Miracle-dz/UniFAR-FTUs huggingface dataset:
IFI16 Partners with KAP1 to Maintain Epstein-Barr Virus Latency

The interferon-gamma inducible protein 16 (IFI16) is a nuclear DNA sensor that mediates antiviral responses by activating the inflammasome, triggering an interferon response, and silencing lytic genes of herpesviruses. The last, which helps maintain latency of the oncoherpesvirus Epstein-Barr virus (EBV), is accomplished via H3K9me3 heterochromatinization through unknown mechanisms. ABSTRACT Herpesviruses establish latency to ensure permanent residence in their hosts. Upon entry into a cell, these viruses are rapidly silenced by the host, thereby limiting the destructive viral lytic phase while allowing the virus to hide from the immune system. Notably, although the establishment of latency by the oncogenic herpesvirus Epstein-Barr virus (EBV) requires the expression of viral latency genes, latency can be maintained with a negligible expression of viral genes. Indeed, in several herpesviruses, the host DNA sensor IFI16 facilitated latency via H3K9me3 heterochromatinization. This silencing mark is typically imposed by the constitutive heterochromatin machinery (HCM). The HCM, in an antiviral role, also silences the lytic phase of EBV and other herpes viruses. We investigated if IFI16 restricted EBV lytic activation by partnering with the HCM and found that IFI16 interacted with core components of the HCM, including the KRAB-associated protein 1 (KAP1) and the site-specific DNA binding KRAB-ZFP SZF1. This partnership silenced the EBV lytic switch protein ZEBRA, encoded by the BZLF1 gene, thereby favoring viral latency. Indeed, IFI16 contributed to H3K9 trimethylation at lytic genes of all kinetic classes. In defining topology, we found that IFI16 coenriched with KAP1 at the BZLF1 promoter, and while IFI16 and SZF1 were each adjacent to KAP1 in latent cells, IFI16 and SZF1 were not. Importantly, we also found that disruption of latency involved rapid downregulation of IFI16 transcription. These findings revealed a previously unknown partnership between IFI16 and the core HCM that supports EBV latency via antiviral heterochromatic silencing. IMPORTANCE The interferon-gamma inducible protein 16 (IFI16) is a nuclear DNA sensor that mediates antiviral responses by activating the inflammasome, triggering an interferon response, and silencing lytic genes of herpesviruses. The last, which helps maintain latency of the oncoherpesvirus Epstein-Barr virus (EBV), is accomplished via H3K9me3 heterochromatinization through unknown mechanisms. Here, we report that IFI16 physically partners with the core constitutive heterochromatin machinery to silence the key EBV lytic switch protein, thereby ensuring continued viral latency in B lymphocytes. We also find that disruption of latency involves rapid transcriptional downregulation of IFI16. These findings point to hitherto unknown physical and functional partnerships between a well-known antiviral mechanism and the core components of the constitutive heterochromatin machinery.
Comprehensive pan-cancer analysis reveals the prognostic value and immunological role of SPIB

It is well-established that SPIB is essential for the survival of mature B cells, playing a key role in diffuse large B-cell lymphoma, colorectal cancer, and lung cancer. However, no study has hitherto conducted a systematic pan-cancer analysis on SPIB. Herein, we analyzed the differential expression of SPIB in pan-cancer using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases and found that SPIB was significantly upregulated in most cancers. In addition, SPIB was positively or negatively associated with prognosis in different cancers. We found that SPIB was significantly associated with tumor immune infiltration and immune checkpoint genes in more than 35 tumors by TIMER database analysis. In addition, SPIB was negatively correlated with Tumor mutational burden (TMB) and Microsatellite instability (MSI) in most tumors. Finally, GO/KEGG enrichment analysis revealed the possible involvement of SPIB in NF-kappa B and B-cell receptor signaling pathways. In conclusion, our comprehensive pan-cancer analysis of SPIB reveals its important role in tumor immunity, suggesting it has huge prospects for clinical application in cancer therapy.
Pharmacotherapeutic treatment options for recurrent epithelial ovarian cancer

ABSTRACT Introduction Almost 80% of epithelial ovarian cancer present in advanced stage at diagnosis and despite excellent response to surgery and chemotherapy, more than 70% cancers recur. Subsequent therapies become decreasingly effective in controlling the disease, with each successful therapy being effective for a shorter duration. As a result, there is a need for novel therapeutic strategies to effectively treat recurrence. Areas covered In this extensive literature review of high-quality articles, we have focused on surveillance strategy to detect recurrence early, classification of recurrence based on timeline, role of surgery, chemotherapy, and targeted agents such as anti-angiogenetic drugs, PARP inhibitors, and immune checkpoint inhibitors in platinum-sensitive and platinum-resistant disease, respectively. Expert opinion Recurrent ovarian cancers (ROC) are represented by a heterogenous group of patient population in terms of platinum-free interval (PFI), histology, molecular characteristics and immune recognition. In today’s era of precision medicine, chemotherapy should be combined with appropriate targeted agent in a multipronged approach to prolong survival and provide better quality of life outcomes by minimizing side effects.
A pilot cost-benefit analysis of a children’s spectacle reimbursement scheme: Evidence for Including children’s spectacles in Mongolia’s Social Health Insurance

Background and aim Globally, 12.8 million children have vision impairment due to uncorrected refractive error (URE). In Mongolia, one in five children needs but do not have access to spectacles. This pilot cost-benefit analysis aims to estimate the net benefits of a children’s spectacles reimbursement scheme in Mongolia. Methods A willingness-to-pay (WTP) survey using the contingent valuation method was administered to rural and urban Mongolia respondents. The survey assessed WTP in additional annual taxes for any child with refractive error to be provided government-subsidised spectacles. Net benefits were then calculated based on mean WTP (i.e. benefit) and cost of spectacles. Results The survey recruited 50 respondents (mean age 40.2 ± 9.86 years; 78.0% women; 100% response rate) from rural and urban Mongolia. Mean WTP was US$24.00 ± 5.15 (95% CI US$22.55 to 25.35). The average cost of a pair of spectacles in Mongolia is US$15.00. Subtracting the average cost of spectacles from mean WTP yielded a mean positive net benefit of US$9.00. Conclusion A spectacle reimbursement scheme is potentially a cost-effective intervention to address childhood vision impairment due to URE in Mongolia. These preliminary findings support the proposal of the inclusion of children’s spectacles into existing Social Health Insurance. A much larger random sample could be employed in future research to increase the precision and generalisability of findings.
Cyclooxygenase-2 is a critical determinant of angiotensin II-induced vascular remodeling and stiffness in resistance arteries of ouabain-treated rats

Objective: To investigate the role of angiotensin II/AT1 receptor signaling and/or cyclooxygenase-2 (COX-2) activation on vascular remodeling and stiffening of the mesenteric resistance arteries (MRA) of ouabain-treated rats. Methods: Ouabain-treated (OUA, 30 μg kg/day for 5 weeks) and vehicle (VEH)-treated Wistar rats were co-treated with losartan (LOS, AT1R antagonist), nimesulide (NIM, COX-2 inhibitor) or hydralazine hydrochloride plus hydrochlorothiazide. MRA structure and mechanics were assessed with pressure myography and histology. Picrosirius red staining was used to determine the total collagen content. Western blotting was used to detect the expression of collagen I/III, MMP-2, Src, NFκB, Bax, Bcl-2 and COX-2. Reactive oxygen species (ROS) and plasma angiotensin II levels were measured by fluorescence and ELISA, respectively. Results: Blockade of AT1R or inhibition of COX-2 prevented ouabain-induced blood pressure elevation. Plasma angiotensin II level was higher in OUA than in VEH. LOS, but not hydralazine hydrochloride with hydrochlorothiazide, prevented inward hypotrophic remodeling, increased collagen deposition and stiffness, and oxidative stress in OUA MRA. LOS prevented the reduction in the total number of nuclei in the media layer and the Bcl-2 expression induced by OUA in MRA. The higher pSrc/Src ratio, NFκB/IκB ratio, and COX-2 expression in OUA MRA were also prevented by LOS. Likewise, COX-2 inhibition prevented vascular remodeling, mechanical changes, oxidative stress and inflammation in OUA MRA. Conclusion: The results suggest that, regardless of hemodynamic adjustments, the angiotensin II/AT1R/pSrc/ROS/NFκB/COX-2 pathway is involved in the development of MRA inward hypotrophic remodeling and stiffness in ouabain-treated rats.
EEG-Based Emotion Recognition Using Spatial-Temporal Graph Convolutional LSTM With Attention Mechanism

The dynamic uncertain relationship among each brain region is a necessary factor that limits EEG-based emotion recognition. It is a thought-provoking problem to availably employ time-varying spatial and temporal characteristics from multi-channel electroencephalogram (EEG) signals. Although deep learning has made remarkable achievements in emotion recognition, the biological topological information among brain regions does not fully exploit, which is vital for EEG-based emotion recognition. In response to this problem, we design a hybrid model called ST-GCLSTM, which comprises a spatial-graph convolutional network (SGCN) module and an attention-enhanced bi-directional Long Short-Term Memory (LSTM) module. The main advantage of ST-GCLSTM is that it can consider the biological topology information of each brain region to extract representative spatial-temporal features from multiple EEG channels. Specifically, we construct two layers SGCN by introducing adjacency matrices to adaptively learn the intrinsic connection among different EEG channels. Moreover, an attention-enhanced mechanism is placed into a bi-directional LSTM module to extract the crucial spatial-temporal features from sequential EEG data, and then these features serve as the input layer of the classifier to learn discriminative emotion-related features. Extensive experiments on the DEAP, SEED, and SEED-IV datasets demonstrate the effectiveness of the proposed ST-GCLSTM model, revealing that our model had an absolute performance improvement over state-of-the-art strategies.
α‐Glucosidase Inhibitory Cycloartanes from the Vietnamese Combretum quadrangulare

Leaves of Combretum quadrangulare Kurz showed potent α‐glucosidase inhibition. Two new cycloartane‐type triterpenes, combretic acids D and E were isolated from the bioactive fraction. The chemical structures were determined using NMR and MS methods. Combretic acid D represents for the first cycloartane having a dihydrofuran ring in the side chain. Combretic acids D and E showed significant α‐glucosidase inhibition, with IC50 values of 13.9 and 30.7 μM, respectively. Combretic acid D was determined to be a non‐competitive type in the kinetic study. The docking study in combination with dynamic simulations of this compound provided the molecular understanding of α‐glucosidase inhibition.
Economic Well-being and Associated Mediating Pathways to Improved Antiretroviral Therapy Adherence Among Adolescents Living With HIV: A Prospective Cohort Study in South Africa

Supplemental Digital Content is Available in the Text. Background: Adolescents living with HIV exhibit lower levels of adherence to antiretroviral therapy (ART) than other age groups. Poverty is a key barrier to ART adherence. This study aims at understanding how alleviating poverty through structural and internal pathways can help increase ART adherence among adolescents. Setting: Eastern Cape province, South Africa. Methods: One thousand forty-six adolescents living with HIV were recruited from 53 public health care facilities and interviewed at 3 data collection waves with a retention rate of 89% and a mortality rate of 3%. Data were collected by face-to-face, device-assisted interviews. Hybrid probit regressions and a structural equation path analysis were used to estimate the association between poverty reduction (increased access to basic necessities) and the pathways by which it could improve ART adherence. Results: Self-reported ART adherence ranged from an average of 66% (n = 615) at baseline to 75% (n = 700) in the last wave. Within-person and between-person improvements in economic well-being were associated with significant increases in adolescent ART adherence. On average, adolescents with access to 3 additional basic needs experienced a 4 percentage-point increase in the probability of ART adherence. Structural pathways to improved ART adherence included participants having enough money to travel to the clinic and sufficient food to eat when taking medication. Internal pathways included improved psychological well-being and reduced internalized HIV stigma. Conclusion: Poverty reduction programs such as HIV-sensitive social protection can address structural and psychological pathways to increase ART adherence among economically disadvantaged adolescents by incentivizing demand-side interventions and the provision of quality essential services.
Cardiovascular Effects of Home Dialysis Therapies: A Scientific Statement From the American Heart Association

Cardiovascular disease is the leading cause of morbidity and mortality in patients with end-stage kidney disease. Currently, thrice-weekly in-center hemodialysis for 3 to 5 hours per session is the most common therapy worldwide for patients with treated kidney failure. Outcomes with thrice-weekly in-center hemodialysis are poor. Emerging evidence supports the overarching hypothesis that a more physiological approach to administering dialysis therapy, including in the home through home hemodialysis or peritoneal dialysis, may lead to improvement in several cardiovascular risk factors and cardiovascular outcomes compared with thrice-weekly in-center hemodialysis. The Advancing American Kidney Health Initiative, which has a goal of increasing the use of home dialysis, is aligned with the American Heart Association’s 2024 mission to champion a full and healthy life and health equity. We conclude that incorporation of interdisciplinary care models to increase the use of home dialysis therapies in an equitable manner will contribute to the ultimate goal of improving outcomes for patients with kidney failure and cardiovascular disease.
Parent-mediated play‐based interventions to improve social communication and language skills of preschool autistic children: A systematic review and meta-analysis protocol

Early years interventions have shown to be effective in improving the social communication and language skills of autistic children. Therefore, various play-based interventions have been developed to support those developmental areas of autistic children. Although researchers have previously reported the overall effectiveness of different types of play-based interventions on the social communication and language skills of autistic children, no previous systematic reviews have yet evaluated the effectiveness of parent-mediated play-based interventions in preschool autistic children. The overarching aims of the study will be to (i) report the key characteristics and (ii) synthesise the results of studies evaluating parent-mediated play-based interventions targeting the social communication and language skills of preschool autistic children using experimental designs. A comprehensive search for and screening of the relevant studies published between 2000 and 2021 will be undertaken. To be included, studies will have to (i) use either a randomised control trial or quasi-experimental design, (ii) focus on preschool autistic children aged six years old or younger, (iii) deliver a play-based intervention in non-educational settings, and (iv) include at least one parent as the mediator of the intervention. Data extraction of all included studies will be undertaken using a specially devised template and they will also be assessed for risk of bias using an adapted form from the Cochrane Risk of Bias tool. The overall characteristics of the included studies will be reported and a narrative synthesis of the results of the included studies will be undertaken. A meta-analysis may be performed (if justified) to report the pooled effect size of the parent-mediated play-based interventions on the social communication and language skills of preschool autistic children. Trial registration: The current study protocol was pre-registered with the international prospective register of systematic reviews (PROSPERO: CRD42022302220).
A Novel Leucyl-tRNA Synthetase Inhibitor, MRX-6038, Expresses Anti-Mycobacterium abscessus Activity In Vitro and In Vivo

Therapeutic options for Mycobacterium abscessus infections are extremely limited, and new drugs are needed. The anti-M. abscessus activity of MRX-6038, ABSTRACT Therapeutic options for Mycobacterium abscessus infections are extremely limited, and new drugs are needed. The anti-M. abscessus activity of MRX-6038, a new leucyl-tRNA synthetase inhibitor, was evaluated in vitro and in vivo. Antimicrobial susceptibility testing was performed on 12 nontuberculosis mycobacteria (NTM) reference strains and 227 clinical NTM isolates. A minimum bactericidal concentration assay was conducted to distinguish the bactericidal versus bacteriostatic activity of MRX-6038. The synergy between MRX-6038 and 12 clinically important antibiotics was determined using a checkerboard assay. The activity of MRX-6038 against M. abscessus residing inside macrophages was also evaluated. Finally, the potency of MRX-6038 in vivo was determined in a neutropenic mouse model that mimicked a pulmonary M. abscessus infection. MRX-6038 exhibited high anti-M. abscessus activity against extracellular M. abscessus in culture, with a MIC50 of 0.063 mg/L and a MIC90 of 0.125 mg/L. Fifty percent of the activity was bactericidal, and fifty percent was bacteriostatic. A synergy between MRX-6038 and clarithromycin or azithromycin was found in 25% of strains. No antagonism was evident between MRX-6038 and 12 antibiotics commonly used to treat NTM infections. MRX-6038 also exhibited activity against intracellular NTM, which caused a significant reduction in the bacterial load in the lungs of M. abscessus-infected neutropenic mice. In conclusion, MRX-6038 was active against M. abscessus in vitro and in vivo, and it represents a potential candidate for incorporation into strategies by which M. abscessus infections are treated.
Biological Treatment of Fish Pond Waste Water by Coelastrum morum , a Green Microalgae

: The use of natural remediation methods to remove contaminants from waste water is becoming more popular. One of the aims of waste water treatment is to reduce nutrient such as nitrate and phosphate level in effluent to a protective level of the receiving water body. Microalgae especially green algae have been used for several decades for biotreatment of fish pond waste water, yet the there is limited or no report on use of Coelastrum morum CoC for bio-treatment of wastes water from fish pond. This study is aim at treatment of used/wastes water discharged from fish pond at Agric, Oke Osun area, Osogbo and assessing wastewater treatment plants performance by Coelastrum morum CoC. Freshly discharge fish pond waste water sample (FPWWS) was collected from Agric Oke osun in Osogbo, Osun State, Nigeria and analyzed for the physicochemical parameters such as pH, Total Dissolved Solid (TDS), Electrical conductivity, dissolved oxygen, total Alkalinity, Biological Oxygen Demand (BOD), Chemical Oxygen Demand (COD), ammonia, phosphate and Nitrate by standard methods. 190ml of the sterilized FPWWS was inoculated with 10ml of Coelastrum morum. The inoculated sample was incubated under 2ft cold fluorescence light for two weeks and determines the physicochemical parameters at 7 days interval. The results observed for raw, biological treated and removal efficiency showed: pH (7.66 and 8.85), TDS (283.33 and 95.33mg/l with 66.35%), Electrical conductivity (449.33 and 195.00µS cm -1 ), Dissolved oxygen(3.57 and 1.13 mg/l with 68.35%), Total Hardness (64.17 and 33.29 mg/l with 48.12%), BOD (274 and 55.36mg/l with 79.80%), COD (420 and 72mg/l with 82.86%), ammonia (31.4 and 4.41 mg/l with 85.96%, phosphate (10.27 and 2.04 with 80.14%) and nitrate (27.11 and 6.57 mg/l with 75.77%). Biological treatment with Coelastrum morum CoC S a potential removal of pollutant and other wastes from the fish pond waste water.
Improving Mean Variance Portfolio Construction With Machine Learning Stock Price Forecasts A di ↵ erent approach to forecasting the sample mean for mean variance optimization

A well known problem in constructing mean-variance portfolios is obtaining good forecasts for the sample mean of stock returns. This research will use the machine learning methods of Gu, Kelly and Xiu (2020) to forecast equity risk premia and use these forecasts instead of the ﬁrst sample moment to construct mean-variance portfolios. The machine learning methods implemented use dimension reduction, penalized objective functions, tree ensemble methods and deep learning methods. A large dataset with 94 stock level characteristics is used to train the models. It is shown that machine learning models are able to outperform the OLS benchmark, but are not able to outperform the more parsimonious OLS-3 model with 3 preselected variables when it comes to constructing mean-variance optimized portfolios. OLS-3 is the only model that is able to outperform using the sample mean for mean-variance portfolios. It is also shown that some machine learning methods are not particularly suited to forecast returns to use in the mean-variance framework, due to the fact that mean-variance optimization can lead to extreme weights and in combination with forecast errors might lead to poor performance of portfolios.
Examining the relative contribution of ventilation and deposition rates on indoor SO 2 concentrations

: - In this study the relative contribution of ventilation and deposition rates that control the levels of indoor SO 2 concentrations in three indoor residential microenvironments with different characteristics were examined. The air quality in the three microenvironments was experimentally studied by probing the indoor and outdoor SO 2 concentrations. The microenvironments were also theoretically examined with respect to the temporal evolution of indoor SO 2 concentrations by constructing a “typical day”, with the aid of the Multi Chamber Indoor Air Quality Model. The model-predicted indoor concentrations are in fairly good agreement with the measured values. From the data obtained during the model simulation, the relative contribution of the transport and deposition mechanisms to the variation of the indoor concentrations was examined. It was found that indoor SO 2 variation rates mainly depend upon the interplay between the transport from the outdoor environment and the deposition upon surfaces, while the transport from indoor to outdoor seems to be insignificant.