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Essential medicines lists aim to improve access, affordability, and quality of medicines, though their impact on pricing and supply varies. Japan's universal coverage addresses key EML policy areas but faces drug shortages linked to generic drug promotion. This cross-sectional analysis of secondary data explores EML inclusion in the context of medicine supply issues in Japan. We analysed Japan's 2024 EML using data from the April 2024 Pharmaceutical Supply Survey. Unique medicines were defined by active ingredient and route. Duplicates, combinations, and non-essential categories were excluded. Supply issues were counted per medicine, but for total supply issue analysis, each medicine was counted only once. We analysed 1107 unique medicines from Japan's 2024 pharmaceutical supply survey. Of these, 401 (36.2%) had shipping or supply issues. Among 167 medicines listed in Japan's 2024 EML, 80 (47.9%) had shipping issues. Most medicines with or without issues were not on the EML. A total of 847 entries described supply limitations for the 401 affected medicines. Causes included drug price deletion, quality issues, manufacturing problems, increased demand, and raw material shortages. For example, widely used essential medicines like amlodipine and metformin, not on Japan's EML, also had reported supply issues. One-third of medicines analysed had shipping issues, affecting nearly half of those on Japan's 2024 EML. Shipping issues spanned therapeutic areas, with antibiotics most affected. This aligns with global findings linking essential medicine status and shortages, though our findings describe shipping issue patterns at a single point in time. Factors include low pricing and quality issues. Ongoing updates to the EML and a national strategy are essential to ensure availability of priority medicines.

Rotavirus vaccination has greatly reduced the number of deaths caused by the virus, lowering childhood mortality by an estimated 37% globally. Although low- and middle-income countries (LMIC) demonstrate reduced efficacy than high-income countries, the vaccines still make a significant impact in these areas and continued efforts to support vaccination are needed. Liquid rotavirus vaccines are desirable for their ease of administration and reduced packing footprint; however, current ready-to-use rotavirus vaccines require refrigerated transport and storage. Here, we describe production methods and stability data for a ready-to use non-aqueous formulation that is suitable for ambient shipping and is shelf-stable. In-line sonication and filtration methods were employed during viral vaccine production to increase viral yields and streamline viral harvest steps. Lyophilized vaccine was formulated with medium-chain triglyceride (MCT) oil and excipients to form a suspension. Stability studies were performed for up to 36 months, and predictive regression analysis was carried out to estimate shelf-life. These results suggest a ready-to-use vaccine candidate with comparable thermostability to lyophilized commercially available products, formulated to a low dosage volume, amenable to ambient shipping with a reduced storage footprint.

Oil pollution is one of the most persistent and harmful anthropogenic pressures on global marine and coastal ecosystems. Accidental discharges, chronic leaks, operational spills from shipping, offshore drilling, and industrial activities release millions of tons of hydrocarbons annually, threatening marine biodiversity, fisheries, and coastal livelihoods. Remote sensing has become the primary technology for oil spill detection, mapping, and monitoring, offering synoptic, repeatable, and objective coverage of extensive marine areas. This paper presents a systematic review of remote sensing for oil spill detection, mapping, and monitoring, grounded in a bibliometric analysis of 2856 verified documents authored by 6473 researchers, retrieved from five major academic databases (OpenAlex, CrossRef, EuropePMC, SemanticScholar, and CORE), spanning the period 2000 to 2026. Annual publication output grew from 16 documents in 2000 to a peak of 244 in 2025, reflecting a 15-fold growth driven by the Deepwater Horizon disaster (2010), the launch of Sentinel-1 (2014-2016), and the proliferation of deep learning frameworks. The review examines the physical principles of oil detection across the electromagnetic spectrum; compares radar, optical, hyperspectral, and thermal sensor platforms; and evaluates developments in artificial intelligence (AI) and data fusion methods for automated detection. Validation protocols, regional case studies from the Gulf of Mexico, North Sea, Mediterranean, Arctic, and Caspian Sea, and the integration of Earth observation with decision-support frameworks are also assessed. Key findings confirm that no single sensor is universally superior: synthetic aperture radar (SAR) provides all-weather, day-night capability, while optical and hyperspectral sensors deliver spectral and compositional insight. Deep learning models, particularly U-Net and transformer-based architectures, have achieved exceptional detection accuracy but face persistent challenges of data scarcity, look-alike discrimination, and limited cross-regional transferability. Emerging innovations in multi-sensor constellations, physics-informed deep learning, and cloud-native processing are identified as pathways toward real-time environmental intelligence and improved ocean governance.

The warming effects of climate change are leading to a reduction in sea ice, which could open new shipping routes across the Arctic, leading to the possibility of hydrocarbon spills washing onto a shoreline. The behavior and biodegradability of new low-sulfur fuels (LSFs), currently being used by vessels worldwide, has not been assessed on Arctic beaches. We deployed mesocosm experiments on a remote Canadian high Arctic beach for 33 days using two LSFs (marine diesel and ultra-low-sulfur fuel oil, ULSFO) and Bunker C fuel oil (currently being phased out). Bunker C was mostly removed from beach sediments by natural attenuation (14.6% biodegradation, 62.8% nonbiological removal), while the LSFs were more easily biodegraded (37.6-72.8% biodegradation, 2.9-10.0% nonbiological removal). Native beach sediment microorganisms, including putatively novel taxa, adapted to the presence of fuel by expressing multiple aliphatic hydrocarbon biodegradation genes, but only few aromatic hydrocarbon degradation genes. Our results suggest that, while not as biodegradable as marine diesel, ULSFO appears to be a more environmentally friendly alternative to Bunker C due to its higher biodegradability under in situ Arctic environmental conditions. However, limited aromatic hydrocarbon biodegradation under cold and nutrient-poor environmental conditions could negatively affect the efficacy of natural attenuation.

Health promotion measures on board seagoing vessels are subject to special requirements due to limited access to health services on board. This study examines the needs and digital possibilities for modern health promotion and digital intervention on board merchant ships considering the different occupational groups. The data was collected using questionnaires completed by 903 seafarers (participation rate 99.4%) from 23 countries on 68 seagoing vessels belonging to two German shipping companies. A comparison of the responses was conducted to identify significant differences between ratings and officers, because this could be relevant for future specific interventions. Adjustments were made for cultural background and age using odds ratio. Ratings assessed the relevance of topics for well-being higher than officers did, especially regarding healthy food (p = 0.83), exercise (p = 0.05), and learning relaxation exercises (p = 0.04). The study shows that ratings are more than twice willing to do more sports (p = 0.04), learn relaxation exercises (p = 0.01), and practice measures against fatigue (p = 0.05). Health apps and sports competitions were highly valued in the communication of health information. Ratings and officers used smartphones to a high degree (98.3%) and would use a health app (87.5% ratings vs. 83.1% officers; OR 1.62 (1.07-2.43)) and both professional groups would like to participate in a bonus system based on a reward principle. In the multivariate analysis, interest in health promotion measures was essentially independent of age and cultural background. Key aspects for intervention measures on board include sports, learning relaxation techniques, offering healthy food, and raising awareness about exemplary health behavior of superiors. Modern digital intervention measures involving e-learning platforms, applications and wearables are of interest to seafarers and should be considered when planning health promotion measures at sea.

Based on observational data from a coastal city in East China, this study integrates meteorological measurements and numerical modeling to identify key drivers and spatiotemporal patterns of regional atmospheric pollution. The findings indicated that the annual 90th percentile concentration of daily maximum 8-h average O3 in Beilun District reached 143.69 μg/m3 in 2022, exceeding the national Class I limit for O3. Seasonal ozone pollution peaked in spring and summer, exhibiting a distinct single-peak diurnal profile. High temperature and low humidity favored photochemical O3 formation, while wind conditions influenced O3 through both local accumulation under weak winds and regional transport under low-to-moderate sea-breeze conditions. Application of the empirical kinetic modelling approach demonstrated that ozone formation was predominantly volatile organic compound (VOC)-limited, with alkenes exhibiting the highest ozone formation potential, followed by alkanes and aromatics. Source apportionment via positive matrix factorization model identified vehicle exhaust (28.7%), solvent usage (24.3%), and oil gas evaporation (24.1%) as the principal sources of ambient VOCs. Backward trajectory analysis indicated that air masses in May were predominantly influenced by eastern marine pathways (38.71%), whereas air masses in July were characterized by transport from inland sources in southwestern Zhejiang Province (62.23%). Potential source contribution function analysis further designated port areas as high-contribution zones for ozone precursors (contribution factors > 0.8), underscoring the significant role of coastal industrial operations and shipping emissions in exacerbating local air pollution.

With the rapid development of intelligent shipping and the autonomy of marine engineering equipment, numerous studies have focused on the advancement of Autonomous Surface Vehicles (ASVs). As a fundamental component of ASV automation systems, path planning directly determines the safety and economy of ship navigation. This paper systematically reviews recent research progress in ASV path planning. First, five key issues are identified for ASV path planning: navigation environment, environment modeling, ship motion model, collision avoidance for safety, and optimization. Second, existing algorithms are classified into four categories: graph search-based, sampling-based, numerical optimization-based, and artificial intelligence-based. The improvement directions and application scenarios of each category are elaborated. Finally, the four types of algorithms are evaluated against three indicators: path quality, scalability and extensibility, and algorithm performance. Analysis of the reviewed literature shows that traditional graph search and sampling algorithms perform well in various aspects under static environments, but are insufficient in adapting to multiple constraints and generalizing to different environments. In contrast, artificial intelligence algorithms represented by deep reinforcement learning exhibit significant advantages in dynamic collision avoidance decision-making, multi-agent coordination, and environmental generalization, and have become the mainstream direction of current research. This paper summarizes the existing challenges in safety and optimization in current ASV path planning research and prospects future development directions.

Purines and pyrimidines are key cellular components for the development, proliferation, and repair of cells and tissues, whose circulating levels are associated with various diseases. Biospecimen processing delays can significantly induce hypoxanthine and inosine levels, among other changes, in blood. We developed a liquid chromatography tandem mass-spectrometry method to quantify metabolites of the purine and pyrimidine pathways and investigated the impact of delayed sample processing on single donor plasma and dried blood spots (DBS). Plasma hypoxanthine increased above the normal reference range to an average 20-fold increase across individual donors when whole blood was kept refrigerated 64 h prior to processing. The same trend was observed in dried blood spots (DBS) prepared from refrigerated whole blood. Plasma inosine also increased above the reference range after a 48-hour delay in processing refrigerated whole blood. In contrast, hypoxanthine remained stable in DBS for up to 48 h, regardless of the card storage temperature. Therefore, DBS is a feasible alternative specimen type to measure hypoxanthine if frozen shipping, delayed centrifugation, or storage interval is a concern. Understanding the impact of specimen handling conditions is essential for successful biomarker discovery, especially when new biomarkers are to be introduced into the clinical laboratory.

Blood biomarkers are central to monitoring disease progression and evaluating treatment responses, yet traditional venipuncture captures a single physiological snapshot in time and becomes burdensome with repeated sampling. Remote blood self-sampling offers a path toward longitudinal, decentralized monitoring, but maintaining protein integrity from draw to analysis remains a critical challenge. Here, we optimized pre-analytical blood collection and stabilization parameters to maintain protein levels at the time of collection for use with remote sampling technology. First, we optimized blood collection time with Tasso remote self-sampling devices to minimize interference from clotting, finding that a 2.5 min collection time best reduces clot formation while collecting enough blood. Next, we found that Protein Plus, a commercial protein stabilizer, limited hemolysis (a metric for stabilizer efficacy) in venous blood for up to 5 days at 25°C-35°C and for 1 day at 40°C. In addition, we optimized the stabilizer volume and acceptable blood volume range for self-sampling as the stabilizer efficacy is impacted by the stabilizer to blood ratio and collection volume can vary with remote self-sampling devices. Finally, we incubated stabilized blood samples collected via Tasso device at 25°C-35°C for 72 h, mimicking a 2-day shipping period. Using a panel of 21 inflammatory proteins, we found that Protein Plus limited intracellular protein release for various proteins (e.g., VEGF-A, CCL11, and IL-8), inhibited protein degradation for CCL2, and enabled minimal hemolysis. These results support Protein Plus as a viable stabilization strategy for remote blood collection technology targeting longitudinal inflammatory protein monitoring.

Steroid esters are a frequently used ergogenic aid among athletes, and their direct detection represents an important approach to anti-doping efforts. However, the presence of esterase enzymes in blood complicates these efforts. Although dried blood spots (DBS) have emerged as a promising solution to the esterase problem, the limited sample volume creates both analytical and practical challenges. The larger collection volume for liquid blood may allow for higher analytical sensitivity, thus offsetting the effects of esterase activity in practical scenarios. First, to evaluate the effects of blood esterases ex vivo, 10 individuals were administered a single dose of either testosterone propionate or testosterone cypionate. Venous blood was collected into serum separator tubes (SST) serum and NaF-containing tubes and stored at varying conditions. Both esters significantly decreased in serum while no ester loss was observed in the NaF-containing plasma. Next, to compare the detectability across matrices stored at conditions meant to mimic real-world scenarios, the individuals administered testosterone propionate collected capillary serum, capillary NaF-containing plasma, and capillary DBS at various times postadministration. Each sample type was stored at different conditions designed to mimic what may be encountered during real-world shipping scenarios. Similar detectability of testosterone propionate was observed between all NaF, DBS, and SST samples stored under cool conditions, whereas detectability was better in NaF and DBS samples under ambient and warm conditions. These results indicate that for samples not shipped in temperature regulated conditions, DBS and NaF-containing plasma are the preferred matrices.

Caspase-6 (casp-6), is a member of the apoptotic family of caspases (cysteine aspartic proteases) and has been shown to be involved in several neurodegenerative diseases, including Alzheimer's disease. Drug discovery efforts have focused on specific inhibition of casp-6, and it is important that lead compounds demonstrate engagement and inhibition of the protease in vivo. A casp-6 overexpressing mouse model was reported, but is no longer available to the scientific community. We developed alternative means of activating casp-6 in commercially available mice as a platform to test potential casp-6 inhibitors. Lipopolysaccharides (LPS) from E. coli was used to stimulate an immunogenic response in WT C57BL/6NJ mice, which has been shown to activate the NLRP1 inflammasome, which activates casp-1 and subsequently, casp-6. Key tissues (brain, colon, and thymus) were sampled and evaluated for casp-6 activation by immunoblotting for both active casp-6 and a cleaved lamin A, a casp-6 substrate, and by directly measuring VEIDase activity in tissue lysates. Using in-house bred WT C57BL/6NJ mice, which had never been subjected to shipping, with a single intraperitoneal dose of LPS (5 mg/kg) and a 4-hour incubation, we observed robust casp-6 activation in the thymus. We also established VEIDase activity assays as a more reliable marker of casp-6 function than monitoring levels of casp-6 or cleaved substrates, and established the importance of using a non-immunogenic vehicle. We observed casp-6 activation in aged mice as a second useful model, which also further implicates casp-6 in age-related neurodegenerative pathways. These are new means to test the efficacy of casp-6 inhibitors using a simple in vivo assay that can robustly activate casp-6 in an easily accessible laboratory mouse strain. We foresee that these developments will drive drug discovery efforts aimed at identifying casp-6 inhibitors in various disease contexts, including neurodegeneration.

Sea lanes of communication (SLOC) are perceived as intricate systems comprising shipping routes, key straits, and canals, which are increasingly vulnerable to external disruptions. This study proposes a holistic framework for resilience assessment on the system by introducing an advanced framework incorporating fuzzy logic, a critic weight calculation approach, and the evidential reasoning (ER) algorithm to assess resilience. Second, a hierarchical influential index is created, assessing the system's capacity to absorb, adjust, and recover from disruptions while incorporating connectivity among key straits and canals to illustrate the risk performance and spatial relationships of the straits and canals within Sea Lanes of Communication. Third, a fuzzy ER algorithm integrates information from diverse sources, taking into account the significance and nonlinear relationships among the influential factors. Finally, we present techniques to assess the resilience performance and validate our models. This proposed framework is implemented through an empirical study of five primary Sea Lanes of Communications that connect the Far East and the rest of the world. This framework provides valuable insights into resilience performance in an environment with high uncertainties and offers guidance for relevant stakeholders.

The M371-Test enables standardized measurement of miR-371a-3p in serum, which represents a highly sensitive and specific biomarker for testicular germ cell tumors (GCTs). The current protocol requires immediate centrifugation, freezing, and cold-chain shipping to the laboratory, which poses significant barriers to practical use of the test. Previous studies suggested that plasma from the S-Monovette cfDNA Exact may offer a simplified preanalytical pathway with extended sample stability at ambient temperature, potentially improving test accessibility. To evaluate this approach, we are conducting a prospective multicenter study with a target enrollment of ≥ 250 patients comparing M371-Test performance in paired plasma and serum samples; this report presents an interim analysis of 109 eligible patients (67 GCT cases, 42 controls). M371-Test performance in plasma was very similar to serum, with sensitivities of 92.5% and 94.0%, respectively, while specificity was 100% in plasma versus 92.9% in serum. Subgroup analysis showed that the difference in specificity was concentrated in the post-treatment remission subgroup (84.6% serum vs. 100% plasma). These findings indicate that plasma and serum yield comparable diagnostic performance with the M371-Test. The simplified preanalytical workflow associated with the S-Monovette cfDNA Exact warrants formal stability and robustness evaluation in the completed study. If confirmed in the full cohort, this approach may offer a more practical pathway for miR-371a-3p-based GCT diagnostics in routine practice.

Oil spills pose a major environmental risk in the Arabian Gulf, a region characterized by intense oil shipping and extensive offshore oil infrastructure. Understanding how spilled oil is transported across the basin under seasonally varying atmospheric and oceanographic forcing is therefore essential for effective contingency planning. This study presents a basin-scale oil spill hazard assessment for the Arabian Gulf over 2018-2022, resolving seasonal variability using a high-resolution three-dimensional hydrodynamic and Lagrangian modeling framework. Oil transport and fate were simulated with MEDSLIK-II, driven by validated regional ocean circulation, atmospheric, and wave datasets. A basin-wide scenario was constructed by distributing hypothetical sources across the Gulf and weighting them according to five years of vessel density data, enriched with offshore oil infrastructure, thereby providing a spatially varying proxy for relative spill occurrence likelihood. A targeted scenario near Kharg island was also simulated to evaluate the basin-wide consequences of localized releases. The results reveal strong seasonal and spatial variability in coastal and seabed contamination across the Gulf. Winter conditions tend to increase exposure along the western and central Gulf coasts, whereas summer circulation shifts contamination toward the Iranian coastline. Bahrain, Qatar, and the UAE remain consistently vulnerable due to their connectivity to multiple spill sources. The Kharg island scenario reveals how localized chronic releases can evolve into basin-wide hazards under favorable seasonal circulation. These findings provide a quantitative framework for identifying high-risk coastlines and highlight the importance of seasonal circulation in shaping spill impacts thereby supporting improved spill preparedness and coordinated environmental protection efforts in the Arabian Gulf.