bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeated cell sorting ensures the homogeneity of ocular cell populations expressing a transgenic protein
Authors: Chen Tsan-Chi , Chang Shu-Wen
Published: March 2022

Transgenic proteins can be routinely expressed in various mammalian cell types via different transgenic systems, but the efficiency of transgene expression is constrained by the complex interplay among factors such as the temporal consistency of expression and compatibility with specific cell types, including ocular cells. Here, we report a more efficient way to express an enhanced green fluorescent protein (EGFP) in human corneal fibroblasts, corneal epithelial cells, and conjunctival epithelial cells through a lentiviral expression system. The relative transducing unit criterion for EGFP-expressing pseudovirions was first determined in HEK-293T cells. Homogeneous populations of EGFP-positive and EGFP-negative cells could be isolated by cell sorting. The half-maximal inhibitory concentration (IC50) value for puromycin was calculated according to viability curves for each cell type. The results revealed that cell types differed with respect to EGFP expression efficiency after transduction with the same amount of EGFP-encoding pseudovirions. Using a cell sorter, the homogeneity of EGFP-positive cells reached >95%. In the initial sorting stage, however, the efficiency of EGFP expression in the sorted cells was noticeably reduced after two rounds of sequential culture, but repeated sorting for up to four rounds yielded homogeneous EGFP-positive human corneal fibroblasts that could be maintained in continuous culture in vitro. The sorted EGFP-positive cells retained their proper morphology and cell type-specific protein expression patterns. Puromycin resistance was found to depend on cell type, indicating that the IC50 for puromycin must be determined for each cell type to ensure the isolation of homogeneous EGFP-positive cells. Taken together, repeated cell sorting is an efficient means of obtaining homogeneous populations of ocular cells expressing a transgenic protein during continuous culture without the potential confounding effects of antibiotics.
Obesity and high myopia in children and adolescents: Korea National Health and Nutrition Examination Survey
Authors: Lee Sami , Lee Haeng-Jin , Lee Kyoung Geun , Kim Jihan
Published: March 2022

Purpose

The prevalence of both obesity and myopia are increasing in Korean children and adolescents. The purpose of this study is to examine the impact of obesity on the prevalence of myopia in Korean children and adolescents.

Methods

This study used the data of a nationally representative cross-sectional survey, the Korea National Health and Nutrition Examination Survey (KNHANES) VII conducted from 2016 to 2018. Of the 1237 children and adolescents aged 5–18 years who participated in the KNHANES VII and underwent ophthalmologic examinations for the survey, 1114 were selected for review, excluding those whose data on refractive error, family history of myopia, or waist circumference were missing. Body mass index (BMI) was classified into four groups: underweight (< 5th percentile), normal weight (≥ 5th percentile, < 85th percentile), overweight (≥ 85th percentile, < 95th percentile), and obese (≥ 95th percentile). Myopia was defined by the level of refractive error ≤ -0.5 diopters (D) and classified as mild (≤ -0.5 D, > -3.0 D), moderate (≤ -3.0 D, > -6.0 D), or high (≤ -6.0 D) myopia. The relationship between BMI and myopia was analyzed using complex sample logistic regression. Age and family history were corrected followed by an analysis of the odds ratios.

Results

Compared to those with normal weights (controls), being underweight, overweight, or obese showed no significant odds of developing mild and moderate myopia. Conversely, when compared with that of controls, the odds ratio of developing high myopia in the underweight, overweight, and obese groups was 0.77 (95% CI, 0.22–2.65), 1.37 (95% CI, 0.51–3.66), and 3.77 (95% CI, 1.98–7.16), respectively. Furthermore, in a separate analysis by sex and BMI, the odds ratio of developing high myopia was 2.84 (95% CI, 1.10–7.35) in boys with obesity and 4.23 (95% CI,1.19–15.09) and 5.04 (95% CI,1.77–14.34) in overweight and obese girls, respectively.

Conclusions

An association exists between obesity in childhood and adolescence and high myopia. Being overweight in girls was also found to be associated with high myopia. Thus, efforts to maintain a healthy weight during childhood and adolescence are of great importance.
Recruitment in randomized clinical trials: The MeMeMe experience
Authors: Baldassari Ivan , Oliverio Andreina , Krogh Vittorio , Bruno Eleonora , Gargano Giuliana , Cortellini Mauro , Casagrande Alice , Di Mauro Maria G. , Venturelli Elisabetta , Del Sette Cerulli Daniela , Manuela Bellegotti , Berrino Franco , Pasanisi Patrizia
Published: March 2022

Introduction

Recruitment is essential for the success of clinical trials. We are conducting a randomized clinical trial to test the effect of a Mediterranean dietary intervention with or without 1700 mg/day of metformin for the prevention of age-related chronic diseases, the MeMeMe trial (Trial registration number: EudraCT number: 2012-005427-32 ClinicalTrials.gov ID: NCT02960711). MeMeMe recruiting experience, highlighting strengths, limitations encountered and results is reported.

Patients and methods

Statistical analysis focused on the reasons for withdrawal according to the recruitment method (“active” versus “passive” criterion) and the time of withdrawal. Logistic regression models were used to explore the associations between the risk of withdrawal and sex, recruitment method, randomization arm, and with markers of compliance to the intervention, such as one-year change in body weight.

Results

Out of 2035 volunteers, 660 (32.4%) were recruited “actively” and 1375 (67.6%) “passively”. Among people who dropped out of the trial after randomization, there were 19.5% for the “active” and 22.0% for the “passive” method (p = 0.28). The risk of withdrawal was significantly higher in women (OR:1.91; 95% CI:1.17–3.12; p = 0.01), in volunteers older at recruitment (OR:1.25; 95% CI:1.07–1.45; p = 0.004), and in those with a higher BMI at baseline (OR:1.23; 95% CI:1.07–1.43; p = 0.004). Volunteers who lost at least 2 kg (the median weight change) in the first year of intervention were significantly less (53%) likely to withdraw from the trial (OR:0.48; 95% CI:0.30–0.75; p = 0.001).

Conclusion

Our findings suggest that the “passive” recruitment method was more effective than the “active” one to advance recruitment. The benefits of “passive” recruitment hardly outweighed the drawbacks.

Trial registration

Trial registration number: EudraCT number: 2012-005427-32. ClinicalTrials.gov ID: NCT02960711.
Development and validation of machine learning-driven prediction model for serious bacterial infection among febrile children in emergency departments
Authors: Lee Bongjin , Chung Hyun Jung , Kang Hyun Mi , Kim Do Kyun , Kwak Young Ho
Published: March 2022

Serious bacterial infection (SBI) in children, such as bacterial meningitis or sepsis, is an important condition that can lead to fatal outcomes. Therefore, since it is very important to accurately diagnose SBI, SBI prediction tools such as ‘Refined Lab-score’ or ‘clinical prediction rule’ have been developed and used. However, these tools can predict SBI only when there are values of all factors used in the tool, and if even one of them is missing, the tools become useless. Therefore, the purpose of this study was to develop and validate a machine learning-driven model to predict SBIs among febrile children, even with missing values. This was a multicenter retrospective observational study including febrile children <6 years of age who visited Emergency departments (EDs) of 3 different tertiary hospitals from 2016 to 2018. The SBI prediction model was trained with a derivation cohort (data from two hospitals) and externally tested with a validation cohort (data from a third hospital). A total of 11,973 and 2,858 patient records were included in the derivation and validation cohorts, respectively. In the derivation cohort, the area under the receiver operating characteristic curve (AUROC) of the RF model was 0.964 (95% confidence interval [CI], 0.943–0.986), and the area under the precision-recall curve (AUPRC) was 0.753 (95% CI, 0.681–0.824). The conventional LR (CLR) model showed corresponding values of 0.902 (95% CI, 0.894–0.910) and 0.573 (95% CI, 0.560–0.586), respectively. In the validation cohort, the AUROC (95% CI) of the RF model was 0.950 (95% CI, 0.945–0.956), the AUPRC was 0.605 (95% CI, 0.593–0.616), and the CLR presented corresponding values of 0.815 (95% CI, 0.789–0.841) and 0.586 (95% CI, 0.553–0.619), respectively. We developed a machine learning-driven prediction model for SBI among febrile children, which works robustly despite missing values. And it showed superior performance compared to CLR in both internal validation and external validation.
Experimental investigations of crater formation as a result of high-velocity impacts on sand bed
Authors: Mazur Rafał , Beczek Michał , Janiszewski Jacek , Koperski Wojciech , Polakowski Cezary , Fikus Bartosz , Sochan Agata , Woźniak Ryszard , Goździk Dawid , Ryżak Magdalena , Bańda Maciej , Bieganowski Andrzej
Published: March 2022

The formation of craters is an important issue in the investigations of the surface of the earth and other planets. The aim of the study was to check whether the different textures of sand beds affect the size and dynamics of the formation of craters and ejection curtain after high-velocity impacts. The experiments were conducted using an aluminium impactor at two impact speeds (~700 and ~1300 m∙s-1) and a sand bed composed of either a broad range of sizes (<2.0 mm) or any of the three fractions obtained from it (<0.5, 0.5–1, 1–2 mm). The diameters, depths, wall slope, and rim heights of the resulting craters were measured. The ejecta curtain was characterized by the inclination angle of walls, base diameter, and expansion velocity. The mass of the transferred material and the depth of the impactor penetration were also determined. Additionally, the results were used to calculate dimensionless parameters commonly considered in crater studies (πV, π2 and α). The texture of the sand most clearly influenced the diameters of the craters, its effect could also be seen in the case of the distance covered by the ejected material. This information appears to be relevant for future research, providing some rationale to help assess in which aspects of the phenomenon the texture may be important.
A quantitative microbial risk assessment for touchscreen user interfaces using an asymmetric transfer gradient transmission mode
Authors: Di Battista Andrew
Published: March 2022

The ubiquitous use of public touchscreen user interfaces for commercial applications has created a credible risk for fomite-mediated disease transmission. This paper presents results from a stochastic simulation designed to assess this risk. The model incorporates a queueing network to simulate people flow and touchscreen interactions. It also describes an updated model for microbial transmission using an asymmetric gradient transfer assumption that incorporates literature reviewed empirical data concerning touch-transfer efficiency between fingers and surfaces. In addition to natural decay/die-off, pathogens are removed from the system by simulated cleaning / disinfection and personal-touching rates (e.g. face, dermal, hair and clothing). The dose response is implemented with an exponential moving average filter to model the temporal dynamics of exposure. Public touchscreens were shown to pose a considerable infection risk (∼3%) using plausible default simulation parameters. Sensitivity of key model parameters, including the rate of surface disinfection is examined and discussed. A distinctive and important advancement of this simulation was its ability to distinguish between infection risk from a primary contaminated source and that due to the re-deposition of pathogens onto secondary, initially uncontaminated touchscreens from sequential use. The simulator is easily configurable and readily adapted to more general fomite-mediated transmission modelling and may provide a valuable framework for future research.
Pentachlorophenol has significant adverse effects on hematopoietic and immune system development in zebrafish (Danio rerio)
Authors: Namit Aleeza , Dowell William , Matiasek Sandrine , Webster Jackson , Stachura David L.
Published: March 2022

In November 2018, the Camp Fire devastated the mountain community of Paradise, CA. The burning of plastic pipes, wiring, construction materials, paint, and car batteries released toxic chemicals into the environment, contaminating the air, soil, and local waterways. Examples of toxins that were identified in the creeks and waterways in and around Paradise included pentachlorophenol (PCP), chrysene, and polyaromatic hydrocarbons. The effects of some of these chemicals on embryonic development, hematopoiesis (blood formation), and the immune system have not been thoroughly studied. Defining safe levels and the long-term effects of exposure is imperative to understanding and mitigating potential negative future outcomes. To perform these studies, we utilized zebrafish (Danio rerio), a commonly used vertebrate model system to study development. We observed the adverse effects of PCP on the development of zebrafish by using fluorescence microscopy, and saw that increased concentrations of PCP decreased the numbers of normal red blood cells and myeloid cells. Additionally, we observed that animal survival decreased in response to increasing concentrations of PCP. Furthermore, the prevalence of characteristic physical deformities such as tail curvature were greater in the treatment groups. Lastly,runx1,cmyb, andcd41expression was reduced in fish treated with PCP. These results suggest that PCP has a previously underappreciated effect on blood and immune cell development and future studies should be performed to determine the molecular mechanisms involved.
Association between urinary N-acetyl-β-glucosaminidase activity–urinary creatinine concentration ratio and risk of disability and all-cause mortality
Authors: Tanaka Shin-ichiro , Fujioka Yoshio , Tsujino Takeshi , Ishida Tatsuro , Hirata Ken-ichi
Published: March 2022

Background

Recent studies have suggested that chronic kidney disease is associated with cardiovascular disease, dementia, and frailty, all of which cause disability and early death. We investigated whether increased activity of urinary N-acetyl-β-glucosaminidase (NAG), a marker of kidney injury, is associated with risk of disability or all-cause mortality in a general population.

Methods

Follow-up data from the Hidaka Cohort Study, a population-based cohort study of members of a Japanese rural community, were obtained via questionnaires completed by participants or their relatives. Multivariable analyses were used to investigate relations between urinary NAG activity–urinary creatinine concentration ratio and risk of disability or all-cause mortality.

Results

A total of 1182 participants were followed up for a median of 12.4 years. The endpoints were receipt of support under the public long-term care insurance program, and all-cause mortality. A total of 122 participants (10.3%) were reported to be receiving long-term care and 230 (19.5%) had died. After adjustment for cardiovascular risk factors along with physical activity, and using the quartile 1 results as a reference, the odds ratio (OR) for disability was 2.12 [95% confidence interval (95% confidence interval [CI]), 1.04–4.33; p = 0.038) and the hazard ratio (HR) for all-cause mortality was 1.65 (95% CI, 1.05–2.62; p = 0.031) in participants with urinary NAG/creatinine ratio in quartile 4. Similar results were obtained in participants without proteinuria: OR for disability, 2.46 (95% CI, 1.18–5.16; p = 0.017); and HR for all-cause mortality, 1.62 (95% CI, 1.00–2.63; p = 0.049).

Conclusions

Increased urinary NAG/creatinine ratio was associated with risk of disability or all-cause mortality in a general population.
Prognostic indicators of disease progression in Duchenne muscular dystrophy: A literature review and evidence synthesis
Authors: Ferizovic Nermina , Summers Jessica , de Zárate Igor Beitia Ortiz , Werner Christian , Jiang Joel , Landfeldt Erik , Buesch Katharina
Published: March 2022

Background

Duchenne muscular dystrophy (DMD) is a rare, severely debilitating, and fatal neuromuscular disease characterized by progressive muscle degeneration. Like in many orphan diseases, randomized controlled trials are uncommon in DMD, resulting in the need to indirectly compare treatment effects, for example by pooling individual patient-level data from multiple sources. However, to derive reliable estimates, it is necessary to ensure that the samples considered are comparable with respect to factors significantly affecting the clinical progression of the disease. To help inform such analyses, the objective of this study was to review and synthesise published evidence of prognostic indicators of disease progression in DMD. We searched MEDLINE (via Ovid), Embase (via Ovid) and the Cochrane Library (via Wiley) for records published from inception up until April 23 2021, reporting evidence of prognostic indicators of disease progression in DMD. Risk of bias was established with the grading system of the Centre for Evidence-Based Medicine (CEBM).

Results

Our search included 135 studies involving 25,610 patients from 18 countries across six continents (Africa, Asia, Australia, Europe, North America and South America). We identified a total of 23 prognostic indicators of disease progression in DMD, namely age at diagnosis, age at onset of symptoms, ataluren treatment, ATL1102, BMI, cardiac medication, DMD genetic modifiers, DMD mutation type, drisapersen, edasalonexent, eteplirsen, glucocorticoid exposure, height, idebenone, lower limb surgery, orthoses, oxandrolone, spinal surgery, TAS-205, vamorolone, vitlolarsen, ventilation support, and weight. Of these, cardiac medication, DMD genetic modifiers, DMD mutation type, and glucocorticoid exposure were designated core prognostic indicators, each supported by a high level of evidence and significantly affecting a wide range of clinical outcomes.

Conclusion

This study provides a current summary of prognostic indicators of disease progression in DMD, which will help inform the design of comparative analyses and future data collection initiatives in this patient population.
Plant different, eat different? Insights from participatory agricultural research
Authors: Azzarri Carlo , Haile Beliyou , Letta Marco
Published: March 2022

We examine the association between on-farm production diversity on household dietary diversity in Malawi using microdata collected as part of an environmentally sustainable agricultural intensification program. The program primarily focuses on the integration of legumes into the cropping system through maize-legume intercropping and legume-legume intercropping. Relative to staple cereals such as maize, legumes are rich in micronutrients, contain better-quality protein, and lead to nitrogen fixation. Given the systematic difference we document between program beneficiaries and randomly sampled non-beneficiary (control) households, we employ causal instrumental variables mediation analysis to account for non-random selection and possible simultaneity between production and consumption decisions. We find a significant positive treatment effect on dietary diversity, led by an increase in production diversity. Analysis of potential pathways show that effects on dietary diversity stem mostly from consumption of diverse food items purchased from the market made possible through higher agricultural income. These findings highlight that, while increasing production for markets can enhance dietary diversity through higher income that would make affordable an expanded set of food items, the production of more nutritious crops such as pulses may not necessarily translate into greater own consumption. This may be due to the persistence of dietary habits, tastes, or other local factors that favor consumption of staples such as maize and encourage sales of more profitable and nutritious food items such as pulses. Pulses are a more affordable and environmentally sustainable source of protein than animal source food, and efforts should be made to enhance their nutritional awareness and contribution to sustainable food systems and healthier diets.
Predictors and outcomes of recognition of intellectual disability for adults during hospital admissions: A retrospective data linkage study in NSW, Australia
Authors: Walker Adrian Raymond , Trollor Julian Norman , Florio Tony , Srasuebkul Preeyaporn
Published: March 2022

Adults with intellectual disability have high health care needs. Despite frequent contact with health services, they often receive inadequate health care. One method to improve health care delivery is reasonable adjustments, that is, the adaptation of health care delivery such that barriers to participation are removed for the person with disability. A starting point for the provision of reasonable adjustments is recognition of intellectual disability during the health care contact. To determine rates and predictors of the recognition of intellectual disability during hospital admissions, and its impact on admission metrics, we examined a population of adults with intellectual disability identified from disability services datasets from New South Wales, Australia between 2005 and 2014. Recognition of intellectual disability was determined by the recording of an International Classification of Diseases 10threvision (ICD-10) diagnostic code for intellectual disability during a given hospital admission. We examined how recognition of intellectual disability related to length of hospital episodes. We found an overall low rate of recognition of intellectual disability (23.79%) across all hospital episodes, with the proportion of hospital episodes recognising intellectual disability decreasing from 2005–2015. Admissions for adults with complex health profiles (e.g., those with many comorbidities, those with Autism Spectrum Disorder, and those admitted for urgent treatment) were more likely to recognise intellectual disability, but admissions for adults with complexity in other domains (i.e., for those in custody, or those with drug and alcohol disorders) were less likely to recognise intellectual disability. Recognition of intellectual disability was associated with longer episodes of care, possibly indicating the greater provision of reasonable adjustments. To improve the recognition of intellectual disability for adults during health service contacts, we advocate for the implementation of targeted initiatives (such as a nationwide disability flag to be included in health service records) to improve the provision of reasonable adjustments.
Role of sphingosine kinase and sphingosine-1-phosphate receptor in the liver pathology of mice infected with Plasmodium berghei ANKA
Authors: Techarang Tachpon , Jariyapong Pitchanee , Punsawad Chuchard
Published: March 2022

Decreased serum sphingosine 1-phosphate (S1P) has been reported in severe malaria patients, but the expression of receptors and enzymes associated with S1P has not been investigated in the liver of malaria patients. Therefore, this study aimed to investigate the expression of sphingosine kinase (SphK) and S1P receptors (S1PRs) in the liver of malaria-infected mice. C57BL/6 male mice were divided into a control group (n = 10) and aPlasmodium berghei(PbA)-infected group (n = 10). Mice in the malaria group were intraperitoneally injected with 1×106P.bergheiANKA-infected red blood cells, whereas control mice were intraperitoneally injected with normal saline. Liver tissues were collected on Day 13 of the experiment to evaluate histopathological changes by hematoxylin and eosin staining and to investigate SphK and S1PR expression by immunohistochemistry and real-time PCR. Histological examination of liver tissues from the PbA-infected group revealed sinusoidal dilatation, hemozoin deposition, portal tract inflammation and apoptotic hepatocytes, which were absent in the control group. Immunohistochemical staining showed significant increases in the expression of SphK1 and SphK2 and significant decreases in the expression of S1PR1, S1PR2, and S1PR3 in the endothelium, hepatocytes, and Kupffer cells in liver tissue from the PbA-infected group compared with the control group. Real-time PCR analysis showed the upregulation of SphK1 and the downregulation of S1PR1, S1PR2, and S1PR3 in the liver in the PbA-infected group compared with the control group. In conclusion, this study demonstrates for the first time that SphK1 mRNA expression is upregulated and that S1PR1, S1PR2, and S1PR3 expression is decreased in the liver tissue of PbA-infected mice. Our findings suggest that the decreased levels of S1PR1, S1PR2, and S1PR3 might play an important role in liver injury during malaria infection.
Microbial metabolite butyrate promotes induction of IL-10+IgM+ plasma cells
Authors: Föh Bandik , Buhre Jana Sophia , Lunding Hanna B. , Moreno-Fernandez Maria E. , König Peter , Sina Christian , Divanovic Senad , Ehlers Marc
Published: March 2022

The microbially-derived short-chain fatty acid butyrate is a central inhibitor of inflammatory innate and adaptive immune responses. Emerging evidence suggests that butyrate induces differentiation of IL-10-producing (IL-10+) regulatory B cells. However, the underlying mechanisms of butyrate-driven modulation of B cell differentiation are not fully defined. Given the dominant role of regulatory plasma cells (PCs) as the main source of anti-inflammatory cytokines including IL-10 and the observation that butyrate also induces the differentiation of PCs, we here investigated the effect of the microbial metabolite butyrate on the induction of regulatory IL-10+ PCs and underlying mechanisms. Here we show that butyrate induces the differentiation of IL-10+IgM+ PCs. Ex vivo, butyrate, but hardly propionate, another microbially-derived short-chain fatty acid, induced the differentiation of IL-10+IgM+ CD138high PCs from isolated splenic murine B cells. In vivo, administration of butyrate via drinking water or by daily intraperitoneal injection increased the number of IL-10+IgM+ CD138high PCs in the spleens of Ovalbumin (Ova)/complete Freund’s adjuvant-immunized mice. The induction of these regulatory PCs was associated with an increase of anti-Ova IgM, but a reduction of anti-Ova class-switched pathogenic IgG2b serum antibodies. Based on the knowledge that butyrate inhibits histone deacetylases (HDACs) thereby increasing histone acetylation, we identified here that HDAC3 inhibition was sufficient to induce PC differentiation and IL-10+ expression. Furthermore, reduced mitochondrial superoxide levels following butyrate treatment and HDAC3 inhibition were necessary for PC differentiation, but not IL-10 expression. In summary, the microbial metabolite butyrate promotes the differentiation of IgM+ PCs and their expression of IL-10. HDAC3 inhibition may be involved as an underlying pathway for both PC differentiation and IL-10 expression, while reduced mitochondrial superoxide levels are crucial only for PC differentiation. The induction of regulatory IL-10+IgM+ PCs and the inhibition of class switching to antigen-specific pathogenic IgG subclasses might represent important pathways of butyrate to limit inflammation.
Effects of chronic mild hyperoxia on retinal and choroidal blood flow and retinal function in the DBA/2J mouse model of glaucoma
Authors: Muir Eric R. , Chandra Saurav B. , Narayanan Divya , Zhang Vincent , Zhang Ike , Jiang Zhao , Kiel Jeffrey W. , Duong Timothy Q.
Published: March 2022

Purpose

To test the hypothesis that mild chronic hyperoxia treatment would improve retinal function despite a progressive decline in ocular blood flow in the DBA/2J mouse model of glaucoma.

Materials and methods

DBA/2J mice were treated with chronic mild hyperoxia (30% O2) beginning at 4.5 months of age or were untreated by giving normal room air. Retinal and choroidal blood flow (RBF and ChBF, respectively) were measured at 4, 6, and 9 months of age by MRI. Blood flow was additionally measured under hypercapnia challenge (5% CO2 inhalation) to assess vascular reactivity. Intraocular pressure (IOP) was measured using a rebound tonometer at the same time points. Scotopic flash electroretinograms (ERGs) were recorded at 9 months of age.

Results

Both ChBF and RBF were reduced and significantly affected by age (p < 0.01), but neither were significantly affected by O2-treatment (p > 0.05). ChBF significantly increased in response to hypercapnia (p < 0.01), which was also unaffected by O2-treatment. Significant effects of age (p < 0.001) and of the interaction of age with treatment (p = 0.028) were found on IOP. IOP significantly decreased in O2-treated mice at 6 months compared to 4 months of age (p < 0.001), while IOP trended to increase with age in untreated mice. The amplitude of the b-wave from ERG was significantly increased in O2-treated DBA/2J compared to the untreated mice (p = 0.012), while the a-wave and oscillatory potentials were not significantly affected (p > 0.05).

Conclusion

This study investigated the effects of chronic mild hyperoxia on retinal function and on retinal and choroidal blood flow in a mouse model of glaucoma. Retinal function was improved in the O2-treated mice at late stage, despite a progressive decline of RBF and ChBF with age that was comparable to untreated mice.
Double drugging of prolyl-tRNA synthetase provides a new paradigm for anti-infective drug development
Authors: Manickam Yogavel , Malhotra Nipun , Mishra Siddhartha , Babbar Palak , Dusane Abhishek , Laleu Benoît , Bellini Valeria , Hakimi Mohamed-Ali , Bougdour Alexandre , Sharma Amit
Published: March 2022

Toxoplasmosis is caused by Toxoplasma gondii and in immunocompromised patients it may lead to seizures, encephalitis or death. The conserved enzyme prolyl-tRNA synthetase (PRS) is a validated druggable target in Toxoplasma gondii but the traditional ‘single target–single drug’ approach has its caveats. Here, we describe two potent inhibitors namely halofuginone (HFG) and a novel ATP mimetic (L95) that bind to Toxoplasma gondii PRS simultaneously at different neighbouring sites to cover all three of the enzyme substrate subsites. HFG and L95 act as one triple-site inhibitor in tandem and form an unusual ternary complex wherein HFG occupies the 3’-end of tRNA and the L-proline (L-pro) binding sites while L95 occupies the ATP pocket. These inhibitors exhibit nanomolar IC50 and EC50 values independently, and when given together reveal an additive mode of action in parasite inhibition assays. This work validates a novel approach and lays a structural framework for further drug development based on simultaneous targeting of multiple pockets to inhibit druggable proteins.
ISG15 deficiency restricts HIV-1 infection
Authors: Jurczyszak Denise , Manganaro Lara , Buta Sofija , Gruber Conor , Martin-Fernandez Marta , Taft Justin , Patel Roosheel S. , Cipolla Melissa , Alshammary Hala , Mulder Lubbertus C. F. , Sachidanandam Ravi , Bogunovic Dusan , Simon Viviana
Published: March 2022

Type I interferons (IFN-Is) are a group of potent inflammatory and antiviral cytokines. They induce IFN stimulated genes (ISGs), which act as proinflammatory mediators, antiviral effectors, and negative regulators of the IFN-I signaling cascade itself. One such regulator is interferon stimulated gene 15 (ISG15). Humans with complete ISG15 deficiency express persistently elevated levels of ISGs, and consequently, exhibit broad spectrum resistance to viral infection. Here, we demonstrate that IFN-I primed fibroblasts derived from ISG15-deficient individuals are more resistant to infection with single-cycle HIV-1 compared to healthy control fibroblasts. Complementation with both wild-type (WT) ISG15 and ISG15ΔGG (incapable of ISGylation while retaining negative regulation activity) was sufficient to reverse this phenotype, restoring susceptibility to infection to levels comparable to WT cells. Furthermore, CRISPR-edited ISG15koprimary CD4+T cells were less susceptible to HIV-1 infection compared to cells treated with non-targeting controls. Transcriptome analysis of these CRISPR-edited ISG15koprimary CD4+T cells recapitulated the ISG signatures of ISG15 deficient patients. Taken together, we document that the increased broad-spectrum viral resistance in ISG15-deficiency also extends to HIV-1 and is driven by a combination of T-cell-specific ISGs, with both known and unknown functions, predicted to target HIV-1 replication at multiple steps.
Non-human primate papillomavirus E6-mediated p53 degradation reveals ancient evolutionary adaptation of carcinogenic phenotype to host niche
Authors: Long Teng , Burk Robert D. , Chan Paul K. S. , Chen Zigui
Published: March 2022

Non-human primates (NHPs) are infected with papillomaviruses (PVs) closely related to their human counterparts, but there are few studies on the carcinogenicity of NHP-PVs. Using an in vitro cell co-transfection assay, we systematically screened the biochemical activity of E6 proteins encoded by macaque PVs for their ability to bind and promote degradation of host p53 proteins. A host species barrier exists between HPV16 and MfPV3 with respect to E6-mediated p53 degradation that is reversed when p53 residue 129 is swapped between human and macaque hosts. Systematic investigation found that E6 proteins encoded by most macaque PV types in the high-risk species α12, but not other Alpha-PV clades or Beta-/Gamma-PV genera, can effectively promote monkey p53 degradation. Interestingly, two macaque PV types (MfPV10 and MmPV1) can simultaneously inhibit the expression of human and monkey p53 proteins, revealing complex cross-host interactions between PV oncogenes and host proteomes. Single point-mutant experiments revealed that E6 residue 47 directly interacts with p53 residue 129 for host-specific degradation. These findings suggest an ancient host niche adaptation toward a carcinogenic phenotype in high-risk primate PV ancestors. Following periods of primate host speciation, a loss-of-function mutation model could be responsible for the formation of a host species barrier to E6-mediated p53 degradation between HPVs and NHP-PVs. Our work lays a genetic and functional basis for PV carcinogenicity, which provides important insights into the origin and evolution of specific pathogens in host pathogenesis.
Extraction of digital surface models from CORONA satellite stereo images
Authors: Meszaros Minucher , Szatmári József , Tobak Zalán , Mucsi László
Published: March 2022

Satellite images can be utilised for observing surficial changes, especially efficient in the monitoring of larger areas. The comparative analysis of high resolution images from earlier periods with recent data can provide insight in the scale of changes in topography, and with meteorological, hydrological and other historic records, can lead to better understanding and more reliable modelling of the predominant processes causing mass movement. More accurate morphometric and visual analysis of the topographic changes is possible using digital surface model (DSM), which can be obtained from satellite stereo images. In this paper, the authors evaluated methods of creation digital surface models obtained from satellite images from the CORONA program in monitoring surficial mass movement processes in the Fruška Gora mountain area, in the southern part of the Vojvodina province in Serbia. This area is of particular interest because of its favourable geographic location, rich geo- and cultural heritage and increasing demand for exploitation, which results in greater impact of natural hazards. The CORONA images were chosen because of good availability of high resolution coverage for the whole area from the period of past four decades.
Physical, chemical and biological aspects of human impacts on urban soils of Szeged (SE Hungary)
Authors: Puskás Irén , Prazsák István , Farsang Andrea , Maróy Péter
Published: March 2022

Urban soils have generally suffered significant alteration both regarding their physical, chemical, as well as biological properties. Soil samples were taken at 25 sites from horizons of soil profiles located in the downtown and surroundings of Szeged in order to examine diagnostic properties different from natural soils (artefacts, humus content, quality of organic matter, pH (H2O, KCl), carbonate content, nitrogen content). Furthermore, topsoils were taken nearby 9 profiles to survey some basic biological properties (i.e. abundance, taxon diversity, dominance, similarity and MGP ratios) of mezofauna elements (Oribatid mites, Collembolans) and their community structure in the three zones (city, suburban, peripheral). The high amount of artefacts, fluctuating humus and nitrogen levels, the poor quality of organic matter, the high and fluctuating carbonate content, the concomitant variance of pH and modified mechanical properties prove that the urban soils of Szeged have been modified by anthropogenic activities. Surprisingly, it seems that the intermediate suburban zone has a more heterogeneous and stable mezofaunal community structure than the other two.
Se persuader de ne penser à rien
Authors: Breeur Roland
Published: March 2022

I would like to suggest how Descartes seems to combine two kinds of "idiocy" in his work: In the first, he urges us to strip ourselves of our accumulated knowledge from early childhood, in order to enter again "ignorant into this world". In short, we must cultivate a form of idiocy before we can stimulate our cognitive power. And yet, in his letters to Elizabeth, he advises those who are too persistent in pursuing serious meditations (for example on the relationship between soul and body) to refrain from doing philosophy: instead, like an ignorant, one should "give all one's time to the relaxation of the senses and the rest of the mind" (FA III, 45).

What is the relation between these two forms of "ignorance"; this is the content of my article.
Pourquoi parler d'union corps/esprit chez Spinoza?
Authors: Jaquet Chantal
Published: March 2022

The paper examines the reasons why Spinoza speaks of an union body/mind instead of an unity. Indeed, according to Ethics II, XXI, scholium, « the mind and the body are one and the same individual, which is conceived now under the attribute of thought, now under the attribute of extension ». The term union implies the conjunction of two things and seems paradoxical because we deal with one and the same individual. Therefore it involves analysing the new meaning of the psychophysical union first, then showing the persistence of a classical meaning of the union concerning not so much the intermodal relation between body and mind as the intramodal relation between their parts.
Large Hepatic Adenomas and Hepatic Adenomatosis: A Multicenter Study of Risk Factors, Interventions, and Complications
Authors: Lammert Craig , Toal Emily , Mathur Karan , Khungar Vandana , House Michael , Roberts Lewis R. , Reddy K. Rajender , Chalasani Naga
Published: March 2022

INTRODUCTION:

Beyond oral contraceptives (OCs), metabolic factors have been suggested to increase the risk of hepatocellular adenoma (HCA). The impact of risks remains poorly defined, particularly among men and those with adenomatosis. Thus, we aimed to examine HCA clinical and outcome characteristics through a large multicenter cohort.

METHODS:

HCA diagnosis was made based on a combination of clinical, radiologic, and histologic criteria. Patient and clinical data including follow-up imaging, complications, and interventions were collected between 2004 and 2018 from 3 large academic centers.

RESULTS:

Among 187 patients (163 female and 24 male) with HCA, 75 had solitary HCA, 58 had multiple HCAs, and 54 had adenomatosis. Over a median follow-up of 3.3 years (quartile 1: 1.2, quartile 3: 8.8), 34 patients (18%) had radiologic interventions, 41 (21%) had surgical resections, 10 (5%) developed tumoral hemorrhage, and 1 had malignant transformation. OC and corticosteroid use were present in 70% and 16%, respectively. Obesity (51%), type 2 diabetes (24%), hypertension (42%), and hypertriglyceridemia (21%) were also common. Metabolic comorbidities were more common in patients with large HCAs and adenomatosis. Compared with women, men had less hepatic steatosis (4% vs 27%), smaller HCAs (2.3 cm vs 4.4 cm), and more corticosteroid use (38% vs 11%) (P < 0.05 for all). With OC cessation, 69% had a decrease in size of HCA, but 25% eventually required advanced interventions.

DISCUSSION:

In this large HCA cohort, obesity and metabolic comorbidities were important risk factors associated with large HCAs and adenomatosis. Long-term adverse outcomes were infrequent, 5% had tumor hemorrhage, and 1 patient exhibited malignant transformation.
Research on Machine Intelligent Perception of Urban Geographic Location Based on High Resolution Remote Sensing Images
Authors: Chen Jun , Yang Cunjian , Yu Zhengyang
Published: March 2022

Machine intelligent perception (MIP ) provides a novel way for human beings to recognize geographical locations automatically. MIP of geographical locations enables computers to describe locations automatically and quantitatively by extracting Earth's surface features and building
relationships. The earth surface fingerprint is established here by mining the relationship between spatial objects with stable characteristics extracted from urban high-resolution remote sensing images, which realizes intelligent perception of geographical location innovatively. Mask Region-based
Convolutional Neural Network is used to automatically extract the spatial objects such as playgrounds, crossroads, and bridges from the images. Then, the extracted spatial objects are encoded according to the landuse type, distance, and angle of 24 nearest objects to construct urban surface
fingerprint database. The urban surface fingerprint database is used to match the geographical location of spatial objects in local images so that the matching algorithm can be used for machine recognition of the geographical location of specific objects in the target image. Taking the main
cities in China as the experimental area, the success rate of location perception is 92%. We have made a useful exploration in the field of MIP of geographical location, hoping to promote the development of human cognition of geographical location.
Floating Solar Park Impacts Urban Land Surface Temperature Distribution Pattern
Authors: Yingjie Bo , Guoqing Li , Yelong Zeng , Zhe Liu
Published: March 2022

In recent years, the global photovoltaic industry has developed rapidly. It is significant for evaluating the impact of large-scale solar parks on the environment for the sustainable development of the photovoltaic industry. At present, researchers have paid attention to changes in
the local thermal environment caused by solar parks. As a new type of solar park, the influence of floating solar parks on urban land surface temperature distribution patterns is still unclear. In this article, we (1) take the floating solar parks in Huainan City, China, as the study area;
(2) calculate the land surface temperature (LST) of the study area and its adjacent areas by using Landsat 8 remote sensing data and the radiation transfer equation method; and (3) judge the influence of solar parks on the distribution pattern of LST. On this basis, we analyzed the influence
range and seasonal differences of floating solar parks on LST. Our results revealed that, first, the floating solar park has a warming effect in the summer and winter, and the warming area is concentrated mainly within 200 m of the photovoltaic panels' coverage area. Second, during the construction
phase and after the completion of the floating solar parks, the average monthly LST of the solar panels is generally higher than the water, and the average annual temperature increase in the above two stages is 3.26°C and 4.50°C, respectively. The change of floating solar parks on
urban LST distribution patterns may impact the local ecosystem. In the future, it is necessary to consider the impact of floating solar parks on local LST during the construction of floating solar parks.
A presença do ideário escolanovista nas primeiras décadas do século XX na educação russa pós-revolução socialista: adaptação ou superação de ideias e práticas educativas?
Authors: Oliveira Marco Aurélio Gomes de , Lucena Carlos Alberto
Published: March 2022

Este artigo tem como objetivo analisar as possíveis contribuições teóricas do ideário escolanovista para a construção da pedagogia socialista na Rússia soviética no início do século XX. Para tanto, temos o desafio de situar no tempo e no espaço as reflexões sobre a escola, a mudança de mentalidade cultural e política da população, a organização social, política e econômica da Rússia soviética. Neste artigo realizamos um recorte teórico das contribuições do ideário escolanovista a partir do referencial deweyano, especialmente, suas observações in locu das experiências educacionais soviéticas no ano de 1928. Ao evidenciar as aproximações existentes entre os princípios pedagógicos defendidos pela pedagogia ativa, de inspiração liberal, com os escritos dos educadores russos e estadistas soviéticos, analisamos as contradições postas no contexto histórico e problematizamos algumas certezas e convicções que temos acerca do “ineditismo” das propostas pedagógicas oriundas da Revolução Russa.
Asap Cair Sebagai Pemacu Pertumbuhan dan Ketahanan Tanaman Pisang terhadap Ralstonia syzygii subsp. celebesensis
Authors: Nurrahmawan Muhammad Evan , Giyanto  , Nawangsih Abdjad Asih , Sulistiani Erina
Published: March 2022

Bibit pisang hasil kultur jaringan diketahui rentan terhadap cekaman pada awal pertumbuhan di lapangan. Pra-pengondisian bibit menggunakan agens priming dilaporkan meningkatkan pertumbuhan dan ketahanan tanaman. Asap cair tempurung kelapa dilaporkan mampu memacu pertumbuhan dan menginduksi ketahanan tanaman. Penelitian ini bertujuan mendapatkan informasi pengaruh asap cair asal tempurung kelapa terhadap pertumbuhan dan aktivitas enzim ketahanan pada plantlet pisang Cavendish pada fase induksi perakaran serta penekanan R. syzygii subsp. celebesensis secara in vitro. Tahapan penelitian mencakup uji fitotoksisitas asap cair, analisis pertumbuhan plantlet, analisis aktivitas enzim peroksidase dan polifenol oksidase, isolasi R. syzygii subsp. celebesensis, dan uji toksisitas asap cair terhadap R. syzygii subsp. celebesensis secara in vitro. Hasil penelitian menunjukkan perlakuan asap cair pada konsentrasi ≥ 1.5% bersifat fitotoksik dengan gejala meliputi klorosis, nekrosis, terbentuk lendir dan kematian plantlet. Perlakuan asap cair pada konsentrasi ≤ 1% tidak bersifat fitotoksik, bahkan peningkatan pertumbuhan plantlet optimum ditunjukkan pada perlakuan asap cair 0.1%. Perlakuan asap cair menyebabkan peningkatan aktivitas enzim ketahanan pada 2, 4 dan 6 hari setelah tanam (HST), tetapi menurun pada 30 HST. Selain itu, asap cair bersifat antibakteri melalui terbentuknya zona hambat dan menyebabkan penurunan nilai kerapatan sel R. syzygii subsp. celebesensis. Penelitian ini menunjukkan potensi teknik priming untuk pengendalian penyakit darah pisang terutama pada bibit pisang hasil kultur jaringan.