Miracle-dz/UniFAR-FTUs huggingface dataset:
Large-Scale Production of Lentiviral Vectors: Current Perspectives and Challenges

Lentiviral vectors (LVs) have gained value over recent years as gene carriers in gene therapy. These viral vectors are safer than what was previously being used for gene transfer and are capable of infecting both dividing and nondividing cells with a long-term expression. This characteristic makes LVs ideal for clinical research, as has been demonstrated with the approval of lentivirus-based gene therapies from the Food and Drug Administration and the European Agency for Medicine. A large number of functional lentiviral particles are required for clinical trials, and large-scale production has been challenging. Therefore, efforts are focused on solving the drawbacks associated with the production and purification of LVsunder current good manufacturing practice. In recent years, we have witnessed the development and optimization of new protocols, packaging cell lines, and culture devices that are very close to reaching the target production level. Here, we review the most recent, efficient, and promising methods for the clinical-scale production ofLVs.
Characterization of the Kenyan Honey Bee (Apis mellifera) Gut Microbiota: A First Look at Tropical and Sub-Saharan African Bee Associated Microbiomes

Gut microbiota plays important roles in many physiological processes of the host including digestion, protection, detoxification, and development of immune responses. The honey bee (Apis mellifera) has emerged as model for gut-microbiota host interaction studies due to its gut microbiota being highly conserved and having a simple composition. A key gap in this model is understanding how the microbiome differs regionally, including sampling from the tropics and in particular from Africa. The African region is important from the perspective of the native diversity of the bees, and differences in landscape and bee management. Here, we characterized the honey bee gut microbiota in sub-Saharan Africa using 16S rRNA amplicon sequencing. We confirm the presence of the core gut microbiota members and highlight different compositions of these communities across regions. We found that bees from the coastal regions harbor a higher relative abundance and diversity on core members. Additionally, we showed that Gilliamella, Snodgrassella, and Frischella dominate in all locations, and that altitude and humidity affect Gilliamella abundance. In contrast, we found that Lactobacillus was less common compared temperate regions of the world. This study is a first comprehensive characterization of the gut microbiota of honey bees from sub-Saharan Africa and underscores the need to study microbiome diversity in other indigenous bee species and regions.
Percutaneous cholecystostomy in the treatment of acute cholecystitis: is there still a role? A 20-year literature review.

OBJECTIVE Percutaneous cholecystostomy (PC) is used for the treatment of acute cholecystitis in patients with high surgical risk due to the severity of cholecystitis and/or the underlying acute or chronic medical comorbidities. The evidence for this strategy is unclear. MATERIALS AND METHODS We searched PubMed and the Cochrane databases for English-language studies published from January 1979 through December 31, 2019, for randomized clinical trials (RCTs), meta-analyses, systematic reviews, and observational studies. RESULTS The two randomized studies that have compared PC with cholecystectomy (CCY) or conservative treatment have shown that the clinical outcomes did not differ significantly between the groups. Similar results have been found in the large majority of retrospective cohorts or single-center studies that have compared PC with CCY. CONCLUSIONS PC does not seem to offer any benefit compared with CCY in the treatment of acute cholecystitis in patients with high surgical risk due to the severity of cholecystitis and/or the underlying acute or chronic medical comorbidities. A large, prospective, randomized study that compares percutaneous PC and CCY in patients with high surgical risk and/or moderate to severe cholecystitis is warranted.
Rainbow Dash: Intuitiveness, Interpretability and Memorability of the Rainbow Color Scheme in Visualization

After demonstrating that rainbow colors are still commonly used in scientific publications, we comparatively evaluate the rainbow and sequential color schemes on choropleth and isarithmic maps in an empirical user study with 544 participants to examine if a) people intuitively associate order for the colors in these schemes, b) they can successfully conduct perceptual and semantic map reading and recall tasks with quantitative data where order may have implicit or explicit importance. We find that there is little to no agreement in ordering of rainbow colors while sequential colors are indeed intuitively ordered by the participants with a strong dark is more bias. Sequential colors facilitate most quantitative map reading tasks better than the rainbow colors, whereas rainbow colors competitively facilitate extracting specific values from a map, and may support hue recall better than sequential. We thus contribute to dark- versus light is more bias debate, demonstrate why and when rainbow colors may impair performance, and add further nuance to our understanding of this highly popular, yet highly criticized color scheme.
Cost-effectiveness analysis of PET/CT surveillance imaging to detect systemic recurrence in resected stage III melanoma: study protocol

Introduction In the new era of effective systemic therapies for advanced melanoma, early detection of lower volume recurrent disease using surveillance imaging can improve survival. However, intensive imaging follow-up strategies are likely to increase costs to health systems and may pose risks to patients. The objective of this study is to estimate from the Australian health system perspective the cost-effectiveness of four follow-up strategies in resected stage III melanoma over a 5-year period following surgical treatment with curative intent. Methods and analysis A decision-analytic model will be built to estimate the costs and benefits of (1) 12 monthly, (2) 6 monthly, (3) 3–4 monthly positron emission tomography/CT imaging for 5 years, compared with (4) no imaging follow-up. The model will be populated with probabilities of disease recurrence, test performance measures using data from >1000 consecutive resected stage III melanoma patients from Melanoma Institute Australia diagnosed between 2000 and 2017. Healthcare resource use, including surveillance imaging, doctor’s visits, subsequent tests and procedures to investigate suspicious findings, will be quantified from detailed patient records and valued using Australian reference pricing. Economic outcomes include cost per new distant melanoma recurrence detected and cost per diagnostic error avoided, for no imaging compared with the other strategies. Deterministic sensitivity analyses will examine the robustness of model results. Ethics and dissemination This study was approved by the Sydney Local Health District, Sydney Local Health District Ethics Review Committee (RPAH Zone), AU/1/830638 and the Australian Institute of Health and Welfare (EO2019-1-454). The results of this study will be published in peer-reviewed medical and health economics journals and will inform melanoma management guidelines.
Inter‐regional digital forensic knowledge management: needs, challenges, and solutions

Increasing demand for digital evidence in criminal investigations is driving decentralization of forensic capabilities closer to the crime scene. Law enforcement agencies are struggling to keep pace with technological developments, cybercrime growth, and scientific advances. In federated environments, digital forensic knowledge and practices vary widely across regions. To reduce delays, wasted resources, missed opportunities, mistakes, and misinterpretations, there is a pressing need to balance the democratization of digital forensic capabilities with knowledge management and sharing between decentralized regions. There are multiple forms of knowledge to be managed, including procedural, technical, investigative, scientific, behavioral, crime analysis, and forensic intelligence. In addition, there are multiple knowledge producers and consumers, including police investigators, digital forensic practitioners, criminal intelligence analysts, attorneys, and judges. Knowledge management becomes even more challenging when multiple interdependent regions are involved, speaking different languages. Taking all of these factors into consideration, this work presents an inter‐regional knowledge management solution for improving the quality, consistency, reliability, efficiency, cost‐effectiveness, and return on investment of digital forensic capabilities. The basis of this work is a community‐driven initiative of Swiss regional police authorities. Interviews were conducted with 15 digital forensic units to determine their current knowledge management practices and needs. The results were then generalized into a prioritized set of requirements for inter‐regional digital forensic knowledge management that may be applicable in other countries. These requirements were used to evaluate knowledge management platforms, and one was selected. Implementation, operations, and maintenance challenges of an inter‐regional digital forensic knowledge management platform are discussed.
Domain Adaptation for Structural Health Monitoring

In recent years, machine learning (ML) algorithms gained a lot of interest within structural health monitoring (SHM) community. Many of those approaches assume the training and test data come from similar distributions. However, real-world applications, where an ML model is trained on numerical simulation data and tested on experimental data, are deemed to fail in detecting the damage, as both domain data are collected under different conditions and they don’t share the same underlying features. This paper proposes the domain adaptation approach as a solution to particular SHM problems where the classifier has access to the labeled training (source) and unlabeled test (target) domains. The proposed domain adaptation method forms a feature space to match the latent features of both source and target domains. To evaluate the performance of this approach, we present a case study where we train three neural network-based classifiers on a three-story test structure: i) Classifier A uses labeled simulation data from the numerical model of the test structure; ii) Classifier B utilizes labeled experimental data from the test structure; and iii) Classifier C implements domain adaptation by training on labeled simulation data (source) and unlabeled experimental data (target). The performance of each classifier is evaluated by computing the accuracy of the discrimination against labeled experimental data. Overall, the results demonstrate that domain adaption can be regarded as a valid approach for SHM applications where access to labeled experimental data is limited.
Folate-conjugated hydrophobicity modified glycol chitosan nanoparticles for targeted delivery of methotrexate in rheumatoid arthritis

Background: Targeted delivery to the Rheumatoid arthritis (RA) which is characterized by destruction and degeneration of bones due to chronic inflammation is of great need. RA being a chronic autoimmune disorder might result in severe disability and morbidity. A targeted delivery system is designed to deliver methotrexate (MTX) for RA. Methods: Here, we synthesized folic acid (FA) conjugated hydrophobically modified glycol chitosan (GC) self-assembled nanoparticles (FA-GC-SA) for the targeted delivery of MTX to RA. The FA conjugation and hydrophobic modification of GC by stearic acid (SA) was confirmed by Fourier-transform infrared spectroscopy (FTIR). The FA-GC-SA was exploited for developing targeted nanoparticles encapsulating MTX by the ionic gelation method. The particles were characterized and evaluated for their targeting potential in in vitro cell culture studies. Further their in vivo efficacy in arthritis induced rats using collagen was also evaluated. Results: FTIR confirms the successful modification of GC-SA and FA-GC-SA. The FA-GC-SA-MTX of size 153 ± 9 nm were prepared with high encapsulation efficiency of MTX. The FA-GC-SA-MTX size was further confirmed by transmission electron microscopy (TEM). In vitro cell studies revealed the superior efficacy of FA-GC-SA-MTX in cell cytotoxicity. Also, significantly higher cellular uptake of FA functionalized FA-GC-SA-MTX was observed in comparison to non-functionalized GC-SA-MTX attributed to folate receptors (FRs) mediated endocytosis. In vivo results confirms the potential of FA-GC-SA-MTX which reduces reduces the pro-inflammatory cytokines, paw thickness, and arthritis score in collagen induced rats. Conclusion: The results shows that FRs targeted FA-GC-SA-MTX has superior efficacy in the treatment of RA.
Assessment of whether the rabbit subscapularis tendon model is suitable for studying the human chronic rotator cuff pathology: Discovery of a new ligament connecting the glenoid and subscapularis tendon.

OBJECTIVE This study aimed to investigate the anatomical relationship between the subscapularis tendon and glenosubscapularal ligament (GSL) that we accidentally identified from our previous study on a rabbit shoulder model and to determine whether this anatomical relationship has an impact on the rabbit shoulder model for studying the human chronic rotator cuff pathology. METHODS In this study, 15 male New Zealand rabbits aged 12 weeks and weighing 2.5 kg were used. Moreover, 3 rabbits were sacrificed for the anatomical and histological investigation of the relationship between the subscapularis tendon and GSL at baseline. The remaining 12 rabbits underwent the subscapularis tendon tenotomy from the lesser tuberosity using a standardized procedure. The GSL was cut on the left side and preserved on the right side. For histomorphometric analysis, 6 rabbits were first sacrificed at 6 weeks and then the remaining 6 rabbits at 12 weeks. RESULTS In all the rabbits, GSL was identified, connecting the upper portion of glenoid and subscapularis muscle-tendon junction. The mean thickness of the middle portion of GSL was 1.1±0.2 mm; the mean length of GSL was 8.4±2.3 mm. The mean widths of the proximal and distal attachments were 2.4±0.3 and 4.2±0.5 mm, respectively. The mean size of the native subscapularis muscle fibers was 122.6±4.3 μm2. The mean size of the muscle fibers in shoulders with tenotomy alone was 112.6±6.2 and 102.6±4.8 μm2 at 6 and 12 weeks, respectively. The mean size of the muscle fibers in shoulders with tenotomy plus GSL cut severing was 88.3±9.7 and 56.4±5.2 μm2 at 6 and 12 weeks, respectively. The significant muscle atrophy was observed both at 6 and 12 weeks in the shoulders with tenotomy plus GSL cut compared with those with tenotomy alone as well as those with the native subscapularis. However, the muscle atrophy was not significantly different in the shoulders with tenotomy alone at different time points. CONCLUSION Because GSL may prevent the subscapularis retraction, the rabbit subscapularis tendon model may not be suitable for studying the human chronic rotator cuff pathology if GSL is neglected or preserved.
Innate and Adaptive Immune Responses against Bordetella pertussis and Pseudomonas aeruginosa in a Murine Model of Mucosal Vaccination against Respiratory Infection

Whole cell vaccines are frequently the first generation of vaccines tested for pathogens and can inform the design of subsequent acellular or subunit vaccines. For respiratory pathogens, administration of vaccines at the mucosal surface can facilitate the generation of a localized mucosal immune response. Here, we examined the innate and vaccine-induced immune responses to infection by two respiratory pathogens: Bordetella pertussis and Pseudomonas aeruginosa. In a model of intranasal administration of whole cell vaccines (WCVs) with the adjuvant curdlan, we examined local and systemic immune responses following infection. These studies showed that intranasal vaccination with a WCV led to a reduction of the bacterial burden in the airways of animals infected with the respective pathogen. However, there were unique changes in the cytokines produced, cells recruited, and inflammation at the site of infection. Both mucosal vaccinations induced antibodies that bind the target pathogen, but linear regression and principal component analysis revealed that protection from these pathogens is not solely related to antibody titer. Protection from P. aeruginosa correlated to a reduction in lung weight, blood lymphocytes and neutrophils, and the cytokines IL-6, TNF-α, KC/GRO, and IL-10, and promotion of serum IgG antibodies and the cytokine IFN-γ in the lung. Protection from B. pertussis infection correlated strongly with increased anti-B-pertussis serum IgG antibodies. These findings reveal valuable correlates of protection for mucosal vaccination that can be used for further development of both B. pertussis and P. aeruginosa vaccines.
Variant analysis of 1,040 SARS-CoV-2 genomes

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral genome is an RNA virus consisting of approximately 30,000 bases. As part of testing efforts, whole genome sequencing of human isolates has resulted in over 1,600 complete genomes publicly available from GenBank. We have performed a comparative analysis of the sequences, in order to detect common mutations within the population. Analysis of variants occurring within the assembled genomes yields 417 variants occurring in at least 1% of the completed genomes, including 229 within the 5’ untranslated region (UTR), 152 within the 3’UTR, 2 within intergenic regions and 34 within coding sequences.
Toxicodendron vernicifluum Stokes extract inhibits solid tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice

Toxicodendron vernicifluum Stokes has long been used as a food supplement and traditional herbal medicine in East Asia. We applied a new extraction method to produce Toxicodendron vernicifluum Stokes extract (TVSE), that doesn’t contain urushiol (an allergenic toxin) but dose have higher levels of some flavonoids such as fustin and fisetin. This study was conducted to investigate the anticancer effects of TVSE in an in vivo system. Fifty BALB/c mice were acclimated for one week and then injected with 4T1 murine mammary carcinoma cells in mammary fat pads. After 7 days, the mice were randomly divided into 5 groups, and orally administered with 0, 50, 100, 200 or 400 mg of TVSE/kg body weight (BW)/day for 20 days. TVSE reduced tumor volume and weight dose-dependently. The expression of Ki67 was significantly reduced and the number of TUNEL-positive apoptotic cells was significantly increased in the TVSE-treated group over 100 mg/kg BW/day. While tumor nodules were not found in the liver, but only in lungs, the number of tumor nodules was reduced in a dose-dependent manner in the TVSE treated groups compared to the control group. In breast tumors, expression of platelet endothelial cell adhesion molecule (PECAM-1) and vascular endothelial growth factor (VEGF) was reduced by TVSE treatment. TVSE treatment significantly suppressed mRNA expression in tumors of matrix metalloproteinase (MMP)-2, tissue inhibitor of metalloproteinase (TIMP)-1, urokinase-type plasminogen activator (uPA), intercellular adhesion molecule (ICAM)-1, and vascular cell adhesion molecule (VCAM)-1 while increasing plasminogen activator inhibitor (PAI)-1. These results suggest that TVSE is potentially beneficial for the suppression of breast cancer growth and its-associated lung metastasis.
Systemic Inflammation Indices in Patients With Acute Ischemic Stroke Treated With Intravenous Tissue Plasminogen Activator: Clinical Yield and Utility

Inflammation indices derived from complete blood counts (CBCs) have been proposed to estimate benefit and risk of intravenous (IV) tissue plasminogen activator (tPA) in acute ischemic stroke. In 165 acute ischemic patients, the neutrophil-to-lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio, and systemic immune-inflammation index (SII) were calculated before and 24 hours after IV tPA. The area under receiver operating characteristic (AUC-ROC) curves, and positive and negative likelihood ratios (+LR,−LR) were produced to measure their diagnostic accuracy and clinical utility for tPA effectiveness, hemorrhage risk and third-month prognosis. None of the indices obtained “before” IV-tPA was found to be useful in determining acute and long-term functional efficacy and bleeding risk. Lymphocyte decrease, neutrophil increase, and parallel NLR and SII increase at the 24th-hour were associated with poor functional outcome. However, their clinical utility was not sufficient due to absence of effective thresholds. NLR threshold >5.65 provided ROC-AUC 0.86, sensitivity 71.3%, specificity 65.7%, −LR 0, +LR 3.76, and SII threshold >1781 had ROC-AUC 0.802, sensitivity 58.7%, specificity 72.7%, −LR 0.11, +LR 4.52, corresponding to an acceptable clinical yield. Systemic immune-inflammation index and NLR, but not other CBC-derived inflammatory parameters, have moderate utility as marker of tPA-related symptomatic hemorrhage occurrence.
A Rejection Gene Expression Score in Indication and Surveillance Biopsies Is Associated with Graft Outcome

Rejection-associated gene expression has been characterized in renal allograft biopsies for cause. The aim is to evaluate rejection gene expression in subclinical rejection and in biopsies with borderline changes or interstitial fibrosis and tubular atrophy (IFTA). We included 96 biopsies. Most differentially expressed genes between normal surveillance biopsies (n = 17) and clinical rejection (n = 12) were obtained. A rejection-associated gene (RAG) score was defined as its geometric mean. The following groups were considered: (a) subclinical rejection (REJ-S, n = 6); (b) borderline changes in biopsies for cause (BL-C, n = 13); (c) borderline changes in surveillance biopsies (BL-S, n = 12); (d) IFTA in biopsies for cause (IFTA-C, n = 20); and (e) IFTA in surveillance biopsies (IFTA-S, n = 16). The outcome variable was death-censored graft loss or glomerular filtration rate decline ≥ 30 % at 2 years. A RAG score containing 109 genes derived from normal and clinical rejection (area under the curve, AUC = 1) was employed to classify the study groups. A positive RAG score was observed in 83% REJ-S, 38% BL-C, 17% BL-S, 25% IFTA-C, and 5% IFTA-S. A positive RAG score was an independent predictor of graft outcome from histological diagnosis (hazard ratio: 3.5 and 95% confidence interval: 1.1–10.9; p = 0.031). A positive RAG score predicts graft outcome in surveillance and for cause biopsies with a less severe phenotype than clinical rejection.