Search Results (208)

Capital investment in longevity science—research targeting the biological processes of aging through interventions like cellular reprogramming, AI-driven drug discovery, and biological age monitoring—may create significant divergence between traditional actuarial projections and emerging mortality improvements. This paper examines how accelerating investment in life extension technologies affects mortality improvement trajectories beyond conventional actuarial assumptions, building on the comprehensive investment landscape analysis documented in “Investors in Longevity” supported by venture capital databases, industry reports, and regulatory filings. We introduce an Investment-Adjusted Mortality Model (IAMM) that incorporates capital allocation trends as leading indicators of mortality improvement acceleration. Under high-investment scenarios (annual funding of USD 15+ billion in longevity technologies), current insurance products may significantly underestimate longevity risk, creating potential solvency challenges. Our statistical analysis demonstrates that investment-driven mortality improvements—actual reductions in death rates resulting from new anti-aging interventions—could exceed traditional projections by 18–31% by 2040. We validate our model by backtesting historical data, showing improved predictive performance (35% reduction in MAPE) compared to traditional Lee–Carter approaches during periods of significant medical technology advancement. Based on these findings, we propose modified insurance structures, including dynamic mortality-linked products and biological age underwriting, quantifying their effectiveness in reducing longevity risk exposure by 42–67%. These results suggest the need for actuarial science to incorporate investment dynamics in response to the changing longevity investment environment detailed in “Investors in Longevity”. The framework presented provides both theoretically grounded and empirically tested tools for incorporating investment dynamics into mortality projections and insurance product design, addressing gaps in current risk management approaches for long-term mortality exposure. Full article

Cancer research faces significant biological, technological, and systemic limitations that hinder the development of effective therapies and improved patient outcomes. Traditional preclinical models, such as 2D and 3D cell cultures, murine xenografts, and organoids, often fail to reflect the complexity of human tumor architecture, microenvironment, and immune interactions. This discrepancy results in promising laboratory findings not always translating effectively into clinical success. A core obstacle is tumor heterogeneity, characterized by diverse genetic, epigenetic, and phenotypic variations within tumors, which complicates treatment strategies and contributes to drug resistance. Hereditary malignancies and cancer stem cells contribute strongly to generating this complex panorama. Current early detection technologies lack sufficient sensitivity and specificity, impeding timely diagnosis. The tumor microenvironment, with its intricate interactions and resistance-promoting factors, further promotes treatment failure. Additionally, we only partially understand the biological processes driving metastasis, limiting therapeutic advances. Overcoming these barriers involves not only the use of new methodological approaches and advanced technologies, but also requires a cultural effort by researchers. Many cancer studies are still essentially observational. While acknowledging their significance, it is crucial to recognize the shift from deterministic to indeterministic paradigms in biomedicine over the past two to three decades, a transition facilitated by systems biology. It has opened the doors of deep metabolism where the functional processes that control and regulate cancer progression operate. Beyond biological barriers, systemic challenges include limited funding, regulatory complexities, and disparities in cancer care access across different populations. These socio-economic factors exacerbate research stagnation and hinder the translation of scientific innovations into clinical practice. Overcoming these obstacles requires multidisciplinary collaborations, advanced modeling techniques that better emulate human cancer, and innovative technologies for early detection and targeted therapy. Strategic policy initiatives must address systemic barriers, promoting health equity and sustainable research funding. While the complexity of cancer biology and systemic challenges are formidable, ongoing scientific progress and collaborative efforts inspire hope for breakthroughs that can transform cancer diagnosis, treatment, and survival outcomes worldwide. Full article

HIV/AIDS remains a global public health concern, with a high prevalence in sub-Saharan Africa. The President’s Emergency Plan for AIDS Relief (PEPFAR) initiatives, including preexposure prophylaxis (PREP) and postexposure prophylaxis (PEP), significantly reduced HIV infections in South Africa and Nigeria. The suspension of United States (U.S.) foreign aid may impact these preventive measures. Although some emergency aid programs were exempted, uncertainty persists, impacting global health initiatives, especially in South Africa and Nigeria. This study investigates the public health impacts of the United States (U.S.) government’s January 2025 suspension of U.S. foreign aid, focusing on its implications for HIV prevention initiatives, such as PREP and PEP, in South Africa and Nigeria. We comprehensively searched keywords such as PEPFAR, PREP, PEP, HIV infection in South Africa or Nigeria, antiretroviral (ARV) drugs, public healthcare impact, 2025 Trump’s foreign aid withdrawal, titles, and abstracts in Google Scholar, PubMed, and Web of Science. The search results were screened from 500 to 150 included articles based on their relevance and quality assessment for inclusion. The review unveiled that Nigeria maintained a continuous increase in HIV/AIDS-related deaths and new HIV infections from 1990, reaching the climax between 1999 and 2005, showing approximately 110,000 HIV/AIDS-related deaths and 200,000 new HIV infections. Notably, due to the PEPFAR intervention in Nigeria, an improved decrease in both HIV/AIDS-related deaths (45,000) and new HIV infections (75,000) was experienced from 2010 to 2023. South Africa experienced a rapid increase between 1990 and 2003 in both HIV/AIDS-related deaths and new HIV infections, reaching the climax around the early 2000s, with about 520,000 new HIV infections and 260,000 HIV/AIDS-related deaths in 2005. Furthermore, there was a continuous decline from 2005 onwards, with 50,000 HIV/AIDS-related deaths and 150,000 new HIV infections by 2023. Therefore, the suspension of this aid threatens disruptions in ARV therapy, possible increases in HIV transmission, shortages in PREP and PEP, the retrenchment of healthcare workers, the suspension of non-governmental organization activities, and the reversal of gains in vulnerable populations, reversing progress toward the 95-95-95 vision, increasing morbidity and mortality rates and financial strain on healthcare systems in these two countries. We recommend proactive measures, such as increased budget allocations for healthcare reforms, exploring local vaccine and health product development and diversifying funding sources in Nigeria, and implementing universal healthcare coverage for South Africans to mitigate the adverse consequences of aid withdrawal. Full article

The integration of advanced computational methods into precision medicine represents a transformative advancement in healthcare, enabling highly personalized treatment strategies based on individual genetic, environmental, and lifestyle factors. These methodologies have significantly enhanced disease diagnostics, genomic analysis, and drug discovery. However, rapid expansion in this field has resulted in fragmented understandings of its evolution and persistent knowledge gaps. This study employs a scientometric approach to systematically map the research landscape, identify key contributors, and highlight emerging trends in precision medicine. Methods: A scientometric analysis was conducted using data retrieved from the Scopus database, covering publications from 2019 to 2024. Tools such as VOSviewer and R-bibliometrix package (version 4.3.0) were used to perform co-authorship analysis, co-citation mapping, and keyword evolution tracking. The study examined annual publication growth, citation impact, research productivity by country and institution, and thematic clustering to identify core research areas. Results: The analysis identified 4574 relevant publications, collectively amassing 70,474 citations. A rapid growth trajectory was observed, with a 34.3% increase in publications in 2024 alone. The United States, China, and Germany emerged as the top contributors, with Harvard Medical School, the Mayo Clinic, and Sichuan University leading in institutional productivity. Co-citation and keyword analysis revealed three primary research themes: diagnostics and medical imaging, genomic and multi-omics data integration, and personalized treatment strategies. Recent trends indicate a shift toward enhanced clinical decision support systems and precision drug discovery. Conclusions: Advanced computational methods are revolutionizing precision medicine, spurring increased global research collaboration and rapidly evolving methodologies. This study provides a comprehensive knowledge framework, highlighting key developments and future directions. The insights derived can inform policy decisions, funding allocations, and interdisciplinary collaborations, driving further advancements in healthcare solutions. Full article

Background/Objectives: Surveillance of antimicrobial resistance (AMR) and antimicrobial use (AMU) is needed to understand risks and implement policies. Collecting AMU data in the context of disease prevalence and therapeutic outcomes has been suggested for improving AMU. We describe the process of developing an information and communication technology (ICT) system to monitor AMU, diseases and treatment outcomes in poultry in East Africa. Methods: A prototype system to register drug sales in veterinary pharmacies, a mobile application for farmers to report their AMU, and a database for monitoring was developed. Contact information for participating veterinarians was included as well as information about poultry diseases, husbandry, AMR and prudent use of antibiotics. The system was pilot-tested for a 6-month period in Kenya. Results: A total of 15,725 records were submitted by the 14 participating pharmacies and 91 records were entered by the 15 participating farmers. Overall, the participants were positive about the system and were able to use it. The information available was appreciated by the farmers. The pharmacy representatives appreciated getting an overview of their sales and stated that it had given them new insights. Conclusions: Despite some challenges, the concept of the developed ICT system could be useful for future monitoring of animal health and the use of pharmaceuticals in animals, and connecting farmers with veterinarians to improve animal health management. Our results underline the importance of close collaboration with stakeholders so that developed tools can be transferred to national ownership after the finalization of externally funded projects. Full article

Background/Objectives: This work aimed to analyze pediatric Post-Authorization Studies (PASs) registered in the European Union electronic Register of Post-Authorization Studies (EU PAS Register) from September 2010 to April 2023 to identify trends in terms of timing, age groups, and therapeutic areas and to discuss pediatric specificities and sources of funding for the PASs. Methods: A screening process identified PASs conducted exclusively on the pediatric population, and instructions were provided to ensure standardized data collection from the EU PAS Register. A univariate linear regression descriptive analysis was performed to assess trends over time, while a multivariate linear regression analysis helped explore additional characteristics of these studies. Results: Of the 2574 PASs extracted from the EU PAS Registry, 165 were included in this analysis. The majority of pediatric PASs were observational studies (86%), and most of them utilized secondary data (53%). The annual number of PASs increased significantly between 2010 and 2023. As envisaged, the largest part was funded by pharmaceutical companies (62%). Anti-infectives for systemic uses (25%), medicines for the nervous system (18%), and antineoplastic and immunomodulating agents (15%) resulted in the most studied drugs. Conclusions: Our findings show that post-marketing observational research in pediatric populations has increased over time. Nevertheless, industry–academia collaboration should be encouraged, and regulatory guidance is needed to prioritize research in areas of unmet therapeutic need. Full article

Nanoparticle technology has emerged as a fundamental component across various industries, including electronics, renewable energy, textiles, and medical biotechnology, particularly for targeted drug delivery applications. Commercialization has profoundly impacted economic growth, especially in the pharmaceutical and electronics industries. Moreover, it has improved workforce education and training, generating millions of employment prospects associated with nanotechnology development. By 2024, the Organisation for Economic Co-operation and Development anticipates that the global market for nanotechnology products will attain a value of United States Dollar (USD) 1 trillion to USD 3 trillion, resulting in the creation of over 2 million new employments globally. The swift progression of nanoparticle technology from 2000 to 2024 is primarily propelled by substantial industrial investment in research and development, alongside collaborations with academic institutions. The National Nanotechnology Initiative in the United States (US) has significantly contributed to these developments, with federal funding exceeding USD 30 billion by 2024 since its establishment in 2001. This funding has catalyzed significant advancements in both commercial and research applications of nanotechnology. Patent data highlights this expansion, with China establishing itself as the preeminent nation in nanotechnology patents. From 2000 to 2024, China steadily raised its proportion of nanotechnology patents, accounting for almost 40% of the global total by 2024. The US, Japan, Germany, and the Republic of Korea continued to be significant contributors, together advancing the frontiers of innovation in nanotechnology. In this timeframe, the quantity of nanotechnology-related patents increased by more than 150%, demonstrating the swift growth of the sector. The regulation of nanotechnology in the US is primarily managed by the Food and Drug Administration, particularly about healthcare and biotechnology applications. As the scope of nanotechnology uses has expanded, there is an increasing demand for more extensive regulations concerning potential long-term environmental and health effects. The future trajectory of nanotechnology, both in the US and worldwide, will hinge on continuous invention, economic advancement, and the progression of governmental policy. By upholding a robust regulatory framework and promoting ongoing collaboration between academics and industry, the complete potential of nanotechnology in advancing industrial and societal progress can be actualized. Full article

Background: Rejected medical claims pose a significant challenge for healthcare facilities accredited by Tanzania’s National Health Insurance Fund (NHIF). Despite the NHIF’s role in reducing out-of-pocket costs, claim rejections have been a persistent issue, largely due to documentation errors, coding mistakes, and non-compliance with NHIF regulations. This study determined the patterns of rejected claims and the strategies employed by NHIF-accredited hospitals to mitigate these challenges. Methodology: This cross-sectional study was conducted between July and August 2024 and used quantitative and qualitative approaches. The study utilized secondary data (August 2023 to January 2024) on the rejected claims from 46 healthcare facilities (HFs) and key informant interviews from the respective selected facilities. Descriptive data analysis was carried out using STATA version 15 and qualitative data analysis was conducted using NViVo2 version 12 software. Results: A total of 46 public (27) and private (19) HFs were included in this study. The data revealed significant variation in the average number of items rejected per claim across HFs, ranging from 0.21 in a regional referral hospital to 1.21 in a zonal hospital. Non-adherence to standard treatment guidelines (STGs) was significantly more common (p < 0.001) in polyclinics, accounting for 17.2% of the items rejected, and with the lowest number (0.8%) seen in zonal hospitals. Overutilization (drugs and investigations) was commonly reported in all HFs, ranging from 12.5% in polyclinics to 31.8% in district hospitals (p < 0.001). Non-applicable consultation charges were only reported in one zonal hospital. To mitigate these rejections, HFs implemented strategies such as immediate error verification, regular communication with NHIF, staff training, technology use, and regular supervision by the internal audit units. Despite these efforts, challenges persisted, particularly those stemming from complex NHIF policies, which account for most rejections in zonal health facilities. Conclusions: There are significant variations in rejection patterns among HFs, with attendance date anomalies, non-adherence to STGs, NHIF pricing, and overutilization being the most common reasons across all HFs. Strategies to address rejections should be tailored to specific health facilities, coupled with electronic systems that will detect errors during patient management. Full article

Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-associated fatty liver disease (MAFLD), is the most prevalent liver disease worldwide. It is associated with an increased risk of developing hepatocellular carcinoma (HCC) in the background of cirrhosis or without cirrhosis. The prevalence of NAFLD-related HCC is increasing all over the globe, and HCC surveillance in NAFLD cases is not that common. In the present review, we attempt to summarize promising treatments and clinical trials focused on NAFLD, nonalcoholic steatohepatitis (NASH), and HCC in the past five to seven years. We categorized the trials based on the type of intervention. Most of the trials are still running, with only a few completed and with conclusive results. In clinical trial NCT03942822, 25 mg/day of milled chia seeds improved NAFLD condition. Completed trial NCT03524365 concluded that Rouxen-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) results in histological resolution of NASH without worsening of fibrosis, while NCT04677101 validated sensitivity/accuracy of blood biomarkers in predicting NASH and fibrosis stage. Moreover, trials with empagliflozin (NCT05694923), curcuvail (NCT06256926), and obeticholic acid (NCT03439254) were completed but did not provide conclusive results. However, trial NCT03900429 reported effective improvement in fibrosis by at least one stage, without worsening of NAFLD activity score (NAS), as well as improvement in lipid profile of the NASH patients by 80 or 100 mg MGL-3196 (resmetirom). Funded by Madrigal Pharmaceuticals, Rezdiffra (resmetirom), used in the clinical trial NCT03900429, is the first FDA-approved drug for the treatment of NAFLD/NASH. Full article

Stingless bees (Hymenoptera; Apidae; Meliponini), with a biodiversity of 605 species, harvest and transport corbicula pollen to the nest, like Apis mellifera, but process and store the pollen in cerumen pots instead of beeswax combs. Therefore, the meliponine pollen processed in the nest was named pot-pollen instead of bee bread. Pot-pollen has nutraceutical properties for bees and humans; it is a natural medicinal food supplement with applications in health, food science, and technology, and pharmaceutical developments are promising. Demonstrated synergism between Tetragonisca angustula pot-pollen ethanolic extracts, and antibiotics against extensively drug-resistant (XDR) bacteria revealed potential to combat antimicrobial resistance (AMR). Reviewed pot-pollen VOC richness was compared between Australian Austroplebeia australis (27), Tetragonula carbonaria (31), and Tetragonula hogkingsi (28), as well as the Venezuelan Tetragonisca angustula (95). Bioactivity and olfactory attributes of the most abundant VOCs were revisited. Bibliometric analyses with the Scopus database were planned for two unrelated topics in the literature for potential scientific advances. The top ten most prolific authors, institutions, countries, funding sponsors, and sources engaged to disseminate original research and reviews on pot-pollen (2014–2023) and direct injection food flavor (1976–2023) were ranked. Selected metrics and plots were visualized using the Bibliometrix-R package. A scholarly approach gained scientific insight into the interaction between an ancient fermented medicinal pot-pollen and a powerful bioanalytical technique for fermented products, which should attract interest from research teams for joint projects on direct injection in pot-pollen flavor, and proposals on stingless bee nest materials. Novel anti-antimicrobial-resistant agents and synergism with conventional antibiotics can fill the gap in the emerging potential to overcome antimicrobial resistance. Full article

Drug discovery and development require significant costs and time, making investment acquisition crucial. However, there are few biopharmaceutical startups with high valuations in Japan. Unlike other countries, entrepreneurship in Japan is relatively inactive, and startups have a minimal presence in the drug-discovery field. Instead, in Japan’s innovation system, research and development (R&D) has been led by large incumbent companies, which are believed to have a wealth of promising assets and talent. This study tested the hypothesis that biopharmaceutical startups leveraging these assets and talent might be more attractive to investors by regression analysis using a dataset of Japanese unlisted biopharmaceutical startups. The results demonstrated that Japanese biopharmaceutical startups showed significantly higher valuations and total funding amounts if they were corporate spin-offs (CSOs). Additionally, they achieved significantly higher valuations and total funding amounts if their R&D lead persons had corporate backgrounds. These findings suggest that in Japan’s innovation system, which is centered on large companies, CSOs and startups leveraging R&D talent with corporate experience may be more appealing to investors. Full article

Background: This study aims to assess the effectiveness and safety of cefiderocol in treating severe infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) in critically ill patients, particularly those in intensive care units (ICUs). Methods: A meta-analysis of studies, including randomized clinical trials and observational studies in adult patients, was performed. Studies with at least 50% of critically ill patients were included. Studies with small sample size or without comparison groups were excluded. Sources included PubMed, Scopus, or Google Scholar, up to 14 August 2024. Risk of bias was assessed according to the Cochrane tool. The main outcome examined was 30-day mortality, while secondary outcomes assessed included clinical cure rates and adverse effects. Results were expressed with odds ratios. No funding was received for this study. It was registered in the International Prospective Register of Systematic Reviews (PROSPERO) with reference CRD42024563041. Results: eight studies, with 1339 patients were included in the meta-analysis. Cefiderocol treatment was associated with a lower 30-day mortality rate than other available therapies (pooled OR 0.47; 95% CI: 0.23–0.97, p = 0.04), particularly in cases of carbapenem-resistant A. baumannii infections (pooled OR 0.29; 95% CI: 0.14–0.60, p < 0.001). Although there was a non-significant trend toward higher clinical cure rates in the cefiderocol group (OR 1.59; 95% CI: 0.96–2.62, p = 0.07), the drug demonstrated at least non-inferiority when compared to other treatment options. Study limitations included moderate heterogeneity between studies, and a high risk of bias in non-RCT studies. (Five cohort studies were included). Another limitation is that five of the eight studies compared cefiderocol versus colistine, an antibiotic with known toxicity. Conclusions: The findings suggest that cefiderocol is a promising therapeutic option for managing severe MDR-GNB infections in critically ill patients, offering a potential global benefit on mortality and at least non-inferiority in the cure rate when compared with other therapies. Full article

The COVID-19 pandemic has significantly accelerated progress in RNA-based therapeutics, particularly through the successful development and global rollout of mRNA vaccines. This review delves into the transformative impact of the pandemic on RNA therapeutics, with a strong focus on lipid nanoparticles (LNPs) as a pivotal delivery platform. LNPs have proven to be critical in enhancing the stability, bioavailability, and targeted delivery of mRNA, facilitating the unprecedented success of vaccines like those developed by Pfizer-BioNTech and Moderna. Beyond vaccines, LNP technology is being explored for broader therapeutic applications, including treatments for cancer, rare genetic disorders, and infectious diseases. This review also discusses emerging RNA delivery systems, such as polymeric nanoparticles and viral vectors, which offer alternative strategies to overcome existing challenges related to stability, immune responses, and tissue-specific targeting. Additionally, we examine the pandemic’s influence on regulatory processes, including the fast-tracked approvals for RNA therapies, and the surge in research funding that has spurred further innovation in the field. Public acceptance of RNA-based treatments has also grown, laying the groundwork for future developments in personalized medicine. By providing an in-depth analysis of these advancements, this review highlights the long-term impact of COVID-19 on the evolution of RNA therapeutics and the future of precision drug delivery technologies. Full article

Cannabinoids represent a highly researched group of plant-derived ingredients. The substantial investment of funds from state and commercial sources has facilitated a significant increase in knowledge about these ingredients. Cannabinoids can be classified into three principal categories: plant-derived phytocannabinoids, synthetic cannabinoids and endogenous cannabinoids, along with the enzymes responsible for their synthesis and degradation. All of these compounds interact biologically with type 1 (CB1) and/or type 2 (CB2) cannabinoid receptors. A substantial body of evidence from in vitro and in vivo studies has demonstrated that cannabinoids and inhibitors of endocannabinoid degradation possess anti-inflammatory, antioxidant, antitumour and antifibrotic properties with beneficial effects. This review, which spans the period from 1940 to 2024, offers an overview of the potential therapeutic applications of natural and synthetic cannabinoids. The development of these substances is essential for the global market of do-it-yourself drugs to fully exploit the promising therapeutic properties of cannabinoids. Full article

Background and Objective: The complexity of antiretroviral therapy (ART) regimens in people living with HIV (PLHIV) poses significant challenges for medication management, impacting adherence and overall health outcomes. The Medication Regimen Complexity Index (MRCI) is a tool that quantifies regimen complexity, yet its correlation with hospitalization rates and adverse drug reactions (ADRs) in PLHIV remains underexplored. Materials and Methods: This prospective study, which was conducted at a government-funded antiretroviral treatment center, investigated the relationships among MRCI scores, hospitalization due to ADRs, and the ADR rates in 285 PLHIV participants over 18 months. Results: The study revealed a significant association between higher baseline MRCI scores and hospitalization due to ADRs, with a threshold MRCI score of 8 indicating increased risk. There was no significant association between average MRCI scores and overall ADR rates or non-ADR-related hospitalizations. Conclusions: These findings emphasize the importance of monitoring medication regimen complexity in PLHIV, particularly in the context of preventing hospitalizations related to ADRs. Further research is needed to understand the multifactorial influences on ADR occurrence and to optimize ART regimens for better patient outcomes. Full article