Miracle-dz/UniFAR-FTUs huggingface dataset:
Outcome prediction in comatose cardiac arrest patients with initial shockable and non‐shockable rhythms

Prognosis after out‐of‐hospital cardiac arrest (OHCA) is presumed poorer in patients with non‐shockable than shockable rhythms, frequently leading to treatment withdrawal. Multimodal outcome prediction is recommended 72 h post‐arrest in still comatose patients, not considering initial rhythms. We investigated accuracy of outcome predictors in all comatose OHCA survivors, with a particular focus on shockable vs. non‐shockable rhythms.
Ataluren improves myelopoiesis and neutrophil chemotaxis by restoring ribosome biogenesis and reducing p53 levels in Shwachman–Diamond syndrome cells

Shwachman–Diamond syndrome (SDS) is characterized by neutropenia, exocrine pancreatic insufficiency and skeletal abnormalities. SDS bone marrow haematopoietic progenitors show increased apoptosis and impairment in granulocytic differentiation. Loss of Shwachman–Bodian–Diamond syndrome (SBDS) expression results in reduced eukaryotic 80S ribosome maturation. Biallelic mutations in the SBDS gene are found in ~90% of SDS patients, ~55% of whom carry the c.183‐184TA>CT nonsense mutation. Several translational readthrough‐inducing drugs aimed at suppressing nonsense mutations have been developed. One of these, ataluren, has received approval in Europe for the treatment of Duchenne muscular dystrophy. We previously showed that ataluren can restore full‐length SBDS protein synthesis in SDS‐derived bone marrow cells. Here, we extend our preclinical study to assess the functional restoration of SBDS capabilities in vitro and ex vivo. Ataluren improved 80S ribosome assembly and total protein synthesis in SDS‐derived cells, restored myelopoiesis in myeloid progenitors, improved neutrophil chemotaxis in vitro and reduced neutrophil dysplastic markers ex vivo. Ataluren also restored full‐length SBDS synthesis in primary osteoblasts, suggesting that its beneficial role may go beyond the myeloid compartment. Altogether, our results strengthened the rationale for a Phase I/II clinical trial of ataluren in SDS patients who harbour the nonsense mutation.
N 6‐methyladenosine‐modified circSTX6 promotes hepatocellular carcinoma progression by regulating the HNRNPD/ATF3 axis and encoding a 144 amino acid polypeptide

Abstract Background Circular RNAs (circRNAs) play a significant role in the initiation and progression of various cancers, including hepatocellular carcinoma (HCC). Circular syntaxin 6 (circSTX6, also known as hsa_circ_0007905) has been identified as a microRNA (miRNA) sponge in pancreatic adenocarcinoma. However, its full range of functions in terms of protein scaffold and translation remain largely unexplored in the context of HCC. Methods The expression of circSTX6 and its encoded protein was examined in HCC tumour tissues. N 6‐methyladenosine (m6A) on circSTX6 was verified and quantified by methylated RNA immunoprecipitation (Me‐RIP), RIP and dual luciferase reporter assays. The biological functions of circSTX6 and its encoded protein in HCC were clarified by in vitro and in vivo experiments. Mechanistically, the interaction between circSTX6 and heterogeneous nuclear ribonucleoprotein D (HNRNPD) was investigated by RNA pull‐down, RIP and fluorescence in situ hybridization (FISH)/IF. The regulatory effects of circSTX6 and HNRNPD on activating transcription factor 3 (ATF3) mRNA were determined by mRNA stability and RIP assays. Furthermore, the presence of circSTX6‐encoded protein was verified by mass spectrometry. Results CircSTX6 and its encoded 144 amino acid polypeptide, circSTX6‐144aa, were highly expressed in HCC tumour tissues and served as independent risk factors for overall survival in HCC patients. The expression of circSTX6 was regulated by METTL14 in an m6A‐dependent manner. Functionally, circSTX6 accelerated HCC proliferation and tumourigenicity and reinforced tumour metastasis in vitro and in vivo. Mechanistically, circSTX6 acted as a sponge for HNRNPD protein, facilitating its binding to ATF3 mRNA, consequently promoting ATF3 mRNA decay. Meanwhile, circSTX6‐144aa promoted HCC proliferation, migration and invasion independent of circSTX6 itself. Conclusion Collectively, our study reveals that m6A‐modified circSTX6 drives malignancy in HCC through the HNRNPD/ATF3 axis, while its encoded circSTX6‐144aa contributes to HCC progression independent of circSTX6. CirSTX6 and its encoded protein hold promise as potential biomarkers and therapeutic targets in HCC.
The ketone body β‐hydroxybutyrate shifts microglial metabolism and suppresses amyloid‐β oligomer‐induced inflammation in human microglia

Fatty acids are metabolized by β‐oxidation within the “mitochondrial ketogenic pathway” (MKP) to generate β‐hydroxybutyrate (BHB), a ketone body. BHB can be generated by most cells but largely by hepatocytes following exercise, fasting, or ketogenic diet consumption. BHB has been shown to modulate systemic and brain inflammation; however, its direct effects on microglia have been little studied. We investigated the impact of BHB on Aβ oligomer (AβO)‐stimulated human iPS‐derived microglia (hiMG), a model relevant to the pathogenesis of Alzheimer's disease (AD). HiMG responded to AβO with proinflammatory activation, which was mitigated by BHB at physiological concentrations of 0.1–2 mM. AβO stimulated glycolytic transcripts, suppressed genes in the β‐oxidation pathway, and induced over‐expression of AD‐relevant p46Shc, an endogenous inhibitor of thiolase, actions that are expected to suppress MKP. AβO also triggered mitochondrial Ca2+ increase, mitochondrial reactive oxygen species production, and activation of the mitochondrial permeability transition pore. BHB potently ameliorated all the above mitochondrial changes and rectified the MKP, resulting in reduced inflammasome activation and recovery of the phagocytotic function impaired by AβO. These results indicate that microglia MKP can be induced to modulate microglia immunometabolism, and that BHB can remedy “keto‐deficiency” resulting from MKP suppression and shift microglia away from proinflammatory mitochondrial metabolism. These effects of BHB may contribute to the beneficial effects of ketogenic diet intervention in aged mice and in human subjects with mild AD.
Myocardial markers are highly altered by higher rates of fluid removal during hemodialysis

Although hemodialysis is lifesaving in patients with kidney failure extensive interdialytic weight gain (IDWG) between dialyses worsens the prognosis. We recently showed a strong correlation between IDWG and predialytic values of cardiac markers. The aim of the present study was to evaluate if the cardiac markers N‐terminal pro‐B‐type natriuretic peptide (proBNP) and troponin T were influenced by IDWG and speed of fluid removal (ultrafiltration‐rate).
The immunometabolic landscape of bone marrow cells in multiple sclerosis

In multiple sclerosis (MS), the bone marrow hematopoietic system supplies immune cells to orchestrate central nervous system (CNS) inflammation and autoimmunity. Understanding the metabolic processes within the bone marrow is essential for unraveling the phenotype and function of immune cells. However, a comprehensive exploration of the metabolic landscape and its association with systemic immune response in MS at the single‐cell level has yet to be elucidated. Herein, we conducted an analysis of 70 289 bone marrow cells obtained from seven patients with MS and seven health controls (referenced as HRA001783) to address this question. Our focus was primarily on investigating the metabolic preferences of diverse immune cell populations and delineating their metabolic manifestations in the bone marrow microenvironment of MS. Through our analysis, we observed the activation of carbohydrate and amino acid metabolic pathways in the bone marrow cells of MS patients. Notably, we discovered significant metabolic alterations in cell–cell communication within the plasma cell population in the MS bone marrow. These findings shed light on the complex metabolic landscape within the bone marrow niche during MS and highlight the distinctive metabolic characteristics of plasma cells in this context, which may provoke novel understanding of MS pathogenesis and promote future design of immune therapies.
Age estimation in the combined long bones and ribs by histomorphometry: Past, present, and future

Numerous age estimation methods in unidentified bone have been a long time developing for application in forensic anthropology. The histomorphometric technique is one of the alternative methods that relied upon the evaluation of the cortical bone microstructure over the lifespan as a result of the remodeling process in bone. Remodeling is a sophisticated event occurring from the coupled function of bone formation and resorption cells for maintaining mineral homeostasis and repairment of microdamage in bone tissue. Products derived from remodeling are primary changes in the osteon or haversian system in various regions in the cortical bone, including periosteum, endosteum, and trabecular bone. Throughout life, bone remodeling rate with osteon alteration can be predictable. In the forensic field, histological methods are getting more attention due to the unavailability of macroscopic methods. Histomorphometry approach can be accomplished in fragmentary or incomplete bone remains indicating the limited use of gross morphological methods. In addition, the microscopic methods can aid to increase the more accuracy of analyses and diminish the biased subjective assessment for determining age. Most histomorphometry method utilizes a cross-section of the midshaft of the long bones including the mandible, rib, and clavicle. This review provides the basic knowledge of bone biology and anatomy, several age-estimating methods of histology, and crucial factors for age methods. Studies regarding overall age determination methods from the past until now contribute to obtaining more benefits for developing methods of histomorphometry using human bone in forensic identification.
A feasibility study on exhaled breath analysis using UV spectroscopy to detect COVID-19

A 23-subject feasibility study is reported to assess how UV absorbance measurements on exhaled breath samples collected from silicon microreactors can be used to detect COVID-19. The silicon microreactor technology chemoselectively preconcentrates exhaled carbonyl volatile organic compounds and subsequent methanol elution provides samples for analysis. The underlying scientific rationale that viral infection will induce an increase in exhaled carbonyls appears to be supported by the results of the feasibility study. The data indicate statistically significant differences in measured UV absorbance values between healthy and symptomatic COVID-19 positive subjects in the wavelength range from 235 nm to 305 nm. Factors such as subject age were noted as potential confounding variables.
Revaccination of patients with systemic lupus erythematosus or rheumatoid arthritis without an initial COVID-19 vaccine response elicits seroconversion in half of the patients.

OBJECTIVES To investigate the effect of COVID-19 mRNA revaccination (two doses) on the antibody response in patients with rheumatic diseases (RD) who were initial vaccine non-responders. Further, to examine if B-cell levels or T-cell responses before revaccination predicted seroconversion. METHODS From a RD cohort vaccinated with the standard two-dose COVID-19 vaccinations, we enrolled cases without detectable antibody responses (n=17) and controls with detectable antibody response (n=29). Blood donors (n=32) were included as additional controls. Samples were collected before and six weeks after completed revaccination. Total antibodies and specific IgG, IgA, and IgM against SARS-CoV-2 spike protein, SARS-CoV-2 neutralising antibodies, and SARS-CoV-2 reacting CD4+ and CD8+ T-cells were measured before and after revaccination. B-cells (CD19+CD45+) were quantified before revaccination. RESULTS Forty-seven percent of cases had detectable neutralising antibodies after revaccination. However, antibody levels were significantly lower than in controls and blood donors. Revaccination induced an antibody class switch in cases with a decrease in IgM and increase in IgG. No significant difference was observed in T-cell responses before and after revaccination between the three groups. Only 29% of cases had measurable B-cells compared to 100% of controls and blood donors. Fifty percent of revaccinated cases who seroconverted had measurable B-cells before revaccination. CONCLUSIONS Forty-seven percent of initial non-responders seroconverted after two-dose revaccination but still had lower levels of SARS-CoV-2 antibodies compared with controls and blood donors. RD patients without a detectable serological response after the initial COVID-19 mRNA vaccine had a T-cell response similar to immunocompetent controls and blood donors.
PERFORMANCES OF FORAGE TURNIP (Brassica rapa L.) CULTIVARS UNDER DIFFERENT NITROGEN TREATMENTS

Karadeniz Bolgesi sahil kosullarinda bes farkli azot dozunun (0, 50, 100, 150 ve 200 kg/ha) dort yem salgami cesidinin (Agressa, Siloganova, Polybra ve Volenda) yumru, yaprak verimi ve verim ogeleri uzerine etkilerinin belirlendigi bu arastirma 2002 ve 2003 yetistirme periyodunda yurutulmustur. Arastirmada yumru verimi, yumru kuru madde verimi, yumru ham protein verimi, yumru capi, yumru boyu, yaprak verimi, yaprak kuru madde verimi ve yaprak ham protein verimi belirlenmistir. Azotlu gubrelemenin artmasiyla yem salgami cesitlerinin yumru ve yaprak verimi ile diger verim ogeleri artmistir. En yuksek yumru ve yaprak kuru madde verimleri hektara 150 kg azotlu gubreleme uygulanan Volenda cesidinden (sirasiyla 7.19 ve 5.24 t/ha) elde edilmistir
Anterior Tibial Artery Danger Zone During Anterolateral Plate Fixation of the Distal Tibia: A 3D Computed Tomography Angiogram Modeling Study

Supplemental Digital Content is Available in the Text. OBJECTIVES: The objective of this study was to define the danger zone at which the anterior tibial artery (ATA) is at risk during anterolateral plating of the distal tibia using a novel 3D computed tomography angiography (CTA) modeling technique. METHODS: 116 patients (232 lower extremities) who underwent lower extremity CTAs between April 2020 and April 2022 were identified. Those with lower extremity trauma, evidence of a previously healed tibial fracture, or poor visualization of the ATA were excluded. The remaining 150 lower extremities (92 patients) were modeled with an anterolateral distal tibia plate using Sectra IDS7 software. The distance of the ATA from bony landmarks was measured perpendicular to the level at which the vessel intersected the plate. RESULTS: The ATA intersected the plate proximally at a mean distance of 10.5 cm (95% confidence intervals, 10.2–10.9) and at a mean distance of 4.6 cm (95% confidence intervals, 4.4–4.9) distally from the central tibial plafond. The ATA intersected with the plate as far distal as hole number 1 and as proximal as hole 14 of the plate. The greatest injury risk was associated with plate holes 3–8. In this region, the artery was at risk in 46–99 percent of specimens. CONCLUSIONS: The ATA is at risk when screws are placed percutaneously in an anterolateral distal tibia plate. The artery can be as close as 4.4 cm and as far as 10.9 cm proximal to the tibial plafond when crossing the plate, correlating to a risk of injury to the ATA at plate holes 1 through 14.
Matrine and Oxymatrine: evaluating the gene mutation potential using in silico tools and the bacterial reverse mutation assay (Ames test)

Abstract The quinolizidine alkaloids matrine and its N-oxide oxymatrine occur in plants of the genus Sophora. Recently, matrine was sporadically detected in liquorice products. Morphological similarity of the liquorice plant Glycyrrhiza glabra with Sophora species and resulting confusion during harvesting may explain this contamination, but use of matrine as pesticide has also been reported. The detection of matrine in liquorice products raised concern as some studies suggested a genotoxic activity of matrine and oxymatrine. However, these studies are fraught with uncertainties, putting the reliability and robustness into question. Another issue was that Sophora root extracts were usually tested instead of pure matrine and oxymatrine. The aim of this work was therefore to determine whether matrine and oxymatrine have potential for causing gene mutations. In a first step and to support a weight-of-evidence analysis, in silico predictions were performed to improve the database using expert and statistical systems by VEGA, Leadscope (Instem®), and Nexus (Lhasa Limited). Unfortunately, the confidence levels of the predictions were insufficient to either identify or exclude a mutagenic potential. Thus, in order to obtain reliable results, the bacterial reverse mutation assay (Ames test) was carried out in accordance with OECD Test Guideline 471. The test set included the plate incorporation and the preincubation assay. It was performed with five different bacterial strains in the presence or absence of metabolic activation. Neither matrine nor oxymatrine induced a significant increase in the number of revertants under any of the selected experimental conditions. Overall, it can be concluded that matrine and oxymatrine are unlikely to have a gene mutation potential. Any positive findings with Sophora extracts in the Ames test may be related to other components. Notably, the results also indicated a need to extend the application domain of respective (Q)SAR tools to secondary plant metabolites.
Reduction is sufficient for the disassembly of ricin and Shiga toxin 1 but not Escherichia coli heat-labile enterotoxin

ABSTRACT Many AB toxins contain an enzymatic A moiety that is anchored to a cell-binding B moiety by a disulfide bridge. After receptor-mediated endocytosis, some AB toxins undergo retrograde transport to the endoplasmic reticulum (ER) where reduction of the disulfide bond occurs. The reduced A subunit then dissociates from the holotoxin and enters the cytosol to alter its cellular target. Intoxication requires A chain separation from the holotoxin, but, for many toxins, it is unclear if reduction alone is sufficient for toxin disassembly. Here, we examined the link between reduction and disassembly for several ER-translocating toxins. We found disassembly of the reduced Escherichia coli heat-labile enterotoxin (Ltx) required an interaction with one specific ER-localized oxidoreductase: protein disulfide isomerase (PDI). In contrast, the reduction and disassembly of ricin toxin (Rtx) and Shiga toxin 1 (Stx1) were coupled events that did not require PDI and could be triggered by reductant alone. PDI-deficient cells accordingly exhibited high resistance to Ltx with continued sensitivity to Rtx and Stx1. The distinct structural organization of each AB toxin thus appears to determine whether holotoxin disassembly occurs spontaneously upon disulfide reduction or requires the additional input of PDI.
Computing Speed-of-Sound From Ultrasound: User-Agnostic Recovery and a New Benchmark

Objective: Medical ultrasound is one of the most accessible imaging modalities, but is a challenging modality for quantitative parameters comparison across vendors and sonographers. B-Mode imaging, with limited exceptions, provides a map of tissue boundaries; crucially, it does not provide diagnostically relevant physical quantities of the interior of organ domains.This can be remedied: the raw ultrasound signal carries significantly more information than is present in the B-Mode image. Specifically, the ability to recover speed-of-sound and attenuation maps from the raw ultrasound signal transforms the modality into a tissue-property modality. Deep learning was shown to be a viable tool for recovering speed-of-sound maps. A major hold-back towards deployment is the domain transfer problem, i.e., generalizing from simulations to real data. This is due in part to dependence on the (hard-to-calibrate) system response. Methods: We explore a remedy to the problem of operator-dependent effects on the system response by introducing a novel approach utilizing the phase information of the IQ demodulated signal. Results: We show that the IQ-phase information effectively decouples the operator-dependent system response from the data, significantly improving the stability of speed-of-sound recovery. We also introduce an improvement to the network topology providing faster and improved results to the state-of-the-art. We present the first publicly available benchmark for this problem: a simulated dataset for raw ultrasound plane wave processing. Conclusion: The consideration of the phase of the IQ-signals presents a promising appeal to traversing the transfer learning problem, advancing the goal of real-time speed-of-sound imaging.
A longitudinal study using B mode ultrasound and power Doppler as monitoring imaging tools in inclusion body myositis.

OBJECTIVES There is growing interest in ultrasound (US) as an outcome measure in IBM. Our study aimed to determine the ability of B mode US and power Doppler (PD) to detect changes in affected muscles over time and if US domains correlate with disease progression. METHODS Participants attended on four occasions over a median follow-up period of 26 months. All completed a patient self-reported health assessment questionnaire (HAQ), patient visual analogue scale (pVAS), manual muscle testing (MMT), and US (fascial thickness-FT, muscle bulk, echogenicity, and PD) on deltoid and vastus lateralis (VL) muscles at each visit. RESULTS This longitudinal observational study had 35 participants: 21 (60%) males, median age 70 (IQR (64-76), and the majority (85.7%) not on immunosuppression. When analysed for sex differences at baseline, males had lower FT-VL (p=0.018) and higher muscle bulk (p=0.002) than females. Only FT-deltoid (p<0.001) increased significantly over time with follow-up. When participants were stratified into progressors and non-progressors, FT at baseline was lower in progressors (0.06 vs. 0.09, p=0.017), who were predominantly male. There were no significant differences in other US domains. CONCLUSIONS Our study highlights previously unreported sex differences in US findings in IBM. Certain US domains, such as FT, showed measurable changes over time and correlated with disease progression. However, further studies with longer follow-up periods and larger patient cohorts will need to be performed to determine whether B mode US could be a useful disease outcome measure for therapeutic trials.