Miracle-dz/UniFAR-FTUs huggingface dataset:
Xenoantigen-Dependent Complement-Mediated Neutralization of Lymphocytic Choriomeningitis Virus Glycoprotein-Pseudotyped Vesicular Stomatitis Virus in Human Serum

Systemic application aims to deliver oncolytic viruses to tumors as well as to metastatic lesions. However, we found that xenoantigens incorporated onto the viral surface from nonhuman production cell lines are recognized by natural antibodies in human serum and that the virus is thereby inactivated by complement lysis. Hence, to maximize the effective dose, careful selection of cell lines for virus production is crucial. ABSTRACT Neutralization by antibodies and complement limits the effective dose and thus the therapeutic efficacy of oncolytic viruses after systemic application. We and others previously showed that pseudotyping of oncolytic rhabdoviruses such as maraba virus and vesicular stomatitis virus (VSV) with the lymphocytic choriomeningitis virus glycoprotein (LCMV-GP) results in only a weak induction of neutralizing antibodies. Moreover, LCMV-GP-pseudotyped VSV (VSV-GP) was significantly more stable in normal human serum (NHS) than VSV. Here, we demonstrate that depending on the cell line used for virus production, VSV-GP showed different complement sensitivities in nonimmune NHS. The NHS-mediated titer reduction of VSV-GP was dependent on activation of the classical complement pathway, mainly by natural IgM antibodies against xenoantigens such as galactose-α-(1,3)-galactose (α-Gal) or N-glycolylneuraminic acid (Neu5Gc) expressed on nonhuman production cell lines. VSV-GP produced on human cell lines was stable in NHS. However, VSV-GP generated in transduced human cells expressing α-Gal became sensitive to NHS. Furthermore, GP-specific antibodies induced complement-mediated neutralization of VSV-GP independently of the producer cell line, suggesting that complement regulatory proteins potentially acquired by the virus during the budding process are not sufficient to rescue the virus from antibody-dependent complement-mediated lysis. Thus, our study points to the importance of a careful selection of cell lines for viral vector production for clinical use. IMPORTANCE Systemic application aims to deliver oncolytic viruses to tumors as well as to metastatic lesions. However, we found that xenoantigens incorporated onto the viral surface from nonhuman production cell lines are recognized by natural antibodies in human serum and that the virus is thereby inactivated by complement lysis. Hence, to maximize the effective dose, careful selection of cell lines for virus production is crucial.
Interview Administration of PROMIS Depression and Anxiety Short Forms

Background: Health literacy reflects a person's reading and numeracy abilities applied to understanding health-related information. These skills may influence how patients report symptoms, leading to underestimates or overestimates of symptom severity. No prior studies have examined health literacy measurement bias. Objective: The purpose of the current study was to determine whether PROMIS (Patient-Reported Outcomes Measurement Information System) anxiety and depression short forms, administered by interview, capture symptoms equally across health literacy groups. We examined the psychometric properties of PROMIS anxiety and depression short forms using differential item functioning (DIF) analysis by level of health literacy. Methods: The sample analyzed included 888 adults, age 55 to 74 years, in Chicago, IL. Health literacy was measured using the Test of Functional Health Literacy in Adults. PROMIS short forms assessed anxiety and depression. Key Results: DIF was present in 3 of 8 depression items, and 3 of 7 anxiety items. All items flagged for DIF had lower item-slopes for people with limited health literacy. Conclusions: Items with DIF were less strongly related to anxiety and depression, and thus less precise. Overall, impact of DIF on PROMIS scores was negligible, likely mitigated by interview administration. Although overall test impact of health literacy was minimal, DIF analyses flagged items that were potentially too complex for people with limited health literacy. Design and validation of patient-reported surveys should incorporate respondents with a range of health literacy and methods to identify and reduce measurement bias. [HLRP: Health Literacy Research and Practice. 2019;3(3):e196–e204. ] Plain Language Summary: This study suggests that people with limited health literacy may respond differently to questions about depression and anxiety than people with adequate health literacy. Therefore, it is important to be aware of differences in literacy ability when creating and using questionnaires.
The Role of Platelet-Rich Fibrin in Increasing the Gingival Thickness and Modifying the Thin Gingival Biotype: A Comparative Clinical Split Mouth Study

Introduction: Thin gingival biotype (GBT) is of clinical relevance in orthodontic and periodontic treatment, so thick biotype is a requisite for good periodontal health. The aim of this study was to evaluate the effectiveness of platelet-rich fibrin (PRF) with tunnel flap compared to connective tissue graft (CTG) with tunnel flap in increasing gingival thickness (GTH). Material and Methods: Twenty orthodontic patients presenting thin GBTs were included in this study. Treatment sites were divided into test group (PRF) and control group (CTG). Clinical parameters as GTH, GBT, and width of keratinized gingiva (WKG) were assessed at baseline and 6 months post-surgically. Statistical analysis was performed using independent T-test for intergroup comparison. Statistical significance was set at 0.05. Results: The mean GTH at 6 months was 1.57 mm for test group and 1.64 mm for control group. The gain of WKG was 1.57 and 2.08 mm in test and control sites, respectively. Conclusion: Within the limits of this study, using PRF in modifying thin GBT is a successful treatment option and could serve as an alternative to connective tissue grafts (CTGs).
Addressing Patient Specificity in the Engineering of Tumor Models

Cancer treatment is challenged by the heterogeneous nature of cancer, where prognosis depends on tumor type and disease stage, as well as previous treatments. Optimal patient stratification is critical for the development and validation of effective treatments, yet pre-clinical model systems are lacking in the delivery of effective individualized platforms that reflect distinct patient-specific clinical situations. Advances in cancer cell biology, biofabrication, and microengineering technologies have led to the development of more complex in vitro three-dimensional (3D) models to act as drug testing platforms and to elucidate novel cancer mechanisms. Mostly, these strategies have enabled researchers to account for the tumor microenvironment context including tumor-stroma interactions, a key factor of heterogeneity that affects both progression and therapeutic resistance. This is aided by state-of-the-art biomaterials and tissue engineering technologies, coupled with reproducible and high-throughput platforms that enable modeling of relevant physical and chemical factors. Yet, the translation of these models and technologies has been impaired by neglecting to incorporate patient-derived cells or tissues, and largely focusing on immortalized cell lines instead, contributing to drug failure rates. While this is a necessary step to establish and validate new models, a paradigm shift is needed to enable the systematic inclusion of patient-derived materials in the design and use of such models. In this review, we first present an overview of the components responsible for heterogeneity in different tumor microenvironments. Next, we introduce the state-of-the-art of current in vitro 3D cancer models employing patient-derived materials in traditional scaffold-free approaches, followed by novel bioengineered scaffold-based approaches, and further supported by dynamic systems such as bioreactors, microfluidics, and tumor-on-a-chip devices. We critically discuss the challenges and clinical prospects of models that have succeeded in providing clinical relevance and impact, and present emerging concepts of novel cancer model systems that are addressing patient specificity, the next frontier to be tackled by the field.
Numerical Investigations of Hepatic Spheroids Metabolic Reactions in a Perfusion Bioreactor

Miniaturized culture systems of hepatic cells are emerging as a strong tool facilitating studies related to liver diseases and drug discovery. However, the experimental optimization of various parameters involved in the operation of these systems is time-consuming and expensive. Hence, developing numerical tools predicting the function of such systems can significantly reduce the associated cost. In this paper, a perfusion-based three dimensional (3D) bioreactor comprising encapsulated human liver hepatocellular carcinoma (HepG2) spheroids are analyzed. The flow and mass transfer equations for oxygen as well as different metabolites such as albumin, glucose, glutamine, ammonia, and urea were solved in three different domains, i.e., free flow, hydrogel, and spheroid porous media sections. Since the spheroids were encapsulated inside the hydrogel, shear stress imposed on them were found to be less than tolerable thresholds. The predicted cumulative albumin concentration over the 7 days of culture period showed a good agreement with the experimental data. Based on the critical role of oxygen supply to the hepatocytes, a parametric study was performed and the effect of various parameters was investigated. Results illustrated that convection mechanism was the dominant transport mechanism in the main-stream section contrary to the intra spheroids parts where the diffusion was the prevailing transport mechanism. In the hydrogel parts, the rate of diffusion and convection mechanisms were almost identical. As expected, higher perfusion rate would provide high oxygen level for the cells and, smaller spheroids with a diameter of 100 μm were at the low risk of hypoxic conditions due to short diffusive oxygen penetration depth. Numerical results evidenced that spheroids with diameter size >200 μm at low porosities (ε = 0.2–0.3) were at risk of oxygen depletion, especially at locations near the core center. Therefore, these results could be beneficial in preventing hypoxic conditions during in vitro experiments. The presented numerical model provides a numerical platform which can help researchers to design and optimize complex bioreactors and obtain numerical indexes of the main metabolites in a very short time prior to any fabrications. Such numerical indexes can be helpful in certifying the outcomes of forensic investigations.
Neural Representation of Overlapping Path Segments and Reward Acquisitions in the Monkey Hippocampus

Disambiguation of overlapping events is thought to be the hallmark of episodic memory. Recent rodent studies have reported that when navigating overlapping path segments in the different routes place cell activity in the same overlapping path segments were remapped according to different goal locations in different routes. However, it is unknown how hippocampal neurons disambiguate reward delivery in overlapping path segments in different routes. In the present study, we recorded monkey hippocampal neurons during performance of three virtual navigation (VN) tasks in which a monkey alternately navigated two different routes that included overlapping path segments (common central hallway) and acquired rewards in the same locations in overlapping path segments by manipulating a joystick. The results indicated that out of 106 hippocampal neurons, 57 displayed place-related activity (place-related neurons), and 18 neurons showed route-dependent activity in the overlapping path segments, consistent with a hippocampal role in the disambiguation of overlapping path segments. Moreover, 75 neurons showed neural correlates to reward delivery (reward-related neurons), whereas 56 of these 75 reward-related neurons showed route-dependent reward-related activity in the overlapping path segments. The ensemble activity of reward-related neurons represented reward delivery, locations, and routes in the overlapping path segments. In addition, ensemble activity patterns of hippocampal neurons more distinctly represented overlapping path segments than non-overlapping path segments. The present results provide neurophysiological evidence of disambiguation in the monkey hippocampus, consistent with a hippocampal role in episodic memory, and support a recent computational model of “neural differentiation,” in which overlapping items are better represented by repeated retrieval with competitive learning.
Remotely Sensed Deformation and Thermal Anomalies at Mount Pagan, Mariana Islands

Mt Pagan is an active volcano in the Mariana Island Arc, having produced a large eruption (>0.1 km3) in 1981, and recent smaller eruptions (>0.001 km3) in2011 and 2012. In this study we examine available Interferometric Synthetic Aperture Radar(InSAR) from Envisat and ALOS between October 2004 and June 2010 for precursory deformationleading up to the most recent eruptions. Although we do not observe evidence for shallowmagma reservoir inflation, we do observe a zone of subsidence of up to -3 cm/yr located onthe northern flank likely caused by continuing scoria compaction of 1981 eruptive deposits.CosmoSkyMed InSAR data spanning the October 2012 eruption also shows deposit subsidence,but no detectable co-eruptive deflation. We also present remotely-sensed thermal time series fromthe MODIS and ASTER instruments spanning over a decade. There are two distinct locationsof anomalous surface temperatures on the island, which correlate with previously documented,fumarolically active vents at South Pagan and Mt. Pagan. While elevated temperatures duringthe eruptions are visible from space in both ASTER and MODIS data, we find no clear thermalprecursors before eruption. The available data may have had insufficient spatial and temporalresolution to detect either deformation or thermal precursors if the magmatic system had rapidtransitions between quiescence and eruption. Looking ahead, satellite sensors with improvedspatial and temporal resolution will help characterize transient dynamics at small and remotevolcanic islands such as Pagan.
Microbial Biomass Responses to Soil Drying-Rewetting and Phosphorus Leaching

Soil drying-rewetting is known to enhance soil phosphorus leaching, which in part is due to osmotic shock and lysis of microbial cells upon rewetting. However, it is not entirely clear how this may be influenced by the intensity and duration of soil drying. We hypothesized that the intensity and duration of soil drying play important roles in determining the extent of dissolved reactive phosphorus (DRP) leaching resulting from microbial biomass mortality. To test this hypothesis soil sub-samples of a loamy grassland soil were dried (30C or 40C for 2-days or 14-days), rewetted, and the leachate was analysed for DRP. Soil drying at 30C for 2-days and 14-days resulted in leachate DRP concentrations which were 71% and 271% respectively higher than those in leachate from a control moist counterpart. Relatively greater DRP leaching losses occurred from the soil dried at 40C for 2-days and 14-days (143% and 300% respectively). To determine the contribution of the microbial biomass to the DRP in leachate, soil sub-samples were fumigated with chloroform either before or after drying (30C or 40C for 2-days or 14-days). All soil treatments were then either leached with water and analysed for DRP or extracted with 0.5M sodium bicarbonate solution and analysed for microbial biomass phosphorus. Fumigating soil samples before or after drying reduced microbial biomass phosphorus. However, the effect of chloroform fumigation was more pronounced in terms of microbial biomass reduction in the DF (drying followed by fumigation) treatment. Moreover, results revealed that in the DF treatment, soils dried at 30C for 2-days and 14-days had 22% and 13% respectively more microbial biomass phosphorus than their counterparts dried at 40C for 2-days and 14-days respectively. These results suggest that soil drying at higher intensity and for prolonged periods significantly (p<0.05) affect microbial biomass and subsequently increases soil phosphorus leaching following rewetting, due to enhanced contributions from the microbial biomass. These findings, however, need to be verified over a range of soil types under natural field conditions to better assess soil drying-rewetting effects on nutrient leaching.
A Single-Stranded Oligonucleotide Inhibits Toll-Like Receptor 3 Activation and Reduces Influenza A (H1N1) Infection

The initiation of an immune response is dependent on the activation and maturation of dendritic cells after sensing pathogen associated molecular patterns by pattern recognition receptors. However, the response needs to be balanced as excessive pro-inflammatory cytokine production in response to viral or stress-induced pattern recognition receptor signaling has been associated with severe influenza A virus (IAV) infection. Here, we use an inhibitor of Toll-like receptor (TLR)3, a single-stranded oligonucleotide (ssON) with the capacity to inhibit certain endocytic routes, or a TLR3 agonist (synthetic double-stranded RNA PolyI:C), to evaluate modulation of innate responses during H1N1 IAV infection. Since IAV utilizes cellular endocytic machinery for viral entry, we also assessed ssON's capacity to affect IAV infection. We first show that IAV infected human monocyte-derived dendritic cells (MoDC) were unable to up-regulate the co-stimulatory molecules CD80 and CD86 required for T cell activation. Exogenous TLR3 stimulation did not overcome the IAV-mediated inhibition of co-stimulatory molecule expression in MoDC. However, TLR3 stimulation using PolyI:C led to an augmented pro-inflammatory cytokine response. We reveal that ssON effectively inhibited PolyI:C-mediated pro-inflammatory cytokine production in MoDC, notably, ssON treatment maintained an interferon response induced by IAV infection. Accordingly, RNAseq analyses revealed robust up-regulation of interferon-stimulated genes in IAV cultures treated with ssON. We next measured reduced IAV production in MoDC treated with ssON and found a length requirement for its anti-viral activity, which overlapped with its capacity to inhibit uptake of PolyI:C. Hence, in cases wherein an overreacting TLR3 activation contributes to IAV pathogenesis, ssON can reduce this signaling pathway. Furthermore, concomitant treatment with ssON and IAV infection in mice resulted in maintained weight and reduced viral load in the lungs. Therefore, extracellular ssON provides a mechanism for immune regulation of TLR3-mediated responses and suppression of IAV infection in vitro and in vivo in mice.
fluoro-2-deoxy-D-glucose positron emission tomography compared with Epstein-Barr virus DNA as prognostic indicators in de novo metastatic nasopharyngeal carcinoma patients

Background: This study aimed to evaluate the prognostic value of maximal standard uptake values (SUVmax) of F-fluoro-2-deoxy-D-glucose positron emission tomography (PET) comparing with Epstein-Barr virus (EBV) DNA levels in de novo metastatic nasopharyngeal carcinoma (NPC) patients. Methods: From December 2006 to December 2016, 253 de novo metastatic NPC patients assessed by PET/ computed tomography were involved in current study. SUVmax-T, SUVmax-N, and SUVmax-M referred to the SUVmax at the primary tumor, cervical lymph nodes, and metastatic lesions respectively. Overall survival (OS) was the primary endpoint. Result: Patients who died during the follow-up had significantly higher SUVmax-N, SUVmax-M, and EBV DNA level than those in the patients who were alive. SUVmax-N and SUVmax-M were positively correlated with EBV DNA level. The cut-off values of SUVmax-T, SUVmax-N, SUVmax-M, and EBV DNA were 17.0, 12.7, and 6.9, and 13,800 copies/mL respectively, which were determined by receiver operating characteristic (ROC) curve analysis. Patients with elevated SUVmax-N, SUVmax-M, and EBV DNA levels had a lower 3-year OS rate. In multivariate analysis, the independent prognostic factors of OS included EBV DNA, metastatic site, and locoregional radiotherapy application, while SUVmax was not an independent prognostic factor. Conclusion: In de novo metastatic NPC patients, higher SUVmax-N and SUVmax-M were associated with worse prognosis. However, the predictive ability of SUVmax-N and SUVmax-M was poorer than that of EBV DNA.
Hepatoprotective and Renoprotective Properties of Lovastatin-Loaded Ginger and Garlic Oil Nanoemulsomes: Insights into Serum Biological Parameters

Background and Objectives: Dyslipidemia is gaining much attention among healthcare professionals because of its high association with the malfunctioning of a number of normal physiological and metabolic processes in the body. Obesity is directly interconnected with dyslipidemia and is said to be a denouement of hyperlipidemia and, if left untreated, may lead to intense damage to organs that are directly involved in fat metabolism. The objective of this study was to investigate the synergistic antiobesity and anti-hyperlipidemic activities along with hepato- and renoprotective potential of nanoemulsomes (NES) of lovastatin (LTN)-loaded ginger (GR) and garlic (GL) oils. Materials and Methods: LTN nanoemulsomes co-encapsulated with GR oil and GL oil were prepared by a thin hydration technique. Eight-week-old male Wistar rats weighing 200–250 g were induced with hyperlipidemia via a high-fat diet (HFD) comprising 40% beef tallow. Body weight, serum biochemical lipid parameters, and those for liver and kidney functions, serum TC, LDL-C, vLDL-C, HDL-C, TG, atherogenic index (AI), ALT, AFT, ALP, γ-GT, total protein (TP), serum albumin and globulin ratio (A/G), serum creatinine, blood urea nitrogen (BUN) and blood urea, and histopathology of hematoxylin and eosin (H&E) stained liver and kidney sections of all aforementioned groups were examined in the treated animals. Results: Nanoemulsomes of LTN-loaded GR and GL oils provided synergistic effects with LTN, exerted better ameliorative actions in reducing serum TC, LDL-C, vLDL-C, triglycerides, and AI, and improved serum HDL-C levels. Serum ALT, AST, ALP, and γ-GT levels were in the normal range for nanoemulsome groups. H&E stained liver and kidney sections of these animals confirmed better hepatoprotective and renoprotective effects than LTN alone. Serum biochemical parameters for renal functions also claimed to be in the moderate range for nanoemulsome-treated groups. Conclusion: This study demonstrated that nanoemulsomes of LTN-loaded GR and GL oils synergistically provided better antihyperlipidemic, hepatoprotective, and renoprotective effects as compared to LTN alone.