drops to critical levels or when they exhibit low situational awareness, ensuring they regain attentiveness promptly, especially during Take-Over Request (TOR) events. This approach fosters a heightened sense of Human-Vehicle Interaction (HVI), thereby building trust in AV technology. While the PPS-AV framework currently provides a foundational level of state diagnosis, future developments are expected to include interaction protocols that utilize interfaces like haptic alerts, visual cues, and auditory signals. In summary, the PPS-AV framework is a pivotal tool for the future of autonomous transportation. By prioritizing safety, comfort, and trust, it aims to make AVs not just a mode of transport but a personalized and trusted experience for passengers, accelerating the adoption and societal integration of autonomous vehicles.

A program for the hematologic patient at very high risk of infections (HAR, from its initials in Spanish) was implemented, based on a multidisciplinary team and six measures intended to reduce the colonization and subsequent sepsis by multidrug-resistant organisms (MDRO). We aimed at evaluating the effectiveness of the HAR program in terms of MDRO infections mainly caused by Klebsiella pneumoniae carbapenemase-producing and multidrug-resistant Pseudomona aeruginosa , and sepsis-related mortality. We established retrospective comparisons between the pre-HAR period (2016-2018) and the post-HAR period (2018-2019), in patients who received a hematopoietic stem cell transplant (HSCT) and/or intensive chemotherapy to treat non-M3 acute myeloid leukemia (CH-AML). We included 262 patients: 176 pre-HAR and 86 post-HAR. MDRO infection was 4.6% at 30 days and 6.1% at 90 days (all the cases during the pre-HAR period). Sepsis-related mortality was 6.5%, considering a median follow-up of 608 days: 6.1% in the HSCT group and 12.4% in the CH-AML group ( p  = 0.306). Sepsis-related mortality was 8.7% in the pre-HAR period and 0% in the post-HAR period ( p  = 0.014). The implementation of this multidisciplinary program based in preventive measures and the appropriate use of antibiotics enabled a decrease in sepsis-related mortality in very high-risk hematologic patients., Competing Interests: Conflict of interestAll authors declare that they have no conflict of interest., (© Indian Society of Hematology and Blood Transfusion 2021.)

Persons living with Human immunodeficiency virus (HIV) are living longer, healthier lives due to advancements in antiretroviral therapies and access to lifelong treatment. Yet, in rural Appalachia, access to adequate medical care is complicated by factors such as geography and lack of access to resources. The purpose of this study was to explore the perceptions of advance care planning (ACP) needs of persons living with HIV (PLWH) in Appalachian Tennessee and Alabama. Using a qualitative-descriptive design, we analyzed patterns of responses to face-to-face, semi-structured interviews of 40 PLWH as part of a larger multi-site mixed method study. Data demonstrated high patient satisfaction with medical care and good relationships with providers. However, common themes arose surrounding stigma, inadequate finances, and dislike of the term "end-of-life." Findings from this study fill a gap in the extant science pertaining to the focus of ACP in the unique population of rural Appalachia.

The World Health Organization (WHO) recommends multidrug therapy (MDT) for the treatment of paucibacillary and multibacillary forms of leprosy, also known as Hansen's disease (HD). MDT combinations of dapsone, rifampin, and clofazimine have reduced the prevalence of the disease but are not without adverse effects impacting regimen adherence. Hence, an urgent need exists to consider alternative MDT regimens with an improved safety profile that promotes treatment adherence. Herein, we described a case series of 10 patients with HD (nine patients with multibacillary leprosy and one with pure neural leprosy) treated with monthly rifampin, moxifloxacin, and minocycline (RMM). The United States National Hansen's Disease Program (NHDP) diagnosed and treated patients across US institutions. All patients received a regimen of 12-24 months of RMM. We reviewed the clinical outcomes, adherence, rate of completion, and adverse events of patients treated with monthly RMM from January 2019 to August 2022. Nine patients had multibacillary leprosy, with some having type-2 reactions. One patient had pure neural leprosy with a reversal reaction. In this case series, we identified that all patients completed the RMM regimen without treatment interruptions. None of the patients experienced any skin hyperpigmentation or any significant side effects. All patients tolerated the monthly RMM regimen with rapid improvement of skin lesions and without logistic hurdles. Based on previous clinical evidence and the results of this case series, the NHDP and other programs should consider the RMM regimen as first-line therapy., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Henao-Martínez reported receiving a K12-clinical trial award as a co-principal investigator for the Expanded Access IND Program (EAP) to provide the Yellow Fever vaccine (Stamaril) to persons in the United States outside the submitted work. The Editor-in-Chief of Therapeutic Advances in Infectious Disease is an author of this paper, therefore, the peer review process was managed by alternative members of the Board and the submitting Editor had no involvement in the decision-making process. No other disclosures were reported., (© The Author(s), 2022.)