Miracle-dz/UniFAR-FTUs huggingface dataset:
Doxorubicin-Loaded Mixed Micelles for the Effective Management of Skin Carcinoma: In Vivo Anti-Tumor Activity and Biodistribution Studies

Skin cancer is an alarming concern due to increased radiation and chemical exposure. Doxorubicin is a drug prescribed for various cancers by parenteral route. Apart from the pharmaceutical challenge of being a biopharmaceutical classification system (BCS) Class III drug, the side effects of doxorubicin are also a great concern. With an aim to enhance its safety and bioavailability, a phospholipid-based micellar system was developed. The developed nanometric and symmetric carriers not only offered substantial drug loading, but also offered a temporal drug release for longer durations. The pH-dependent drug release assured the spatial delivery at the target site, without loss of drug in the systemic circulation. The cancer cell toxicity studies along with the in vivo anti-tumor studies established the superior efficacy of the developed system. The blood profile studies and the biochemical estimations confirmed the safety of the developed nanocarriers. Lesser amount of drug was available for the microsomal degradation, as inferred by the biodistribution studies. The findings provide a proof of concept for the safer and effective doxorubicin delivery employing simple excipients like phospholipids for the management of skin cancer.
Exploring Strategies for Investigating the Mechanisms Linking Climate and Individual-Level Child Health Outcomes: An Analysis of Birth Weight in Mali

The goal of this article is to consider data solutions to investigate the differential pathways that connect climate/weather variability to child health outcomes. We apply several measures capturing different aspects of climate/weather variability to different time periods of in utero exposure. The measures are designed to capture the complexities of climate-related risks and isolate their impacts based on the timing and duration of exposure. Specifically, we focus on infant birth weight in Mali and consider local weather and enviromnental conditions associated with the three most frequently posited potential drivers of adverse health outcomes: disease (malaria), heat stress, and food insecurity. We focus this study on Mali, where seasonal trends facilitate the use of measures specifically designed to capture distinct aspects of climate/weather conditions relevant to the potential drivers. Results indicate that attention to the timing of exposures and employing measures designed to capture nuances in each of the drivers provides important insight into climate and birth weight outcomes, especially in the case of factors impacted by precipitation. Results also indicate that high temperatures and low levels of agricultural production are consistently associated with lower birth weights, and exposure to malarious conditions may increase likelihood of nonlive birth outcomes.
Subconcussive Head Impacts and Neurocognitive Function Over 3 Seasons of Youth Football

Objective: To determine the association between repetitive subconcussive head impacts and neurobehavioral outcomes in youth tackle football players. Methods: Using helmet-based sensors, we measured head impacts for 3 consecutive seasons of play in 29 male players age 9-11. Cumulative impact g’s were calculated. Players completed a battery of outcome measures before and after each season, including neuropsychological testing, vestibular-ocular sensitivity, and self- and parent-reported measures of symptoms and attention-deficit hyperactivity disorder (ADHD). Results: Average cumulative impact over 3 seasons was 13 900g. High-intensity hits predicted worse change for self-reported social adjustment (P = .001). Cumulative impact did not predict change in any of the outcome measures. History of ADHD, anxiety, and depression predicted worse change for self-reported symptoms and social adjustment, independent of head impacts. When players were stratified into 3 groups based on cumulative impact across all 3 seasons, differences in outcome measures existed prior to the start of the first season. These differences did not further increase over the course of the 3 seasons. Conclusion: Over 3 consecutive seasons of youth tackle football, we found no association between cumulative head impacts and neurobehavioral outcomes. Larger sample sizes and longer follow-up times would further assist in characterizing this relationship.
Benzo[e][1,2,4]triazino[2,3-c][1,2,3]triazin-2-ones electro-deficient heterocyclic compounds with promising anticancer activity

Abstract The synthesis and antitumor activity of substituted benzo[e][1,2,4]triazino[2,3-c][1,2,3]triazin-2-ones – novel electro-deficient tricyclic compounds – are described. These compounds were prepared by treatment of 3-(2-amino-3-R2-5-R3-phenyl)-6-R1-1,2,4-triazin-5(2H)-ones with sodium nitrite in acetic acid. Spectral properties of synthesized compounds were studied and compared with spectral data of known 3-R-8-R1-10-R2-2H-[1,2,4]triazino[2,3-c]quinazolin-2-ones. These compounds are promising antitumor agents. The most active anticancer compound 3d was studied in dose-depended anticancer activity assay and its selective growth inhibition against breast cancer MDA-MB-468 cell line was established (GI50=0.41 μm).
ABCC Transporters Mediate the Vacuolar Accumulation of Crocins in Saffron Stigmas[OPEN]

A transportomics approach allows identification of crocin vacuolar transporters from saffron stigmas. Compartmentation is a key strategy enacted by plants for the storage of specialized metabolites. The saffron spice owes its red color to crocins, a complex mixture of apocarotenoid glycosides that accumulate in intracellular vacuoles and reach up to 10% of the spice dry weight. We developed a general approach, based on coexpression analysis, heterologous expression in yeast (Saccharomyces cerevisiae), and in vitro transportomic assays using yeast microsomes and total plant metabolite extracts, for the identification of putative vacuolar metabolite transporters, and we used it to identify Crocus sativus transporters mediating vacuolar crocin accumulation in stigmas. Three transporters, belonging to both the multidrug and toxic compound extrusion and ATP binding cassette C (ABCC) families, were coexpressed with crocins and/or with the gene encoding the first dedicated enzyme in the crocin biosynthetic pathway, CsCCD2. Two of these, belonging to the ABCC family, were able to mediate transport of several crocins when expressed in yeast microsomes. CsABCC4a was selectively expressed in C. sativus stigmas, was predominantly tonoplast localized, transported crocins in vitro in a stereospecific and cooperative way, and was able to enhance crocin accumulation when expressed in Nicotiana benthamiana leaves.
Taking the body off the mind: Decreased functional connectivity between somatomotor and default‐mode networks following Floatation‐REST

Floatation‐Reduced Environmental Stimulation Therapy (REST) is a procedure that reduces stimulation of the human nervous system by minimizing sensory signals from visual, auditory, olfactory, gustatory, thermal, tactile, vestibular, gravitational, and proprioceptive channels, in addition to minimizing musculoskeletal movement and speech. Initial research has found that Floatation‐REST can elicit short‐term reductions in anxiety, depression, and pain, yet little is known about the brain networks impacted by the intervention. This study represents the first functional neuroimaging investigation of Floatation‐REST, and we utilized a data‐driven exploratory analysis to determine whether the intervention leads to altered patterns of resting‐state functional connectivity (rsFC). Healthy participants underwent functional magnetic resonance imaging (fMRI) before and after 90 min of Floatation‐REST or a control condition that entailed resting supine in a zero‐gravity chair for an equivalent amount of time. Multivariate Distance Matrix Regression (MDMR), a statistically‐stringent whole‐brain searchlight approach, guided subsequent seed‐based connectivity analyses of the resting‐state fMRI data. MDMR identified peak clusters of rsFC change between the pre‐ and post‐float fMRI, revealing significant decreases in rsFC both within and between posterior hubs of the default‐mode network (DMN) and a large swath of cortical tissue encompassing the primary and secondary somatomotor cortices extending into the posterior insula. The control condition, an active form of REST, showed a similar pattern of reduced rsFC. Thus, reduced stimulation of the nervous system appears to be reflected by reduced rsFC within the brain networks most responsible for creating and mapping our sense of self.
Molecular data reshape our understanding of the life cycles of three digeneans (Monorchiidae and Gymnophallidae) infecting the bivalve, Donax variabilis: it’s just a facultative host!

The coquina, Donax variabilis, is a known intermediate host of monorchiid and gymnophallid digeneans. Limited morphological criteria for the host and the digeneans’ larval stages have caused confusion in records. Herein, identities of coquinas from the United States (US) Atlantic coast were verified molecularly. We demonstrate that the current GenBank sequences for D. variabilis are erroneous, with the US sequence referring to D. fossor. Two cercariae and three metacercariae previously described in the Gulf of Mexico and one new cercaria were identified morphologically and molecularly, with only metacercariae occurring in both hosts. On the Southeast Atlantic coast, D. variabilis’ role is limited to being a facultative second intermediate host, and D. fossor, an older species, acts as both first and second intermediate hosts. Sequencing demonstrated 100% similarities between larval stages for each of the three digeneans. Sporocysts, single tail cercariae, and metacercariae in the incurrent siphon had sequences identical to those of monorchiid Lasiotocus trachinoti, for which we provide the complete life cycle. Adults are not known for the other two digeneans, and sequences from their larval stages were not identical to any in GenBank. Large sporocysts, cercariae (Cercaria choanura), and metacercariae in the coquinas’ foot were identified as Lasiotocus choanura (Hopkins, 1958) n. comb. Small sporocysts, furcocercous cercariae, and metacercariae in the mantle were identified as gymnophallid Parvatrema cf. donacis. We clarify records wherein authors recognized the three digenean species but confused their life stages, and probably the hosts, as D. variabilis is sympatric with cryptic D. texasianus in the Gulf of Mexico.
“More of a Girl Thing?” Examining the Role of Gender and Campus Context in Perceptions of Risk and the Shadow of Sexual Assault

One of the most consistent predictors of fear of crime is gender, whereby women are more fearful of crime than men, despite their lower rates of victimization. An often-cited explanation for this apparent paradox is the “shadow” of sexual assault, which has received overwhelming support in studies among college students. However, this work has been largely quantitative and rarely comparative in nature. Using in-depth qualitative interviews with 70 undergraduates attending a suburban and an urban university, the focus of the current study was to understand if and how gender shapes students’ fear of crime and perceptions of risk on campus, as well as whether the influence of gender varies across contexts. Consistent with the shadow hypothesis, this study found that students attending university in the relatively affluent suburban setting were most concerned about the sexual assault and rape of their female peers, especially by non-student outsiders. Yet in the less advantaged urban context, the shadow was missing from students’ remarks. Instead, participants believed they were most likely to be robbed and generally knew someone who had been a victim of the crime, had they not been robbed themselves. The findings from this study have theoretical implications for the role of context in the shadow of sexual assault hypothesis, as well as methodological implications for how scholars examine gender and students’ fear of crime.
Assembly of Nanofluidic MXene Fibers with Enhanced Ionic Transport and Capacitive Charge Storage by Flake Orientation.

MXenes are an emerging class of highly conductive two-dimensional (2D) materials with electrochemical storage features. Oriented macroscopic Ti3C2Tx fibers can be fabricated from a colloidal 2D nematic phase dispersion. The layered conductive Ti3C2Tx fibers are ideal candidates for constructing high-speed ionic transport channels to enhance the electrochemical capacitive charge storage performance. In this work, we assemble Ti3C2Tx fibers with a high degree of flake orientation by a wet spinning process with controlled spinning speeds and morphology of the spinneret. In addition to the effects of cross-linking of magnesium ions between Ti3C2Tx flakes, the electronic conductivity and mechanical strength of the as-prepared fibers have been improved to 7200 S cm-1 and 118 MPa, respectively. The oriented Ti3C2Tx fibers present a volumetric capacitive charge storage capability of up to 1360 F cm-3 even in a Mg-ion based neutral electrolyte, with contributions from both nanofluidic ion transport and Mg-ion intercalation pseudocapacitance. The oriented 2D Ti3C2Tx driven nanofluidic channels with great electronic conductivity and mechanical strength endows the MXene fibers with attributes for serving as conductive ionic cables and active materials for fiber-type capacitive electrochemical energy storage, biosensors, and potentially biocompatible fibrillar tissues.
Overlapping Allografts Provide Superior and More Reliable Surface Topography Matching Than Oblong Allografts: A Computer-Simulated Model Study

Background: Osteochondral allograft transplantation is 1 treatment option for focal articular cartilage defects of the knee. Large irregular defects, which can be treated using an oblong allograft or multiple overlapping allografts, increase the procedure’s technical complexity and may provide suboptimal cartilage and subchondral surface matching between donor grafts and recipient sites. Purpose: To quantify and compare cartilage and subchondral surface topography mismatch and cartilage step-off for oblong and overlapping allografts using a 3-dimensional simulation model. Study Design: Controlled laboratory study. Methods: Human cadaveric medial femoral hemicondyles (n = 12) underwent computed tomography and were segmented into cartilage and bone components using 3-dimensional reconstruction and modeling software. Segments were then exported into point-cloud models. Modeled defect sizes of 17 × 30 mm were created on each recipient hemicondyle. There were 2 types of donor allografts from each condyle utilized: overlapping and oblong. Grafts were virtually harvested and implanted to optimally align with the defect to provide minimal cartilage surface topography mismatch. Least mean squares distances were used to measure cartilage and subchondral surface topography mismatch and cartilage step-off. Results: Cartilage and subchondral topography mismatch for the overlapping allograft group was 0.27 ± 0.02 mm and 0.80 ± 0.19 mm, respectively. In comparison, the oblong allograft group had significantly increased cartilage (0.62 ± 0.43 mm; P < .001) and subchondral (1.49 ± 1.10 mm; P < .001) mismatch. Cartilage step-off was also found to be significantly increased in the oblong group compared with the overlapping group (P < .001). In addition, overlapping allografts more reliably provided a significantly higher percentage of clinically acceptable (0.5- and 1-mm thresholds) cartilage surface topography matching (overlapping: 100% for both 0.5 and 1 mm; oblong: 90% for 1 mm and 56% for 0.5 mm; P < .001) and cartilage step-off (overlapping: 100% for both 0.5 and 1 mm; oblong: 86% for 1 mm and 12% for 0.5 mm; P < .001). Conclusion: This computer simulation study demonstrated improved topography matching and decreased cartilage step-off with overlapping osteochondral allografts compared with oblong osteochondral allografts when using grafts from donors that were not matched to the recipient condyle by size or radius of curvature. These findings suggest that overlapping allografts may be superior in treating large, irregular osteochondral defects involving the femoral condyles with regard to technique. Clinical Relevance: This study suggests that overlapping allografts may provide superior articular cartilage surface topography matching compared with oblong allografts and do so in a more reliable fashion. Surgeons may consider overlapping allografts over oblong allografts because of the increased ease of topography matching during placement.
Wildfires in the Chornobyl exclusion zone—Risks and consequences

Following the 1986 Chornobyl accident, an area approaching 5000 km2 surrounding the nuclear plant was abandoned, creating the Chornobyl exclusion zone (CEZ). Although this area likely contains the most radioactive terrestrial ecosystem on earth, the absence of humans and associated activities for nearly 35 years since the accident has resulted in increases in wildlife numbers. Both the Belarussian and Ukrainian components of the CEZ are now designated as nature reserves; together they form one of Europe's largest protected areas and have been described as an iconic example of rewilding. Forests and former agricultural land (now scrub) dominate the CEZ and wildfires are an annual event. In April 2020, the CEZ suffered its most widespread fires to date when greater than 800 km2 of the 2600 km2 Ukrainian portion of the CEZ was burnt. Large‐scale fires in the CEZ have implications for wildlife, as they do elsewhere, but they also pose additional radioecological and radiological protection questions. We discuss the implications of wildfires in the CEZ, considering effects on wildlife and changes in radionuclide mobility. We also demonstrate that the risk to firefighters and the wider public from the inhalation of radionuclides in smoke resulting from fires in the CEZ is likely to be low. However, further experimental and modeling work to evaluate potential doses to firefighters from inhaled radioactive particles would be valuable, not least for reassurance purposes. Integr Environ Assess Manag 2021;17:1141–1150 © 2021 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).
Clinical effects of ursodeoxycholic acid on patients with ulcerative colitis may improve via the regulation of IL-23-IL-17 axis and the changes of the proportion of intestinal microflora

Background: We aimed to evaluate the therapeutic effect of additional ursodeoxycholic acid (UDCA) with mesalazine, compared to mesalazine alone in patients with ulcerative colitis (UC). The mechanism was evaluated by monitoring the changes of IL-23-IL-17 axis and the intestinal microflora. Methods: In this prospective, single center study, patients with UC were randomly assigned to the Mesalazine group (n=20) or the UDCA + Mesalazine group (n=20). Mayo score and Inflammatory Bowel Disease Questionnaire (IBDQ), and fecal samples for 16S rRNA sequencing and blood samples for IL-23 and IL-17 ELISA were collected for analysis. Results: Mayo scores and IBDQ score of the UDCA + Mesalazine group were significantly better than those of the Mesalazine group (P = 0.015 and P < 0.001, respectively). At post-treatment week 4, IL-23 and IL-17 levels were significantly lower in the UDCA + Mesalazine group compared to those in the Mesalazine group (both P < 0.038). In patients with UC after treatment, Firmicutes in the UDCA + Mesalazine group was higher than those in the Mesalazine group (P < 0.001). The UDCA + Mesalazine group showed lower percentage of Proteobacteria compared to those in the Mesalazine group (P < 0.001). Conclusion: Additional UDCA could provide better therapeutic effects than mesalazine alone, possibly due to the change of IL-23 and IL-17 and the proportional distribution of intestinal microflora.
Macrophage‐derived exosomes mediate silica‐induced pulmonary fibrosis by activating fibroblast in an endoplasmic reticulum stress‐dependent manner

Macrophages play a key role in silicosis, and exosomes are potent mediators of intercellular communication. This suggests that macrophage‐derived exosomes have a potential contribution to the pathogenesis of silicosis. To investigate whether macrophage‐derived exosomes promote or inhibit lung fibrosis, in vitro, silica‐exposed macrophage‐derived exosomes (SiO2‐Exos) were collected and cocultured with fibroblasts. The expression of collagen I and α‐SMA was evaluated. Furthermore, the endoplasmic reticulum (ER) stress markers BIP, XBP1s and P‐eIF2α were assessed after treatment with or without the ER stress inhibitor 4‐PBA. In vivo, mice were pre‐treated with the exosome secretion inhibitor GW4869 prior to silica exposure. After sacrifice, lung tissues were histologically examined, and the expression of proinflammatory cytokines (TNF‐α, IL‐1β and IL‐6) in bronchoalveolar lavage fluid (BALF) was measured. The results showed that the expression of collagen I and α‐SMA was up‐regulated after treatment with SiO2‐Exos, accompanied by increased expression of BIP, XBP1s and P‐eIF2α. Pre‐treatment with 4‐PBA reversed this effect. More importantly, an in vivo study demonstrated that pre‐treatment with GW4869 decreased lung fibrosis and the expression of TNF‐α, IL‐1β and IL‐6 in BALF. These results suggested that SiO2‐Exos are profibrogenic and that the facilitating effect is dependent on ER stress.
Efficacy and Safety of Mulberry Twig Alkaloids Tablet for the Treatment of Type 2 Diabetes: A Multicenter, Randomized, Double-Blind, Double-Dummy, and Parallel Controlled Clinical Trial

OBJECTIVE This study aimed to evaluate the efficacy and safety of mulberry twig alkaloids (Sangzhi alkaloids [SZ-A]) in the treatment of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS This was a multicenter, randomized, double-blind, double-dummy, and parallel controlled noninferiority clinical trial that was conducted for 24 weeks. A total of 600 patients were randomly allocated to the SZ-A group (n = 360) or acarbose group (n = 240). The primary efficacy end point was the change of glycosylated hemoglobin (HbA1c) compared with baseline. In addition, adverse events (AEs), severe AEs (SAEs), treatment-related AEs (TAEs), and gastrointestinal disorders (GDs) were monitored. RESULTS After treatment for 24 weeks, the change in HbA1c was –0.93% (95% CI –1.03 to –0.83) (–10.2 mmol/mol [–11.3 to –9.1]) and –0.87% (–0.99 to –0.76) (–9.5 mmol/mol [–10.8 to –8.3]) in the SZ-A and acarbose groups, respectively, and the least squares mean difference was –0.05% (95% CI –0.18 to 0.07) (–0.5 mmol/mol [–2.0 to 0.8]) between the two groups, with no significant difference on the basis of covariance analysis (P > 0.05). The incidence of TAEs and GDs was significantly lower in the SZ-A group than the acarbose group (P < 0.01), but no differences for AEs or SAEs between the two groups were observed (P > 0.05). CONCLUSIONS SZ-A exhibited equivalent hypoglycemic effects to acarbose in patients with T2D. Nevertheless, the incidence of TAEs and GDs was lower following SZ-A treatment than acarbose treatment, suggesting good safety.