Miracle-dz/UniFAR-FTUs huggingface dataset:
Network Analysis Based on Unique Spectral Features Enables an Efficient Selection of Genomically Diverse Operational Isolation Units

Culturomics-based bacterial diversity studies benefit from the implementation of MALDI-TOF MS to remove genomically redundant isolates from isolate collections. We previously introduced SPeDE, a novel tool designed to dereplicate spectral datasets at an infraspecific level into operational isolation units (OIUs) based on unique spectral features. However, biological and technical variation may result in methodology-induced differences in MALDI-TOF mass spectra and hence provoke the detection of genomically redundant OIUs. In the present study, we used three datasets to analyze to which extent hierarchical clustering and network analysis allowed to eliminate redundant OIUs obtained through biological and technical sample variation and to describe the diversity within a set of spectra obtained from 134 unknown soil isolates. Overall, network analysis based on unique spectral features in MALDI-TOF mass spectra enabled a superior selection of genomically diverse OIUs compared to hierarchical clustering analysis and provided a better understanding of the inter-OIU relationships.
Circulating Levels of Dephosphorylated-Uncarboxylated Matrix Gla Protein in Patients with Acute Coronary Syndrome

Vascular calcification contributes to the pathogenesis of coronary artery disease while matrix Gla protein (MGP) was recently identified as a potent inhibitor of vascular calcification. MGP fractions, such as dephosphorylated-uncarboxylated MGP (dp-ucMGP), lack post-translational modifications and are less efficient in vascular calcification inhibition. We sought to compare dp-ucMGP levels between patients with acute coronary syndrome (ACS), stratified by ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) status. Physical examination and clinical data, along with plasma dp-ucMGP levels, were obtained from 90 consecutive ACS patients. We observed that levels of dp-ucMGP were significantly higher in patients with NSTEMI compared to STEMI patients (1063.4 ± 518.6 vs. 742.7 ± 166.6 pmol/L, p < 0.001). NSTEMI status and positive family history of cardiovascular diseases were only independent predictors of the highest tertile of dp-ucMGP levels. Among those with NSTEMI, patients at a high risk of in-hospital mortality (adjudicated by GRACE score) had significantly higher levels of dp-ucMGP compared to non-high-risk patients (1417.8 ± 956.8 vs. 984.6 ± 335.0 pmol/L, p = 0.030). Altogether, our findings suggest that higher dp-ucMGP levels likely reflect higher calcification burden in ACS patients and might aid in the identification of NSTEMI patients at increased risk of in-hospital mortality. Furthermore, observed dp-ucMGP levels might reflect differences in atherosclerotic plaque pathobiology between patients with STEMI and NSTEMI.
In Situ Synthesis of Poly(butyl methacrylate) in Anodic Aluminum Oxide Nanoreactors by Radical Polymerization: A Comparative Kinetics Analysis by Differential Scanning Calorimetry and 1H-NMR

In this work, we explore the ability to generate well-defined poly(butyl methacrylate) (PBMA) nanostructures by “in situ” polymerization of butyl methacrylate monomer (BMA). PBMA nanostructures of high and low aspect ratios have been successfully obtained through the free radical polymerization (FRP) of a BMA monomer in anodic aluminum oxide (AAO) nanoreactors of suitable size. A polymerization kinetics process has been followed by differential scanning calorimetry (DSC) and proton Nuclear Magnetic Resonance spectroscopy (1H-NMR). The determination of the kinetics of polymerization through DSC is based on a quick and direct analysis of the exothermic polymerization process, whereas the analysis through 1H-NMR also allows the unambiguous chemical analysis of the resulting polymer. When compared to bulk polymerization, both techniques demonstrate confinement effects. Moreover, DSC and 1H-NMR analysis give the same kinetics results and show a gel-effect in all the cases. The number average molecular weight (Mn) of the PBMA obtained in AAO of 60–300 nm are between 30·103–175·103 g/mol. Even if the Mn value is lower with respect to that obtained in bulk polymerization, it is high enough to maintain the polymer properties. As determined by SEM morphological characterization, once extracted from the AAO nanoreactor, the polymer nanostructures show controlled homogeneous aspect/size all throughout the length of nanopillar over a surface area of few cm2. The Young’s modulus of low aspect ratio PBMA nanopillars determined by AFM gives a value of 3.1 ± 1.1 MPa. In this work, a 100% of PBMA polymer nanostructures are obtained from a BMA monomer in AAO templates through a quick double process: 30 min of monomer immersion at room temperature and 90 min of polymerization reaction at 60 °C. While the same nanostructures are obtained by polymer infiltration of PBMA at 200 °C in about 6 h, polymerization conditions are much softer than those corresponding to the polymer infiltration process. Furthermore, the 1H-NMR technique has been consolidated as a tool for studying the kinetics of the copolymerization reactions in confinement and the determination of monomer reactivity ratios.
Extracellular Protein Aggregates Colocalization and Neuronal Dystrophy in Comorbid Alzheimer’s and Creutzfeldt–Jakob Disease: A Micromorphological Pilot Study on 20 Brains

Alzheimer’s disease (AD) and sporadic Creutzfeldt–Jakob disease (sCJD) are both characterized by extracellular pathologically conformed aggregates of amyloid proteins—amyloid β-protein (Aβ) and prion protein (PrPSc), respectively. To investigate the potential morphological colocalization of Aβ and PrPSc aggregates, we examined the hippocampal regions (archicortex and neocortex) of 20 subjects with confirmed comorbid AD and sCJD using neurohistopathological analyses, immunohistochemical methods, and confocal fluorescent microscopy. Our data showed that extracellular Aβ and PrPSc aggregates tended to be, in most cases, located separately, and “compound” plaques were relatively rare. We observed PrPSc plaque-like structures in the periphery of the non-compact parts of Aβ plaques, as well as in tau protein-positive dystrophic structures. The AD ABC score according to the NIA-Alzheimer’s association guidelines, and prion protein subtype with codon 129 methionine–valine (M/V) polymorphisms in sCJD, while representing key characteristics of these diseases, did not correlate with the morphology of the Aβ/PrPSc co-aggregates. However, our data showed that PrPSc aggregation could dominate during co-aggregation with non-compact Aβ in the periphery of Aβ plaques.
Is There a Relationship between the Morphology of Connective Tissue and Reactivity during a Drop Jump? Influence of Sex and Athletic Performance Level

The influence of the morphologic characteristics of connective tissue, which plays an essential role during sports activities, on sporting tasks needs further research given the controversial findings reported in the literature. This study aimed at examining the relationship between lower limb connective tissue morphology and drop jump reactivity and determining the influence of sex and athletic performance level. A total of 30 men and 14 women, runners, executed 6 drop jumps (3 × 20 cm and 30 cm height respectively) and their thickness and cross-sectional area were recorded for Achilles and patellar tendons and plantar fascia. No significant results were found in the relationship between the morphology of the connective tissue and reactivity strength index for both sexes. Significant sex differences were found, while women showed greater values (p < 0.005) for Achilles tendon and plantar fascia; men showed greater values for reactivity strength index and drop jump performance (p < 0.001). The present study shows a limited relationship between connective tissue morphology and drop jump reactivity. Additionally, women showed greater normalized values for Achilles tendon and plantar fascia, and men showed greater reactivity strength index and jumping performance values. No relationships between athletic performance level and connective tissue were found.
Mothers’ Views About Lumbar Puncture for Their Children in a Maternity and Children’s Hospital in Najran, Saudi Arabia

Background Refusal rates for offered pediatric lumbar puncture (LP) are high in many parts of the world, potentially hindering diagnosis and treatment for thousands of children. There is relatively little research about why such rates are so high. Understanding the formation and development of mothers’ opinions about LP could help identify barriers to accessing this modality to improve diagnostic and treatment outcomes in children with neurological and systemic diseases. Methods We surveyed mothers of hospitalized children in the Maternity and Children’s Hospital in Najran in November and December 2018. We queried their familiarity with LP and their decision to accept or refuse LP when it was offered. The team recorded demographic data on survey respondents, as well as their stated reasons for their LP decisions, and used chi-square tests to evaluate the correlation between patient or parent characteristics and the decision to accept or refuse LP. Results A total of 202 mothers responded to the survey, with a mean age of 30.7 (± 6.9); nearly all women were stay-at-home mothers (93.1%). Most (61.4%) lived in urban settings. Four in 10 respondents (40.6%) were not familiar with LP. A sizable minority of 89 mothers (44.0%) refused LP for their children when offered, most commonly citing fear of paralysis (39.3%) as the reason for refusal. Those who accepted LP were more likely to do so following physician advice than for any other reason (p <0.001). Conclusion Lumbar puncture refusal rates may be even higher than previously reported, and there is a pressing need to educate women on the diagnostic and therapeutic benefits of LP for their children. Maternal education from physicians may help improve acceptance rates for the procedure.
Macrophage Migration Inhibitory Factor (MIF) Plasma Concentration in Critically Ill COVID-19 Patients: A Prospective Observational Study

Mortality in critically ill coronavirus disease 2019 (COVID-19) patients is high and pharmacological treatment strategies remain limited. Early-stage predictive biomarkers are needed to identify patients with a high risk of severe clinical courses and to stratify treatment strategies. Macrophage migration inhibitory factor (MIF) was previously described as a potential predictor for the outcome of critically ill patients and for acute respiratory distress syndrome (ARDS), a hallmark of severe COVID-19 disease. This prospective observational study evaluates the predictive potential of MIF for the clinical outcome after severe COVID-19 infection. Plasma MIF concentrations were measured in 36 mechanically ventilated COVID-19 patients over three days after intensive care unit (ICU) admission. Increased compared to decreased MIF was significantly associated with aggravated organ function and a significantly lower 28-day survival (sequential organ failure assessment (SOFA) score; 8.2 ± 4.5 to 14.3 ± 3, p = 0.009 vs. 8.9 ± 1.9 to 12 ± 2, p = 0.296; survival: 56% vs. 93%; p = 0.003). Arterial hypertension was the predominant comorbidity in 85% of patients with increasing MIF concentrations (vs. decreasing MIF: 39%; p = 0.015). Without reaching significance, more patients with decreasing MIF were able to improve their ARDS status (p = 0.142). The identified association between an early MIF response, aggravation of organ function and 28-day survival may open future perspectives for biomarker-based diagnostic approaches for ICU management of COVID-19 patients.
Functions of Forkhead Box O on Glucose Metabolism in Abalone Haliotis discus hannai and Its Responses to High Levels of Dietary Lipid

The forkhead box O (FoxO) subfamily is a member of the forkhead transcription factor family. It has regulation functions in glucose metabolism in mammals and fish. In the present study, a gene of the foxo homolog in abalone Haliotis discus hannai was cloned. A conservative forkhead (FH) domain and a transactivation (FoxO-TAD) domain were identified. Abalone foxo-specific siRNA (small interfering RNA) was injected to investigate the functions of foxo on glucose metabolism. Knockdown of foxo inhibited expression of phosphoenolpyruvate carboxykinase (pepck) and significantly increased expressions of hexokinase (hk) and pyruvate kinase (pk), but it failed to inhibit the relative mRNA level of glucose-6-phosphatase (g6pase). Then, a 100-day feeding trial was conducted to investigate the response of foxo and glucose metabolism in abalone fed with 1.57% (LFD, low-fat diet), 3.82% (MFD, middle-fat diet) and 6.72% (HFD, high-fat diet) of dietary lipid, respectively. The insulin-signaling pathway (AKT) was depressed and FoxO was activated by the HFD, but it did not inhibit glycolysis (hk) or improved gluconeogenesis significantly (pepck and g6pase). At the same time, impaired hepatopancreas glycogen storage raised hemolymph glucose levels. In conclusion, abalone foxo can be regulated by dietary lipid and can regulate gluconeogenesis or glycolysis in response to changes of dietary lipid levels, in which glycogen metabolism plays an important role.
Artificial Intelligence Clinicians Can Use Chest Computed Tomography Technology to Automatically Diagnose Coronavirus Disease 2019 (COVID-19) Pneumonia and Enhance Low-Quality Images

Purpose Nowadays, the number of patients with COVID-19 pneumonia worldwide is still increasing. The clinical diagnosis of COVID-19 pneumonia faces challenges, such as the difficulty to perform RT-PCR tests in real time, the lack of experienced radiologists, clinical low-quality images, and the similarity of imaging features of community-acquired pneumonia and COVID-19. Therefore, we proposed an artificial intelligence model GARCD that uses chest CT images to assist in the diagnosis of COVID-19 in real time. It can show better diagnostic performance even facing low-quality CT images. Methods We used 14,129 CT images from 104 patients. A total of 12,929 samples were used to build artificial intelligence models, and 1200 samples were used to test its performance. The image quality improvement module is based on the generative adversarial structure. It improves the quality of the input image under the joint drive of feature loss and content loss. The enhanced image is sent to the disease diagnosis model based on residual convolutional network. It automatically extracts the semantic features of the image and then infers the probability that the sample belongs to COVID-19. The ROC curve is used to evaluate the performance of the model. Results This model can effectively enhance the low-quality image and make the image that is difficult to be recognized become recognizable. The model proposed in this paper reached 97.8% AUC, 96.97% sensitivity and 91.16% specificity in an independent test set. ResNet, GADCD, CNN, and DenseNet achieved 80.9%, 97.3%, 70.7% and 85.7% AUC in the same test set, respectively. By comparing the performance with related works, it is proved that the model proposed has stronger clinical usability. Conclusion The method proposed can effectively assist doctors in real-time detection of suspected cases of COVID-19 pneumonia even faces unclear image. It can quickly isolate patients in a targeted manner, which is of positive significance for preventing the further spread of COVID-19 pneumonia.
What Do Lithuanian Hunters Think of African Swine Fever and Its Control—Perceptions

Simple Summary Effectiveness and successful implementation of control measures greatly depend on hunters’ willingness and motivation to carry out these measures. Therefore, assessing their opinions regarding the current system is paramount in order to achieve the best possible results. The present study provides insights of hunters’ attitudes and perceptions about measures to control African swine fever (ASF) in wild boar in Lithuania. This study highlights several measures that are not supported by hunters (i.e., restriction of hunting, selective female hunting, ban of supplementary feeding, involvement of additional forces in ASF control) and possible motivational options (i.e., reduction of work, financial incentives and improved feedback and relationships with government officials). Considering these findings when planning and altering control measures for ASF could improve their successful implementation in the field. Abstract After the introduction of African swine fever (ASF) into Lithuania in 2014, continuous spread of the disease resulted in infection of the wild boar populations in most parts of Lithuania. The virus has been moving closer to other Western European countries where pig density is high. An efficient surveillance system detecting ASF cases early in domestic and wild animals is necessary to manage this disease. To make surveillance appropriate and effective, it is critical to understand how key players perceive the implemented control measures. This study investigated the attitudes and beliefs of hunters in Lithuania regarding currently implemented or proposed measures for the control of ASF in the wild boar population. Study data were collected through questionnaires distributed via the internet and by hunting associations in Lithuania. In total, 621 fully completed questionnaires were received and analyzed. All measures interfering with extensive hunting, like ban of driven or individual hunting or ban of supplementary feeding were considered as unacceptable and as ineffective measures to control ASF in wild boar. However, selective hunting of female wild boar was generally considered as an unethical act and therefore rejected. Some measures that seem to have been successful in other countries, like involvement of additional forces, were rejected by Lithuanian hunters, thus implementation of these measures could be difficult. The study highlighted that there is a need for improving important relationships with other stakeholders, since many hunters expressed a lack of trust in governmental institutions and regarded cooperation with them as insufficient. Hunters emphasized that their motivation to support passive surveillance measures could be improved with financial compensation and reduction of workload. The present study provides insights into hunters’ perceptions, which may be used as a foundation for additional discussions with these important stakeholders and for adapting measures to improve their acceptance if appropriate.
Digital Immunophenotyping Predicts Disease Free and Overall Survival in Early Stage Melanoma Patients

Background: the prognostic significance of tumor infiltrating lymphocytes (TILs) in intermediate/thick primary cutaneous melanoma (PCM) remains controversial, partially because conventional evaluation is not reliable, due to inter-observer variability and diverse scoring methods. We aimed to assess the prognostic impact of the density and spatial distribution of immune cells in early stage intermediate/thick PCM. Materials and Methods: digital image acquisition and quantitative analysis of tissue immune biomarkers (CD3, CD4, CD8, CD68, PD-L1, CD163, FOX-P3, and PD-1) was carried out in a training cohort, which included patients with primary PCM ≥ 2 mm diagnosed, treated, and followed-up prospectively in three Italian centers. Results were validated in an independent Italian cohort. Results: in the training cohort, 100 Stage II–III melanoma patients were valuable. At multivariable analysis, a longer disease free survival (DFS) was statistically associated with higher levels of CD4+ intratumoral T-cells (aHR [100 cell/mm2 increase] 0.98, 95%CI 0.95–1.00, p = 0.041) and CD163+ inner peritumoral (aHR [high vs. low] 0.56, 95%CI 0.32–0.99, p = 0.047). A statistically significant longer DFS (aHR [high-high vs. low-low] 0.52, 95%CI 0.28–0.99, p = 0.047) and overall survival (OS) (aHR [high-high vs. low-low] 0.39, 95%CI 0.18–0.85, p = 0.018) was found in patients with a high density of both intratumoral CD8+ T-cells and CD68+ macrophages as compared to those with low density of both intratumoral CD8+ T-cells and CD68+ macrophages. Consistently, in the validation cohort, patients with high density of both intratumoral CD8+ and CD3+ T-cells were associated to a statistically better DFS (aHR[high-high vs. low-low] 0.24, 95%CI 0.10–0.56, p < 0.001) and those with high density of both intratumoral CD8+ and CD68+ were associated to a statistically longer OS (aHR[high-high vs. low-low] 0.28, 95%CI 0.09–0.86, p = 0.025). Conclusion: our findings suggest that a specific preexisting profile of T cells and macrophages distribution in melanomas may predict the risk of recurrence and death with potential implications for the stratification of stage II–III melanoma patients.
Cardiac Adiposity and Arrhythmias: The Role of Imaging

Increased cardiac fat depots are metabolically active tissues that have a pronounced pro-inflammatory nature. Increasing evidence supports a potential role of cardiac adiposity as a determinant of the substrate of atrial fibrillation and ventricular arrhythmias. The underlying mechanism appears to be multifactorial with local inflammation, fibrosis, adipocyte infiltration, electrical remodeling, autonomic nervous system modulation, oxidative stress and gene expression playing interrelating roles. Current imaging modalities, such as echocardiography, computed tomography and cardiac magnetic resonance, have provided valuable insight into the relationship between cardiac adiposity and arrhythmogenesis, in order to better understand the pathophysiology and improve risk prediction of the patients, over the presence of obesity and traditional risk factors. However, at present, given the insufficient data for the additive value of imaging biomarkers on commonly used risk algorithms, the use of different screening modalities currently is indicated for personalized risk stratification and prognostication in this setting.
Interleukin-18 and −10 may be associated with lymph node metastasis in breast cancer

Reports on the expression of interleukin (IL)-10 in breast cancer are rare. The present study investigated the correlation between IL-18 and −10 in breast cancer, and assessed their clinical significance. Breast cancer (n=104) and breast fibroadenoma (n=31) tissues that were surgically removed and pathologically confirmed at Jinan Central Hospital Affiliated to Shandong University (Jinan, China) between November 2016 and January 2019 were collected. The expression of IL-18 and −10 was observed via immunohistochemistry. Breast cancer tissues were positive for IL-18 expression, which was primarily located in the cell membrane and cytoplasm. A significant difference in IL-18 expression was observed between breast cancer and fibroadenoma tissues (75.0 vs. 19.4%; P<0.001). IL-10 was expressed in breast cancer tissues and primarily located in the cytoplasm. Breast cancer tissues showed a significantly higher level of IL-10 expression compared with breast fibroadenoma tissues (78.8 vs. 22.6%; P<0.001). The regions of positive IL-18 and −10 expression were consistent. Tissues with positive expression of IL-18 and/or −10 had a significantly higher rate of lymph node metastasis than those with negative expression (IL-18: 67.9 vs. 42.3%; P=0.035; and IL-10: 67.1 vs. 40.9%; P=0.047). In conclusion, IL-18 is highly expressed in breast cancer and correlates positively with IL-10. Both IL-18 and −10 may correlate positively with lymph node metastasis in breast cancer.