Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of p38γ in Cancer: From review to outlook

p38γ is a member of the p38 Mitogen Activated Protein Kinases (p38 MAPKs). It contains four subtypes in mammalian cells encoded by different genes including p38α (MAPK14), p38β (MAPK11), p38γ (MAPK12), and p38δ (MAPK13). Recent studies revealed that p38γ may exhibit a crucial role in tumorigenesis and cancer aggressiveness. Despite the large number of published literatures, further researches are demanded to clarify its role in cancer development, the tissue-specific function and associated novel treatment strategies. In this article, we provide the latest view on the connection between p38γ and malignant tumors, highlighting the function of p38γ. The clinical value of p38γ is also discussed, helping the translation into the remarkable therapeutic strategy in tumor diseases.
Magnetic Resonance Imaging Image Segmentation under Edge Detection Intelligent Algorithm in Diagnosis of Surgical Wrist Joint Injuries

Background Wrist joint injury refers to the injury of the wrist joint caused by excessive stretching of the ligaments and joint capsules around the joint caused by indirect violence. The tissue structure of the wrist joint is complex, and the clinical diagnosis effect is poor. Methods The purpose of this study was to improve the diagnostic accuracy of wrist joint injuries and provide evidence for imaging analysis and automatic diagnosis of lesions in patients with wrist joint injuries. The Canny algorithm was adopted to extract the edge features of the patient's magnetic resonance imaging (MRI) image, and the particle swarm optimization-support vector machine (PSO-SVM) algorithm was applied to segment the lesion. The image processing effect of the algorithm was evaluated by taking peak signal to noise ratio (PSNR), mean square error (MSE), figure of merit (FOM), and structural similarity (SSIM) as indicators. The accuracy, sensitivity, specificity, and Dice similarity coefficient of the algorithm were analyzed to evaluate the diagnostic accuracy in WJI. Results Compared with the Gradient Vector Flo (GVF) algorithm and the Elastic Automatic Region Growing (ERG) algorithm, the edge stability of the PSO-SVM algorithm was stable above 0.9. After the quality of images processed using different algorithms was analyzed, it was found that the PSNR of the PSO-SVM algorithm was 26.891 ± 5.331 dB, the MSE was 0.0014 ± 0.0003, the FOM was 0.8832 ± 0.0957, and the SSIM was 0.9032 ± 0.0807. The four indicators were all much better than those of the GVF algorithm and the EARG algorithm, showing statistically obvious differences (P < 0.05). Analysis on diagnostic accuracy of different algorithms for WJI suggested that the diagnostic accuracy of the PSO-SVM algorithm was 0.9413, the sensitivity was 0.9129, the specificity was 0.9088, and the Dice similarity coefficient was 0.8715. The four indicators all showed statistically great difference compared with those of the GVF algorithm and the EARG algorithm (P < 0.05). Conclusions The PSO-SVM algorithm showed excellent edge detection performance and higher accuracy in the diagnosis of WJI, which can assist clinicians in the clinical auxiliary diagnosis of WJI.
Synergistic Antibacterial Potential and Cell Surface Topology Study of Carbon Nanodots and Tetracycline Against E. coli

Increasing drugs and antibiotic resistance against pathogenic bacteria create the necessity to explore novel biocompatible antibacterial materials. This study investigated the antibacterial effect of carbon dot (C-dot) against E. coli and suggested an effective synergistic dose of tetracycline with C-dot, using mathematical modeling of antibacterial data. Colony count and growth curve studies clearly show an enhanced antibacterial activity against E. coli synergistically treated with C-dot and tetracycline, even at a concentration ten times lower than the minimum inhibitory concentration (MIC). The Richards model-fit of growth curve clearly showed an increase in doubling time, reduction in growth rate, and early stationary phase in the synergistic treatment with 42% reduction in the growth rate (μm) compared to the control. Morphological studies of E. coli synergistically treated with C-dot + tetracycline showed cell damage and deposition of C-dots on the bacterial cell membrane in scanning electron microscopy imaging. We further validated the topological changes, cell surface roughness, and significant changes in the height profile (ΔZ) with the control and treated E. coli cells viewed under an atomic force microscope. We confirmed that the effective antibacterial doses of C-dot and tetracycline were much lower than the MIC in a synergistic treatment.
High SARS-CoV-2 seroprevalence in persons experiencing homelessness and shelter workers from a day-shelter in São Paulo, Brazil

Brazil presents one of the highest COVID-19 death tolls in the world. The initial SARS-CoV-2 epicenter was São Paulo city. As of 2019, the homeless population of São Paulo city was estimated at 24,344 individuals, the largest national homeless population. The present study aimed to concomitantly assess the molecular and serological prevalence and associated risk factors of SARS-CoV-2 infection in a homeless population and related shelter workers from a day-shelter. Serum samples, nasopharyngeal and oropharyngeal swabs of persons who are homeless and shelter workers collected from August 25th to 27th, 2020 were tested for the presence of anti-SARS-CoV-2 IgM and IgG antibodies by ELISA and SARS-CoV-2 RNA by RT-qPCR, respectively. All swab samples tested negative by RT-qPCR. Seropositivity of IgM and IgG was 5/203 (2.5%) and 111/203 (54.7%) in persons who are homeless, and 5/87 (5.7%) and 41/87 (47.1%) in shelter workers, respectively, with no statistical differences between groups. The high seroprevalence found herein indicates early environmental and urban spreading of SARS-CoV-2, associated with sociodemographic and economic vulnerability.
Newborn infant skin gene expression: Remarkable differences versus adults

At birth, human infants are poised to survive in harsh, hostile conditions. An understanding of the state of newborn skin development and maturation is key to the maintenance of health, optimum response to injury, healing and disease. The observational study collected full-thickness newborn skin samples from 27 infants at surgery and compared them to skin samples from 43 adult sites protected from ultraviolet radiation exposure, as the standard for stable, mature skin. Transcriptomics profiling and gene set enrichment analysis were performed. Statistical analysis established over 25,000 differentially regulated probe sets, representing 10,647 distinct genes, in infant skin compared to adult skin. Gene set enrichment analysis showed a significant increase in 143 biological processes (adjusted p < 0.01) in infant skin, versus adult skin samples, including extracellular matrix (ECM) organization, cell adhesion, collagen fibril organization and fatty acid metabolic process. ECM organization and ECM structure organization were the biological processes in infant skin with the lowest adjusted P-value. Genes involving epidermal development, immune function, cell differentiation, and hair cycle were overexpressed in adults, representing 101 significantly enriched biological processes (adjusted p < 0.01). The processes with the highest significant difference were skin and epidermal development, e.g., keratinocyte differentiation, keratinization and cornification intermediate filament cytoskeleton organization and hair cycle. Enriched Gene Ontology (GO) biological processes also involved immune function, including antigen processing and presentation. When compared to ultraviolet radiation-protected adult skin, our results provide essential insight into infant skin and its ability to support the newborn’s preparedness to survive and flourish, despite the infant’s new environment laden with microbes, high oxygen tension and potential irritants. This fundamental knowledge is expected to guide strategies to protect and preserve the features of unperturbed, young skin.
Early Prediction of Sepsis Based on Machine Learning Algorithm

Sepsis is an organ failure disease caused by an infection resulting in extremely high mortality. Machine learning algorithms XGBoost and LightGBM are applied to construct two processing methods: mean processing method and feature generation method, aiming to predict early sepsis 6 hours in advance. The feature generation methods are constructed by combining different features, including statistical strength features, window features, and medical features. Miceforest multiple interpolation method is applied to tackle large missing data problems. Results show that the feature generation method outperforms the mean processing method. XGBoost and LightGBM algorithms are both excellent in prediction performance (AUC: 0.910∼0.979), among which LightGBM boasts a faster running speed and is stronger in generalization ability especially on multidimensional data, with AUC reaching 0.979 in the feature generation method. PTT, WBC, and platelets are the key risk factors to predict early sepsis.
Event-Triggered Practical Prescribed Time Output Feedback Neuroadaptive Tracking Control Under Saturated Actuation

This work focuses on the issue of event-triggered practical prescribed time tracking control for a type of uncertain nonlinear systems subject to actuator saturation and unmeasurable states as well as time-varying unknown control coefficients. First, a state observer with simple structure is constructed by means of neural network technology to estimate the unmeasurable system states under time-varying control coefficients. Then, with the help of one-to-one nonlinear mapping of the tracking error, an event-triggered output feedback control scheme is developed to steer the tracking error into a residual set of predefined accuracy within a preassigned settling time. Unlike existing related control methods, there is no need to involve finite-time state observer or fractional power feedback of system states, and thus, the control solution presented here is less complex and more acceptable. The key technique in control design lies in the establishment of an alternative first-order auxiliary system for dealing with the impact arisen from the input saturation. In our proposed approach, a new bounded function related to auxiliary variable and new dynamics of the auxiliary system are skillfully utilized such that the upper bound of the difference between actual input and designed input signal is not involved in implementation of the controller.
Seven-Weeks Gait-Retraining in Minimalist Footwear Has No Effect on Dynamic Stability Compared With Conventional Footwear

ABSTRACT Purpose: To investigate the effects of two different running footwear conditions (transition to minimalist footwear and conventional running footwear) on dynamic postural stability before and after 7 weeks of gait retraining program, and to evaluate the effect of fatigue on dynamic stability. Method: This randomized controlled clinical trial was carried out by 42 recreational male runners, who were randomly divided into two groups; Conventional Footwear Group (CFG) (n = 22) and Minimalist Footwear Group (MFG) (n = 20). Dynamic Postural Stability Index (DPSI), in a fatigued and non-fatigued state, were assessed before and after a gait retraining program. The gait retraining program consisted of three guided training sessions per week for 7 weeks. Training program was mainly focused on running technique and submaximal aerobic training with step-frequency exercises. Minimalist footwear was progressively introduced in the MFG. The CFG and MFG performed the same training exercises and a full body conditioning program. Fatigue was induced using a 30-minute running test at individual 85% of the maximal aerobic speed. Results: No differences in dynamic stability variables were found between MFG and CFG in any of the study condition. MFG and CFG showed better dynamic stability after the intervention program (CFG: 13.1% of change, DPSIpre = 0.3221 ± 0.04, DPSIpost = 0.2799 ± 0.04; p < .05; MFG: 6.7% of change, DPSIpre = 0.3117 ± 0.04, DPSIpost = 0.2907 ± 0.05). Finally, dynamic stability was significatively lower in both groups after fatigue protocol (p < .05). Conclusions: Following a 7-week gait retraining program, footwear did not affect the results, being the gait retraining program more relevant on improving dynamic stability.
The P2X7 purinergic receptor in intervertebral disc degeneration

Mechanisms involved in the development of intervertebral disc (IVD) degeneration are only partially known, thus making the implementation of effective therapies very difficult. In this study, we investigated P2X7 purinergic receptor (P2X7R), NLRP3 inflammasome, and interleukin (IL)‐1β expression in IVD specimens at different stages of disease progression, and during the in vitro dedifferentiation process of the primary cells derived thereof. We found that P2X7R, NLRP3, and IL‐1β expression was higher in the IVD samples at a more advanced stage of degeneration and in the expanded IVD cells in culture which partially recapitulated the in vivo degeneration process. In IVD cells, the P2X7R showed a striking nuclear localization, while NLRP3 was mainly cytoplasmic. Stimulation with the semiselective P2X7R agonist benzoyl ATP together with lipopolysaccharide treatment triggered P2X7R transfer to the cytoplasm and P2X7R/NLRP3 colocalization. Taken together, these findings support pathophysiological evidence that the degenerated disc is a highly inflamed microenvironment and highlight the P2X7R/NLRP3 axis as a suitable therapeutic target. The immunohistochemical analysis and the assessment of subcellular localization revealed a substantial expression of P2X7R also in normal disc tissue. This gives us the opportunity to contribute to the few studies performed in natively expressed human P2X7R so far, and to understand the possible physiological ATP‐mediated P2X7R homeostasis signaling. Therefore, collectively, our findings may offer a new perspective and pave the way for the exploration of a role of P2X7R‐mediated purinergic signaling in IVD metabolism that goes beyond its involvement in inflammation.
Label‐free characterization of an extracellular vesicle‐based therapeutic

Abstract Interest in mesenchymal stem cell derived extracellular vesicles (MSC‐EVs) as therapeutic agents has dramatically increased over the last decade. Current approaches to the characterization and quality control of EV‐based therapeutics include particle tracking techniques, Western blotting, and advanced cytometry, but standardized methods are lacking. In this study, we established and verified quartz crystal microbalance (QCM) as highly sensitive label‐free immunosensing technique for characterizing clinically approved umbilical cord MSC‐EVs enriched by tangential flow filtration and ultracentrifugation. Using QCM in conjunction with common characterization methods, we were able to specifically detect EVs via EV (CD9, CD63, CD81) and MSC (CD44, CD49e, CD73) markers. Furthermore, analysis of QCM dissipation versus frequency allowed us to quantitatively determine the ratio of marker‐specific EVs versus non‐vesicular particles (NVPs) – a parameter that cannot be obtained by any other technique so far. Additionally, we characterized the topography and elasticity of these EVs by atomic force microscopy (AFM), enabling us to distinguish between EVs and NVPs in our EV preparations. This measurement modality makes it possible to identify EV sub‐fractions, discriminate between EVs and NVPs, and to characterize EV surface proteins, all with minimal sample preparation and using label‐free measurement devices with low barriers of entry for labs looking to widen their spectrum of characterization techniques. Our combination of QCM with impedance measurement (QCM‐I) and AFM measurements provides a robust multi‐marker approach to the characterization of clinically approved EV therapeutics and opens the door to improved quality control.
eIF2A‐knockout mice reveal decreased life span and metabolic syndrome

Eukaryotic initiation factor 2A (eIF2A) is a 65 kDa protein that functions in minor initiation pathways, which affect the translation of only a subset of messenger ribonucleic acid (mRNAs), such as internal ribosome entry site (IRES)‐containing mRNAs and/or mRNAs harboring upstream near cognate/non‐AUG start codons. These non‐canonical initiation events are important for regulation of protein synthesis during cellular development and/or the integrated stress response. Selective eIF2A knockdown in cellular systems significantly inhibits translation of such mRNAs, which rely on alternative initiation mechanisms for their translation. However, there exists a gap in our understanding of how eIF2A functions in mammalian systems in vivo (on the organismal level) and ex vivo (in cells). Here, using an eIF2A‐knockout (KO) mouse model, we present evidence implicating eIF2A in the biology of aging, metabolic syndrome and central tolerance. We discovered that eIF2A‐KO mice have reduced life span and that eIF2A plays an important role in maintenance of lipid homeostasis, the control of glucose tolerance, insulin resistance and also reduces the abundance of B lymphocytes and dendritic cells in the thymic medulla of mice. We also show the eIF2A KO affects male and female mice differently, suggesting that eIF2A may affect sex‐specific pathways. Interestingly, our experiments involving pharmacological induction of endoplasmic reticulum (ER) stress with tunicamycin did not reveal any substantial difference between the response to ER stress in eIF2A‐KO and wild‐type mice. The identification of eIF2A function in the development of metabolic syndrome bears promise for the further identification of specific eIF2A targets responsible for these changes.
In-situ electrochemical polymerization of aniline on flexible conductive substrates for supercapacitors and non-enzymatic ascorbic acid sensors

Polyaniline, as a kind of conductive polymer with commercial application prospects, is still under researches in its synthesis and applications. In this work, polyaniline was fabricated on flexible substrates including carbon cloths and polyethylene naphthalate by in situ electropolymerization method. The synthesized flexible electrodes were characterized by scanning electron microscopy, High resolution transmission electron microscope, atomic force microscope, Fourier transform infrared, x-ray diffraction, and x-ray photoelectron spectroscopy. Owing to the conductivity and the reversible redox property, the polyaniline/carbon cloth electrodes show excellent properties such as decent supercapacitor performance and good detection capability toward ascorbic acid. As supercapacitors, the electrodes exhibit a specific capacitance as high as 776 F g–1 at a current density of 1 A g–1 and a long cycle life of 20 000 times in the three-electrode system. As ascorbic acid sensors, the flexible electrodes demonstrate stable response to ascorbic acid in the range of 1–3000 μM with an outstanding sensitivity (4228 μA mM–1 cm–2), low detection limit (1 μM), and a fast response time. This work holds promise for high-performance and low-cost flexible electrodes for both supercapacitors and non-enzymatic ascorbic acid sensors, and may inspire inventions of self-powered electrochemical sensor.
Characteristics of Long‐Term Femoral Neck Bone Loss in Postmenopausal Women: A 25‐Year Follow‐Up

The aim of this study was to monitor long‐term changes in bone mineral density (BMD) after menopause and factors affecting BMD. The study population consisted of a random sample of 3222 women from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study, of which 62.1% were postmenopausal at the beginning of the study. This group of women underwent dual‐energy X‐ray absorptiometry (DXA) measurements at the femoral neck every 5 years from baseline (in 1989) up to 25‐year follow‐up. They also responded to risk‐factor questionnaires at 5‐year intervals. During the 25‐year follow‐up, the baseline cohort decreased to 686 women. The women were divided into quartiles based on their baseline BMD. Self‐reported hormone replacement therapy (HRT) and corticosteroid use were divided into ever users and never users. Morbidity was assessed as the total number of self‐reported diseases and BMD‐affecting diseases. The mean 25‐year BMD change was found to be −10.1%, p < 0.001. Higher baseline BMD was associated with higher bone loss rate; the reduction in the highest quartile BMD was 11.1% and in the lowest quartile 7.4% (p = 0.0031). Lower baseline body mass index (BMI) and a greater increase in BMI were found to protect against postmenopausal bone loss (p < 0.001). The lowest bone loss quartile included 15.2% more HRT users than the highest bone loss quartile (p = 0.004). The number of diseases/bone‐affecting diseases, use of vitamin D/calcium supplementation, use of corticosteroids, smoking or alcohol use had no statistical significance for annual bone loss rate. This study presents hitherto the longest (25‐year) BMD follow‐up in postmenopausal women. The linear femoral neck bone loss of 10% was less than previously assumed. A 5‐year BMD change appeared to predict long‐term bone loss in postmenopausal women. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
The injury response to DNA damage in live tumor cells promotes antitumor immunity

Description Inducing a DNA damage response in tumor cells ex vivo creates an immunogenic live-cell adjuvant. Tailoring cancer vaccines to patients Immunotherapies boost the body’s immune system to detect and kill cancer cells. The immune response can be enhanced by molecules released from dying tumor cells, leading to proposals to use dead tumor cells as adjuvants in immunotherapeutics and cancer vaccines. However, Sriram et al. found that, in some cases, it is the remaining live tumor cells that are immunogenic. Treating cultured tumor cells with select DNA-damaging chemotherapies (and specific doses thereof) stimulated cytotoxic T cell activation when the live, not dead, cell fraction was injected back into the tumor in mice. Combining these cells with clinically used immune checkpoint inhibitors resulted in tumor regression and antitumor immune memory. The findings potentially identify a patient-specific approach to making immunotherapies more durably and broadly effective. Although immune checkpoint blockade (ICB) has strong clinical benefit for treating some tumor types, it fails in others, indicating a need for additional modalities to enhance the ICB effect. Here, we identified one such modality by using DNA damage to create a live, injured tumor cell adjuvant. Using an optimized ex vivo coculture system, we found that treating tumor cells with specific concentrations of etoposide, mitoxantrone, or doxorubicin markedly enhanced dendritic cell–mediated T cell activation. These immune-enhancing effects of DNA damage did not correlate with immunogenic cell death markers or with the extent of apoptosis or necroptosis; instead, these effects were mediated by live injured cells with activation of the DNA-PK, ATR, NF-κB, p38 MAPK, and RIPK1 signaling pathways. In mice, intratumoral injection of ex vivo etoposide–treated tumor cells in combination with systemic ICB (by anti-PD-1 and anti-CTLA4 antibodies) increased the number of intratumoral CD103+ dendritic cells and circulating tumor-antigen–specific CD8+ T cells, decreased tumor growth, and improved survival. These effects were absent in Batf3−/− mice and in mice in which the DNA-damaging drug was injected directly into the tumor, due to DNA damage in the immune cells. The combination treatment induced complete tumor regression in a subset of mice that were then able to reject tumor rechallenge, indicating that the injured cell adjuvant treatment induced durable antitumor immunological memory. These results provide a strategy for enhancing the efficacy of immune checkpoint inhibition in tumor types that do not respond to this treatment modality by itself.