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Abstract Background Positron emission tomography (PET) traditionally uses coincident annihilation photons emitted from a positron interacting with an electron to localize cancer within the body. The formation of positronium (Ps), a bonded electron-positron pair, has not been utilized in clinical applications of PET due to the need to detect either the emission of a prompt gamma ray or the decay of higher-order coincident events. Assessment of the lifetime of the formed Ps, however, can potentially yield additional diagnostic information of the surrounding tissue because Ps properties vary due to void size and molecular composition. To assess the feasibility of measuring Ps lifetimes with a PET scanner, experiments were performed in a Biograph Vision Quadra (Siemens Healthineers). Quadra is a long-axial field-of-view (LA-FOV) PET scanner capable of producing list-mode data from single interaction events. Results Ortho-Ps (o-Ps) lifetimes were measured for quartz-glass and polycarbonate samples using a $$^{22}\text{Na}$$ 22 Na positron source. Results produced o-Ps lifetimes of 1.538 ± 0.036 ns for the quartz glass and 1.927 ± 0.042 ns for the polycarbonate. Both o-Ps lifetimes were determined using a double-exponential fit to the time-difference distribution between the emission of a prompt gamma ray and the annihilation of the correlated positron. The measured values match within a single standard deviation of previously published results. The quartz-glass samples were additional measured with $${^{82}}\text{Rb}$$ 82 Rb , $$^{68}$$ 68 Ga and $$^{124}\text{I}$$ 124 I to validate the lifetime using clinically available sources. A double-exponential fit was initially chosen as a similar methodology to previously published works, however, an exponentially-modified Gaussian distribution fit to each lifetime more-accurately models the data. A Bayesian method was used to estimate the variables of the fit and o-Ps lifetime results are reported using this methodology for the three clinical isotopes: 1.59 ± 0.03 ns for $$^{82}\text{Rb}$$ 82 Rb , 1.58 ± 0.07 ns for $$^{68}\text{Ga}$$ 68 Ga and 1.62 ± 0.01 ns for $$^{124}\text{I}$$ 124 I . The impact of scatter and attenuation on the o-Ps lifetime was also assessed by analyzing a water-filled uniform cylinder (20 $$\phi$$ ϕ $$\times$$ × 30 cm $$^{3}$$ 3 ) with an added $$^{82}\text{Rb}$$ 82 Rb solution. Lifetimes were extracted for various regions of the cylinder and while there is a shape difference in the lifetime due to scatter, the extracted o-Ps lifetime of the water, 1.815 ± 0.013 ns, agrees with previously published results. Conclusion Overall, the methodology presented in this manuscript demonstrates the repeatability of Ps lifetime measurements with clinically available isotopes in a commercially-available LA-FOV PET scanner. This validation work lays the foundation for future in-vivo patient scans with Quadra.

A significant increase in the use of hydrogen, expected to reach between 667 and 4000 TWh, is forecasted for the whole EU in 2050. Electrolysis is believed to be a “silver bullet” due to its synergy with the needs of the grid. However, biohydrogen generation could be complimentary to electrolysis since it does not depend on electricity prices. This review presents a comprehensive picture of the landscape in biohydrogen production, showing state-of-the-art research on different biohydrogen production processes and highlighting potential problems and shortcomings for different processes, including microbial-based production and thermal processes. The work shows that “colour coding” used nowadays is insufficient in terms of providing accurate information regarding the sustainability of particular biohydrogen production technologies. Instead, LCA can provide substantial information for each investigated process. However, there is a need for a wider scope of LCA studies since currently published studies present a syndrome of “carbon tunnel vision”, often ignoring impacts other than global warming. Moreover, studies often tend to exclude the impact of capital goods production, which might provide an incomplete overview of such technologies. Moreover, it should not be overlooked that biohydrogen is capable of achieving negative values of CO2 emissions if CCS is implemented.

Abstract Background Herein, we report results from a genome-wide study conducted to identify protein quantitative trait loci (pQTL) for circulating angiogenic and inflammatory protein markers in patients with metastatic colorectal cancer (mCRC). The study was conducted using genotype, protein marker, and baseline clinical and demographic data from CALGB/SWOG 80405 (Alliance), a randomized phase III study designed to assess outcomes of adding VEGF or EGFR inhibitors to systemic chemotherapy in mCRC patients. Germline DNA derived from blood was genotyped on whole-genome array platforms. The abundance of protein markers was quantified using a multiplex enzyme-linked immunosorbent assay from plasma derived from peripheral venous blood collected at baseline. A robust rank-based method was used to assess the statistical significance of each variant and protein pair against a strict genome-wide level. A given pQTL was tested for validation in two external datasets of prostate (CALGB 90401) and pancreatic cancer (CALGB 80303) patients. Bioinformatics analyses were conducted to further establish biological bases for these findings. Results The final analysis was carried out based on data from 540,021 common typed genetic variants and 23 protein markers from 869 genetically estimated European patients with mCRC. Correcting for multiple testing, the analysis discovered a novel cis-pQTL in LINC02869, a long non-coding RNA gene, for circulating TGF-β2 levels (rs11118119; AAF = 0.11; P-value

ABSTRACT The gold standard for measuring insulin sensitivity (IS) is the hyperinsulinemic–euglycemic clamp, a time, costly, and labor‐intensive research tool. A low insulin sensitivity is associated with a complication‐risk in type 1 diabetes. Various formulae using clinical data have been developed and correlated with measured IS in type 1 diabetes. We consolidated multiple formulae into an online calculator (bit.ly/estimated‐GDR), enabling comparison of IS and its probability of IS 6.50 mg/kg/min (high), as measured in a validation set of clamps in 104 adults with type 1 diabetes. Insulin sensitivity calculations using different formulae varied significantly, with correlations (R2) ranging 0.005–0.87 with agreement in detecting low and high glucose disposal rates in the range 49–93% and 89–100%, respectively. We demonstrate that although the calculated IS varies between formulae, their interpretation remains consistent. Our free online calculator offers a user‐friendly tool for individual IS calculations and also offers efficient batch processing of data for research.

Abstract Unlocking the full dimensionality of single-cell RNA sequencing data (scRNAseq) is the next frontier to a richer, fuller understanding of cell biology. We introduce q-diffusion, a framework for capturing the coexpression structure of an entire library of genes, improving on state-of-the-art analysis tools. The method is demonstrated via three case studies. In the first, q-diffusion helps gain statistical significance for differential effects on patient outcomes when analyzing the CALGB/SWOG 80405 randomized phase III clinical trial, suggesting precision guidance for the treatment of metastatic colorectal cancer. Secondly, q-diffusion is benchmarked against existing scRNAseq classification methods using an in vitro PBMC dataset, in which the proposed method discriminates IFN-γ stimulation more accurately. The same case study demonstrates improvements in unsupervised cell clustering with the recent Tabula Sapiens human atlas. Finally, a local distributional segmentation approach for spatial scRNAseq, driven by q-diffusion, yields interpretable structures of human cortical tissue.

Background and Aims: Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions influenced heavily by environmental factors. DNA methylation is a form of epigenetic regulation linking environmental stimuli to gene expression changes and inflammation. Here, we investigated how DNA methylation of the tumor necrosis factor (TNF) promoter differs between inflamed and uninflamed mucosa of IBD patients, including anti-TNF responders and nonresponders. Methods: We obtained mucosal biopsies from 200 participants (133 IBDs and 67 controls) and analyzed TNF promoter methylation using bisulfite sequencing, comparing inflamed with uninflamed segments, in addition to paired inflamed/uninflamed samples from individual patients. We conducted similar analyses on purified intestinal epithelial cells from bowel resections. We also compared TNF methylation levels of inflamed and uninflamed mucosa from a separate cohort of 15 anti-TNF responders and 17 nonresponders. Finally, we sequenced DNA methyltransferase genes to identify rare variants in IBD patients and functionally tested them using rescue experiments in a zebrafish genetic model of DNA methylation deficiency. Results: TNF promoter methylation levels were decreased in inflamed mucosa of IBD patients and correlated with disease severity. Isolated intestinal epithelial cells from inflamed tissue showed proportional decreases in TNF methylation. Anti-TNF nonresponders showed lower levels of TNF methylation than responders in uninflamed mucosa. Our sequencing analysis revealed 2 missense variants in DNA methyltransferase 1, 1 of which had reduced function in vivo. Conclusion: Our study reveals an association of TNF promoter hypomethylation with mucosal inflammation, suggesting that IBD patients may be particularly sensitive to inflammatory environmental insults affecting DNA methylation. Together, our analyses indicate that TNF promoter methylation analysis may aid in the characterization of IBD status and evaluation of anti-TNF therapy response.

Use of capillary blood devices for exposome research can deepen our understanding of the intricate relationship between environment and health, and open up new avenues for preventive and personalized medicine, particularly for vulnerable populations. While the potential of these whole blood devices to accurately measure chemicals and metabolites has been demonstrated, how untargeted metabolomics data from these samplers can be integrated with previous and ongoing environmental health studies that have used conventional blood collection approaches is not yet clear. Therefore, we performed a comprehensive comparison between relative-quantitative metabolite profiles measured in venous blood collected with dried whole blood microsamplers (DBM), dried whole blood spots (DBS), and plasma from 54 mothers in an ethnically diverse population. We determined that a majority of the 309 chemicals and metabolites showed similar median intensity rank, moderate correlation, and moderate agreement between participant-quantiled intraclass correlation coefficients (ICCs) for pair-wise comparisons among the three biomatrices. In particular, whole blood sample types, DBM and DBS, were in highest agreement across metabolite comparison metrics, followed by metabolites measured in DBM and plasma, and then metabolites measured in DBS and plasma. We provide descriptive characteristics and measurement summaries as a reference database. This includes unique metabolites that were particularly concordant or discordant in pairwise comparisons. Our results demonstrate that the range of metabolites from untargeted metabolomics data collected with DBM, DBS, and plasma provides biologically relevant information for use in independent exposome investigations. However, before meta-analysis with combined datasets are performed, robust statistical approaches that integrate untargeted metabolomics data collected on different blood matrices need to be developed.

Abstract Feedstock properties play a crucial role in thermal conversion processes, where understanding the influence of these properties on treatment performance is essential for optimizing both feedstock selection and the overall process. In this study, a series of van Krevelen diagrams were generated to illustrate the impact of H/C and O/C ratios of feedstock on the products obtained from six commonly used thermal conversion techniques: torrefaction, hydrothermal carbonization, hydrothermal liquefaction, hydrothermal gasification, pyrolysis, and gasification. Machine learning methods were employed, utilizing data, methods, and results from corresponding studies in this field. Furthermore, the reliability of the constructed van Krevelen diagrams was analyzed to assess their dependability. The van Krevelen diagrams developed in this work systematically provide visual representations of the relationships between feedstock and products in thermal conversion processes, thereby aiding in optimizing the selection of feedstock and the choice of thermal conversion technique.

Abstract Background Alongside the benefits of Total-Body imaging modalities, such as higher sensitivity, single-bed position, low dose imaging, etc., their final construction cost prevents worldwide utilization. The main aim of this study is to present a simulation-based comparison of the sensitivities of existing and currently developed tomographs to introduce a cost-efficient solution for constructing a Total-Body PET scanner based on plastic scintillators. Methods For the case of this study, eight tomographs based on the uEXPLORER configuration with different scintillator materials (BGO, LYSO), axial field-of-view (97.4 cm and 194.8 cm), and detector configurations (full and sparse) were simulated. In addition, 8 J-PET scanners with different configurations, such as various axial field-of-view (200 cm and 250 cm), different cross sections of plastic scintillator, and multiple numbers of plastic scintillator layers (2, 3, and 4), based on J-PET technology have been simulated by GATE software. Furthermore, Siemens’ Biograph Vision has been simulated to compare the results with standard PET scans. Two types of simulations have been performed. The first one with a centrally located source with a diameter of 1 mm and a length of 250 cm, and the second one with the same source inside a water-filled cylindrical phantom with a diameter of 20 cm and a length of 183 cm. Results With regards to sensitivity, among all the proposed scanners, the ones constructed with BGO crystals give the best performance ( $$\sim$$ ∼ 350 cps/kBq at the center). The utilization of sparse geometry or LYSO crystals significantly lowers the achievable sensitivity of such systems. The J-PET design gives a similar sensitivity to the sparse LYSO crystal-based detectors while having full detector coverage over the body. Moreover, it provides uniform sensitivity over the body with additional gain on its sides and provides the possibility for high-quality brain imaging. Conclusion Taking into account not only the sensitivity but also the price of Total-Body PET tomographs, which till now was one of the main obstacles in their widespread clinical availability, the J-PET tomography system based on plastic scintillators could be a cost-efficient alternative for Total-Body PET scanners.

Streptococcus mutans is a major pathogenic habitant of oral caries. Owing to its physiological and biochemical features, it prevails in the form of plaque biofilm together with another important mutans streptococci species, Streptococcus sobrinus. Both species are considered as initiators of cavity lesions, and biofilm is essential to the dental caries process. Compared with the planktonic populations, the biofilm form has higher resistance to environmental conditions and antibiotics. Dental plaques also secure the long-term survival of microorganisms and protection from any stress conditions. To address the need for new antibiofilm agents, we have focused on L-carnitine-fumarate, a fumarate-conjugated quaternary ammonium compound. Using the macro-broth susceptibility testing method, we established its MIC value as 6.0 mg/mL. The MBC value, determined from the broth dilution minimum inhibitory concentration test by sub-culturing it to BHI agar plates, was established as 7.0 mg/mL. Antibiofilm efficacy was tested in 96-well plates coated with saliva using BHI broth supplemented with 1% sucrose as a standard approach. The obtained results allowed us to assess the MIBC as 7.5 mg/mL and the MBBC value as 10.0 mg/mL. The latter concentration also caused approximately 20% eradication of pre-existing biofilm. EPS-rich matrix, forming the core of the biofilm and enabling a confined acidic microenvironment, was also examined and confirmed the effectiveness of 10.0 mg/mL L-carnitine-fumarate concentration in inhibiting EPS formation. Furthermore, the anti-adherent and anti-aciduric impacts of L-carnitine-fumarate were investigated and revealed significant inhibitory effects at sub-MIC concentrations. The influence of L-carnitine-fumarate on the phosphotransferase system was investigated as well. Our results provide a new insight into the antibacterial potential of L-carnitine-fumarate as a valuable compound to be considered for alternative or adjunct anti-caries and antibiofilm preventive approaches.