Regulatory insights into nanomedicine and gene vaccine innovation: Safety assessment, challenges, and regulatory perspectives.

This analysis explores the principal regulatory concerns linked to nanomedicines and gene vaccines, including the complexities involved and the perspectives on how to navigate them. In the realm of nanomedicines, ensuring the safety of nanomaterials is paramount due to their unique characteristics and potential interactions with biological systems. Regulatory bodies are actively formulating guidelines and standards to assess the safety and risks associated with nanomedicine products, emphasizing the need for standardized characterization techniques to accurately gauge their safety and effectiveness. Regarding gene vaccines, regulatory frameworks must be tailored to address the distinct challenges posed by genetic interventions, necessitating special considerations in safety and efficacy evaluations, particularly concerning vector design, target specificity, and long-term patient monitoring. Ethical concerns such as patient autonomy, informed consent, and privacy also demand careful attention, alongside the intricate matter of intellectual property rights, which must be balanced against the imperative of ensuring widespread access to these life-saving treatments. Collaborative efforts among regulatory bodies, researchers, patent offices, and the private sector are essential to tackle these challenges effectively, with international cooperation being especially crucial given the global scope of nanomedicine and genetic vaccine development. Striking the right balance between safeguarding intellectual properties and promoting public health is vital for fostering innovation and ensuring equitable access to these ground-breaking technologies, underscoring the significance of addressing these regulatory hurdles to fully harness the potential benefits of nanomedicine and gene vaccines for enhancing healthcare outcomes on a global scale. STATEMENT OF SIGNIFICANCE: Several biomaterials are being proposed for the development of nanovaccines, from polymeric micelles, PLGA-/PEI-/PLL-nanoparticles, solid lipid nananoparticles, cationic lipoplexes, liposomes, hybrid materials, dendrimers, carbon nanotubes, hydrogels, to quantum dots. Lipid nanoparticles (LNPs) have gained tremendous attention since the US Food and Drug Administration (FDA) approval of Pfizer and Moderna's COVID-19 vaccines, raising public awareness to the regulatory challenges associated with nanomedicines and genetic vaccines. This review provides insights into the current perspectives and potential strategies for addressing these issues, including clinical trials. By navigating these regulatory landscapes effectively, we can unlock the full potential of nanomedicine and genetic vaccines using a range of promising biomaterials towards improving healthcare outcomes worldwide.

Beyond the adverse effects of the systemic route: Exploiting nanocarriers for the topical treatment of skin cancers.

Skin cancer is a heterogeneous disease that can be divided into two main groups, melanoma and nonmelanoma skin cancers. Conventional therapies for skin cancer have numerous systemic side effects and a high recurrence rate. Topical treatment is an alternative approach, but drug permeability remains a challenge. Therefore, nanocarriers appear as important nanotechnology tools that reduces both the side effects and improves clinical outcomes. This is why they are attracting growing interest. In this review, scientific articles on the use of nanocarriers for the topical treatment of skin cancer were collected. Despite the promising results of the presented nanocarriers and considering that some of them are already on the market, there is an urgent need for investment in the development of manufacturing methods, as well as of suitable toxicological and regulatory evaluations, since the conventional methods currently used to develop these nanocarriers-based products are more time-consuming and expensive than conventional products.

Polymersomes as the Next Attractive Generation of Drug Delivery Systems: Definition, Synthesis and Applications.

Polymersomes are artificial nanoparticles formed by the self-assembly process of amphiphilic block copolymers composed of hydrophobic and hydrophilic blocks. They can encapsulate hydrophilic molecules in the aqueous core and hydrophobic molecules within the membrane. The composition of block copolymers can be tuned, enabling control of characteristics and properties of formed polymersomes and, thus, their application in areas such as drug delivery, diagnostics, or bioimaging. The preparation methods of polymersomes can also impact their characteristics and the preservation of the encapsulated drugs. Many methods have been described, including direct hydration, thin film hydration, electroporation, the pH-switch method, solvent shift method, single and double emulsion method, flash nanoprecipitation, and microfluidic synthesis. Considering polymersome structure and composition, there are several types of polymersomes including theranostic polymersomes, polymersomes decorated with targeting ligands for selective delivery, stimuli-responsive polymersomes, or porous polymersomes with multiple promising applications. Due to the shortcomings related to the stability, efficacy, and safety of some therapeutics in the human body, polymersomes as drug delivery systems have been good candidates to improve the quality of therapies against a wide range of diseases, including cancer. Chemotherapy and immunotherapy can be improved by using polymersomes to deliver the drugs, protecting and directing them to the exact site of action. Moreover, this approach is also promising for targeted delivery of biologics since they represent a class of drugs with poor stability and high susceptibility to in vivo clearance. However, the lack of a well-defined regulatory plan for polymersome formulations has hampered their follow-up to clinical trials and subsequent market entry.

Select Agent Regulatory Challenges in a Patient Care Setting: Review and Recommendations.

The Federal Select Agent Program ensures the safe and secure possession, use, and transfer of biological select agents and toxins through the select agent regulations (42 CFR §73, 7 CFR §331, and 9 CFR §121). These regulations are primarily written for interpretation by diagnostic and research laboratories, with limited text pertaining to the care of individuals infected with a select agent. The regulations applicable to patient care settings are ambiguous, resulting in challenges with regulatory compliance. The COVID-19 pandemic called attention to these shortcomings and the need to clarify and modify the select agent regulations. In this article, we discuss 3 select agent regulation phrases regarding patient care that need clarification-specifically, the window of time to transfer, patient care setting, and conclusion of patient care-and provide recommendations for improvement. These recommendations include implementing minimum security standards to safeguard patient specimens against theft, loss, or release prior to the appropriate transfer or destruction of the material and increasing the time allowed for the transfer or destruction of specimens before entities are subject to the select agent regulations. We encourage the Federal Select Agent Program to release a policy statement clarifying the select agent regulations regarding patient care discussed herein and to lengthen the designated time to destroy or transfer agents to a registered entity. Addressing these challenges will aid in compliance with the select agent regulations in patient care settings.

What an International Declaration on Neurotechnologies and Human Rights Could Look like: Ideas, Suggestions, Desiderata.

International institutions such as UNESCO are deliberating on a new standard setting instrument for neurotechnologies. This will likely lead to the adoption of a soft law document which will be the first global document specifically tailored to neurotechnologies, setting the tone for further international or domestic regulations. While some stakeholders have been consulted, these developments have so far evaded the broader attention of the neuroscience, neurotech, and neuroethics communities. To initiate a broader debate, this target article puts to discussion twenty-five considerations and desiderata for recognition by a future instrument. They are formulated at different levels of abstraction, from the big picture to technical details, seek to widen the perspective of preparatory reports and transcend the narrow debate about "neurorights" which overshadows many richer and more relevant aspects. These desiderata are not an exhaustive enumeration but a starting point for discussions about what deserves and what requires protection by an international instrument.

Sustainable Pickering Emulsions with Nanocellulose: Innovations and Challenges.

The proper mix of nanocellulose to a dispersion of polar and nonpolar liquids creates emulsions stabilized by finely divided solids (instead of tensoactive chemicals) named Pickering emulsions. These mixtures can be engineered to develop new food products with innovative functions, potentially more eco-friendly characteristics, and reduced risks to consumers. Although cellulose-based Pickering emulsion preparation is an exciting approach to creating new food products, there are many legal, technical, environmental, and economic gaps to be filled through research. The diversity of different types of nanocellulose makes it difficult to perform long-term studies on workers' occupational health, cytotoxicity for consumers, and environmental impacts. This review aims to identify some of these gaps and outline potential topics for future research and cooperation. Pickering emulsion research is still concentrated in a few countries, especially developed and emerging countries, with low levels of participation from Asian and African nations. There is a need for the development of scaling-up technologies to allow for the production of kilograms or liters per hour of products. More research is needed on the sustainability and eco-design of products. Finally, countries must approve a regulatory framework that allows for food products with Pickering emulsions to be put on the market.

Three-Dimensional Scaffolds for Bone Tissue Engineering.

Immobilization using external or internal splints is a standard and effective procedure to treat minor skeletal fractures. In the case of major skeletal defects caused by extreme trauma, infectious diseases or tumors, the surgical implantation of a bone graft from external sources is required for a complete cure. Practical disadvantages, such as the risk of immune rejection and infection at the implant site, are high in xenografts and allografts. Currently, an autograft from the iliac crest of a patient is considered the "gold standard" method for treating large-scale skeletal defects. However, this method is not an ideal solution due to its limited availability and significant reports of morbidity in the harvest site (30%) as well as the implanted site (5-35%). Tissue-engineered bone grafts aim to create a mechanically strong, biologically viable and degradable bone graft by combining a three-dimensional porous scaffold with osteoblast or progenitor cells. The materials used for such tissue-engineered bone grafts can be broadly divided into ceramic materials (calcium phosphates) and biocompatible/bioactive synthetic polymers. This review summarizes the types of materials used to make scaffolds for cryo-preservable tissue-engineered bone grafts as well as the distinct methods adopted to create the scaffolds, including traditional scaffold fabrication methods (solvent-casting, gas-foaming, electrospinning, thermally induced phase separation) and more recent fabrication methods (fused deposition molding, stereolithography, selective laser sintering, Inkjet 3D printing, laser-assisted bioprinting and 3D bioprinting). This is followed by a short summation of the current osteochondrogenic models along with the required scaffold mechanical properties for in vivo applications. We then present a few results of the effects of freezing and thawing on the structural and mechanical integrity of PLLA scaffolds prepared by the thermally induced phase separation method and conclude this review article by summarizing the current regulatory requirements for tissue-engineered products.

Ethical Responsibilities for Companies That Process Personal Data.

It has become increasingly difficult for individuals to exercise meaningful control over the personal data they disclose to companies or to understand and track the ways in which that data is exchanged and used. These developments have led to an emerging consensus that existing privacy and data protection laws offer individuals insufficient protections against harms stemming from current data practices. However, an effective and ethically justified way forward remains elusive. To inform policy in this area, we propose the Ethical Data Practices framework. The framework outlines six principles relevant to the collection and use of personal data-minimizing harm, fairly distributing benefits and burdens, respecting autonomy, transparency, accountability, and inclusion-and translates these principles into action-guiding practical imperatives for companies that process personal data. In addition to informing policy, the practical imperatives can be voluntarily adopted by companies to promote ethical data practices.

Dose-efficiency quantification of computed tomography systems using a model-observer.

BACKGROUND: Recent advances in computed tomography (CT) technology have considerably improved the quality of CT images and reduced radiation exposure in patients. At present, however, there is no generally accepted figure of merit (FOM) for comparing the dose efficiencies of CT systems. PURPOSE: (i) To establish an FOM that characterizes the quality of CT images in relation to the radiation dose by means of a mathematical model observer and (ii) to evaluate the new FOM on different CT systems and image reconstruction algorithms. METHODS: Images of a homogeneous phantom with four low-contrast inserts were acquired using three different CT systems at three dose levels and a representative protocol for CT imaging of low-contrast objects in the abdomen. The images were reconstructed using filtered-back projection and iterative algorithms. A channelized hotelling observer with difference-of-Gaussian channels was applied to compute the detectability ( d ' $d^{\prime}$ ). This was done for each insert and each of the considered imaging conditions from square regions of interest (ROIs) that were (semi-)automatically centered on the inserts. The estimated detectabilities ( d ' $d^{\prime}$ ) were averaged in the first step over the three dose levels ( ⟨ d ' ⟩ $\langle {d^{\prime}} \rangle $ ), and subsequently over the four contrast inserts ( ⟨ d ' ⟩ w ${\langle {d^{\prime}} \rangle _{\rm{w}}}$ ). All calculation steps included a dedicated assessment of the related uncertainties following accepted metrological guidelines. RESULTS: The determined detectabilities ( d ' $d^{\prime}$ ) varied considerably with the contrast and diameter of the four inserts, as well as with the radiation doses and reconstruction algorithms used for image generation ( d ' $d^{\prime}\;$ = 1.3-5.5). Thus, the specification of a single detectability as an FOM is not well suited for comprehensively characterizing the dose efficiency of a CT system. A more comprehensive and robust characterization was provided by the averaged detectabilities ⟨ d ' ⟩ $\langle {d^{\prime}} \rangle $ and, in particular, ⟨ d ' ⟩ w ${\langle {d^{\prime}} \rangle _{\rm{w}}}$ . Our analysis reveals that the model observer analysis is very sensitive to the exact position of the ROIs. CONCLUSIONS: The presented automatable software approach yielded with the weighted detectability ⟨ d ' ⟩ w ${\langle {d^{\prime}} \rangle _{\rm{w}}}$ an objective FOM to benchmark different CT systems and reconstruction algorithms in a robust and reliable manner. An essential advantage of the proposed model-observer approach is that uncertainties in the FOM can be provided, which is an indispensable prerequisite for type testing.

Etiology, Classification, Diagnostics, and Conservative Management of Osteochondral Lesions of the Talus. 2023 Recommendations of the Working Group "Clinical Tissue Regeneration" of the German Society of Orthopedics and Traumatology.

METHODS: Peer-reviewed literature was analyzed regarding different topics relevant to osteochondral lesions of the talus (OLTs) treatment. This process concluded with a statement for each topic reflecting the best scientific evidence available for a particular diagnostic or therapeutic concept, including the grade of recommendation. Besides the scientific evidence, all group members rated the statements to identify possible gaps between literature and current clinical practice. CONCLUSION: In patients with minimal symptoms, OLT progression to ankle osteoarthritis is unlikely. Risk factors for progression are the depth of the lesion on MRI, subchondral cyst formation, and the extent of bone marrow edema. Conservative management is the adaptation of activities to the performance of the ankle joint. A follow-up imaging after 12 months helps not to miss any progression. It is impossible to estimate the probability of success of conservative management from initial symptoms and imaging. Cast immobilization is an option in OLTs in children, with a success rate of approximately 50%, although complete healing, estimated from imaging, is rare. In adults, improvement by conservative management ranges between 45% and 59%. Rest and restrictions for sports activities seem to be more successful than immobilization. Intra-articular injections of hyaluronic acid and platelet-rich plasma can improve pain and functional scores for more than 6 months. If 3 months of conservative management does not improve symptoms, surgery can be recommended.

Teleradiology: good practice guide.

Teleradiology is the electronic transmission of radiological images from one location to another with the main purpose of interpreting or consulting a diagnosis and must be subject to codes of conduct agreed upon by professional societies. The content of fourteen teleradiology best practice guidelines is analyzed. Their guiding principles are: the best interest and benefit of the patient, quality and safety standards homologous to the local radiology service, and use as a complement and support of the same. As legal obligations: guaranteeing rights by applying the principle of the patient's country of origin, establishing requirements in international teleradiology and civil liability insurance. Regarding the radiological process: integration with the local service process, guaranteeing the quality of images and reports, access to previous studies and reports and complying with the principles of radioprotection. Regarding professional requirements: compliance with the required registrations, licenses and qualifications, training and qualification of the radiologist and technician, prevention of fraudulent practices, respect for labor standards and remuneration of the radiologist. Subcontracting must be justified, managing the risk of commoditization. Compliance with the system's technical standards.

Telerradiología: guía de buenas prácticas / Teleradiology: good practice guide

La telerradiología es la trasmisión electrónica de imágenes radiológicas de una localización a otra con el propósito principal de interpretar o consultar un diagnóstico y debe estar sujeta a códigos de conducta consensuados por sociedades profesionales. Se analiza el contenido de 14 guías de buenas prácticas de telerradiología. Sus principios rectores son: el mejor interés y beneficio del paciente, estándares de calidad y seguridad homologables al servicio de radiología local, y utilización como complemento y apoyo del mismo. Como obligaciones legales: garantizar los derechos aplicando el principio de país de origen del paciente, establecer requisitos en telerradiología internacional y seguro de responsabilidad civil. Con respecto al proceso radiológico: integración con el proceso del servicio local, garantizar la calidad de imágenes e informes, el acceso a los estudios e informes previos y cumplir los principios de radioprotección. En relación con los requisitos profesionales: cumplir con los registros, licencias y cualificaciones exigidas, formación y capacitación del radiólogo y técnico, prevención de prácticas fraudulentas, respeto a las normas laborales y remuneración del radiólogo. La subcontratación debe estar justificada, gestionando el riesgo de comoditización. Cumplimiento de estándares técnicos del sistema (AU)

Teleradiology is the electronic transmission of radiological images from one location to another with the main purpose of interpreting or consulting a diagnosis and must be subject to codes of conduct agreed upon by professional societies. The content of fourteen teleradiology best practice guidelines is analyzed. Their guiding principles are: the best interest and benefit of the patient, quality and safety standards homologous to the local radiology service, and use as a complement and support of the same. As legal obligations: guaranteeing rights by applying the principle of the patient's country of origin, establishing requirements in international teleradiology and civil liability insurance. Regarding the radiological process: integration with the local service process, guaranteeing the quality of images and reports, access to previous studies and reports and complying with the principles of radioprotection. Regarding professional requirements: compliance with the required registrations, licenses and qualifications, training and qualification of the radiologist and technician, prevention of fraudulent practices, respect for labor standards and remuneration of the radiologist. Subcontracting must be justified, managing the risk of commoditization. Compliance with the system's technical standards (AU)

Timing and monitoring of financial disclosures in publications: A cross-institutional assessment of financial conflict of interest reports.

A consistent mitigation strategy used in sponsored research to manage a financial conflict of interest (FCOI) is disclosure in publications. While federal funding regulations require mitigation strategies to be monitored through the end of the project's term, manuscripts are often published after the project term has ended. We examined whether it would be valuable to extend monitoring of publications for compliance with requirements for disclosure beyond the end date of a project's term and, if so, for how long after the term has ended. Using publicly available databases, we identified FCOI reports from public universities and analyzed disclosure completion in the years before and after the end of the project's term. We found that 80.2% of FCOI reports in our sample had a publication in which a conflicted Investigator served as an author, yet less than half (43.6%) of these publications contained disclosure statements acknowledging the known FCOI. We also found that publication most commonly occurred one year after the end of the project's term. These findings indicate that an effective way to support accountability and accuracy of the scientific record would be to extend monitoring of disclosure in publications through one year following the end of the project's term.

Assessment criteria for research misconduct: Taiwanese researchers' perceptions.

Assessing the severity of an instance of research misconduct is undoubtedly challenging, especially when the result of the assessment may be key to suggesting subsequent sanctions. However, only a few references are currently available in the Taiwanese academic context. In a previous study, the present authors developed The Assessment Criteria for Research Misconduct (The Criteria) based on existing international policies and guidelines and reviewed by local research scholars for content validity. The Criteria, with a total of 28 items, were organized into three sections: general criteria for determining case severity, aggravating criteria, and mitigating criteria. In the current study, the authors further conducted a survey and collected data on 277 Taiwanese researchers' perceived importance of each criterion included in The Criteria. The results showed that participants generally agreed with the importance of all criteria. However, the group that lacked case-handling experience attributed significantly greater levels of importance to the criterion of original will (proactive, passive, or coercive) toward participation in misconduct than did the experienced group. In addition, the participants exhibited greater variation in the perceived importance of the mitigating criteria. Finally, the possible utility of The Criteria in real contexts and training materials is suggested in the study.

Materialized Oppression in Medical Tools and Technologies.

It is well-known that racism is encoded into the social practices and institutions of medicine. Less well-known is that racism is encoded into the material artifacts of medicine. We argue that many medical devices are not merely biased, but materialize oppression. An oppressive device exhibits a harmful bias that reflects and perpetuates unjust power relations. Using pulse oximeters and spirometers as case studies, we show how medical devices can materialize oppression along various axes of social difference, including race, gender, class, and ability. Our account uses political philosophy and cognitive science to give a theoretical basis for understanding materialized oppression, explaining how artifacts encode and carry oppressive ideas from the past to the present and future. Oppressive medical devices present a moral aggregation problem. To remedy this problem, we suggest redundantly layered solutions that are coordinated to disrupt reciprocal causal connections between the attitudes, practices, and artifacts of oppressive systems.

Training undergraduate students in HIPAA compliance.

The Health Insurance Portability and Accountability Act (HIPAA) has radically changed the way healthcare is conducted, and its relevance continues to expand as healthcare technology evolves. This article describes a method for training inexperienced undergraduate students to become HIPAA-compliant clinical research volunteers in a pediatric traumatic brain injury (TBI) study. Volunteers are trained to use the hospital's electronic health records (EHR) system to identify potential study candidates for approach, and they develop this skill set through google classroom modules/quizzes along with routine zoom calls to solidify their consenting approach. Since the inception of this study in 2018, there have been over one hundred different undergraduate research volunteers involved, and there has not been a single HIPAA violation to date. This compliance success rate is indicative of the efficacy of this training protocol. This paper serves as a guide to implementing HIPAA compliance training and ensuring accountability in new and existing clinical research studies.

Distinguishing appropriate from inappropriate conditions on research participation.

Individuals do not have a right to participate in clinical trials. But, they do have a right against being denied participation for inappropriate reasons. Despite the widespread endorsement of these two claims, there has been little discussion regarding which conditions for participation in clinical trials are appropriate and which are inappropriate. The present manuscript attempts to address this gap in the literature. We first describe and then argue against the claim that conditions on enrollment or continued participation are appropriate only when they are needed to answer the scientific question(s) posed by the trial. We then offer an alternative view according to which the appropriateness of conditions depends on whether they help to satisfy the ethical requirements of clinical research. Because these requirements include social value, the present view implies that promoting social value is an acceptable reason to impose conditions on research participation. With this in mind, we explain why it is not coercive to require potential participants to accept conditions on enrollment that promote a trial's social value, even when the participants find those conditions unwelcome. We conclude by evaluating the present proposal's implications for the common practice of requiring participants to agree to the possible use of their leftover biospecimens in a broad range of future research. We argue, contra current regulatory policy, that this practice can be acceptable even when the present trial offers participants the prospect of clinical benefit and the samples are being reserved for future research that is unrelated to the present trial.

Plant Molecular Pharming and Plant-Derived Compounds towards Generation of Vaccines and Therapeutics against Coronaviruses.

The current century has witnessed infections of pandemic proportions caused by Coronaviruses (CoV) including severe acute respiratory syndrome-related CoV (SARS-CoV), Middle East respiratory syndrome-related CoV (MERS-CoV) and the recently identified SARS-CoV2. Significantly, the SARS-CoV2 outbreak, declared a pandemic in early 2020, has wreaked devastation and imposed intense pressure on medical establishments world-wide in a short time period by spreading at a rapid pace, resulting in high morbidity and mortality. Therefore, there is a compelling need to combat and contain the CoV infections. The current review addresses the unique features of the molecular virology of major Coronaviruses that may be tractable towards antiviral targeting and design of novel preventative and therapeutic intervention strategies. Plant-derived vaccines, in particular oral vaccines, afford safer, effectual and low-cost avenues to develop antivirals and fast response vaccines, requiring minimal infrastructure and trained personnel for vaccine administration in developing countries. This review article discusses recent developments in the generation of plant-based vaccines, therapeutic/drug molecules, monoclonal antibodies and phytochemicals to preclude and combat infections caused by SARS-CoV, MERS-CoV and SARS-CoV-2 viruses. Efficacious plant-derived antivirals could contribute significantly to combating emerging and re-emerging pathogenic CoV infections and help stem the tide of any future pandemics.

Concepts to Bolster Biorisk Management.

The rapid increase in the power of the life sciences has not been accompanied by a proportionate increase in the sophistication of biorisk management. Through conversations with thought leaders in biosafety and biosecurity, we have identified 19 concepts that are critical for biorisk management to continue to ensure the responsible and safe conduct of the life sciences in the future. Our work is not meant to be a comprehensive list, but rather a collection of topics that we hope will spark dialogue in the policy, research, and biorisk management communities.