Miracle-dz/UniFAR-FTUs huggingface dataset:
Fifty Years of JC Polyomavirus: A Brief Overview and Remaining Questions

In the fifty years since the discovery of JC polyomavirus (JCPyV), the body of research representing our collective knowledge on this virus has grown substantially. As the causative agent of progressive multifocal leukoencephalopathy (PML), an often fatal central nervous system disease, JCPyV remains enigmatic in its ability to live a dual lifestyle. In most individuals, JCPyV reproduces benignly in renal tissues, but in a subset of immunocompromised individuals, JCPyV undergoes rearrangement and begins lytic infection of the central nervous system, subsequently becoming highly debilitating—and in many cases, deadly. Understanding the mechanisms allowing this process to occur is vital to the development of new and more effective diagnosis and treatment options for those at risk of developing PML. Here, we discuss the current state of affairs with regards to JCPyV and PML; first summarizing the history of PML as a disease and then discussing current treatment options and the viral biology of JCPyV as we understand it. We highlight the foundational research published in recent years on PML and JCPyV and attempt to outline which next steps are most necessary to reduce the disease burden of PML in populations at risk.
Sestrin2 Expression Has Regulatory Properties and Prognostic Value in Lung Cancer

Lung cancer remains the most dangerous type of cancer despite recent progress in therapeutic modalities. Development of prognostic markers and therapeutic targets is necessary to enhance lung cancer patient survival. Sestrin family genes (Sestrin1, Sestrin2, and Sestrin3) are involved in protecting cells from stress. In particular, Sestrin2, which mainly protects cells from oxidative stress and acts as a leucine sensor protein in mammalian target of rapamycin (mTOR) signaling, is thought to affect various cancers in different ways. To investigate the role of Sestrin2 expression in lung cancer cells, we knocked down Sestrin2 in A549, a non-small cell lung cancer cell line; this resulted in reduced cell proliferation, migration, sphere formation, and drug resistance, suggesting that Sestrin2 is closely related to lung cancer progression. We analyzed Sestrin2 expression in human tissue using various bioinformatic databases and confirmed higher expression of Sestrin2 in lung cancer cells than in normal lung cells using Oncomine and the Human Protein Atlas. Moreover, analyses using Prognoscan and KMplotter showed that Sestrin2 expression is negatively correlated with the survival of lung cancer patients in multiple datasets. Co-expressed gene analysis revealed Sestrin2-regulated genes and possible associated pathways. Overall, these data suggest that Sestrin2 expression has prognostic value and that it is a possible therapeutic target in lung cancer.
The E3 Ubiquitin-Protein Ligase Cullin 3 Regulates HIV-1 Transcription

The infectious life cycle of the human immunodeficiency virus type 1 (HIV-1) is characterized by an ongoing battle between a compendium of cellular proteins that either promote or oppose viral replication. On the one hand, HIV-1 utilizes dependency factors to support and sustain infection and complete the viral life cycle. On the other hand, both inducible and constitutively expressed host factors mediate efficient and functionally diverse antiviral processes that counteract an infection. To shed light into the complex interplay between HIV-1 and cellular proteins, we previously performed a targeted siRNA screen to identify and characterize novel regulators of viral replication and identified Cullin 3 (Cul3) as a previously undescribed factor that negatively regulates HIV-1 replication. Cul3 is a component of E3-ubiquitin ligase complexes that target substrates for ubiquitin-dependent proteasomal degradation. In the present study, we show that Cul3 is expressed in HIV-1 target cells, such as CD4+ T cells, monocytes, and macrophages and depletion of Cul3 using siRNA or CRISPR/Cas9 increases HIV-1 infection in immortalized cells and primary CD4+ T cells. Conversely, overexpression of Cul3 reduces HIV-1 infection in single replication cycle assays. Importantly, the antiviral effect of Cul3 was mapped to the transcriptional stage of the viral life cycle, an effect which is independent of its role in regulating the G1/S cell cycle transition. Using isogenic viruses that only differ in their promotor region, we find that the NF-κB/NFAT transcription factor binding sites in the LTR are essential for Cul3-dependent regulation of viral gene expression. Although Cul3 effectively suppresses viral gene expression, HIV-1 does not appear to antagonize the antiviral function of Cul3 by targeting it for degradation. Taken together, these results indicate that Cul3 is a negative regulator of HIV-1 transcription which governs productive viral replication in infected cells.
Exploring the Reaction Paths on the Potential Energy Surfaces of the S1 and T1 States in Methylenecyclopropane

The reaction paths of methylenecyclopropane 1 on the potential energy surfaces (PESs) of the lowest triplet (T1) state and the lowest excited singlet (S1) state, as well as that of the ground state (S0), were explored by using the nudged elastic band method at the MRMP2//MCSCF/6‐31++G(d,p) and DFT(B3LYP)/6‐31++G(d,p) levels of theory. After vertical excitation of 1, three transition states on the PES of the lowest triplet state and one transition state on the S1 PES were found along the reaction path to produce a carbene, cyclobutylidene 2. All of these transition states are lower in energy than the S1 state produced by vertical excitation at the S0 energy minimum in 1. Fast transition is predicted to occur from the T1 state or from the S1 state to the S0 state due to strong spin‐orbit coupling or nonadiabatic coupling in the geometrical vicinity of 2. On the MRMP2 S0 PES, the energy barriers of 5.0, 10.3 and 13.5 kcal mol−1 were obtained for C migration reaction (backward reaction), 1,2‐H migration reaction to cyclobutene 3, and 1,3‐H migration reaction to bicyclopropane 4, respectively, started at 2. The introduction of phenyl groups makes the energy barriers smaller due to the π conjugation between the carbene center and phenyl groups.
Rosemary Flowers as Edible Plant Foods: Phenolic Composition and Antioxidant Properties in Caenorhabditis elegans

Rosmarinus officinalis L. , commonly known as rosemary, has been largely studied for its wide use as food ingredient and medicinal plant; less attention has been given to its edible flowers, being necessary to evaluate their potential as functional foods or nutraceuticals. To achieve that, the phenolic profile of the ethanolic extract of R. officinalis flowers was determined using LC-DAD-ESI/MSn and then its antioxidant and anti-ageing potential was studied through in vitro and in vivo assays using Caenorhabditis elegans. The phenolic content was 14.3 ± 0.1 mg/g extract, trans rosmarinic acid being the predominant compound in the extract, which also exhibited a strong antioxidant capacity in vitro and increased the survival rate of C. elegans exposed to lethal oxidative stress. Moreover, R. officinalis flowers extended C. elegans lifespan up to 18%. Therefore, these findings support the potential use of R. officinalis flowers as ingredients to develop products with pharmaceutical and/or nutraceutical potential.
Lateral modulation of orientation perception in center-surround sinusoidal stimuli: Divisive inhibition in perceptual filling-in

The perception of a target stimulus may be altered by its context. Perceptual filling-in is thought to be one example of lateral modulation, in which the percept of a central blank area is replaced by that of the surround. We investigated the mechanisms in eccentric vision underlying filling-in by selectively adapting the center (pedestal adapter), surround (annulus adapter), or both (disk adapter) in a sinusoidal grating and observed how the adaptation influences the orientation percept of a subsequently presented Gabor target, located at the same position as the adapter center. In a binary choice task, observers were to judge the orientation (clockwise or counterclockwise) of the target after adaptation. The tilt aftereffect (TAE), corresponding to an illusory tilt of a physically vertical Gabor target, depended both on the adapter orientation and the adapter type. The TAE, peaked between 10 degrees and 20 degrees adapter orientation, was strongest in the pedestal, followed by the disk, and weakest in the annulus adapter conditions. The difference between the disk and pedestal conditions implies lateral inhibition from the surround. Lacking physical overlap with the target, the annulus adapter nonetheless induced a small but significant TAE in the central area. The effect of filling-in on the TAE was estimated by comparing the results from trials with and without subjectively reported filling-in during adaptation to the annulus adapter. The TAE was greater when filling-in occurred during adaptation, suggesting a stronger lateral modulation effect on trials where filling-in was induced. The data were fit by a variant of a divisive inhibition model, in which the adaptation effect is captured by the increase of an additive constant in the denominator of the response function, whereas the surround modulation in the adapter is modeled by an excitatory sensitivity in the numerator.
Toxicity and human health assessment of an alcohol-to-jet (ATJ) synthetic kerosene

ABSTRACT A toxicological investigation was conducted for alcohol-to-jet (ATJ) fuels intended as a 50:50 blend with petroleum-derived fuel Jet Propulsion (JP)-8. The ATJ synthetic paraffinic kerosene (SPK) fuel was produced by Gevo (Englewood CO) and derived either from biomass (bio) or non-biomass sources. All toxicity tests were performed with one or both ATJ fuels following addition of a standard additive package required for JP-8. The primary fuel, Gevo (bio) ATJ SPK produced from biomass-derived iso-butanol, exhibited the same dermal irritation potential in rabbits as JP-8; the non-biomass-derived fuel was less irritating. The Gevo (bio) fuel was non-clastogenic in micronucleus testing with rats and neither version was mutagenic in the bacterial reverse mutation assay. A 90-day study was performed with Gevo (bio) ATJ SPK by exposing male and female Fischer 344 rats to target concentrations of 0, 200, 700 or 2000 mg/m3 of fuel, 6 hr per day, 5 days a week for 69 exposure days and included neurobehavioral assays and reproductive health evaluations in the study design. Results were negative or limited to irritant effects in the respiratory system due to exposure to a vapor and aerosol mixture in the 2000 mg/m3 exposure group. Occupational exposure limits for JP-8 were proposed for these ATJ fuels since these fuels display similar or somewhat lower toxicity than JP-8. As both versions of the Gevo ATJ jet fuel were similar, handling of either fuel alone or in a blend with petroleum-derived JP-8 appears unlikely to increase human health risks for workers.
A New Shoulder Orthosis to Dynamically Support Glenohumeral Subluxation

Objective: In this paper we presented a novel shoulder subluxation support that aims to reduce the stress on the passive structures around the shoulder of patients with glenohumeral subluxation and glenohumeral-related shoulder pain. The device applies a force to the upper arm without impeding the functional range of motion of the arm. Our design contains a mechanism that statically balances the arm with two elastic bands. Methods: A technical evaluation study was conducted to assess the performance of the orthosis. Additionally, two patients evaluated the orthosis. Results: The results of the technical validation confirm the working of the balancing mechanism. The pilot study demonstrated that the shoulder support increased the feeling of stability of the shoulder joint and, to a lesser extent, decreased shoulder pain. Furthermore, both patients reported that the orthosis did not impede their range of motion. Conclusion: In this research we developed a shoulder orthosis based on two statically balanced springs that support the shoulder of patients with glenohumeral subluxation that have residual shoulder muscle force. Compared to existing shoulder supports, our design does not impede the range of motion of the arm, and continues to provide a stabilizing force to the shoulder, even if the arm is moved away from the neutral position. Tests with two participants showed promising results. Significance: The device presented in this work could have a significant impact on the shoulder function which may improve rehabilitation outcome and improve the quality of life of patients suffering from glenohumeral subluxation and shoulder pain.
Contrasting marine carbonate systems in two fjords in British Columbia, Canada: Seawater buffering capacity and the response to anthropogenic CO2 invasion

The carbonate system in two contrasting fjords, Rivers Inlet and Bute Inlet, on the coast of British Columbia, Canada, was evaluated to characterize the mechanisms driving carbonate chemistry dynamics and assess the impact of anthropogenic carbon. Differences in the character of deep water exchange between these fjords were inferred from their degree of exposure to continental shelf water and their salinity relationships with total alkalinity and total dissolved inorganic carbon, which determined seawater buffering capacity. Seawater buffering capacity differed between fjords and resulted in distinct carbonate system characteristics with implications on calcium carbonate saturation states and sensitivity to increasing anthropogenic carbon inputs. Saturation states of both aragonite and calcite mineral phases of calcium carbonate were seasonally at or below saturation throughout the entire water column in Bute Inlet, while only aragonite was seasonally under-saturated in portions of the water column in Rivers Inlet. The mean annual saturation states of aragonite in Rivers Inlet and calcite in Bute Inlet deep water layers have declined to below saturation within the last several decades due to anthropogenic carbon accumulation, and similar declines to undersaturation are projected in their surface layers as anthropogenic carbon continues to accumulate. This study demonstrates that the degree of fjord water exposure to open shelf water influences the uptake and sensitivity to anthropogenic carbon through processes affecting seawater buffering capacity, and that reduced uptake but greater sensitivity occurs where distance to ocean source waters and freshwater dilution are greater.
Adventitious bud formation and plantlet regeneration from leaves of fig (Ficus carica L.)

Summary Leaf fragments of fig (Ficus carica L. ‘Masui Dauphine’) regenerated from in vitro shoot culture were excised and inoculated on MS medium supplemented with different combinations of 2, 4-D, TDZ, and 0.5 mM phloroglucinol. Addition of 2, 4-D induced root formation directly on the explant, and the presence of phloroglucinol significantly increased root formation. When a combination of 2, 4-D and TDZ was added to MS medium containing phloroglucinol, the explants started to produce adventitious buds at the edges. The addition of phloroglucinol was effective in inducing adventitious bud formation. Excised shoots were rooted successfully in MS medium that was either hormone free or supplemented with 1.0 mg l–1 indolebutyric acid. Regenerated plantlets were successfully established in soil after a short period of acclimatization. This is the first protocol of organogenesis and plant regeneration from vegetative organs of Ficus carica L.
Childhood Mortality After Fluid Bolus With Septic or Severe Infection Shock: A Systematic Review and Meta-Analysis

Supplemental Digital Content is available in the text ABSTRACT Background: A considerable debate on whether fluid bolus could decrease childhood mortality in pediatric patients with septic or severe infection shock is still unresolved. A systematic review and meta-analysis was conducted to investigate the mortality rates after fluid bolus among children with septic or severe infection shock. Methods: A systematic electronic search of PubMed, MEDLINE, Cochrane Library, and EMBASE databases was conducted to identify relevant published studies till March 30, 2020. Results: A total of 19 studies with 9,321 severe sepsis or septic shock pediatric patients were included and exhibited an acceptable quality. Of the 17 studies that reported mortality at 48 h, no bolus group decreased the mortality rate when compared with bolus group with a risk ratio (RR) of 0.74 [95% confidence interval (CI) = 0.62–0.88, P < 0.01], and showed no heterogeneity (I2 = 0%). Similar results were observed on colloids and crystalloids solution in malaria shock cases with a RR of 0.79 (95% CI = 0.62–1.02). For the subgroup of general shock patients, no significant difference was shown with an RR of 0.79 (95% CI = 0.62–1.02, P = 0.07) and no significant heterogeneity (I2 = 0%). Two studies reported mortality at week 4 and pooled results indicated that no bolus group was protective against mortality when compared with bolus group with RR of 0.71 (95% CI = 0.57–0.88, I2 = 0%). Conclusion: For the mortality at 48 h, the no bolus group showed decreased mortality when compared with the bolus group, especially in the malaria group. Similar results were found in the colloids and crystalloids solution in patients with malaria shock. Meta-analysis studies with long-term follow-up period and larger sample size are warranted to address the conclusion in the future.
Score performance of SAPS 2 and SAPS 3 in combination with biomarkers IL-6, PCT or CRP

Objective We aimed to evaluate the effects of combining the Simplified-Acute-Physiology-Score (SAPS) 2 or the SAPS 3 with Interleukin-6 (IL-6) or Procalcitonin (PCT) or C-Reactive Protein (CRP) concentrations for predicting in-hospital mortality. Material and methods This retrospective study was conducted in an interdisciplinary 22-bed intensive care unit (ICU) at a German university hospital. Within an 18-month period, SAPS 2 and SAPS 3 were calculated for 514 critically ill patients that were admitted to the internal medicine department. To evaluate discrimination performance, the area under the receiver operating characteristic curves (AUROCs) and the 95% confidence intervals (95% CIs) were calculated for each score, exclusively or in combination with IL-6 or PCT or CRP. DeLong test was used to compare different AUROCs. Results The SAPS 2 exhibited a better discrimination performance than SAPS 3 with AUROCs of 0.81 (95% CI, 0.76–0.86) and 0.72 (95% CI, 0.66–0.78), respectively. Overall, combination of the SAPS 2 with IL-6 showed the best discrimination performance (AUROC 0.82; 95% CI, 0.77–0.87), albeit not significantly different from SAPS2. IL-6 performed better than PCT and CRP with AUROCs of 0.75 (95% CI, 0.69–0.81), 0.72 (95% CI, 0.66–0.77) and 0.65 (95% CI, 0.59–0.72), respectively. Performance of the SAPS 3 improved significantly when combined with IL-6 (AUROC 0.76; 95% CI, 0.69–0.81) or PCT (AUROC 0.73; 95% CI, 0.67–0.78). Conclusions Our analysis provided evidence that the risk stratification performance of the SAPS 3 and, to a lesser degree, also of the SAPS 2 can increase when combined with IL-6. A more accurate detection of aberrant or dysregulated systemic immunological responses (by IL-6) may explain the higher performance achieved by SAPS 3 + IL-6 vs. SAPS 3. Thus, implementation of IL-6 in critical care scores can improve prediction outcomes, especially in patients experiencing acute inflammatory conditions; however, statistical results may vary across hospital types and/or patient populations with different case mix.
Performance of Air-Stable Cs2SnI6 Perovskite as Electron Transport Layer in Inverted Bulk Heterojunction Solar Cell

In recent years, perovskite material has been extensively studied due to its unique physical properties and promising application in the third generation of solar cells. In particular, Sn-based perovskite has been considered to replace Pb-based perovskite because of the toxic effects and it can lead to other serious problems related to the environment. Cs2SnI6 perovskite has been known to be synthesized in a simple chemical process and it can be produced on a large scale. Moreover, this material is also oxygen and moisture stable due to the high oxidation state of tin. In this study, we synthesize air-stable Cs2SnI6 perovskite by the use of the wet chemical process at room temperature. Next, we attempt to fabricate the inverted bulk heterojunction solar cells incorporated Cs2SnI6 as electron transport layer in the configuration of ITO/ZnO/Cs2SnI6/P3HT:PCBM/PEDOT:PSS/Ag to improve device performance. The Cs2SnI6 perovskite shows an Fm-3m space group with a cubic lattice parameter of 11. 62Å confirmed by X-Ray Diffraction (XRD) measurement, while UV-Vis measurement indicates this type of perovskite has direct band gap ~3.1 eV. The fabricated solar cell device reveals the enhancement in current density at short circuit condition (Jsc) from 64.69 mA/cm2 to 77.02 mA/cm2 with the addition of 2.25 mg/ml Cs2SnI6 along with the enhancement of power conversion efficiency (PCE) from 7.05% to 9.75% as characterized by J-V measurement. In our case, the voltage at open circuit condition (Voc) of the device does not perform significant improvement. Besides, it is found that the solar cell devices are quite stable even after exposure in the air for six weeks after fabrication, as indicated by PCE performance.
The Effect of Herbal Infusion on Fasting Blood Glucose (FBS) and Malondyaldehyde (MDA) Levels in Diabetic Rats

Aloe vera, ginger, and sappan wood have recently gained attention as a potent antioxidant. This study was undertaken to analyze the possible effects of oral administration of herbal infusion (the combination of Aloe vera, ginger, and sapang wood) on fasting blood glucose (FBS) and malondialdehyde (MDA) levels in diabetic rats. Forty male albino rats (150-250 gm) were divided into five groups (n=8 in each group): alloxan-induced diabetic (negative control group/K-), acarbose treated (positive control group/K+), diabetic rats treated with herbal infusion dose 6.75 mg/150 gmbw (P1), diabetic rats treated with herbal infusion dose 13.5 mg/150 gmbw (P2), and diabetic rats treated with herbal infusion dose 20.25 mg/150 gmbw (P3). Male albino rats induced with a dose of alloxan 120 mg/kgbw and also 5% glucose after 6 hours of alloxan induction. FBS and MDA levels of each rat were measured before induction of alloxan was performed as a control sample. After seven days and 14 days of herbal infusion administration, FBS parameters was investigated with a glucometer. In the last week, the concentration of MDA in serum blood was determined using a UV-VIS spectrophotometer with a wavelength of 545 nm. Diabetic rats exhibited a significant decrease in FBS and MDA. Administration of herbal infusion was reduced FBS significantly between groups (ANOVA, Bonferroni, p<0.05). The concentration of MDA in serum blood was decreased significantly on K-, K+, P1, P2, P3 compared to the control group (ANOVA, LSD, P<0.05). It could be postulated herbal infusion has anti-hyperglycemic and anti-diabetic effects of FBS and MDA in male albino rats Wistar strain.