Miracle-dz/UniFAR-FTUs huggingface dataset:
Retinol Saturase Knock-Out Mice are Characterized by Impaired Clearance of Apoptotic Cells and Develop Mild Autoimmunity

Apoptosis and the proper clearance of apoptotic cells play a central role in maintaining tissue homeostasis. Previous work in our laboratory has shown that when a high number of cells enters apoptosis in a tissue, the macrophages that engulf them produce retinoids to enhance their own phagocytic capacity by upregulating several phagocytic genes. Our data indicated that these retinoids might be dihydroretinoids, which are products of the retinol saturase (RetSat) pathway. In the present study, the efferocytosis of RetSat-null mice was investigated. We show that among the retinoid-sensitive phagocytic genes, only transglutaminase 2 responded in macrophages and in differentiating monocytes to dihydroretinol. Administration of dihydroretinol did not affect the expression of the tested genes differently between differentiating wild type and RetSat-null monocytes, despite the fact that the expression of RetSat was induced. However, in the absence of RetSat, the expression of numerous differentiation-related genes was altered. Among these, impaired production of MFG-E8, a protein that bridges apoptotic cells to the αvβ3/β5 integrin receptors of macrophages, resulted in impaired efferocytosis, very likely causing the development of mild autoimmunity in aged female mice. Our data indicate that RetSat affects monocyte/macrophage differentiation independently of its capability to produce dihydroretinol at this stage.
The Importance of HLA Assessment in “Off-the-Shelf” Allogeneic Mesenchymal Stem Cells Based-Therapies

The need for more effective therapies of chronic and acute diseases has led to the attempts of developing more adequate and less invasive treatment methods. Regenerative medicine relies mainly on the therapeutic potential of stem cells. Mesenchymal stem cells (MSCs), due to their immunosuppressive properties and tissue repair abilities, seem to be an ideal tool for cell-based therapies. Taking into account all available sources of MSCs, perinatal tissues become an attractive source of allogeneic MSCs. The allogeneic MSCs provide “off-the-shelf” cellular therapy, however, their allogenicity may be viewed as a limitation for their use. Moreover, some evidence suggests that MSCs are not as immune-privileged as it was previously reported. Therefore, understanding their interactions with the recipient’s immune system is crucial for their successful clinical application. In this review, we discuss both autologous and allogeneic application of MSCs, focusing on current approaches to allogeneic MSCs therapies, with a particular interest in the role of human leukocyte antigens (HLA) and HLA-matching in allogeneic MSCs transplantation. Importantly, the evidence from the currently completed and ongoing clinical trials demonstrates that allogeneic MSCs transplantation is safe and seems to cause no major side-effects to the patient. These findings strongly support the case for MSCs efficacy in treatment of a variety of diseases and their use as an “off-the-shelf” medical product.
Resistive Switching and Charge Transport in Laser-Fabricated Graphene Oxide Memristors: A Time Series and Quantum Point Contact Modeling Approach

This work investigates the sources of resistive switching (RS) in recently reported laser-fabricated graphene oxide memristors by means of two numerical analysis tools linked to the Time Series Statistical Analysis and the use of the Quantum Point Contact Conduction model. The application of both numerical procedures points to the existence of a filament connecting the electrodes that may be interrupted at a precise point within the conductive path, resulting in resistive switching phenomena. These results support the existing model attributing the memristance of laser-fabricated graphene oxide memristors to the modification of a conductive path stoichiometry inside the graphene oxide.
Mathematical relationships of patterns of 35 rat haemodynamic parameters for conditions of hypertension resulting from decreased nitric oxide bioavailability

What is the central question of this study? Can the cross‐relationship between 35 rat arterial pulse waveform (APW) parameters be described by known mathematical functions and can mathematical parameters be obtained for conditions in a model of hypertension resulting from decreased NO bioavailability? What is the main finding and its importance? Mathematical functions and their parameters were obtained that approximate the cross‐relationships of 35 APW parameters to systolic blood pressure and to the augmentation index in conditions of decreased NO bioavailability. The results enable APW parameters to be assigned to decreased NO bioavailability, which may have predictive or diagnostic value.
Overcoming Ibrutinib Resistance in Chronic Lymphocytic Leukemia

Ibrutinib is the first Bruton’s tyrosine kinase (BTK) inhibitor, which showed significant clinical activity in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) patients regardless of cytogenetic risk factors. Recent results of phase III clinical trials in treatment-naïve CLL patients shift the importance of the agent to frontline therapy. Nevertheless, beside its clinical efficacy, ibrutinib possesses some off-target activity resulting in ibrutinib-characteristic adverse events including bleeding diathesis and arrhythmias. Furthermore, acquired and primary resistance to the drug have been described. As the use of ibrutinib in clinical practice increases, the problem of resistance is becoming apparent, and new methods of overcoming this clinical problem arise. In this review, we summarize the mechanisms of BTK inhibitors’ resistance and discuss the post-ibrutinib treatment options.
Prevalência e aspectos clínicos da infecçäo congênita por citomegalovirus

Objectives: The objectives of the present study were to determine the prevalence of congenital CMV infection, as well as to evaluate the importance of this agent as cause of congenital disease, and to describe the clinical manifestations in children attended at a General Hospital in Ribeirao Preto, SP, Brazil. Population and methods: A first group including 189 newborns and their mothers was evaluated for the prevalence of the congenital CMV infection. A second group including 130 newborns and 74 infants who presented clinical manifestations of congenital disease were also investigated to evaluate the importance of the CMV as a cause of this disease and to describe the clinical findings. Diagnosis of congenital CMV infection was established by detecting the virus using viral isolation in tissue culture, polymerase chain reaction DNA amplification in urine samples and detection of specific anti-CMV IgM and IgG by immunofluorescence indirect test.
Delmarva (DMV/1639) Infectious Bronchitis Virus (IBV) Variants Isolated in Eastern Canada Show Evidence of Recombination

Infectious bronchitis virus (IBV) infection in chickens can lead to an economically important disease, namely, infectious bronchitis (IB). New IBV variants are continuously emerging, which complicates vaccination-based IB control. In this study, five IBVs were isolated from clinical samples submitted to a diagnostic laboratory in Ontario, Canada, and subjected to detailed molecular characterization. Analysis of the spike (S)1 gene showed that these five IBVs were highly related to the Delmarva (DMV/1639) strain (~97.0% nucleotide sequence similarity) that was firstly isolated from an IB outbreak in the Delmarva peninsula, United States of America (USA), in 2011. However, the complete genomic sequence analysis showed a 93.5–93.7% similarity with the Connecticut (Conn) vaccine strain, suggesting that Conn-like viruses contributed to the evolution of the five Canadian IBV/DMV isolates. A SimPlot analysis of the complete genomic sequence showed evidence of recombination for at least three different IBV strains, including a Conn vaccine-like strain, a 4/91 vaccine-like strain, and one strain that is yet-unidentified. The unidentified strain may have contributed the genomic regions of the S, 3, and membrane (M) genes of the five Canadian IBV/DMV isolates. The study outcomes add to the existing knowledge about involvement of recombination in IBV evolution.
Bioactive Plant Compounds in Coffee Charcoal (Coffeae carbo) Extract Inhibit Cytokine Release from Activated Human THP-1 Macrophages

The herbal preparation coffee charcoal is produced by over-roasting and milling green dried Coffea arabica L. seeds, and has a long-standing tradition in the treatment of inflammatory and gastrointestinal disorders. Its therapeutic properties are commonly attributed to adsorptive and astringent effects. This insufficiently explains its mode of action, especially when used in the treatment of inflammatory diseases in lower dosages. Our investigations aimed to identify bioactive secondary plant metabolites affecting cytokine-signaling. Thus, a phytochemical analysis of coffee charcoal extract was conducted using HPLC and LC/MS. Trigonelline, neochlorogenic acid, chlorogenic acid, caffeine, cryptochlorogenic acid, feruloylquinic acid isomers, and a caffeoylquinolacton were identified in the extract. Subsequently, the effects of coffee charcoal extract, chlorogenic acid isomers, their metabolite caffeic acid, caffeine, and trigonelline on cytokine (TNF, IL-6, MCP-1) release from LPS-challenged human THP-1 macrophages were examined to evaluate anti-inflammatory activity. Coffee charcoal showed concentration-dependent mild-to-medium inhibitory effects. The chlorogenic acid isomers and caffeic acid inhibited the TNF release, with cryptochlorogenic acid exerting the most distinct effects, as well as decreasing the release of IL-6 and MCP-1. In addition, scanning electron microscopic images provided an impression of the particle constitution, indicating a larger particle size and less structured surface of coffee charcoal in comparison to activated charcoal. In conclusion, our findings underline that beyond adsorptive effects, coffee charcoal exhibits pharmacological properties, which derive from a spectrum of secondary plant metabolites and support the therapeutic use in inflammatory diseases. Chlorogenic acids, particularly cryptochlorogenic acid, appear as pivotal bioactive compounds.
Is there a difference in women’s experiences of care with medication vs. manual vacuum aspiration abortions? Determinants of person-centered care for abortion services

Little evidence exists on women’s experiences of care during abortion care, partly due to limitations in existing measures. Moreover, globally, the development and rapid growth in the availability of medication abortions (MA) has radically changed the options for safe abortions for women. It is therefore important to understand how women’s experiences of care may differ across medication and manual vacuum aspiration (MVA) abortions. This study uses a validated person-centered abortion care scale (categorized as low, medium, and high levels, with high levels representing the greatest level of person-centered care) to assess women’s experiences of care undergoing medication abortions vs. MVA. This paper reports on a cross-sectional study of 353 women undergoing abortions at one of six family planning clinics in Nairobi County, Kenya in 2018. Comparing abortion types, we found that the MVA sample was more likely to report “high” levels of person-centered abortion care compared to the MA sample (36.3% vs. 23.0%, p = 0.005). No differences were detected with respect to Respectful and Supportive Care; however, the MVA sample was significantly more likely to report “high” levels of Communication and Autonomy compared to the MA sample (23.6% vs. 11.2%, p<0.0001). In multivariable ordered logistic regression, we found that the MVA sample had a 92% greater likelihood of reporting higher person-centered abortion care scores compared to MA clients (aOR1.92, CI: 1.17–3.17). Being employed and reporting higher self-rated health were associated with higher person-centered abortion care scores, while reporting higher levels of stigma were associated with lower person-centered abortion care scores. Our findings suggest that more efforts are needed to improve the domain of Communication and Autonomy, particularly for MA clients.
Location, location, location: Close ties among older continuing care retirement community residents

This study examines two theoretical explanations for the existence of close ties among continuing care retirement community residents: the attractiveness theory, which suggests that residents who possess certain attributes are more likely to be perceived as appealing to others; and the homophily theory, which argues that individuals are more likely to have close ties with people who share similar attributes. As a variant of the homophily theory, we also examined whether sharing a physical location makes the existence of certain connections more likely. Data from four continuing care retirement communities were used. To test the attractiveness theory, correlations between the number of individuals who named a person as a significant contact (ego’s in-degree) and ego attributes were examined. To test the homophily theory, the median value of existing ties was compared against all possible social ties as though they were randomly formed. Finally, to further test the role of the institutional culture against various motivations that drive social ties—attractiveness and homophily—we used link prediction models with random forests. In support of the homophily theory, beyond the institutional culture, the only consistent predictor of the existence of close ties among residents was sharing a wing in the retirement community (geographic proximity). Therefore, we discuss the role of the physical location in the lives of older adults.
Ex Vivo Urinary Bactericidal Activity and Urinary Pharmacodynamics of Fosfomycin after Two Repeated Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Subjects

The ex vivo bactericidal activity and pharmacodynamics of fosfomycin in urine were evaluated in 18 healthy subjects. Subjects received 3 g every other day (QOD) for 3 doses and then every day (QD) for 7 doses or vice versa. Serial urine samples were collected before and up to 24 h after dosing on days 1 and 5. Eight bacterial strains with various genotypic and phenotypic susceptibilities to fosfomycin were used for all experiments (5 Escherichia coli, 2 Klebsiella pneumoniae, and 1 Proteus mirabilis). ABSTRACT The ex vivo bactericidal activity and pharmacodynamics of fosfomycin in urine were evaluated in 18 healthy subjects. Subjects received 3 g every other day (QOD) for 3 doses and then every day (QD) for 7 doses or vice versa. Serial urine samples were collected before and up to 24 h after dosing on days 1 and 5. Eight bacterial strains with various genotypic and phenotypic susceptibilities to fosfomycin were used for all experiments (5 Escherichia coli, 2 Klebsiella pneumoniae, and 1 Proteus mirabilis). MICs were performed via agar dilution. Urinary bactericidal titers (UBTs) were performed via modified Schlichter test using participant’s drug-free urine as the diluent. Urinary time-kill analyses were performed on pooled 24-h urine aliquots from days 1 and 5. All experiments were performed in triplicate with and without the addition of 25 mg/liter of glucose-6-phosphate (G6P). Mean 24-h urine concentrations of fosfomycin ranged from 324.7 to 434.6 mg/liter regardless of study day or dosing regimen. The urinary antibacterial activity of fosfomycin was also similar across study days and dosing regimens. UBT values did not correlate with MICs determined in the presence of G6P. Fosfomycin was reliably bactericidal in urine only against the 5 E. coli strains, regardless of genotype or MIC value. Together, these data do not support the use of oral fosfomycin tromethamine for pathogens other than E. coli or at a dosing frequency higher than QOD. Fosfomycin MICs determined in the presence of G6P may not accurately reflect the in vivo activity given the lack of G6P in human urine. (This study has been registered at ClinicalTrials.gov under identifier NCT02570074.)
Impact of Carbon Nanomaterials on the Antioxidant System of Tomato Seedlings

Tomato is one of the most economically important vegetables worldwide and is constantly threatened by various biotic and abiotic stress factors reducing the quality and quantity in the production of this crop. As an alternative to mitigate stress in plants, carbon nanomaterials (CNMs) have been used in agricultural areas. Therefore, the objective of the present work was to evaluate the antioxidant responses of tomato seedlings to the application via foliar and drench of carbon nanotubes (CNTs) and graphene (GP). Different doses (10, 50, 100, 250, 500, and 1000 mg L−1) and a control were evaluated. The results showed that the fresh and dry root weight increased with the application of CNMs. Regarding the antioxidant responses of tomato seedlings, the application of CNMs increased the content of phenols, flavonoids, ascorbic acid, glutathione, photosynthetic pigments, activity of the enzyme’s ascorbate peroxidase, glutathione peroxidase, catalase, and phenylalanine ammonia lyase as well as the content of proteins. Therefore, the use of carbon-based nanomaterials could be a good alternative to induce tolerance to different stress in tomato crop.
Effect of parity number on the dry matter intake of dairy cows during the first week after calving.

We investigated the effect of parity number on the dry matter intake (DMI) of cows during the first week after calving. Eighty-three cows were evaluated from 14 days before to 7 days after calving. DMI and milk yield were measured for 7 days after calving, and the calving score was measured. Blood samples were collected throughout the experiment. The average DMI during the first week after calving was reduced in the first-lactation heifers and high-parity number cows. A quadratic relationship between the parity number and the DMI was observed. The first-lactation heifers had lower prepartum serum total protein (TP) concentration and milk yield, higher prepartum serum nonesterified fatty acid (NEFA) concentration and calving score than the multiparous cows. The recovery rate of serum calcium (Ca) after calving was slow in the cows in the parity 6. The DMI was positively affected by the serum Ca concentration after calving, milk yield, and prepartum serum TP concentration and was negatively affected by the calving score and prepartum serum NEFA concentration. We conclude that the DMI immediately after calving tends to be lower in first-lactation heifers and high-parity number cows, but factors that reduce the DMI differ according to parity number.
The Role of Health Literacy in Explaining the Relation between Educational Level and Decision Making about Colorectal Cancer Screening

Little is known about why educational inequalities exist in informed decision making in colorectal cancer (CRC) screening. Insight into the role and impact of health literacy is essential for intervention development. This study investigates associations between health literacy and informed decision making in CRC screening and explores to what extent health literacy mediates the association between education and informed decision making in CRC screening. In total, 696 individuals eligible for CRC screening (55–75 years of age) were recruited from online panels and filled in an online questionnaire at T0 (n = 696), T1 (n = 407) and T2 (n = 327). A hypothetical mediation model was tested using structural equation modelling. Outcomes included CRC knowledge, CRC screening knowledge, attitude, injunctive norm, descriptive norm, risk perception, self-efficacy, decisional conflict and decisional certainty. Health literacy domains included Comprehension, Application, Numeracy and Communication. Comprehension, Application and Numeracy, were found to mediate the association between education and knowledge about CRC and CRC screening, injunctive norm, descriptive norm, decisional conflict and decisional certainty. In light of these findings, targeting multiple health literacy domains in decision-support interventions is essential for facilitating informed decision making in CRC screening.
Growth Performance, Body Measurements, Carcass and Some Internal Organs Characteristics of Pekin Ducks

Simple Summary The protection and conservation of native poultry breeds, including ducks, is important for biological, cultural, emotional and scientific reasons. The objective of this study was to compare three lines of Pekin ducks for growth performance, body measurements, carcass and digestive system characteristics. The results showed significant differences between the tested lines of ducks in body weight and body measurements, as well as a small number of significant differences in carcass and digestive system characteristics. This may suggest that the tested lines of ducks are different and distinct, mainly in terms of growth and body measurements. Abstract Native breeds of ducks have been the subject of many studies in the past, yet the relevant knowledge is still incomplete and needs to be further expanded. The objective of this study was to provide information about differences in growth performance, dressing percentage, carcass composition and digestive morphometry among three lines of Pekin ducks from conservation flocks raised in Poland. The study used 180 sexed Pekin ducks—30 males and 30 females of line P33 (ducks of Polish origin), 30 males and 30 females of line P8 (ducks of Danish origin), and 30 males and 30 females of line P9 (ducks of French origin). Throughout the study (49 d), ducks were confined indoors in six pens. Birds were fed complete commercial diets ad libitum and had unrestricted access to water. The compared lines of ducks differed significantly in body weight from 1 to 49 d of age except of ducks of both sexes at 14 d. At 49 d of age, significant differences were observed between the tested ducks in all the body measurements. Duck genotype had a significant effect on preslaughter body weight, carcass weight and breast muscle, neck and remainders contents, caeca length, liver weight and gizzard percentage. The results show that the tested ducks were significantly different and unique, mainly in terms of the body biometric characteristics.
Availability of splicing factors in the nucleoplasm can regulate the release of mRNA from the gene after transcription

Gene expression dynamics can be measured in single living cells. Using a detectable transcriptionally active gene in living cells, we previously found that an mRNA undergoing several splicing events was retained at this gene after transcription until completion of mRNA processing. To determine the reason for this delay in release and whether mRNA retention on the gene might depend on splicing factor availability, we modulated the levels of splicing factors in the nucleus. Increasing the abundance of the diffusing fraction of splicing factors by their overexpression or by Clk1 kinase overexpression to disassemble nuclear speckles, led to a reduction in splicing factor residence times on the active gene, and the retained mRNA was rapidly released from the gene. Other treatments such as overexpression of a mutant inactive Clk1, the downregulation of MALAT1 lncRNA or of the Son protein, or the overexpression of the splicing factor import factor TNPO3, did not affect the dynamics of mRNA release from the gene. We found that the faster release of the mRNA from the gene mediated by increased availability of splicing factors, was dependent on the RS domain of the splicing factors and its phosphorylation state. We propose that the relative abundancies of splicing factors in the nucleoplasm can affect their availability for the splicing events taking place, and regulate the kinetics of mRNA release from the gene after processing.