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The role of sickle cell trait (SCT) in sudden exertional death is well‐recognized in sports and military training. However, it is not yet studied for non‐firearm arrest‐related death (NF‐ARD). With extensive multi‐pronged searches, a large database (n = 1389) of NF‐ARDs was established. For the years 2006–2021 (inclusive) there were 50 NF‐ARDs of Black persons in which postmortem evidence of SCT was found. A control cohort consisted of 414 NF‐ARDs of Black persons with no reported SCT. The mean age for SCT cases was 33.1 ± 10.4 years versus 37.0 ± 10.4 years for the control group (p = 0.01). The body‐mass index for SCT cases was 28.3 ± 6.6 kg/m2 versus 30.7 ± 7.6 kg/m2 for the control group (p = 0.03). The prevalence of cardiomegaly was 21% for SCT cases versus 39% in the control cohort (p = 0.008). The postmortem prevalence of SCT in NF‐ARDs of Black persons (n = 50, 10.7%) was higher than the prevalence of SCT in the US Black population, which is 7.1% (p = 0.003). In this study of NF‐ARDs in Black persons, the prevalence of SCT and the differences between the SCT cases and the control cohort suggest that exertional collapse associated with sickle cell trait may be a contributory factor in NF‐ARDs. [ABSTRACT FROM AUTHOR]

Na+/taurocholate cotransporting polypeptide (NTCP, gene symbol SLC10A1) is a hepatic bile acid uptake carrier participating in the enterohepatic circulation of bile acids. Apart from its transporter function, NTCP acts as the high-affinity liver-specific receptor for the hepatitis B virus (HBV), which attaches via its preS1-peptide domain of the large surface protein to NTCP, subsequently leading to endocytosis of the virus/NTCP-receptor complex. Although the process of NTCP-dependent HBV infection of hepatocytes has received much attention over the last decade, the precise molecular sites of the virus/NTCP interaction have not been fully identified. Inspection of the primary protein sequence of human NTCP revealed 139YIYSRGIY146 as a highly conserved tyrosine-rich motif. To study the role of Y139, Y141 and Y146 amino acids in NTCP biology, the aforementioned residues were substituted with alanine, phenylalanine or glutamate (mimicking phosphorylation) using site-directed mutagenesis. Similar to wt NTCP, the Y139A, Y141A, Y146A, Y141F, Y146F, and Y146E mutants were expressed at the plasma membrane of HEK293 cells and exhibited intact bile acid transport function. Y146A, Y146E, and Y146F demonstrated transport kinetics comparable to wild-type NTCP with Km values of 57.3–112.4 µM and Vmax values of 6683–7579 pmol/mg protein/min. Only Y141E was transport deficient, most likely due to an intracellular accumulation of the mutant protein. Most importantly, Y146A and Y146E mutation completely abrogated binding of the viral preS1-peptide to NTCP, while the Y146F mutant of NTCP showed some residual binding competence for preS1. Consequently, the NTCP mutants Y146A and Y146E, when expressed in HepG2 hepatoma cells, showed complete loss of susceptibility for in vitro HBV infection. In conclusion, tyrosine 146, and to some extent tyrosine 141, both belonging to the tyrosine-rich motif 139YIYSRGIY146 of human NTCP, are newly identified amino acid residues that play an essential role in the interaction of HBV with its receptor NTCP and, thus, in the process of virus entry into hepatocytes. [ABSTRACT FROM AUTHOR]

Blunt force traumas by footwear can result in severe and even fatal head and upper body injuries. Oftentimes, footwear impressions are only partially available and evidential value is limited. DNA evidence on shoe soles could provide crucial evidence helping to solve crimes by linking target DNA to the activity of interest. Little is known about the persistence and detectability of biological material post such offenses and the interplay of factors affecting the analytical success. In this study, we assessed the persistence of blood on shoe soles under varying parameters such as blood location, different sneakers, weather condition, gait, amount of blood, underground and step count. We applied an optimized DNA/RNA workflow adapted to micro-traces without constraints for the primary DNA pipeline. There is a high probability to link donor DNA to the shoe sole for up to 300–400 steps, regardless of the underground, blood location, and amount of blood. Depending on the sole material and the degree of abrasion of the sole, a longer blood persistence can be observed. Considering blood, 98.2% of the initial DNA amount (1 μl initial blood volume) was lost after 100 steps walked on sole areas that are in constant contact with the ground. Proportion of foreign DNA was marginal (avg. 4.4 alleles), minimizing the probability of unintentional DNA transfer in this context. RNA typing showed high specificity but lower sensitivity than presumptive tests used for body fluid identification (BFI). Luminol is essential for targeted sampling on shoe soles, as latent blood traces (>100–200 steps) provided sufficient biological material for DNA/RNA typing. The generated data help to address the activity of interest and evaluate probabilities about prevalence of target DNA important for casework implications and assessments on activity level. • Persistence of blood depends on various investigated parameters. • Optimized DNA/RNA analysis strategy provides promising results. • Number of foreign alleles detected is marginal. • Luminol has a high sensitivity and thus is important for targeted blood sampling. [ABSTRACT FROM AUTHOR]

Fluorophore-coupled bile acids (BA) represent an important tool for intravital analysis of BA flux in animal models of cholestatic diseases. However, addition of a fluorophore to a BA may alter transport properties. We developed and validated a 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole-coupled taurocholic acid (3β-NBD-TCA) as a probe for intravital analysis of BA homeostasis. We compared transport of 3β-NBD-TCA to [3H]-TCA in HEK293 cells stably expressing the mouse hepatic or renal BA carriers mNtcp or mAsbt, respectively. We also studied distribution kinetics intravitally in livers and kidneys of anesthetized wildtype and mOatp1a/1b cluster knockout mice (OatpKO) with and without administration of the Ntcp inhibitor Myrcludex B and the ASBT inhibitor AS0369. In vitro, 3β-NBD-TCA and [3H]-TCA showed comparable concentration- and time-dependent transport via mNtcp and mAsbt as well as similar inhibition kinetics for Myrcludex B and AS0369. Intravital analysis in the livers of wildtype and OatpKO mice revealed contribution of both mNtcp and mOatp1a/1b in the 3β-NBD-TCA uptake from the sinusoidal blood into hepatocytes. Combined deletion of mOatp1a/1b and inhibition of mNtcp by Myrcludex B blocked the uptake of 3β-NBD-TCA from sinusoidal blood into hepatocytes. This led to an increase of 3β-NBD-TCA signal in the systemic circulation including renal capillaries, followed by strong enrichment in a subpopulation of proximal renal tubular epithelial cells (TEC). The enrichment of 3β-NBD-TCA in TEC was strongly reduced by the systemic ASBT inhibitor AS0369. NBD-coupled TCA has similar transport kinetics as [3H]-TCA and can be used as a tool to study hepatorenal BA transport. See also the graphical abstract(Fig. 1)., Competing Interests: Nothing to disclose., (Copyright © 2024 Ghallab et al.)

In forensic age determination, e.g. for legal proceedings, exceeded age limits may be relevant. To investigate age-related differences in skeletal development, the recommendations of the Study Group on Forensic Age Diagnostics (AGFAD) rely on imaging techniques using ionizing radiation (including orthopantomograms and radiographs of the hand). Vieth et al. and Ottow et al. have proposed MRI classifications for epi-/diaphyseal fusion of the knee joint to determine different age limits. The aim of the present study was to verify whether these two classifications could also be applied to MRI of the ankle.MRI images of the ankle from 333 patients (160 female, 173 male) ranging in age from 10 to 28 years were retrospectively analyzed. T1-weighted turbo spin-echo (TSE) sequences and T2-weighted fat-suppressed sequences were analyzed for the two classifications. The different ossification stages of the two classifications were determined and the corresponding chronological ages were assigned. In addition, gender-specific differences were analyzed. Intra- and inter-observer variability was determined using Cohen's kappa.With the classification of Ottow et al., the completion of the 14 th year of life could be determined in both sexes. With the classification of Vieth et al, the completion of the 14 th year of life could be determined in both sexes and the 18 th year of life in male patients. Intra-observer and inter-observer variability was very good and good, respectively (κ > 0.87 and κ > 0.72).In the present study, it was also possible to use both classifications for MRI of the ankle joint. The method offers the potential of an alternative or at least supplementary radiation-free assessment criterion in forensic age estimation. · MRI scans of the ankle can be used for forensic age determination.. · Classifications developed for the knee joint can also be used on the ankle.. · The applied classifications based on Vieth et al. and Ottow et al. can be used as an alternative or, at the least, an additional method when determining legally relevant age limits.. · Wernsing MF, Malokaj V, Kunz SN et al. Forensic Age Determination Using MRI Scans of the Ankle: Applying Two Classifications to Assess Ossification. Fortschr Röntgenstr 2024; DOI 10.1055/a-2379-8785., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

In the project presented here, we used NLP tools for annotating German medical trainings documents with SNOMED CT codes. Following research question was addressed: Is it possible to automate the annotation of training documents with an NLP pipeline especially designed for this task but requiring translation into English? The goal of our stakeholder, an institution responsible for the continuing education of physicians, was to facilitate the switch between different medical trainings programs by coding the same requirement with the same SNOMED CT code, even if the wording is different. We first describe how we chose the concrete NLP tools, after which the concrete steps for implementing our prototype are outlined: the NLP pipeline construction, the implementation, and the validation. We infer three important lessons from our results: (i) self-supervision is no free lunch and should be based on a sophisticated task, (ii) the translation via DeepL can be too context-dependent for a peculiar use case, and (iii) ontology extraction can increase efficiency as well as accuracy.