Miracle-dz/UniFAR-FTUs huggingface dataset:
Interferon Gamma Inhibits Varicella-Zoster Virus Replication in a Cell Line-Dependent Manner

Our results showed that IFN-γ significantly inhibited VZV replication in a cell line-dependent manner. IFN-γ inhibited VZV gene expression after the immediate early stage of infection and abrogated IE62-mediated transactivation. These results suggest that IFN-γ blocks VZV replication by inhibiting IE62 function in a cell line-dependent manner. Understanding the mechanisms by which IFN-γ plays a role in VZV gene programming may be important in determining the tissue restriction of VZV. ABSTRACT The major immediate early 62 (IE62) protein of varicella-zoster virus (VZV) is delivered to newly infected cell nuclei, where it initiates VZV replication by transactivating viral immediate early (IE), early (E), and late (L) genes. Interferon gamma (IFN-γ) is a potent cytokine produced following primary VZV infection. Furthermore, VZV reactivation correlates with a decline in IFN-γ-producing immune cells. Our results showed that treatment with 20 ng/ml of IFN-γ completely reduced intracellular VZV yield in A549 lung epithelial cells, MRC-5 lung fibroblasts, and ARPE-19 retinal epithelial cells at 4 days post-VZV infection. However, IFN-γ reduced virus yield only 2-fold in MeWo melanoma cells compared to that of untreated cells. IFN-β significantly inhibited VZV replication in both ARPE-19 and MeWo cells. In luciferase assays with VZV open reading frame 61 (ORF61) promoter reporter plasmid, IFN-γ abrogated the transactivation activity of IE62 by 95%, 97%, and 89% in A549, ARPE-19, and MRC-5 cells, respectively. However, IFN-γ abrogated IE62’s transactivation activity by 16% in MeWo cells, indicating that IFN-γ inhibits VZV replication as well as IE62-mediated transactivation in a cell line-dependent manner. The expression of VZV IE62 and ORF63 suppressed by IFN-γ was restored by JAK1 inhibitor treatment, indicating that the inhibition of VZV replication is mediated by JAK/STAT1 signaling. In the presence of IFN-γ, knockdown of interferon response factor 1 (IRF1) increased VZV replication. Ectopic expression of IRF1 reduced VZV yields 4,000-fold in MRC-5 and ARPE-19 cells but 3-fold in MeWo cells. These results suggest that IFN-γ blocks VZV replication by inhibiting IE62 function in a cell line-dependent manner. IMPORTANCE Our results showed that IFN-γ significantly inhibited VZV replication in a cell line-dependent manner. IFN-γ inhibited VZV gene expression after the immediate early stage of infection and abrogated IE62-mediated transactivation. These results suggest that IFN-γ blocks VZV replication by inhibiting IE62 function in a cell line-dependent manner. Understanding the mechanisms by which IFN-γ plays a role in VZV gene programming may be important in determining the tissue restriction of VZV.
Examining Influences of an Early Whole-School Immersive Field Experience on Preservice Teachers

ABSTRACT Although much is known about the benefits of student teaching in developing preservice teachers, less is known about preservice teachers’ earlier field experiences at the freshman and sophomore academic levels. This study examined a student-led educational organization that provided an early, whole-school immersive field experience through the creation of the third space. The Whole-School Immersive Program (WISP) that created this third space brought together university faculty, preservice teachers, P-12 educators, and their administrators. Through a qualitative case study approach that utilized semi-structured focus group and individual interviews, alumni surveys, and participants’ applications, this study examined the program’s influences on preservice teachers. The findings indicated that these preservice teachers gained a deeper understanding of the school context, (dis)confirmed their desire to become educators, and gained knowledge of personal inquiry from participating in this student-led educational organization.
In Vitro Activity of a Novel Antifungal Compound, MYC-053, against Clinically Significant Antifungal-Resistant Strains of Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis spp.

An urgent need exists for new antifungal compounds to treat fungal infections in immunocompromised patients. The aim of the current study was to investigate the potency of a novel antifungal compound, MYC-053, against the emerging yeast and yeast-like pathogens Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis species. ABSTRACT An urgent need exists for new antifungal compounds to treat fungal infections in immunocompromised patients. The aim of the current study was to investigate the potency of a novel antifungal compound, MYC-053, against the emerging yeast and yeast-like pathogens Candida glabrata, Candida auris, Cryptococcus neoformans, and Pneumocystis species. MYC-053 was equally effective against the susceptible control strains, clinical isolates, and resistant strains, with MICs of 0.125 to 4.0 μg/ml. Notably, unlike other antifungals such as azoles, polyenes, and echinocandins, MYC-053 was effective against Pneumocystis isolates, therefore being the only synthetic antifungal that may potentially be used against Pneumocystis spp. , Candida spp. , and Cryptococcus spp. MYC-053 was highly effective against preformed 48-h-old C. glabrata and C. neoformans biofilms, with minimal biofilm eradication concentrations equal to 1 to 4 times the MIC. Together, these data indicated that MYC-053 may be developed into a promising antifungal agent for the treatment and prevention of invasive fungal infections caused by yeasts and yeast-like fungi.
Bioengineered human acellular vessels recellularize and evolve into living blood vessels after human implantation

Bioengineered human acellular vessels repopulate with host cells and evolve into self-sustaining living blood vessels in hemodialysis patients. Vital vessels Vascular access is critically important for hemodialysis. An arteriovenous fistula generated from native blood vessels has long been thought to be optimal for long-term access; however, some people with kidney disease require vascular grafts. Kirkton et al. studied bioengineered human acellular vessels (HAVs) implanted as hemodialysis access vessels in subjects with end-stage renal disease. Sixteen tissue samples from HAVs were explanted from subjects participating in phase 2 clinical studies over the course of nearly 4 years. The authors characterized cellular repopulation of the implanted vessels over time, noting increases in CD90+ cells, lumen-lining CD31+ endothelium, and the presence of aligned alpha smooth muscle actin–expressing cells. This study provides valuable insight into human vascular remodeling. Traditional vascular grafts constructed from synthetic polymers or cadaveric human or animal tissues support the clinical need for readily available blood vessels, but often come with associated risks. Histopathological evaluation of these materials has shown adverse host cellular reactions and/or mechanical degradation due to insufficient or inappropriate matrix remodeling. We developed an investigational bioengineered human acellular vessel (HAV), which is currently being studied as a hemodialysis conduit in patients with end-stage renal disease. In rare cases, small samples of HAV were recovered during routine surgical interventions and used to examine the temporal and spatial pattern of the host cell response to the HAV after implantation, from 16 to 200 weeks. We observed a substantial influx of alpha smooth muscle actin (αSMA)–expressing cells into the HAV that progressively matured and circumferentially aligned in the HAV wall. These cells were supported by microvasculature initially formed by CD34+/CD31+ cells in the neoadventitia and later maintained by CD34−/CD31+ endothelial cells in the media and lumen of the HAV. Nestin+ progenitor cells differentiated into either αSMA+ or CD31+ cells and may contribute to early recellularization and self-repair of the HAV. A mesenchymal stem cell–like CD90+ progenitor cell population increased in number with duration of implantation. Our results suggest that host myogenic, endothelial, and progenitor cell repopulation of HAVs transforms these previously acellular vessels into functional multilayered living tissues that maintain blood transport and exhibit self-healing after cannulation injury, effectively rendering these vessels like the patient’s own blood vessel.
Perspectives of women experiencing Menorrhagia: A descriptive qualitative study.

OBJECTIVE To describe the perspectives and support needs of women experiencing menorrhagia in Singapore. BACKGROUND Women with menorrhagia lack awareness regarding the severity of menorrhagia. There is a dearth of literature understanding the support needs of women with menorrhagia. DESIGN A descriptive qualitative study design was adopted. The Consolidated crieteria for Reportig Qualitative Research (COREQ) was used to report the findings of this study. METHODS The study was conducted at a tertiary public hospital in Singapore from July 2017-October 2017. Semi-structured interviews were used to collect data from 16 women who were diagnosed with menorrhagia. The total number of interviews was concluded based on data saturation. The interviews were transcribed verbatim, and thematic analysis was used to analyse the interview transcripts. The COREQ was used to report the findings of this study. RESULTS Participants reported that they were unaware about menorrhagia and its severity. Various internal and external factors influenced the participants' awareness and understanding of menorrhagia. Although the participants received support to cope with menorrhagia, the support was deemed insufficient. The women shared that menorrhagia had affected their lives physically, emotionally, socially and financially. They used both external and internal coping mechanisms to cope with their conditions and looked for information through close contacts and the Internet. They longed to learn more about their conditions. CONCLUSION Multiethnic Singaporean women with menorrhagia lacked awareness about their conditions and the severity, which affected their lives negatively. There should be greater efforts to raise the public's awareness of menorrhagia so that women can seek medical help early and minimise its negative influence on their lives. RELEVANCE TO CLINICAL PRACTICE Healthcare providers need to pay greater attention to menorrhagia in order to provide more holistic care and support for those experiencing this condition. Healthcare professionals should understand their patients' experiences with menorrhagia and evaluate their current support resources in order to create a strong support system.
Cross-Level Mediation in School-Randomized Studies of Teacher Development: Experimental Design and Power

Abstract Professional development for teachers is regarded as one of the principal pathways through which we can understand and cultivate effective teaching and improve student outcomes. A critical component of studies that seek to improve teaching through professional development is the detailed assessment of the intermediate teacher development processes that scaffold program content through three key types of outcomes—teacher knowledge, instruction, and student learning. Cross-level and sequential mediation strategies that probe and connect these processes and outcomes emerge as an important design consideration in these studies. We derive formulas that track the power with which school-randomized designs can detect professional development effects as they operate through a sequence of teacher-level mediators to affect student outcomes (e.g., school-randomized professional development studies). The results suggest that the sample sizes typically seen in well-planned experiments targeting total effects (e.g., 30–100 schools) can produce comparably high or disparately low levels of power for mediation effects—the similarity depends heavily on context and concomitant parameter values. The results are implemented in the PowerUpR package and in the PowerUpR Shiny application.
Definition of an Emission Factor for VOC Emitted from Italian and European Refineries

Refineries are a major source of atmospheric emissions, which typically include CO, SO2, NOX, particulates, and volatile organic compounds (VOCs). There has been an increasing level of attention toward the emissions of VOCs related to their environmental impact as well as their potential to cause adverse effects on human health and the discomfort associated with their unpleasant odor. In general, an emission factor (EF) represents a model for a first order estimate of emissions, which correlates the quantity of pollutant released into the atmosphere with a so-called “activity index” related to the release of that pollutant. Based on the study of the scientific and technical literature regarding the Italian and European refining scenarios, an attempt was made to verify the existence of a correlation between the size of a refinery and the related total VOC emissions. Once this correlation was evaluated, it was possible to develop an emission factor for VOC emissions considering the plant capacity as the related activity index. After collecting and analyzing data concerning operative capacity and total VOCs emitted from 15 refineries in 2018, the resulting emission factor turned out to be equal to 188 ± 166 g per ton of crude oil processed. This value is in agreement with the range of 50–1000 g/ton reported in the European Best Available Techniques Reference Document for the Refining of Mineral Oil and Gas.
Perceived underemployment and couple relationships among African American parents: A dyadic approach.

OBJECTIVE In the United States, underemployment is more common among ethnic minorities, especially African Americans. At the same time, African American couples are at higher risks of marital difficulties than other racial/ethnic groups. This study used a dyadic approach to examine implications of underemployment, as perceived by African American mothers and fathers, for their own and their partners' couple relationship experiences, including relational love and coparenting satisfaction. The vulnerability-stress-adaptation framework of couple relationships guided tests of moderation by depressive symptoms, work hours, workplace discrimination, and expressive personality. METHOD The sample included 164 African American dual-earner parents (mean age = 40.53 and 43.11 for mothers and fathers) who were interviewed on two occasions across two years. Actor-partner interdependence modeling was used for the analyses. RESULTS Fathers' underemployment perceptions negatively predicted their own reports of love and coparenting satisfaction. Significant interactions indicated that the negative effects of fathers' perceived underemployment on their own relational love were stronger for fathers with more depressive symptoms, and, for less expressive mothers, on mothers' love and coparenting satisfaction. However, mothers' perceived underemployment was a positive predictor of mothers' love when they worked fewer hours and a negative predictor of mothers' coparenting satisfaction when they had high expressive personality. CONCLUSION Implications of underemployment experiences for couple relationships differ across gender and need to be considered in the context of partners' vulnerabilities, adaptive characteristics and other stressors. Findings advance understanding of underemployment and work-marriage linkages among African Americans, and highlight the utility of a dyadic approach. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Genesis of placental sequestration in malaria and possible targets for drugs for placental malaria

Malaria during pregnancy results in intrauterine growth restriction, fetal anemia, and infant mortality. Women are more susceptible to malaria during pregnancy due to malaria‐induced inflammation and the sequestration of infected red blood cells in the placenta, which bind to the chondroitin sulfate portion of syndecan‐1 on the syncytiotrophoblast and in the intervillous space. Syndecan‐1 is a dimeric proteoglycan with an extracellular ectodomain that is cleaved from the transmembrane domain (referred to as “shedding”) by matrix metalloproteinases (MMPs), likely the secreted MMP‐9. The ectodomain includes four binding sites for chondroitin sulfate, which are proximal to the transmembrane domain, and six distal binding sites primarily for heparan sulfate. This “shedding” of syndecan‐1 is inhibited by the presence of the heparan sulfate chains, which can be removed by heparanase. The intervillous space contains fibrin strands and syndecan‐1 ectodomains free of heparan sulfate. The following is proposed as the sequence of events that leads to and is primarily responsible for sequestration in the intervillous space of the placenta. Inflammation associated with malaria triggers increased heparanase activity that degrades the heparan sulfate on the membrane‐bound syndecan‐1. Inflammation also upregulates MMP‐9 and the removal of heparan sulfate gives MMP‐9 access to cleave syndecan‐1, thereby releasing dimeric syndecan‐1 ectodomains with at least four chondroitin sulfate chains attached. These multivalent ectodomains bind infected RBCs together leading to their aggregation and entrapment in intervillous fibrin. This mechanism suggests possible new targets for anti‐placental malaria drugs such as the inhibition of MMP‐9. Doxycycline is an antimalarial drug which inhibits MMP‐9.
Zebrafish Larvae as a Behavioral Model in Neuropharmacology

Zebrafish larvae show a clear and distinct pattern of swimming in response to light and dark conditions, following the development of a swim bladder at 4 days post fertilization. This swimming behavior is increasingly employed in the screening of neuroactive drugs. The recent emergence of high-throughput techniques for the automatic tracking of zebrafish larvae has further allowed an objective and efficient way of finding subtle behavioral changes that could go unnoticed during manual observations. This review highlights the use of zebrafish larvae as a high-throughput behavioral model for the screening of neuroactive compounds. We describe, in brief, the behavior repertoire of zebrafish larvae. Then, we focus on the utilization of light-dark locomotion test in identifying and screening of neuroactive compounds.
Retrieval Practice or Overall Donor and Recipient Risk: What Impacts on Outcomes After Donation After Circulatory Death Liver Transplantation in the United Kingdom?

Parameters of retrieval surgery are meticulously documented in the United Kingdom, where up to 40% of livers are donation after circulatory death (DCD) donations. This retrospective analysis focuses on outcomes after transplantation of DCD livers, retrieved by different UK centers between 2011 and 2016. Donor and recipient risk factors and the donor retrieval technique were assessed. A total of 236 DCD livers from 9 retrieval centers with a median UK DCD risk score of 5 (low risk) to 7 points (high risk) were compared. The majority used University of Wisconsin solution for aortic flush with a median hepatectomy time of 27‐44 minutes. The overall liver injury rate appeared relatively high (27.1%) with an observed tendency toward more retrieval injuries from centers performing a quicker hepatectomy. Among all included risk factors, the UK DCD risk score remained the best predictor for overall graft loss in the multivariate analysis (P < 0.001). In high‐risk and futile donor‐recipient combinations, the occurrence of liver retrieval injuries had negative impact on graft survival (P = 0.023). Expectedly, more ischemic cholangiopathies (P = 0.003) were found in livers transplanted with a higher cumulative donor‐recipient risk. Although more biliary complications with subsequent graft loss were found in high‐risk donor‐recipient combinations, the impact of the standardized national retrieval practice on outcomes after DCD liver transplantation was minimal.
Family planning, antenatal and post partum care in multiple sclerosis: a review and update

Multiple sclerosis is more prevalent in women of childbearing age than in any other group. As a result, the impact of multiple sclerosis and its treatment on fertility, planned and unplanned pregnancies, post partum care and breastfeeding presents unique challenges that need to be addressed in everyday clinical practice. Given the increasing number of disease‐modifying agents now available in Australia for the treatment of multiple sclerosis, there is a growing need for clinicians to provide their patients with appropriate counselling on family planning. Providing better evidence regarding the relative risks and benefits of continuing therapy before, during and after pregnancy is an important research priority. International pregnancy registries are essential in developing better evidence‐based practice guidelines, and neurologists should be encouraged to contribute to these when possible. The management of women with multiple sclerosis, especially when they are taking disease‐modifying agents, requires careful assessment of fertility and disease characteristics as well as a multidisciplinary approach to ensure positive outcomes in both mothers and their children.
Multi-professional IAPT CBT training: clinical competence and patient outcomes

Abstract Background: There is international interest in the training of psychological therapists to deliver evidence-based treatment for common mental health problems. The UK Improving Access to Psychological Therapies (IAPT) programme, one of the largest training initiatives, relies on competent therapists to successfully deliver cognitive behaviour therapy (CBT) and promote good patient outcome. Aims: To evaluate an IAPT CBT training course by assessing if trainees’ clinical skills improve during training and reach competency standards, and to report patient outcome for submitted training cases. To investigate a possible relationship between trainee competence and patient outcome. To explore professional differences during training. Method: CBT trainee (n = 252) competence was assessed via audio recordings of therapy sessions at the beginning, middle and end of training. Patient pre- to post-treatment outcomes were extracted from submitted training cases (n = 1927). Differences in professional background were examined across competence, academic final grade and tutorial support. Results: CBT trainees attained competence by the end of the course with 77% (anxiety recordings) and 72% (depression recordings) improving reliably. Training cases reported pre- to post-treatment effect sizes of 1.08–2.26 across disorders. CBT competence predicted a small variance in clinical outcome for depression cases. Differences in professional background emerged, with clinical psychologists demonstrating greater competence and higher academic grades. Trainees without a core professional background required more additional support to achieve competence. Conclusions: Part of a new CBT therapist workforce was successfully trained to deliver relatively brief treatment effectively. Trainees without a core profession can be successfully trained to competence, but may need additional support. This has implications for workforce training.