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Objective Data sharing promotes the scientific progress. However, not all data can be shared freely due to privacy issues. This work is intended to foster FAIR sharing of sensitive data exemplary in the biomedical domain, via an integrated computational approach for utilizing and enriching individual datasets by scientists without coding experience. Methods We present an in silico pipeline for openly sharing controlled materials by generating synthetic data. Additionally, it addresses the issue of inexperience to computational methods in a non-IT-affine domain by making use of a cyberinfrastructure that runs and enables sharing of computational notebooks without the need of local software installation. The use of a digital twin based on cancer datasets serves as exemplary use case for making biomedical data openly available. Quantitative and qualitative validation of model output as well as a study on user experience are conducted. Results The metadata approach describes generalizable descriptors for computational models, and outlines how to profit from existing data resources for validating computational models. The use of a virtual lab book cooperatively developed using a cloud-based data management and analysis system functions as showcase enabling easy interaction between users. Qualitative testing revealed a necessity for comprehensive guidelines furthering acceptance by various users. Conclusion The introduced framework presents an integrated approach for data generation and interpolating incomplete data, promoting Open Science through reproducibility of results and methods. The system can be expanded from the biomedical to any other domain while future studies integrating an enhanced graphical user interface could increase interdisciplinary applicability.

The quantum approximate optimization algorithm (QAOA) is an approach for near-term quantum computers to potentially demonstrate computational advantage in solving combinatorial optimization problems. However, the viability of the QAOA depends on how its performance and resource requirements scale with problem size and complexity for realistic hardware implementations. Here, we quantify scaling of the expected resource requirements by synthesizing optimized circuits for hardware architectures with varying levels of connectivity. Assuming noisy gate operations, we estimate the number of measurements needed to sample the output of the idealized QAOA circuit with high probability. We show the number of measurements, and hence total time to solution, grows exponentially in problem size and problem graph degree as well as depth of the QAOA ansatz, gate infidelities, and inverse hardware graph degree. These problems may be alleviated by increasing hardware connectivity or by recently proposed modifications to the QAOA that achieve higher performance with fewer circuit layers.

High-density polyethylene (HDPE) is widely used for above-ground storage tanks (ASTs). However, there are currently no guidelines for the non-destructive testing (NDT) and evaluation (NDE) of HDPE ASTs. Moreover, the feasibility, limitations, and challenges of using NDT techniques for the field inspection of HDPE ASTs have not been well established. This study used both infrared thermography (IRT) and ultrasonic testing (UT) for the field inspection of HDPE ASTs. Highlighting the implementation challenges in the field, this study determined that: (1) ambient environmental parameters can affect IRT accuracy; (2) there is an ideal time during the day to perform IRT; (3) the heating source and infrared camera orientation can affect IRT accuracy; and (4) with proper measures taken, IRT is a promising method for flaw detection in HDPE ASTs. Additionally, UT can be used following IRT for detailed investigation to quantify the size and depth of defects. The manuscript concludes with a discussion of the limitations and best practices for the implementing of IRT and UT for HDPE AST inspections in the field.

Methylation is a widely occurring modification that requires the methyl donor S-adenosylmethionine (SAM) and acts in regulation of gene expression and other processes. SAM is synthesized from methionine, which is imported or generated through the 1-carbon cycle (1 CC). Alterations in 1 CC function have clear effects on lifespan and stress responses, but the wide distribution of this modification has made identification of specific mechanistic links difficult. Exploiting a dynamic stress-induced transcription model, we find that two SAM synthases in Caenorhabditis elegans , SAMS-1 and SAMS-4 , contribute differently to modification of H3K4me3, gene expression and survival. We find that sams-4 enhances H3K4me3 in heat shocked animals lacking sams-1 , however, sams-1 cannot compensate for sams-4 , which is required to survive heat stress. This suggests that the regulatory functions of SAM depend on its enzymatic source and that provisioning of SAM may be an important regulatory step linking 1 CC function to phenotypes in aging and stress.

Precision medicine promises to transform healthcare for groups and individuals through early disease detection, refining diagnoses and tailoring treatments. Analysis of large-scale genomic–phenotypic databases is a critical enabler of precision medicine. Although Asia is home to 60% of the world’s population, many Asian ancestries are under-represented in existing databases, leading to missed opportunities for new discoveries, particularly for diseases most relevant for these populations. The Singapore National Precision Medicine initiative is a whole-of-government 10-year initiative aiming to generate precision medicine data of up to one million individuals, integrating genomic, lifestyle, health, social and environmental data. Beyond technologies, routine adoption of precision medicine in clinical practice requires social, ethical, legal and regulatory barriers to be addressed. Identifying driver use cases in which precision medicine results in standardized changes to clinical workflows or improvements in population health, coupled with health economic analysis to demonstrate value-based healthcare, is a vital prerequisite for responsible health system adoption. This Perspective article discusses Singapore’s efforts to implement a National Precision Medicine Strategy through the integration of genomic, clinical and lifestyle data of up to one million Singaporean individuals.

Waste tire rubber is regarded as a potential source for Zn recovery and recycling. In this study, the occurrence of modes of Zn was first characterized by an electron probe microanalyzer (EPMA), and the result indicated both ZnO and ZnS were present in the tire rubber. The Zn leaching recovery was optimized by response surface methodology, and temperature was identified as the most significant variable. The highest recovery of over 98% was obtained at 90 °C for 400 min when using 2.0 mol/L HNO 3 as the lixiviant. After that, the Zn-containing leach liquor was subjected to solvent extraction for further separation and purification using bis(2,4,4-trimethylpentyl) phosphinic acid (Cyanex 272) and 2-ethylhexylphosphonic mono-2-ethylhexyl (PC88A) as extractants. Various parameters, such as equilibrium pH, extractant concentration, and organic-to-aqueous (O/A) ratio, were investigated to maximize the Zn extraction while minimizing the contamination of impurities. The result indicated that 0.1 mol/L Cyanex 272 exhibited a higher separation factor for Zn over major impurities compared to PC88A under the same conditions. To produce the high-purity ZnO, the Zn-loaded organic phase was subjected to stripping tests, and over 92% of Zn was stripped out with trace amounts of impurities. Finally, the pH value of the stripped solution was increased to precipitate Zn, and a final ZnO product with a purity of over 99% was obtained. This study provided a reference for waste tire rubber management and utilization. Graphical Abstract

Primary bone malignancies, including osteosarcoma (OS), are rare but aggressive. Current OS treatment, involving surgical resection and chemotherapy, has improved survival for non-metastatic cases but remains ineffective for recurrent or metastatic OS. Oncolytic viral therapy (OVT) is a promising alternative, using naturally occurring or genetically modified viruses to selectively target and lyse cancer cells and induce a robust immune response against remaining OS cells. Various oncolytic viruses (OVs), such as adenovirus, herpes simplex virus, and measles virus, have demonstrated efficacy in preclinical OS models. Combining OVT with other therapeutics, such as chemotherapy or immunotherapy, may further improve outcomes. Despite these advances, challenges in reliability of preclinical models, safety, delivery, and immune response must be addressed to optimize OVT for clinical use. Future research should focus on refining delivery methods, exploring combination treatments, and clinical trials to ensure OVT’s efficacy and safety for OS. Overall, OVT represents a novel approach with the potential to drastically improve survival outcomes for patients with OS.

Aneurysmal subarachnoid haemorrhage (aSAH) is associated with significant morbidity and mortality. The International Subarachnoid Aneurysm Trial (ISAT) reported reduced morbidity in patients treated with endovascular coiling versus surgical clipping. However, recent studies suggest that there is no significant difference in clinical outcomes. This study examines the outcomes of either technique for treating aSAH during the 15 years post-ISAT at a Canadian quaternary centre. We reviewed prospectively collected data of patients admitted with aSAH from January 2002 to December 2017. Glasgow Outcome Scale (GOS) was compared at discharge, 6 months and 12 months' follow-up using univariate and multivariable ordinal logistic regression. Post-operative complications were assessed using binary logistic regression. Two-hundred and eighty-seven patients were treated with coiling and 95 patients with clipping. The mean age of clipped patients was significantly younger, and hypertension was significantly commoner in coiled patients. A greater proportion of coiled aneurysms were located in the posterior circulation. No difference in the odds of having a favourable GOS was seen between patients who were clipped versus coiled at any of follow-up time points on univariate or multivariable analysis. In both treatment groups, patient recovery to independence (GOS 4-5) was seen from discharge to 6 months, but not from 6 to 12 months' follow-up, without difference between clipping and coiling. These real-world findings suggest clipping remains an effective and important treatment option for patients with aSAH who do not meet ISAT inclusion criteria. The results can assist in clinical decision-making processes and understanding of the natural recovery progression of aSAH.

Purpose of ReviewThis review summarizes current findings regarding limb amputation within the context of cancer, especially in osteosarcomas and other bony malignancies. We seek to answer the question of how amputation is utilized in the contemporary management of cancer as well as explore current advances in limb-sparing techniques.Recent FindingsThe latest research on amputation has been sparse given its extensive history and application. However, new research has shown that rotationplasty, osseointegration, targeted muscle reinnervation (TMR), and regenerative peripheral nerve interfaces (RPNI) can provide patients with better functional outcomes than traditional amputation.SummaryWhile limb-sparing surgeries are the mainstay for managing musculoskeletal malignancies, limb amputation is useful as a palliative technique or as a primary treatment modality for more complex cancers. Currently, rotationplasty and osseointegration have been valuable limb-sparing techniques with osseointegration continuing to develop in recent years. TMR and RPNI have also been of interest in the modern management of patients requiring full or partial amputations, allowing for better control over myoelectric prostheses.

Objectives Recent research has demonstrated that platelet-rich fibrin (PRF) is an appropriate carrier for ampicillin/sulbactam. The aim of the study was to investigate whether PRF is also a suitable bio-carrier for clindamycin (CLI). Methods PRF membranes were produced from 36 patients receiving intravenous therapy with CLI (e.g. due to the diagnosis of an osteonecrosis of the jaw or infections). Concentrations of CLI in PRF membranes were measured with liquid chromatography-tandem mass spectrometry, and the antimicrobial effects were investigated in vitro in agar diffusion tests with fresh PRF and PRF stored for 24 h. Storage was performed in an incubator at 36 °C to simulate the in-vivo situation. Results The mean concentration of CLI in plasma was 1.0 ± 0.3 μg/100 mg plasma; in resulting PRF membranes 0.7 ± 0.4 μg/100 mg PRF. Agar diffusion tests were performed with Staphylococcus aureus , Streptococcus pneumoniae , Streptococcus mitis , Porphyromonas gingivalis,  and Fusobacterium nucleatum . Mean inhibition zones, in mm, for fresh PRF were 17.3, 12.2, 18.8, 17.1, 25.8 and 18.1, 12.7, 19.2, 17.3, and 26.3 for stored PRF, respectively. Conclusion The results demonstrate that PRF is a suitable bio-carrier for CLI when administered systemically to patients. The concentration in PRF generated from patients after infusion of 600 mg CLI dose suffices to target clinically relevant bacteria. Clinical relevance Using PRF as a carrier for local antibiotic application can prevent infections in oral and maxillofacial surgery. Within the study limitations, the findings could expand the scope of PRF application by adding CLI as a new antibiotic to the spectrum of PRF therapy.