Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacokinetic variables of medium molecular weight cross linked chitosan nanoparticles to enhance the bioavailability of 5-fluorouracil and reduce the acute oral toxicity

Abstract To prepare glutaraldehyde-based cross-linked medium molecular weight chitosan nanoparticles encapsulated with 5-Fluorouracil (5-FU), to overcome dosing frequency as well as reducing acute oral toxicity and poor bioavailability of the drug. Medium molecular weight chitosan nanoparticles (MMWCH-NPs) were prepared by reverse micelles method based on glutaraldehyde (GA) cross-linking and optimized by the process as well as formulation variables like a various drug to polymer ratio, cross-linker volumes, varying stirring speeds (rpm), different time of rotation/stirring, respectively and their effects on the mean particles size distribution and entrapment efficiency %EE and %LC of NPs. Characterization of formulations was done by FTIR studies, TEM, PXRD, TGA, Stability, and dissolution drug release studies were performed by dialysis bag technique at both pH (1.2 & 7.4) and acute oral toxicity studies in albino rabbits. The formulated nanoparticles showed a smooth morphology with smaller particle size distribution (230–550 nm), zeta potential (−15 to −18 mV) required to achieve enhanced permeation and retention effect (EPR), entrapment efficiency (%EE 12–59%). These NPs exhibited a controlled drug release profile with 84.36% of the drug over a period of 24 h. Drug release data were fitted to different kinetic models which predominantly followed Fickian diffusion mechanism (R2 = 0.972–0.976, N = 0.326–0.256). The optimized formulation (5-FU6) was observed under DSC/TGA, TEM. PXRD curves, FTIR, which confirmed thermal stability, structural integrity, amorphous state, compatibility between drug and polymer of optimized (5-FU6) as well as reduced acute oral toxicity in albino rabbits. Cross-linked medium molecular weight chitosan nanoparticles are nontoxic, well-tolerated therefore could be the future candidate for therapeutic effects as novel drug delivery carrier for anticancer drug(s).
Oral Antibiotics and Risk of New Colorectal Adenomas During Surveillance Follow-up

Background: Antibiotics may increase colorectal neoplasia risk by modifying the gut microbiome. It is unknown whether use is associated with the risk of new colorectal adenomas among individuals with prior adenomas. Methods: We performed a secondary analysis of four randomized clinical trials for the chemoprevention of colorectal adenomas. Participants self-reported all currently used prescription drugs shortly after an initial colorectal adenoma diagnosis and two or three times a year thereafter over 3 to 5 years of follow-up. We estimated adjusted risk ratios (RR) with 95% confidence intervals (CI) for incident adenomas, analyzing the four trials together. Results: Cumulatively, the four trials enrolled 5,174 participants (3,491 men and 1,683 women), of whom 4,769 (92%) completed ≥1 follow-up colonoscopy. A total of 763 (15%) participants reported using oral antibiotics on ≥2 occasions. Overall, 39% of those using oral antibiotics at least twice developed new colorectal adenomas compared with 40% of those with no use or a single report of use (RR, 0.99; 95% CI, 0.90–1.10). No statistically significant associations were found in study-specific analyses, and results were similar for high- and low-risk adenoma findings, antibiotic class, anatomic location of adenomas, and analyses excluding those with interim colorectal exams. Conclusions: Oral antibiotic use during colonoscopic surveillance after an initial adenoma diagnosis was not associated with risk of these polyps. Impact: Any changes to the gut microbiome as a consequence of oral antibiotic use during surveillance may not affect the development of metachronous colorectal adenomas.
Timing and dosage of FES cycling early after acute spinal cord injury: A case series report

Objective To understand the progression in parameters of functional electrical stimulation (FES) cycling dosage (including duration, velocity, stimulation amplitudes, power output), and the resulting changes in muscle mass early after acute spinal cord injury (SCI). Methods Three participants, 24–38 years old, with neurological injury level C4–T4, severity AIS (American Spinal Injury Association Impairment Scale) A–C, started FES cycling 16–20 days post injury while admitted at a level-1 trauma center in Canada, and continued for 8–13 weeks in a rehabilitation hospital. They performed three sessions/week of 15–45 min FES cycling, supine or sitting. FES parameters, cycling performance, and muscle cross-sectional area (CSA) in thighs and calves were measured every 2 weeks. Results Progression in power output, but not in session duration, was limited in two participants who experienced stimulation-associated referred pain or apprehension, requiring limitation of stimulation amplitudes for up to 65 days after the start of FES cycling. Participants started with 15 min cycling at 20 RPM with no resistance (0 W), and progressed to 30–45 min at 30 RPM producing 8.8–19.0 W average power/session after 2–3 months. Initially, muscle CSA decreased in all 3 participants (up to 16% after 6 weeks), and recovered later after a variable period of FES cycling (up to 16% at 13.3 weeks). Conclusion Progression of FES cycling in the first 3 months after injury required a highly individualized approach, guided by participant response, rather than standardized increments in stimulation intensity or duration. Changes in muscle CSA did not always correspond with the dose of FES cycling.
Using decision tree analysis to understand the influence of social networks on disclosure of HIV infection status

ABSTRACT Disclosure of human immunodeficiency virus (HIV) infection status improves treatment adherence and HIV prevention. Social networks influence such disclosure by people living with HIV/AIDS (PLWH). This study aimed to investigate the disclosure status of Korean PLWH and determine the social network characteristics associated with disclosure. A cross-sectional study design was used, and 148 Korean PLWH answered self-report questionnaires that included items on the characteristics of social networks and disclosure. Logistic regression and decision tree analysis were performed. In total, 81 participants (54.7%) reported disclosing HIV status to the most important supporter. Five factors were found to influence disclosure: age, self-help group participation, living arrangement, social network relationship, and tie strength; three groups had higher percentages of nondisclosure. The findings suggest that healthcare practitioners should provide adequate counseling by considering the characteristics of social networks and disclosure status of PLWH. Researchers should identify high-risk populations using decision tree analysis.
Binocular vision supports the development of scene segmentation capabilities: Evidence from a deep learning model

The application of deep learning techniques has led to substantial progress in solving a number of critical problems in machine vision, including fundamental problems of scene segmentation and depth estimation. Here, we report a novel deep neural network model, capable of simultaneous scene segmentation and depth estimation from a pair of binocular images. By manipulating the arrangement of binocular image pairs, presenting the model with standard left-right image pairs, identical image pairs or swapped left-right images, we show that performance levels depend on the presence of appropriate binocular image arrangements. Segmentation and depth estimation performance are both impaired when images are swapped. Segmentation performance levels are maintained, however, for identical image pairs, despite the absence of binocular disparity information. Critically, these performance levels exceed those found for an equivalent, monocularly trained, segmentation model. These results provide evidence that binocular image differences support both the direct recovery of depth and segmentation information, and the enhanced learning of monocular segmentation signals. This finding suggests that binocular vision may play an important role in visual development. Better understanding of this role may hold implications for the study and treatment of developmentally acquired perceptual impairments.
Systematic Review of Self-Monitoring of Blood Glucose in Patients With Type 2 Diabetes

Background The benefit of self-monitoring of blood glucose in reducing HbA1c in non-insulin-treated participants remains unclear. HbA1c may be improved in this population with said self-monitoring. Objective The aim of this study was to conduct meta-analyses of glycemic control in non-insulin-treated participants with Type 2 diabetes: self-monitoring of blood glucose versus usual care, structured versus unstructured self-monitoring of blood glucose, and use of self-monitoring of blood glucose readings by clinicians to adjust (or modify) therapy versus usual care. Methods MEDLINE, Embase, and Cochrane Central were electronically searched to identify articles published from January 1, 2000, to June 30, 2020. Trials investigating changes in HbA1c were selected. Screening was performed independently by two investigators. Two investigators extracted HbA1c at baseline and follow-up for each trial. Results Nineteen trials involving 4,965 participants were included. Overall, self-monitoring of blood glucose reduced HbA1c. Preplanned subgroup analysis showed that using self-monitoring of blood glucose readings to adjust therapy contributed significantly to the reduction. No significant improvement in HbA1c was shown in self-monitoring of blood glucose without therapy adjustment. The same difference was observed in structured versus unstructured self-monitoring of blood glucose. Discussion HbA1c is improved with clinician therapy modification based on structured self-monitoring of blood glucose readings. Implications are for clinicians to prescribe structured self-monitoring of blood glucose to modify therapy based on the readings and not prescribe unstructured self-monitoring of blood glucose. Participants with suboptimal glycemic control may benefit most. A self-monitoring of blood glucose regimen that improves clinical and cost-effectiveness is presented. Future studies can investigate this regimen specifically.
SRSF5 regulates alternative splicing of DMTF1 pre-mRNA through modulating SF1 binding

ABSTRACT Among the three DMTF1 splicing isoforms, DMTF1α acts as a tumour suppressor through promoting p14ARF expression, while DMTF1β exhibits an oncogenic role likely through antagonizing DMTF1α. However, the molecular mechanism underlying alternative splicing of DMTF1 pre-mRNA has not been delineated. In the current study, we discovered SRSF5 as a regulatory protein binding to a region located between DMTF1β and α acceptor splice sites to promote DMTF1β and γ splicing. We demonstrated that SRSF5 expression positively correlated with DMTF1β/α ratio in breast cancer samples, and ectopically expressed SRSF5 promoted the splicing of DMTF1β and γ, but not DMTF1α, when testing endogenous DMTF1 pre-mRNA and a reporter construct. Upon SRSF5 knockdown, we observed significantly decreased DMTF1β and γ ratios of endogenous transcripts. An RNA sequence just upstream of the α acceptor site contains two adjacent SRSF5 binding elements, one of which overlaps with an SF1 binding site. Our mechanistic studies revealed that SRSF5 binding to both elements in this region could consign SF1 to its distal-binding sites close to the β and γ acceptor sites, favouring splicing of their isoforms. Overall, our study revealed SRSF5 as a key regulator to promote DMTF1β and γ splicing, and consequently reduce DMTF1α splicing. Abbreviations ARF: alternative reading frame, that is, p14ARF, or CDKN2A (cyclin-dependent kinase inhibitor 2A); β-gal: β-galactosidase; CLIP-seq: crosslinking and immunoprecipitation-sequencing; DMTF1: the cyclin D binding myb-like transcription factor 1; ESS/ESE: exonic splicing silencer/enhancer; Ex: exon; FBS: fetal bovine serum; Gluc: Gaussia luciferase; hnRNPs: heterogeneous nuclear ribonucleoproteins; In: intron; ISS/ISE: intronic splicing silencer/enhancer; PBS: phosphate-buffered saline; PCR: polymerase chain reaction; PSI: percent-splice-in; qPCR: quantitative real-time PCR; RIP: RNA immunoprecipitation; RNAseq: RNA sequencing; RT: reverse transcription; SF1: splicing factor 1; SR: serine/arginine-rich proteins; SRSF5: serine and arginine-rich splicing factor 5; TCGA: the cancer genome atlas; UCSC: University of California, Santa Cruz. WT: Wild type
Induction of mucosal immunity by pulmonary administration of a cell-targeting nanoparticle

Abstract We previously found that a nanoparticle constructed with an antigen, benzalkonium chloride (BK) and γ-polyglutamic acid (γ-PGA) showed high Th1 and Th2-type immune induction after subcutaneous administration. For prophylaxis of respiratory infections, however, mucosal immunity should be induced. In this study, we investigated the effect of pulmonary administration of a nanoparticle comprising ovalbumin (OVA) as a model antigen, BK, and γ-PGA on induction of mucosal immunity in the lungs and serum. The complex was strongly taken up by RAW264.7 and DC2.4cells. After pulmonary administration, lung retention was longer for the OVA/BK/γ-PGA complex than for OVA alone. OVA-specific serum immunoglobulin (Ig)G was highly induced by the complex. High IgG and IgA levels were also induced in the bronchoalveolar lavage fluid, and in vivo toxicities were not observed. In conclusion, we effectively and safely induced mucosal immunity by pulmonary administration of an OVA/BK/γ-PGA complex.
Serum N‐terminal pro‐B‐type natriuretic peptide, macrophage inhibitor cytokine‐1, and cognitive functions in hemodialysis patients

I read with great interest the article by Akkus et al., examining the association of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and macrophage inhibitor cytokine-1 (MIC-1) with cognitive functions in hemodialysis patients. They found that 77% patients had impaired cognitive functions, defined as a Montreal Cognitive Assessment (MoCA) total score <24. Although the NT-proBNP level was inversely associated with the MoCA Test Delayed Recall and Total Scores, MIC-1 exhibited no significant association with cognitive functions. I have two comments regarding the discrepancies in the association of NT-proBNP and MIC-1 with cognitive functions and other health outcomes. First, Chen et al. reported that serum NT-proBNP could predict recurrent emergency department (ED) visits, hospitalization, admission to intensive-care units, cardiovascular events, and mortality in hemodialysis patients. Specifically, NT-proBNP could predict ED visits in the short term, and mortality in the long term. The predictive ability of serum NT-proBNP for clinical outcomes differed over different follow-up times. I suspect that cognitive functions in hemodialysis patients may change with time and the interaction between multiple factors in aging hemodialysis patients. A causal relationship should thus be assessed via comprehensive prospective/intervention studies. Second, Rothenbacher et al. investigated the association of the baseline levels of growth differentiation factor-15 (GDF-15) with mortality in community dwelling older adults. GDF-15 is identical to MIC-1, and its levels are significantly associated with the levels of CRP, IL-6, NT-proBNP, high-sensitive troponins, lipids, and metabolic and endocrine markers, as well as with kidney function. Moreover, GDF-15 was significantly associated with gait speed, hand grip strength, and walking duration. Furthermore, the adjusted hazard ratio (95% confidence interval) per unit increase of log-transformed GDF-15 for mortality was 1.72 (1.35–2.18). The authors thus concluded that GDF-15 could be recommended as a useful biomarker for predicting 8-year all-cause mortality. As GDF-15 is closely related to kidney function in older adults, I suspect that GDF-15 may have different implications in individuals without renal failure. In any case, the lack of an association between MIC-1 and cognitive function should be investigated in further studies.
Construction of an immune-related lncRNA pairs model to predict prognosis and immune landscape of lung adenocarcinoma patients

ABSTRACT The model of immune-related lncRNA pairs (IRLPs) seems to be an available predictor in lung adenocarcinoma (LUAD) patients. The aim of our study was to construct a model with IRLPs to predict the survival status and immune landscape of LUAD patients. Based on TCGA-LUAD dataset, a risk assessment model with IRLPs was established. Then, ROC curves were used to assess the predictive accuracy and effectiveness of our model. Next, we identified the difference of survival, immune cell infiltration, immune checkpoint inhibitor-related (ICI-related) biomarkers, and chemotherapeutics between high-risk group and low-risk group. Finally, A nomogram was built for predicting the survival rates of LUAD patients. 464 LUAD samples were randomly and equally divided into a training set and a test set. Six IRLPs were screened out to construct a risk model. K-M analysis and risk-plot suggested the prognosis of high-risk group was worse than low-risk group (p < 0.001). Multivariate analysis shows risk score was independent risk factor of LUAD (p < 0.001). In addition, the expression of immune cell infiltration, ICI-related biomarkers, chemotherapeutics all demonstrate significant difference in two groups. A nomogram was built that could predict the 1-, 3-, and 5-year survival rates of LUAD patients. Our immune-related lncRNA pairs risk model is expected to be a reliable model for predicting the prognosis and immune landscape of LUAD patients. Graphical Abstract
Contrast-enhanced ultrasound Liver Imaging Reporting and Data System category M: a systematic review and meta-analysis

Purpose A meta-analysis was conducted to determine the proportion of contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System category M (LR-M) in hepatocellular carcinomas (HCCs) and non-HCC malignancies and to investigate the frequency of individual CEUS LR-M imaging features. Methods The MEDLINE and Embase databases were searched from January 1, 2016 to July 23, 2020 for studies reporting the proportion of CEUS LR-M in HCC and non-HCC malignancies. The meta-analytic pooled proportions of HCC and non-HCC malignancies in the CEUS LR-M category were calculated. The meta-analytic frequencies of CEUS LR-M imaging features in nonHCC malignancies were also determined. Risk of bias and applicability were evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results Twelve studies reporting the diagnostic performance of the CEUS LR-M category were identified, as well as seven studies reporting the frequencies of individual CEUS LR-M imaging features. The pooled proportions of HCC and non-HCC malignancies in the CEUS LR-M category were 54% (95% confidence interval [CI], 44% to 65%) and 40% (95% CI, 28% to 53%), respectively. The pooled frequencies of individual CEUS LR-M imaging features in non-HCC malignancies were 30% (95% CI, 17% to 45%) for rim arterial phase hyperenhancement, 79% (95% CI, 66% to 90%) for early (<60 s) washout, and 42% (95% CI, 21% to 64%) for marked washout. Conclusion In total, 94% of CEUS LR-M lesions were malignancies, with HCCs representing 54% and non-HCC malignancies representing 40%. The frequencies of individual CEUS LR-M imaging features varied; early washout showed the highest frequency for non-HCC malignancies.
Cytotoxicity of Sarcosphaera crassa and Tricholoma terreum extracts on colon cancer cell line (HT-29) in conjunction with their antioxidant properties

ABSTRACT The purpose of this study was to investigate and compare the antioxidant and cytotoxic activities of Sarcosphaera crassa and Tricholoma terreum extracts. Phenolic compounds analysis of both mushroom extracts has been carried out by HPLC. Antioxidant activities of the extracts were tested by using in vitro assays. The cytotoxicity of extracts on HT-29 cell line were determined by the WST assay. The total phenolic and total flavonoid contents of T. terreum extracts were higher than those S. crassa. Also, we detected that T. terreum extracts had higher total antioxidant activity and scavenging ability on DPPH radicals than S. crassa extracts. However, the T. terreum methanol extracts showed 27% cytotoxic effect in HT-29 cell line whereas the ethanolic extracts of S. crassa showed cytotoxicity 45%. These results indicate that both mushroom extracts have considerable cytotoxic and antioxidant properties and may be utilized as a promising source of therapeutics.
Monoamine Oxidase-B Inhibition Facilitates α-Synuclein Secretion In Vitro and Delays Its Aggregation in rAAV-Based Rat Models of Parkinson's Disease

Cell-to-cell transmission of α-synuclein (α-syn) pathology is considered to underlie the spread of neurodegeneration in Parkinson's disease (PD). Previous studies have demonstrated that α-syn is secreted under physiological conditions in neuronal cell lines and primary neurons. However, the molecular mechanisms that regulate extracellular α-syn secretion remain unclear. In this study, we found that inhibition of monoamine oxidase-B (MAO-B) enzymatic activity facilitated α-syn secretion in human neuroblastoma SH-SY5Y cells. Both inhibition of MAO-B by selegiline or rasagiline and siRNA-mediated knock-down of MAO-B facilitated α-syn secretion. However, TVP-1022, the S-isomer of rasagiline that is 1000 times less active, failed to facilitate α-syn secretion. Additionally, the MAO-B inhibition-induced increase in α-syn secretion was unaffected by brefeldin A, which inhibits endoplasmic reticulum (ER)/Golgi transport, but was blocked by probenecid and glyburide, which inhibit ATP-binding cassette (ABC) transporter function. MAO-B inhibition preferentially facilitated the secretion of detergent-insoluble α-syn protein and decreased its intracellular accumulation under chloroquine-induced lysosomal dysfunction. Moreover, in a rat model (male Sprague Dawley rats) generated by injecting recombinant adeno-associated virus (rAAV)-A53T α-syn, subcutaneous administration of selegiline delayed the striatal formation of Ser129-phosphorylated α-syn aggregates, and mitigated loss of nigrostriatal dopaminergic neurons. Selegiline also delayed α-syn aggregation and dopaminergic neuronal loss in a cell-to-cell transmission rat model (male Sprague Dawley rats) generated by injecting rAAV-wild-type α-syn and externally inoculating α-syn fibrils into the striatum. These findings suggest that MAO-B inhibition modulates the intracellular clearance of detergent-insoluble α-syn via the ABC transporter-mediated non-classical secretion pathway, and temporarily suppresses the formation and transmission of α-syn aggregates. SIGNIFICANCE STATEMENT The identification of a neuroprotective agent that slows or stops the progression of motor impairments is required to treat Parkinson's disease (PD). The process of α-synuclein (α-syn) aggregation is thought to underlie neurodegeneration in PD. Here, we demonstrated that pharmacological inhibition or knock-down of monoamine oxidase-B (MAO-B) in SH-SY5Y cells facilitated α-syn secretion via a non-classical pathway involving an ATP-binding cassette (ABC) transporter. MAO-B inhibition preferentially facilitated secretion of detergent-insoluble α-syn protein and reduced its intracellular accumulation under chloroquine-induced lysosomal dysfunction. Additionally, MAO-B inhibition by selegiline protected A53T α-syn-induced nigrostriatal dopaminergic neuronal loss and suppressed the formation and cell-to-cell transmission of α-syn aggregates in rat models. We therefore propose a new function of MAO-B inhibition that modulates α-syn secretion and aggregation.