Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum-Derived Exosomal Proteins as Potential Candidate Biomarkers for Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the most common form of hepatic malignancies. The diagnosis of HCC remains challenging due to the low sensitivity and specificity of the diagnostic method. Exosomes, which are abundant in various proteins from parent cells, play pivotal roles in intercellular communication and have been confirmed as promising sources of disease biomarkers. Herein, we performed a simple but robust proteomic profiling on exosomes derived from 1 μL of serum using a data-independent acquisition (DIA) method for the first time, to screen potential biomarkers for the diagnosis of HCC. Ten pivotal differentially expressed proteins (DEPs) (von Willebrand factor (VWF), LGALS3BP, TGFB1, SERPINC1, HPX, HP, HBA1, FGA, FGG, and FGB) were screened as a potential candidate biomarker panel, which could completely discriminate patients with HCC from normal control (NC). Interestingly, Gene Expression Profiling Interactive Analysis (GEPIA) revealed that the expression levels of four genes increased and those of six genes decreased in HCC tissues compared with normal tissues, which were in concordance with protein expression levels. In conclusion, we screened 10 exosomal proteins holding promise for acting as a potential candidate biomarker panel for detection of HCC through a simple but robust proteomic profiling.
Extrusion-Based Bioprinting of Multilayered Nanocellulose Constructs for Cell Cultivation Using In Situ Freezing and Preprint CaCl2 Cross-Linking

Extrusion-based bioprinting with a preprint cross-linking agent and an in situ cooling stage provides a versatile method for the fabrication of 3D structures for cell culture. We added varying amounts of calcium chloride as a precross-linker into native nanofibrillated cellulose (NFC) hydrogel prior to 3D bioprinting to fabricate structurally stable multilayered constructs without the need for a separate cross-linking bath. To further enhance their stability, we bioprinted the multilayered structures onto an in situ temperature-controlled printing stage at 25, 0, and −10 °C. The extruded and subsequently freeze-dried volumetric constructs maintained their structures after being immersed into a cell culture medium. The ability to maintain the shape after immersion in cell media is an essential feature for the fabrication of stem cell-based artificial organs. We studied the viability and distribution of mouse embryonic fibroblast cells into the hydrogels using luminescence technique and confocal microscopy. Adding CaCl2 increased the stability of the multilayered nanocellulose structures, making them suitable for culturing cells inside the 3D hydrogel environment. Lower stage temperature considerably improved the structural stability of the 3D printed structures, however, had no effect on cell viability.
Low Rate of Return to Preinjury Tegner Activity Level Among Recreational Athletes: Results at 1 Year After Primary ACL Reconstruction

Background: There is limited information about the functional recovery and rate of return to preinjury levels of sports among recreational athletes after anterior cruciate ligament reconstruction (ACLR). Purpose: To investigate the recovery of quadriceps or hamstring strength, assess functional performance, and determine the rate of return to preinjury sports levels among recreational athletes at 1 year after ACLR. Study Design: Cohort study; Level of evidence, 3. Methods: A total of 91 recreational-level athletes who underwent anatomic single-bundle ACLR were enrolled. We evaluated the limb symmetry index (LSI) of the quadriceps and hamstring peak torque strength at 60°, in addition to hop test performance (single-leg, triple, crossover, and 6-m timed), patient-reported outcomes, and pre- versus postoperative Tegner activity levels. Outcomes were compared between younger (age <25 years) and older patients (age ≥25 years). Results: There were 48 patients in the younger group and 43 patients in the older group. At 1-year follow-up, the overall LSIs for quadriceps strength and hamstring strength were 77% and 86%, respectively, and the LSIs of the hop tests were 79% for single-leg, 81% for triple, 84% for crossover, and 85% for 6-m timed hop. Overall, only 24% patients returned to their preinjury Tegner level, and only 8% of patients met the criteria for return to pivoting, cutting, and jumping sports. At 1-year follow-up, the younger group showed significantly more quadriceps strength than the older group (85% vs 64%; P = .0001), better single, triple, crossover, and 6-m timed hop test results (85% vs 69%, P = .003; 84% vs 75%, P = .046; 91% vs. 74%, P < .001; and 91% vs 76%, P = .003, respectively), higher Lysholm score (87 vs 74; P < 0.001) and International Knee Document Committee score (82 vs 66; P < .001), and a higher rate of return to preinjury Tegner level (35% vs 12%; P = .009). Conclusion: Only 24% of patients returned to the preinjury Tegner level at 1 year after ACLR (35% younger group vs 12% older group; P = .009). This information might be helpful in setting realistic expectations for recreational athletes after surgery.
Subpopulations of exosomes purified via different exosomal markers carry different microRNA contents

The heterogeneity of exosome populations presents a great challenge to their study. The current study was designed to investigate the potential heterogeneity miRNA contents in circulating exosomes purified via different exosomal markers. In this study, exosomes from the serum of C57BL/6 mice after cecum ligation and perforation (CLP) or sham operation were isolated by precipitation using ExoQuick-TC and affinity purified with anti-Rab5b, anti-CD9, anti-CD31, and anti-CD44 antibodies using the Exo-Flow Exosome Capture kit to collect exosome subpopulations. RNA extracted from the exosomes isolated by ExoQuick-TC were profiled by next-generation sequencing (NGS). Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was also employed to determine the expression profiles of four representative exosomal miRNAs (mmu-miR-486-5p, mmu-miR-10a-5p, mmu-miR-143-3p, and mmu-miR-25-3p) selected from the NGS analysis. The results revealed that the expression patterns of these miRNAs in exosomes isolated by ExoQuick-TC as determined by RT-qPCR and NGS were similar, showing upregulation of mmu-miR-10a-5p and mmu-miR-143-3p but downregulation of mmu-miR-25-3p and mmu-miR-486-5p following CLP when compared to the levels in exosomes from sham control mice. However, their expression levels in the antibody-captured exosome subpopulations varied. The miRNAs in the exosomes captured by anti-Rab5b or anti-CD9 antibodies were more similar to those isolated by ExoQuick-TC than to those captured by anti-CD44 antibodies. However, there were no significant differences in these four miRNAs in CD31-captured exosomes. This study demonstrated that purification with different exosomal markers allows the collection of different exosome subpopulations with various miRNA contents. The results of this study demonstrate the heterogeneity of circulating exosomes and suggest the importance of stratifying exosome subpopulations when using circulating exosomes as biomarkers or investigating exosome function. In addition, this study also emphasized the necessity of using a consistent exosome marker across different samples as detecting biomarkers.
Conventional disease-modifying agents in rheumatoid arthritis – a review of their current use and role in treatment algorithms

Despite the development of targeted therapies, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) remain the cornerstone of treatment of rheumatoid arthritis (RA). A literature search was conducted on treatment recommendations and relevant papers regarding new insights on therapeutics in rheumatoid arthritis. Methotrexate is considered the “anchor drug” due to its high efficacy as monotherapy and in combination with other conventional and targeted agents. Leflunomide and sulfasalazine are sound alternatives, whereas (hydroxy)chloroquine is primarily used in combination with other csDMARDs. Their use is encouraged in all treatment phases – in combination with targeted agents, and with other csDMARDs. Combining different csDMARDs is especially attractive in lower income settings given the evidence proving (almost) equal efficacy and safety of the csDMARD combination approach compared to the combination of targeted agents with a csDMARD. The aim of this review is to provide a clinically oriented insight into the pharmacology of each csDMARD and their place in treatment algorithms.
Facilitators of the health advocacy role practice of the nurse in Ghana: A qualitative study

Identifying facilitators of health advocacy role practice of nurses is important in reducing health disparities and inequities in Ghana. The struggle to reducing these disparities and inequities needs a combination of bravery, courage, and professionalism. In many instances, many barriers hinder nurses from practicing their health advocacy role in Ghana. Facilitators that motivate nurses who would perform this health advocacy role have not been identified and adequately described in Ghana.
Retrospective analyzes of adverse events during biologic agents in children with juvenile idiopathic arthritis from a single center in Turkey

Objectives Juvenile idiopathic arthritis is the most common rheumatic disease in childhood. Biologic agents have changed the course of juvenile idiopathic arthritis. However, there are concerns regarding the occurrence of serious adverse events in patients receiving biologic agents. The aim of this study was to evaluate adverse events in children with juvenile idiopathic arthritis receiving biologic agents. Material and methods This retrospective study includes juvenile idiopathic arthritis patients receiving biologic agents. Demographic features and adverse events during biologic agents were collected from medical files. Adverse events that either resulted in death, were life-threatening, required inpatient hospitalization, or resulted in persistent or significant disability/incapacity were considered as serious adverse events. Results In total, 162 juvenile idiopathic arthritis patients (55.6% female) receiving biologic agents were enrolled: 101 (62.3%) patients treated with etanercept, 27 (16.7) with tocilizumab, 14 (8.6%) with adalimumab, 15 (9.2%) with anti-interleukin 1 agents (13 canakinumab, 2 anakinra), and 5 (3.1%) with infliximab. 75.9% of the patients received concomitantly disease-modifying anti-rheumatic drugs, and 20.4% received disease-modifying anti-rheumatic drugs plus corticosteroid. The mean age at initiation of the biologic agent was 10.5 ±4.3 years. The mean age at the study enrolment was 12.1 ±4.5 years. The mean follow-up duration was 19.7 ±2.1 months. The most frequent adverse event was upper respiratory tract infections (54.3%) followed by urinary tract infections (21%). Anaphylaxis occurred in 3 patients (1.9%): 2 with tocilizumab and one with infliximab. Macrophage activation syndrome occurred in 1 patient (0.6%) receiving tocilizumab. Lung tuberculosis developed in 2 patients (1.2%) receiving canakinumab. The frequency of serious adverse events in total was 6.7%. Conclusions While the most frequent adverse events during biologic agents was upper respiratory tract infections, the frequency of serious adverse events was 6.7%; therefore, juvenile idiopathic arthritis patients receiving biologic agents should be carefully evaluated for these adverse events in clinical practice.
CONTRIBUTION TO UNDERSTANDING THE MECHANISM OF TITANIUM ACTION IN PLANT

The biological effects of titanium (Ti) in the form of Ti(IV)-ascorbate on oats (Avena sativa L. cv. Zlaták) were studied in hydroponic experiments on defined nutrient solutions, determining the influence (i) of the chemical form of nitrogen (N) in nutrient solution on the Ti effects on plants (nitrate and an ammonium salt (acetate) were the only N species used) and (ii) of various Ti concentrations in nutrient solution while changing the magnesium (Mg) concentration on the Ti, Mg, iron (Fe), and potassium (K) content in tops and roots, top and root dry weights, chlorophyll a and b content, top height, and root length. It was found that (i) Ti was beneficial for plants grown on the nitrate-containing nutrient solutions as compared to the ammonium-containing nutrient solutions where Ti results in inhibitory effects on plant health status (decrease of top and root dry weights, chlorophyll a and b contents, top height, and root length), therefore, it was deducted that the increase of nitrate reductase activity was mainly responsible for the Ti beneficial effect on plants and (ii) Ti increased the Fe, Mg, and Ti content in plant tissues and this effect was independent of N form in the nutrient solution, chlorophyll a and b content or plant health status. It is suggested that the biological effects of Ti (the synthesis of the Ti chelating α -hydroxy carboxylic acids (citric and malic), and ascorbic acid, the increase of the Fe and Mg contents in plant tissues, the increased nitrate reductase activity, the increased chlorophyll a and b biosynthesis, and the effects on the other enzymatic activities) are the defense mechanisms of the plant against Ti replacing some essential elements from their binding sites (probably mainly from the phosphate-based ones). These defense mechanisms are, in the case of the usual Ti application doses, much stronger than adequate for the elimination of the Ti toxic effects (this ‘‘paradox’’ effect called hormesis has already been described for lead (Pb) and its effect on the hemoglobin content in blood of animals and humans).
Intention to accept pertussis vaccination among Chinese people older than age 5

ABSTRACT Background: The intention of Chinese people older than age 5 to accept the pertussis vaccination is unknown, which is important for the future design of an effective pertussis vaccination program in China. Method: We conducted a cross-sectional survey among people older than age 5 in China. A 24-item questionnaire was used to explore the determinants of intention to accept a pertussis vaccination, and for children and adolescents (≦15 years old), their guardian was required to help answer the questionnaire on their behalf. Univariate and multivariate logistic regression was used to analyze the influencing factors of intention. Results: A total of 3,041 individuals participated in our survey and 3025 completed the questionnaire, among which 1938 (64.07%) reported a positive intention to be vaccinated. A multiple logistic regression analysis revealed that the main positive factors for the intention to accept pertussis vaccination were younger age (Odd ratio [OR] 0.838, P < .001), higher educational attainment (OR 1.171, P = .002), no hospitalization because of the most recent cough (OR 2.468, P < .001), awareness about pertussis (OR 1.958, P < .001), and consideration of pertussis vaccination to be safe (OR 1.450, P = .026). Conclusion: There is a relatively high level of intention to receive the pertussis vaccine among people older than age 5 in China. Future pertussis vaccination strategies geared at them should consider focusing on middle-aged and older individuals and those with a low education as well as strengthen the promotion of disease characteristics, vaccine effectiveness, and safety.
On the Conductivity of Dispersions

Experiments on suspensions of glass beads in electrolytes indicate that Bruggemann's approximation represents the dependence of effective conductance on volume fraction very satisfactorily when the dispersed phase contains a broad range of particle sizes. Data on narrow size ranges fall in between values predicted by the Maxwell and Bruggemann equations. These findings are consistent with the physical assumptions implicit in both theoretical developments.
Levels of Processing Affect Perceptual Features in Visual Associative Memory

The levels of processing (LOP) account has inspired thousands of studies with verbal material. The few studies investigating levels of processing with nonverbal stimuli used images with nameable objects that, like meaningful words, lend themselves to semantic processing. Thus, nothing is known about the effects of different levels of processing on basic visual perceptual features, such as color. Across four experiments, we tested 187 participants to investigate whether the LOP framework also applies to basic perceptual features in visual associative memory. For Experiments 1 and 2, we developed a paradigm to investigate recognition memory for associations of basic visual features. Participants had to memorize object–color associations (Experiment 1) and fractal–color associations (Experiment 2, to suppress verbalization). In Experiments 3 and 4, we extended our account to cued recall. All experiments revealed reliable LOP effects for basic perceptual features in visual associative memory. Our findings demonstrate that the LOP account is more universal than the current literature suggests.
Synthesis, Spectroscopy and Electrochemistry of Cobalt(III) Schiff Base Complexes

Three Co(III) complexes of the type [Co(chel)(PBu3)]ClO4.H2O, (chel = 5-BrSalen, 5-MeOSalen and 4-MeOSalen), were synthesised and characterised by elemental analysis, IR, UV-Vis and 1H NMR spectroscopy. In their electronic spectra, the absorptions between 550 and 750 nm of these complexes are attributable to the lowest d–d transition. The axial ligands affect this transition through a σ-intraction with the dz2 orbital and the equatorial ligands affect it by π-interaction with populated d-orbitals. On the basis of an electronic structural model, in which the dz2 orbital is populated in forming cobalt(II), it is suggested that equatorial ligand substitution affects the reduction potentials less than axial ligand substitution.
Involvement of SUT1 and SUT2 Sugar Transporters in the Impairment of Sugar Transport and Changes in Phloem Exudate Contents in Phytoplasma-Infected Plants

Phytoplasmas inhabit phloem sieve elements and cause abnormal growth and altered sugar partitioning. However, how they interact with phloem functions is not clearly known. The phloem responses were investigated in tomatoes infected by “Candidatus Phytoplasma solani” at the beginning of the symptomatic stage, the first symptoms appearing in the newly emerged leaf at the stem apex. Antisense lines impaired in the phloem sucrose transporters SUT1 and SUT2 were included. In symptomatic sink leaves, leaf curling was associated with higher starch accumulation and the expression of defense genes. The analysis of leaf midribs of symptomatic leaves indicated that transcript levels for genes acting in the glycolysis and peroxisome metabolism differed from these in noninfected plants. The phytoplasma also multiplied in the three lower source leaves, even if it was not associated with the symptoms. In these leaves, the rate of phloem sucrose exudation was lower for infected plants. Metabolite profiling of phloem sap-enriched exudates revealed that glycolate and aspartate levels were affected by the infection. Their levels were also affected in the noninfected SUT1- and SUT2-antisense lines. The findings suggest the role of sugar transporters in the responses to infection and describe the consequences of impaired sugar transport on the primary metabolism.
A Luminescence-Based Human TRPV1 Assay System for Quantifying Pungency in Spicy Foods

The quantitation of pungency is difficult to achieve using sensory tests because of persistence, accumulation, and desensitization to the perception of pungency. Transient receptor vanilloid 1 (TRPV1), which is a chemosensory receptor, plays a pivotal role in the perception of many pungent compounds, suggesting that the activity of this receptor might be useful as an index for pungency evaluation. Although Ca2+-sensitive fluorescence dyes are commonly used for measuring human TRPV1 (hTRPV1) activity, their application is limited, as foods often contain fluorescent substances that interfere with the fluorescent signals. This study aims to design a new pungency evaluation system using hTRPV1. Instead of employing a fluorescent probe as the Ca2+ indicator, this assay system uses the luminescent protein aequorin. The luminescence assay successfully evaluated the hTRPV1 activity in foods without purification, even for those containing fluorescent substances. The hTRPV1 activity in food samples correlated strongly with the pungency intensity obtained by the human sensory test. This luminescence-based hTRPV1 assay system will be a powerful tool for objectively quantifying the pungency of spicy foods in both laboratory and industrial settings.
Immunotherapeutic Strategies for Neuroblastoma: Present, Past and Future

Neuroblastoma is the most common extracranial pediatric solid tumor with a heterogeneous clinical course, ranging from spontaneous regression to metastatic disease and death, irrespective of intensive chemotherapeutic regimen. On the basis of several parameters, children affected by neuroblastoma are stratified into low, intermediate and high risk. At present, more than 50% of high-risk patients with metastatic spread display an overall poor long-term outcome also complicated by devastating long-term morbidities. Thus, novel and more effective therapies are desperately needed to improve lifespan of high-risk patients. In this regard, adoptive cell therapy holds great promise and several clinical trials are ongoing, demonstrating safety and tolerability, with no toxicities. Starting from the immunological and clinical features of neuroblastoma, we here discuss the immunotherapeutic approaches currently adopted for high-risk patients and different innovative therapeutic strategies currently under investigation. The latter are based on the infusion of natural killer (NK) cells, as support of consolidation therapy in addition to standard treatments, or chimeric antigen receptor (CAR) T cells directed against neuroblastoma associated antigens (e.g., disialoganglioside GD2). Finally, future perspectives of adoptive cell therapies represented by γδ T lymphocyes and CAR NK cells are envisaged.
Temporal orienting in Parkinson’s disease

Temporal orienting of attention can affect multiple stages of processing to guide adaptive behaviour. We tested whether temporal expectation in different task contexts is compromised in individuals with Parkinson's disease (PD). In Experiment 1 two temporal‐orienting tasks were used: a speeded task emphasizing motor preparation and a non‐speeded task emphasizing perceptual discrimination using rapid serial visual presentation. In both tasks, auditory cues indicated the likelihood of a target appearing after a short or long interval. In the speeded‐response task, participants used the cues to anticipate an easily detectable target stimulus. In the non‐speeded perceptual‐discrimination task, participants used the cues to help discriminate a target letter embedded in a stream of letters. Relative to healthy participants, participants with PD did not show altered temporal orienting effects in the speeded‐response task. However, they were impaired in using temporal cues to improve perceptual discrimination. In Experiment 2, we tested whether the temporal‐orienting deficits in the perceptual‐discrimination task depended on the requirement to ignore temporally distracting stimuli. We replicated the impaired temporal orienting for perceptual discrimination in an independent group of individuals with PD, and showed the impairment was abolished when individuals were on their dopaminergic medication. In a task without any distracting letters, however, patients off or on medication benefited normally from temporal orienting cues. Our findings suggest that deficits in temporal orienting in individuals with PD interact with specific task demands, such as the requirement to select target from temporally competing distractors.