Miracle-dz/UniFAR-FTUs huggingface dataset:
Microvascularization and Expression of Fibroblast Growth Factor and Vascular Endothelial Growth Factor and Their Receptors in the Mare Oviduct

Simple Summary The oviduct provides the ideal conditions for fertilization and early embryonic development. Adequate vascularization is essential for proper oviduct physiological function. In this work on the mare oviduct, differences in the oviductal artery and arterioles and their ramifications in the infundibulum, ampulla and isthmus were examined. Locally, vascularization is modulated by the action of angiogenic factors, mediated by their specific receptors. In the present study, the isthmus presented the largest vascular area and the highest number of vascular structures in the follicular phase. We have also shown that the relative abundance of angiogenic transcripts and proteins, such as fibroblast growth factor 1 (FGF1) and 2 (FGF2) and vascular endothelial growth factor (VEGF), and their respective receptors (FGFR1, FGFR2, VEGFR2 = KDR), were present in all portions of the oviduct throughout the estrous cycle. There was an increase in the transcripts of angiogenic receptors FGF1 and FGFR1 in the ampulla and isthmus, and of FGF2 and KDR in the isthmus. This was also observed in the isthmus, where the relative abundance of proteins FGFR1 and KDR was the highest. This study shows that the equine oviduct presents differences in microvascular density in its portions. The angiogenic factors VEGF, FGF1, FGF2 and their respective receptors are expressed in all studied regions of the mare oviduct, in agreement with microvascular patterns. Abstract The oviduct presents the ideal conditions for fertilization and early embryonic development. In this study, (i) vascularization pattern; (ii) microvascular density; (iii) transcripts of angiogenic factors (FGF1, FGF2, VEGF) and their receptors—FGFR1, FGFR2, KDR, respectively, and (iv) the relative protein abundance of those receptors were assessed in cyclic mares’ oviducts. The oviductal artery, arterioles and their ramifications, viewed by means of vascular injection-corrosion, differed in the infundibulum, ampulla and isthmus. The isthmus, immunostained with CD31, presented the largest vascular area and the highest number of vascular structures in the follicular phase. Transcripts (qPCR) and relative protein abundance (Western blot) of angiogenic factors fibroblast growth factor 1 (FGF1) and 2 (FGF2) and vascular endothelial growth factor (VEGF), and their respective receptors (FGFR1, FGFR2, VEGFR2 = KDR), were present in all oviduct portions throughout the estrous cycle. Upregulation of the transcripts of angiogenic receptors FGF1 and FGFR1 in the ampulla and isthmus and of FGF2 and KDR in the isthmus were noted. Furthermore, in the isthmus, the relative protein abundance of FGFR1 and KDR was the highest. This study shows that the equine oviduct presents differences in microvascular density in its three portions. The angiogenic factors VEGF, FGF1, FGF2 and their respective receptors are expressed in all studied regions of the mare oviduct, in agreement with microvascular patterns.
GSK-3α Inhibition in Drug-Resistant CML Cells Promotes Susceptibility to NK Cell-Mediated Lysis in an NKG2D- and NKp30-Dependent Manner

Simple Summary Glycogen synthase kinase-3 (GSK-3) is a serine/threonine protein kinase that has gained considerable interest as a therapeutic target for cancer due to its key involvement in growth arrest and apoptosis of tumor cells. Moreover, GSK-3, especially GSK-3β, limits the activation of NK cells, key innate effectors in cancer immunosurveillance, triggered by diverse activating receptors. However, the role of GSK-3 in the regulation of activating ligands on target cells that confer susceptibility to NK cells remains unclear and is the aim of this study. Here, we provide evidence that GSK-3α primarily restrains the expression of ligands for activating receptors such as NKG2D, NKp30 but not DNAM-1, thereby reducing target susceptibility to NK cells. Thus, our results suggest a distinct role of GSK-3 isoforms in target cells vs NK cells for regulating NK cell reactivity and GSK-3α inhibition as a relevant strategy to enhance target susceptibility to NK cells. Abstract Natural killer (NK) cells are innate cytotoxic lymphocytes that provide early protection against cancer. NK cell cytotoxicity against cancer cells is triggered by multiple activating receptors that recognize specific ligands expressed on target cells. We previously demonstrated that glycogen synthase kinase (GSK)-3β, but not GSK-3α, is a negative regulator of NK cell functions via diverse activating receptors, including NKG2D and NKp30. However, the role of GSK-3 isoforms in the regulation of specific ligands on target cells is poorly understood, which remains a challenge limiting GSK-3 targeting for NK cell-based therapy. Here, we demonstrate that GSK-3α rather than GSK-3β is the primary isoform restraining the expression of NKG2D ligands, particularly ULBP2/5/6, on tumor cells, thereby regulating their susceptibility to NK cells. GSK-3α also regulated the expression of the NKp30 ligand B7-H6, but not the DNAM-1 ligands PVR or nectin-2. This regulation occurred independently of BCR-ABL1 mutation that confers tyrosine kinase inhibitor (TKI) resistance. Mechanistically, an increase in PI3K/Akt signaling in concert with c-Myc was required for ligand upregulation in response to GSK-3α inhibition. Importantly, GSK-3α inhibition improved cancer surveillance by human NK cells in vivo. Collectively, our results highlight the distinct role of GSK-3 isoforms in the regulation of NK cell reactivity against target cells and suggest that GSK-3α modulation could be used to enhance tumor cell susceptibility to NK cells in an NKG2D- and NKp30-dependent manner.
The Efficacy of a Long-Acting Injectable Selenium Preparation Administered to Pregnant Ewes and Lambs

Simple Summary Lack of selenium (Se) is a global problem that leads to increased exposure of animals to various diseases, as well as a reduction in productive and reproductive performance. Mineral supplementation can improve the immune system and could therefore be of assistance for lambs. We studied the effects of injectable supplementation with selenium. Supplementation of the Se lead to improved immune status, blood parameters, body weights, and average daily gain of lambs. Abstract The aim of this study was to evaluate the effects of a long-acting selenium (Se) preparation administered to sheep. The experiment was conducted on 30 dams and 36 lambs divided into three equal groups of 10 dams and 12 lambs each: Control—C, and two experimental groups—E (Se administered to pregnant ewes) and EI (Se administered directly to lambs after the colostral period). The Se preparation (Barium Selenate Injection, BVP Animal Care, 50 mg/mL) was administered by injection at 1 mL/50 kg (1 mg Se/kg) body weight (BW) to group E ewes in the third month of pregnancy (between 70 and 90 days) and to group EI lambs between 4 and 7 days of age. The following parameters were determined: Se concentration in the blood of ewes, milk yield, milk composition, Se concentration in milk; hematological, biochemical, and immunological parameters and Se concentration in the blood of lambs; growth rate and in vivo measurements of lean meat and fat content in lambs. Barium selenate significantly improved the Se status of dams and lambs, regardless of whether it was administered to pregnant ewes or directly to lambs in the first week of their life. The milk of ewes receiving the Se preparation was characterized by higher concentrations of fat and dry matter. The Se preparation induced significant changes in immunological parameters, thus enhancing defense mechanisms in lambs. The Se preparation exerted more stimulatory effects on humoral and cellular immune responses when administered directly to lambs after the colostral period (group EI) than to pregnant ewes (group E). The results of this study indicate that the long-acting Se preparation delivers benefits to sheep by boosting their immunity and, therefore, improving performance.
Effect of biannual azithromycin distribution on antibody responses to malaria, bacterial, and protozoan pathogens among children: A cluster-randomized, placebo-controlled trial in Niger

Background: The Macrolides Oraux pour Reeduire les Deeces avec un Oeil sur la Resistance (MORDOR) trial in Niger, Malawi, and Tanzania found that biannual mass distribution of azithromycin to children younger than 5 years led to a 13.5% reduction in all-cause mortality. Additional endpoints in the trial have attempted to elucidate the mechanisms for mortality reduction. In this pre-specified secondary analysis, we assessed the effect of azithromycin compared with placebo on IgG-based measures of infectious disease exposure with a multiplex bead assay that included antigens to malaria parasites (Plasmodium falciparum, P. vivax, P. malariae, P. ovale), bacterial pathogens (Campylobacter spp., enterotoxigenic Escherichia coli, Vibrio cholerae, Salmonella enterica, Streptococcus pyogenes) and protozoans (Cryptosporidium parvum, Giardia duodenales). Methods and Findings: Thirty communities in rural Niger were randomized 1:1 to biannual distributions of azithromycin or placebo among children ages 1-59 months. The analysis included 5,642 blood specimens collected from 3,814 children ages 1-59 months, measured at 6, 12, 24, and 36 months of follow-up in a repeated cross-sectional design. Campylobacter spp. seroprevalence averaged over all study visits was lower in azithromycin communities compared to placebo (91% vs 94%, difference = -3%, 95% CI: -5%, -1%; P=0.03), which corresponded to a 29% lower seroconversion rate (1.30 versus 1.84 seroconversions per year, hazard ratio = 0.71, 95% CI: 0.56, 0.89; P=0.004). Antibody-based measures of infection with P. falciparum and group A streptococcus were consistently lower in azithromycin communities, but were not statistically different from placebo, and there were no other differences across pathogens. Strengths of the study included masking of participants, investigators, and analysts, high treatment coverage, large sample size, and objective outcomes. Principal limitations included the timing of blood collection with respect to treatment (approximately 6 months later, which could have missed transient effects in the weeks immediately following treatment), and the durability of IgG response following clearance of infection. Both limitations would lead the trial to under-estimate effects on antibody-based measures of infection. Conclusions: The reduction in Campylobacter spp. despite these limitations suggests an effect on carriage, findings which align with an independent metagenomic analysis of rectal swabs collected in the same villages and with previously reported reductions in dysentery-associated mortality. Given significant sequelae of Campylobacter infection among preschool aged children, our results support at least one possible mechanism through which biannual mass distribution of azithromycin likely reduced mortality in this study population.
Knowledge of the epidemiology and transmission dynamics of SARS-CoV-2, the causative

16 SARS-CoV-2, the coronavirus causing COVID-19, has infected and killed several millions of 17 people worldwide. Since the first COVID-19 outbreak in December 2019, SARS-CoV-2 has 18 evolved with a few genetic variants associated with higher infectivity. We aimed to identify 19 polymorphic loci in SARS-CoV-2 that can be used to define and monitor the viral 20 epidemiology and population genetics in different geographical regions. Between December 21 2019 and September 2020, we sampled 5,959 SARS-CoV-2 genomes. More than 80% of the 22 genomes sampled in Africa, Asia, Europe, North America, Oceania and South America were 23 reportedly isolated from clinical infections in older patients, ≥ 20 years. We used the first 24 indexed genome (NC_045512.2) as a reference and constructed multilocus genotypes (MLGs) 25 for each sampled genome based on amino acids detected at 74 polymorphic loci located in 26 ORF1ab, ORF3a, ORF8, matrix (M), nucleocapsid (N) and spike (S) genes. Eight of the 74 27 loci were informative in estimating the risk of carrying infections with mutant alleles among 28 different age groups, gender and geographical regions. Four mutant alleles ORF1ab L4715, S 29 G614, and N K203 and R204 reached 90% prevalence globally, coinciding with peaks in 30 transmission but not COVID-19 severity, from March to August 2020. During this period, the 31 MLG genetic diversity was moderate in Asia, Oceania and North America; in contrast to 32 Africa, Europe and South America, where lower genetic diversity and absence of linkage 33 disequilibrium indicated clonal SARS-CoV-2 transmission. Despite close relatedness to Asian 34 MLGs, MLGs in the global population were genetically differentiated by geographic region, 35 suggesting structure in SARS-CoV-2 populations. Our findings demonstrate the utility of the 36 74 loci as a genetic tool to study and monitor SARS-CoV-2 transmission dynamics and 37 evolution, which can inform future control interventions. 38 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted April 26, 2021. ; https://doi.org/10.1101/2021.04. 25.21255897 doi: medRxiv preprint NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
Systematic review and meta-analysis of outcomes in patients with suspected pulmonary embolism.

Prompt evaluation and therapeutic intervention of suspected pulmonary embolism (PE) are of paramount importance for improvement in outcomes. We systematically reviewed outcomes in patients with suspected PE, including mortality, incidence of recurrent PE, major bleeding, intracranial hemorrhage, and postthrombotic sequelae. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for eligible studies, reference lists of relevant reviews, registered trials, and relevant conference proceedings. We included 22 studies with 15 865 patients. Among patients who were diagnosed with PE and discharged with anticoagulation, 3-month follow-up revealed that all-cause mortality was 5.69% (91/1599; 95% confidence interval [CI], 4.56-6.83), mortality from PE was 1.19% (19/1597; 95% CI, 0.66-1.72), recurrent venous thromboembolism (VTE) occurred in 1.38% (22/1597; 95% CI: 0.81-1.95), and major bleeding occurred in 0.90% (2/221%; 95% CI, 0-2.15). In patients with a low pretest probability (PTP) and negative D-dimer, 3-month follow-up revealed mortality from PE was 0% (0/808) and incidence of VTE was 0.37% (4/1094; 95% CI: 0.007-0.72). In patients with intermediate PTP and negative D-dimer, 3-month follow-up revealed that mortality from PE was 0% (0/2747) and incidence of VTE was 0.46% (14/3015; 95% CI: 0.22-0.71). In patients with high PTP and negative computed tomography (CT) scan, 3-month follow-up revealed mortality from PE was 0% (0/651) and incidence of VTE was 0.84% (11/1302; 95% CI: 0.35-1.34). We further summarize outcomes evaluated by various diagnostic tests and diagnostic pathways (ie, D-dimer followed by CT scan).
Mutation Rates and Selection on Synonymous Mutations in SARS-CoV-2

Abstract The COVID-19 pandemic has seen an unprecedented response from the sequencing community. Leveraging the sequence data from more than 140,000 SARS-CoV-2 genomes, we study mutation rates and selective pressures affecting the virus. Understanding the processes and effects of mutation and selection has profound implications for the study of viral evolution, for vaccine design, and for the tracking of viral spread. We highlight and address some common genome sequence analysis pitfalls that can lead to inaccurate inference of mutation rates and selection, such as ignoring skews in the genetic code, not accounting for recurrent mutations, and assuming evolutionary equilibrium. We find that two particular mutation rates, G →U and C →U, are similarly elevated and considerably higher than all other mutation rates, causing the majority of mutations in the SARS-CoV-2 genome, and are possibly the result of APOBEC and ROS activity. These mutations also tend to occur many times at the same genome positions along the global SARS-CoV-2 phylogeny (i.e., they are very homoplasic). We observe an effect of genomic context on mutation rates, but the effect of the context is overall limited. Although previous studies have suggested selection acting to decrease U content at synonymous sites, we bring forward evidence suggesting the opposite.
I’ve Got a Girl Crush: Parents’ Responses to Stories about Sexuality in Children’s Television

ABSTRACT People harbor unique biases about the relative influence of popular media on themselves compared to others. Broadly, they expect others to experience greater harm from exposure to negative depictions (e.g., violent content) and to derive fewer benefits from exposure to positive depictions (e.g., educational content). The current experiment examined if these biases impact how parents monitor their children’s television exposure, specifically programs about same-sex attraction. Parents (N = 702) watched a cartoon about a young girl who expresses romantic interest in another girl. Although biases emerged with regard to parents’ beliefs that this content would harm or benefit their own (vs. other) children, these biases did not influence their monitoring intentions. Instead, parents with conservative (vs. liberal) attitudes perceived the show as more threatening and less valuable for all children, which enhanced their desire to criticize, restrict, and censor that content.
Surgical Management and Recent Advances in Chemical Injury: A 5-year Review

ABSTRACT Purpose To review the surgical management options in ocular chemical burn, including newer advances. Methods Online literature search of published articles over last 5 years on surgical management of ocular chemical burn and newer advances were performed on December 30, 2020. Results Following literature search and screening using adequate filters, 67 review articles on surgical management of ocular chemical burns were retrieved. The review talks about the surgical management options starting from Debridement in acute stage to various visual rehabilitative procedures in the chronic stage. The review also highlights the evolving surgical advances in this field. Conclusion It is imperative to choose adequate surgical tool wherever applicable; current review discusses the role of each surgical option at different clinical stages in detail.
Phase inversion of a solid‐stabilized emulsion: Effect of particle concentration

Tiny water droplets in oil emulsions are commonly encountered in the petroleum industry. The high viscosity of the oil hampers the physical separation of the water droplets from the oil. [1] Phase inversion could be a potential workaround for this problem by making water, a much less viscous phase, the continuous medium. In the present work, we focused on triggering phase inversion of a solid-stabilized emulsion. We induced a catastrophic phase inversion by the continuous addition of a dispersed phase. The evolution of droplet morphology during the phase inversion process was observed and was measured in-line using a particle vision microscope, which proved to be a powerful tool for monitoring this rapid, unstable process. A linear relationship between the droplet size and the dispersed phase volume fraction before the phase inversion was observed, indicating that a higher dispersed phase volume fraction was needed for the phase inversion to occur with higher particle concentrations. The phase inversion conditions were applied in a regime where the particles were insufficient to fully cover the interface. Our findings indicated that the number of particles per surface area appears to be a crucial parameter in triggering phase inversion, regardless of the particle concentration. The phase inversion mechanism of our solid-stabilized emulsion can be explained by the relationship between the initial particle coverage of the interface and the coalescence rate of the system.
Antifungal agents and the kidney: pharmacokinetics, clinical nephrotoxicity, and interactions

ABSTRACT Introduction Invasive fungal infections continue to be important causes of morbidity and mortality in severely ill and immunocompromised patient populations. The past three decades have seen a considerable expansion in antifungal drug research, resulting in the clinical development of different classes of antifungal agents with different pharmacologic properties. Among drug-specific characteristics of antifungal agents, renal disposition and nephrotoxicity are important clinical considerations as many patients requiring antifungal therapy have compromised organ functions or are receiving other potentially nephrotoxic medications. Areas covered The present article reviews incidence, severity and mechanisms of nephrotoxicity associated with antifungal agents used for prevention and treatment of invasive fungal diseases by discussing distribution, metabolism, elimination and drug-related adverse events in the context of safety data from phase II and III clinical studies. Expert opinion Based on the available data amphotericin B deoxycholate has the highest relative potential for nephrotoxicity, followed by the lipid formulations of amphotericin B, and, to a much lesser extent and by indirect mechanisms, the antifungal triazoles.
Combined analysis of gut microbiota, diet and PNPLA3 polymorphism in biopsy‐proven non‐alcoholic fatty liver disease

Non‐alcoholic fatty liver disease (NAFLD) is a global health burden. Risk factors for disease severity include older age, increased body mass index (BMI), diabetes, genetic variants, dietary factors and gut microbiota alterations. However, the interdependence of these factors and their individual impact on disease severity remain unknown.
Role of indoleamine 2,3-dioxygenase in ischemia-reperfusion injury of renal tubular epithelial cells

The present study evaluated indoleamine 2,3-dioxygenase 1 (IDO) kinetics and how it affects cell survival during the two distinct phases of ischemia-reperfusion (I-R) injury. Primary renal proximal tubular epithelial cells (RPTECs) were cultured under anoxia or reoxygenation with or without the IDO inhibitor 1-DL-methyltryptophan, the aryl-hydrocarbon receptor (AhR) inhibitor CH223191 or the ferroptosis inhibitor α-tocopherol. Using cell imaging, colorimetric assays, PCR and western blotting, it was demonstrated that IDO was upregulated and induced apoptosis during anoxia. The related molecular pathway entails tryptophan degradation, general control non-derepressible-2 kinase (GCN2K) activation, increased level of phosphorylated eukaryotic translation initiation factor 2α, activating transcription factor (ATF)4, ATF3, C/EBP homologous protein, phosphorylated p53, p53, Bax, death receptor-5 and eventually activated cleaved caspase-3. Reoxygenation also upregulated IDO, which, in this case, induced ferroptosis. The related molecular pathway encompasses kynurenine production, AhR activation, cytochrome p450 enzymes increase, reactive oxygen species generation and eventually ferroptosis. In conclusion, in RPTECs, both anoxia and reoxygenation upregulated IDO, which in turn induced GCN2K-mediated apoptosis and AhR-mediated ferroptosis. Since both phases of I-R injury share IDO upregulation as a common point, its inhibition may prove a useful therapeutic strategy for preventing or attenuating I-R injury.