Miracle-dz/UniFAR-FTUs huggingface dataset:
Alpha-Particle Exposure Induces Mainly Unstable Complex Chromosome Aberrations which do not Contribute to Radiation-Associated Cytogenetic Risk

The mechanism underlying the carcinogenic potential of α radiation is not fully understood, considering that cell inactivation (e.g., mitotic cell death) as a main consequence of exposure efficiently counteracts the spreading of heritable DNA damage. The aim of this study is to improve our understanding of the effectiveness of α particles in inducing different types of chromosomal aberrations, to determine the respective values of the relative biological effectiveness (RBE) and to interpret the results with respect to exposure risk. Human peripheral blood lymphocytes (PBLs) from a single donor were exposed ex vivo to doses of 0–6 Gy X rays or 0–2 Gy α particles. Cells were harvested at two different times after irradiation to account for the mitotic delay of heavily damaged cells, which is known to occur after exposure to high-LET radiation (including α particles). Analysis of the kinetics of cells reaching first or second (and higher) mitosis after irradiation and aberration data obtained by the multiplex fluorescence in situ hybridization (mFISH) technique are used to determine of the cytogenetic risk, i.e., the probability for transmissible aberrations in surviving lymphocytes. The analysis shows that the cytogenetic risk after α exposure is lower than after X rays. This indicates that the actually observed higher carcinogenic effect of α radiation is likely to stem from small scale mutations that are induced effectively by high-LET radiation but cannot be resolved by mFISH analysis.
Deep learning enabled ultra-fast-pitch acquisition in clinical X-ray Computed Tomography.

OBJECTIVE In x-ray Computed Tomography (CT), many important clinical applications may benefit from a fast acquisition speed. Helical scan is the most widely used acquisition mode in clinical CT, where a fast helical pitch can improve the acquisition speed. However, on a typical single-source CT (SSCT) system, the helical pitch p typically cannot exceed 1.5; otherwise, reconstruction artifacts will result from data insufficiency. The purpose of this work is to develop a deep convolutional neural network to correct for artifacts caused by an ultra-fast pitch, which can enable faster acquisition speed than what is currently achievable. METHODS A customized convolutional neural network (denoted as UFP-net) was developed to restore the underlying anatomical structure from the artifact-corrupted post-reconstruction data acquired from SSCT with ultra-fast pitch (i.e. p ≥ 2). UFP-net employed residual learning to capture the features of image artifacts. UFP-net further deployed in-house-customized functional blocks with spatial-domain local operators and frequency-domain non-local operators, to explore multi-scale feature representation. Images of contrast-enhanced patient exams (n = 83) with routine pitch setting (i.e. p < 1) were retrospectively collected, which were used as training and testing datasets. This patient cohort involved CT exams over different scan range of anatomy (chest, abdomen and pelvis) and CT systems (Siemens Definition, Definition Flash, Definition AS+, Siemens Healthcare, Inc.), and the corresponding base CT scanning protocols used consistent settings of major scan parameters (e.g. collimation and pitch). Forward projection of the original images was calculated to synthesize helical CT scans with one regular pitch setting (p = 1) and two ultra-fast-pitch setting (p = 2, and 3). All patient images were reconstructed using standard filtered-back-projection (FBP) algorithm. A customized multi-stage training scheme was developed to incrementally optimize the parameters of UFP-net, using ultra-fast-pitch images as network inputs and regular pitch images as labels. Visual inspection was conducted to evaluate image quality. Structural similarity index (SSIM) and relative root-mean-square-error (rRMSE) were used as quantitative quality metrics. RESULTS The UFP-net dramatically improved image quality over standard FBP at both ultra-fast-pitch settings. At p = 2, UFP-net yielded higher mean SSIM (>0.98) with lower mean rRMSE (<2.9%), compared to FBP (mean SSIM <0.93; mean rRMSE > 9.1%). Quantitative metrics at p = 3: UFP-net - mean SSIM [0.86, 0.94], and mean rRMSE [5.0%, 8.2%]; FBP - mean SSIM [0.36, 0.61], and mean rRMSE [36.0%, 58.6%]. CONCLUSION The proposed UFP-net has the potential to enable ultra-fast data acquisition in clinical CT without sacrificing image quality. This method has demonstrated reasonable generalizability over different body parts, when the corresponding CT exams involved consistent base scan parameters. This article is protected by copyright. All rights reserved.
Ultrasensitive and Simultaneous Detection of Two Specific SARS-CoV-2 Antigens in Human Specimens Using Direct/Enrichment Dual-Mode Fluorescence Lateral Flow Immunoassay

Sensitive point-of-care methods for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in clinical specimens are urgently needed to achieve rapid screening of viral infection. We developed a magnetic quantum dot-based dual-mode lateral flow immunoassay (LFIA) biosensor for the high-sensitivity simultaneous detection of SARS-CoV-2 spike (S) and nucleocapsid protein (NP) antigens, which is beneficial for improving the detection accuracy and efficiency of SARS-CoV-2 infection in the point-of-care testing area. A high-performance magnetic quantum dot with a triple-QD shell (MagTQD) nanotag was first fabricated and integrated into the LFIA system to provide superior fluorescence signals, enrichment ability, and detectability for S/NP antigen testing. Two detection modes were provided by the proposed MagTQD-LFIA. The direct mode was used for rapid screening or urgent detection of suspected samples within 10 min, and the enrichment mode was used for the highly sensitive and quantitative analysis of SARS-CoV-2 antigens in biological samples without the interference of the “hook effect. ” The simultaneous detection of SARS-CoV-2 S/NP antigens was conducted in one LFIA strip, and the detection limits for two antigens under direct and enrichment modes were 1 and 0.5 pg/mL, respectively. The MagTQD-LFIA showed high accuracy, specificity, and stability in saliva and nasal swab samples and is an efficient tool with flexibility to meet the testing requirements for SARS-CoV-2 antigens in various situations.
Adherence to the dietary approaches to stop hypertension dietary pattern and rheumatoid arthritis in Iranian adults

Abstract Objective: To examine the hypothesis that rheumatoid arthritis (RA) patients are less likely than healthy individuals to adhere to the dietary approaches to stop hypertension (DASH) dietary pattern. Design: A multi-centre cross-sectional study involving a total of 300 eligible Iranian adults (aged >19 years; 93·0 % female) recruited during 2019–2020. Participants’ actual dietary intakes were measured via self-administered 3-d dietary records. The DASH score was computed based on the energy-adjusted intakes of eight major dietary components usually emphasised (i.e. fruits, vegetables, nuts and legumes, low-fat dairy products and whole grains) or minimised (i.e. sweets, red or processed meats and sodium) in the DASH diet. The higher the DASH score of subjects, the greater their adherence to the DASH pattern. Setting: The outpatient clinics of major general hospitals in Shiraz, Iran. Participants: 100 incident cases with definite RA according to the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria for RA and 200 apparently healthy controls frequency-matched by gender and age. Results: After adjusting for several potential covariates in the binary logistic regression analysis, RA cases were less likely than controls to have high adherence to the DASH pattern (OR = 0·08; 95 % CI 0·03, 0·20; P = 0·001). Conclusions: Our findings in a sample of Iranian adults revealed that RA patients are less likely than healthy individuals to adhere to the DASH dietary pattern. However, the potential causal association of greater adherence to the DASH pattern and lower risk of RA needs to be confirmed by prospective studies of high methodological quality.
A Bayesian nonparametric approach to dynamic item‐response modeling: An application to the GUSTO cohort study

Statistical analysis of questionnaire data is often performed employing techniques from item‐response theory. In this framework, it is possible to differentiate respondent profiles and characterize the questions (items) included in the questionnaire via interpretable parameters. These models are often crosssectional and aim at evaluating the performance of the respondents. The motivating application of this work is the analysis of psychometric questionnaires taken by a group of mothers at different time points and by their children at one later time point. The data are available through the GUSTO cohort study. To this end, we propose a Bayesian semiparametric model and extend the current literature by: (i) introducing temporal dependence among questionnaires taken at different time points; (ii) jointly modeling the responses to questionnaires taken from different, but related, groups of subjects (in our case mothers and children), introducing a further dependency structure and therefore sharing of information; (iii) allowing clustering of subjects based on their latent response profile. The proposed model is able to identify three main groups of mother/child pairs characterized by their response profiles. Furthermore, we report an interesting maternal reporting bias effect strongly affecting the clustering structure of the mother/child dyads.
Detection of Rift Valley Fever virus inter-epidemic activity in Kilimanjaro Region, North Eastern Tanzania

ABSTRACT Background Rift Valley Fever virus (RVFV) is a zoonotic arbovirus of public health impact infecting livestock, wildlife, and humans mainly in Africa and other parts of the world. Despite its public health importance, mechanisms of RVFV maintenance during interepidemic periods (IEPS) remain unclear. Objective We aimed to examine comparatively exposure to RVFV between humans and goats and RVFV infection between humans, goats and mosquitoes. Methods A cross sectional study was performed in the Lower Moshi area of the Kilimanjaro region from March to June 2020. RVFV exposure was determined by detecting IgG/IgM to RVFV using a competitive enzyme linked immunosorbent assay whereas infection was determined by real time quantitative polymerase chain reaction (RT-qPCR) assay. Results Results show that the male gender was related to RVFV seropositivity (χ2 = 5.351; p=0.030). Being 50 years and above was related to seropositivity (χ2 =14.430; p=0.006) whereas bed net use, larger numbers of persons living in the same house (>7 persons) and RVFV seropositivity in goats were related to higher seropositivity to RVFV among humans χ2 =6.003; p=0.021, χ2 =23.213; p < 0.001 and χ2 =27.053; p < 0.001), respectively. By the use of RT-qPCR, goats exhibited the highest RVFV infection rate of 4.1%, followed by humans (2.6%), Ae. aegypti (2.3%), and Cx. pipiens complex(1.5%). Likewise, a higher proportion of goats (23.3%) were RVFV seropositive as compared with humans (13.2%). Conclusion Our findings suggest the Lower Moshi area as a potential hotspot for Rift Valley Fever (RVF), posing the danger of being a source of RVFV spread to other areas. Goats had the highest infection rate, suggesting goats as important hosts for virus maintenance during IEPs. We recommend the implementation of strategies that will warrant active RVF surveillance through the identification of RVF hotspots for targeted control of the disease.
Anatomic and Clinical Pathology Characterization of Drug-Induced Sinusoidal Obstruction Syndrome (Veno-Occlusive Disease) in Cynomolgus Macaques

Sinusoidal obstruction syndrome (SOS) is a unique form of liver injury that occurs after exposure to chemotherapeutic drugs and toxins. The diagnosis of SOS in humans remains a challenge as the clinical criteria have low specificity and there are no reliable noninvasive biomarkers. The mechanism of injury is believed to be damage to liver endothelial cells, primarily sinusoidal endothelial cells (SECs), which leads to sinusoidal dilation, central venous fibrosis, and/or nodular regeneration. Nonclinical data suggest that this uncommon liver toxicity can be recapitulated in cynomolgus monkeys, and it is critical that pathologists are familiar with its characteristic clinicopathologic features. Elevations in liver enzymes, in particular aspartate aminotransferase, associated with isolated thrombocytopenia, should raise the suspicion of SEC injury for specific drug classes. Characterization of liver microscopic findings in monkeys benefits from the use of appropriate stains, such as reticulin stain, and VEGFR2 and CD34 immunohistochemical (IHC) stains. CD41 IHC demonstrates platelet accumulation in injured sinusoids, the likely cause of thrombocytopenia commonly reported in SOS. In conclusion, this report provides a comprehensive characterization of the pathology findings of drug-induced SOS in monkeys with the objectives of ensuring appropriate nonclinical recognition of the liability and informing clinical development strategy and monitoring.
SARS‐CoV‐2 RNAemia with a higher nasopharyngeal viral load is strongly associated with disease severity and mortality in patients with COVID‐19

This study aimed to determine the frequency of SARS‐CoV‐2 RNA in serum and its association with the clinical severity of COVID‐19. This retrospective cohort study performed at Toyama University Hospital included consecutive patients with confirmed COVID‐19. The prevalence of SARS‐CoV‐2 RNAemia and the strength of its association with clinical severity variables were examined. Fifty‐six patients were included in this study. RNAemia was detected in 19.6% (11/56) patients on admission, and subsequently in 1.0% (1/25), 50.0% (6/12), and 100.0% (4/4) moderate, severe, and critically ill patients, respectively. Patients with RNAemia required more frequent oxygen supplementation (90.0% vs. 13.3%), ICU admission (81.8% vs. 6.7%), and invasive mechanical ventilation (27.3% vs. 0.0%). Among patients with RNAemia, the median viral loads of nasopharyngeal (NP) swabs that were collected around the same time as the serum sample were significantly higher in critically ill (5.4 log10 copies/μl; interquartile range [IQR]: 4.2–6.3) than in moderate‐severe cases (2.6 log10 copies/μl; [IQR: 1.1–4.5]; p = 0.030) and were significantly higher in nonsurvivors (6.2 log10 copies/μl [IQR: 6.0–6.5]) than in survivors (3.9 log10 copies/μl [IQR: 1.6–4.6]; p = 0.045). This study demonstrated a relatively high proportion of SARS‐CoV‐2 RNAemia and an association between RNAemia and clinical severity. Moreover, among the patients with RNAemia, the viral loads of NP swabs were correlated with disease severity and mortality, suggesting the potential utility of combining serum testing with NP tests as a prognostic indicator for COVID‐19, with higher quality than each separate test.
Phase 1 study in healthy participants of the safety, pharmacokinetics, and pharmacodynamics of enpatoran (M5049), a dual antagonist of toll‐like receptors 7 and 8

This study evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple oral doses of enpatoran (formerly named M5049), a new toll‐like receptor (TLR) 7 and 8 dual antagonist, and the effect of food on a single dose in healthy participants. In this single phase 1, randomized (3:1), double‐blind, placebo‐controlled study, 96 participants received single and multiple ascending oral doses of enpatoran. Participants in single‐dose cohorts received one dose of enpatoran (1, 3, 9, 25, 50, 100, or 200 mg) or placebo using a sentinel dosing strategy. Multiple‐dose cohorts received enpatoran (9, 25, or 200 mg once daily, or 25 or 50 mg twice daily) or placebo for 14 days. Safety, tolerability, PK, and PD (ex vivo‐stimulated cytokine secretion) were assessed in both parts. The effect of food was assessed in an open‐label, one‐way crossover study in the 25 mg single‐dose cohort. Single‐ and multiple‐oral doses of enpatoran up to 200 mg were well tolerated and no significant dose‐limiting adverse events or safety signals were observed under fasting or fed conditions. PK parameters were linear and dose‐proportional across the dose range evaluated, with a slightly delayed absorption and lower peak concentration observed at 25 mg with food. Exposure‐dependent inhibition of ex vivo‐stimulated interleukin‐6 secretion was observed, with maximum inhibition at 200 mg. Enpatoran was well tolerated at doses up to 200 mg. Further investigation of enpatoran is warranted as a potential treatment for diseases driven by TLR7/8 overactivation, such as systemic lupus erythematosus and COVID‐19 pneumonia.
Microextraction and Determination of Poly- and Perfluoroalkyl Substances, Challenges, and Future Trends

Abstract Per- and polyfluoroalkyl substances (PFAS) are fluorocarbon compounds in which hydrogen atoms have been partly or entirely replaced by fluorine. They have a very wide range of applications, while they are persistent in the environment and exhibit bioaccumulative and toxic properties. Neither chemical nor biological mechanisms can decompose PFAS due to their strong C-F bonds. PFAS have shown adverse effects on various organisms, even at trace levels. Accordingly, highly sensitive and selective analytical methods are required for their tracing in biological and environmental matrices. The physicochemical properties of PFAS like surfactant characteristics and high-water solubility are unique and different from other known pollutants. Accordingly, the number of articles on the analysis of PFAS is less than the other well-known contaminants. The routine PFAS sample preparation methods (like solvent extraction) coupled with chromatographic systems, face challenges such as high limits of detection, need for laborious derivatization, limited selectivity, and expensive instrumentation. Recent efforts to address these limitations have aroused considerable attention to the development of microextraction techniques, which are consistent with the principles of green chemistry and can be made easily portable and automated. Moreover, these methods have shown enough sensitivity and selectivity for the analysis of different analytes (including PFAS) in a wide range of samples with different matrices. This research aims to review the microextraction methods and detection techniques, applied for the sample pretreatment of PFAS in various matrices, along with a critical discussion of the challenges and potential future trends.
My child's future mental health: Carer's engagement with risk identification in an intervention study for youth with at‐risk mental states

Prevention and early intervention efforts of serious mental illnesses has yielded promising results. However, alongside benefits, several ethical concerns have been raised, including the effects of being identified as being at‐risk. In these debates, the voice of parents or carers is conspicuously absent. This is especially concerning as several at‐risk interventions are trialled in under‐age youth where parents consent on behalf of young people. Therefore, this study aimed to understand carer's experiences of their teenager being identified as at risk for psychosis.
3D printing and enteric coating of a hollow capsular device with controlled drug release characteristics prepared using extruded Eudragit® filaments

Abstract This work focuses on the extrusion of a brittle, tacky, cationic copolymer i.e. Eudragit® E-100 to prepare filament and subsequent 3D printing of hollow capsular device using the extruded filament. An optimum amount of talc and triethyl citrate was used for the possible extrusion of the polymer. There was no thermal and chemical degradation of the polymer observed after extrusion confirmed by DSC and FTIR analysis. Microscopic analysis of the printed capsule showed the layer-by-layer manner of 3D printing. Capsule parts were printed according to the set dimensions (00 size) with minimal deviation. Printed capsule showed the soluble behaviour in gastric fluid pH 1.2 where within 15 min the encapsulated drug encounters with the dissolution medium and almost 70% drug was dissolved within 4 hr. In case of phosphate buffer pH 6.8, the printed capsule showed a longed swelling behaviour up to 12 hr and then gradually bursting of capsule occurred wherein more than 90% encapsulated drug was dissolved within 36 hr. Enteric coating of the printed capsule showed similar behaviour in alkaline medium that observed with non-enteric capsule. This indicates the potential application of this printed capsules for both gastric and intestinal specific delayed drug delivery by a single step enteric coating process. Graphical Abstract
Strategies for feature extraction from structural brain imaging in lesion‐deficit modelling

High‐dimensional modelling of post‐stroke deficits from structural brain imaging is highly relevant to basic cognitive neuroscience and bears the potential to be translationally used to guide individual rehabilitation measures. One strategy to optimise model performance is well‐informed feature selection and representation. However, different feature representation strategies were so far used, and it is not known what strategy is best for modelling purposes. The present study compared the three common main strategies: voxel‐wise representation, lesion‐anatomical componential feature reduction and region‐wise atlas‐based feature representation. We used multivariate, machine‐learning‐based lesion‐deficit models to predict post‐stroke deficits based on structural lesion data. Support vector regression was tuned by nested cross‐validation techniques and tested on held‐out validation data to estimate model performance. While we consistently found the numerically best models for lower‐dimensional, featurised data and almost always for principal components extracted from lesion maps, our results indicate only minor, non‐significant differences between different feature representation styles. Hence, our findings demonstrate the general suitability of all three commonly applied feature representations in lesion‐deficit modelling. Likewise, model performance between qualitatively different popular brain atlases was not significantly different. Our findings also highlight potential minor benefits in individual fine‐tuning of feature representations and the challenge posed by the high, multifaceted complexity of lesion data, where lesion‐anatomical and functional criteria might suggest opposing solutions to feature reduction.
Ceruloplasmin correlates with immune infiltration and serves as a prognostic biomarker in breast cancer

Breast-invasive carcinoma (BRCA) is the most frequent and malignant tumor in females. Ceruloplasmin (CP) is a multifunctional molecule involved in iron metabolism, but its expression profile, prognostic potential and relationship with immune cell infiltration in BRCA are unknown. Ceruloplasmin mRNA and protein expression was significantly decreased in BRCA patients according to the Oncomine, UALCAN, GEPIA and TCGA databases. Ceruloplasmin expression was strongly correlated with various clinicopathological features of BRCA patients. BRCA patients with high ceruloplasmin expression exhibited shorter survival times than those with low ceruloplasmin expression based on the Kaplan-Meier plotter and PrognoScan databases. GO and KEGG analyses and GSEA revealed a strong correlation between ceruloplasmin and various immune-related pathways. Ceruloplasmin expression was significantly associated with the infiltration of immune cells into tumor sites by analyzing the TIMER and CIBERSORT. Additionally, ceruloplasmin was positively correlated with immune checkpoints in BRCA. These findings suggest that low ceruloplasmin expression correlates with a favorable prognosis and tumor immune cell infiltration in BRCA patients. Ceruloplasmin may serve as a therapeutic target and predict the efficacy of immunotherapy for BRCA.