Miracle-dz/UniFAR-FTUs huggingface dataset:
Quality by design enabled the development of stable and effective oil-in-water emulsions at compounding pharmacy: the case of a sunscreen formulation

Abstract It is widely accepted that the use of topical sunscreens has medical importance with potential to prevent skin damage by protecting from solar ultraviolet radiation (UVR) effects. Pharmaceutical emulsions require an optimal qualitative and quantitative combination of emollients, emulsifiers and others compounds such as softening agents and, for sunscreens, a combination of chemical and physical UV filters. Herein, we applied the quality by design (QbD) concept to achieve stable and effective compounded sunscreen emulsions. By using the statistical tool of design of experiments, it was possible to identify the influence of emulsifier type (with low and high Hydrophile-Lipophile Balance) and concentrations of emollient and softening agent on the achievement of formulations with suitable organoleptic and physicochemical features. Compounded emulsions with pleasant macroscopic aspects were obtained. Three formulations with physicochemical properties in targeted ranges were selected, namely pH ∼6.0, conductivity > 0.0 µS/cm2, spreadability factor ∼1–1.5 g/mm2, viscosity ∼12000 mPa.s and sunscreen protection factor ∼30. Freeze-thaw cycle and accelerated stability study under different storage conditions allowed selecting a stable emulsion that ensured photoprotection in biological assays. The QbD approach was essential to select the best, low-cost compounded sunscreen emulsion, with targeted physicochemical parameters.
Temporal relationship between systemic endothelial dysfunction and alterations in erythrocyte function in a murine model of chronic heart failure

Abstract Aims Endothelial dysfunction (ED) and red blood cell distribution width (RDW) are both prognostic factors in heart failure (HF), but the relationship between them is not clear. In this study, we used a unique mouse model of chronic HF driven by cardiomyocyte-specific overexpression of activated Gαq protein (Tgαq*44 mice) to characterize the relationship between the development of peripheral ED and the occurrence of structural nanomechanical and biochemical changes in red blood cells (RBCs). Methods and results Systemic ED was detected in vivo in 8-month-old Tgαq*44 mice, as evidenced by impaired acetylcholine-induced vasodilation in the aorta and increased endothelial permeability in the brachiocephalic artery. ED in the aorta was associated with impaired nitric oxide (NO) production in the aorta and diminished systemic NO bioavailability. ED in the aorta was also characterized by increased superoxide and eicosanoid production. In 4- to 6-month-old Tgαq*44 mice, RBC size and membrane composition displayed alterations that did not result in significant changes in their nanomechanical and functional properties. However, 8-month-old Tgαq*44 mice presented greatly accentuated structural and size changes and increased RBC stiffness. In 12-month-old Tgαq*44 mice, the erythropathy was featured by severely altered RBC shape and elasticity, increased RDW, impaired RBC deformability, and increased oxidative stress (gluthatione (GSH)/glutathione disulfide (GSSG) ratio). Moreover, RBCs taken from 12-month-old Tgαq*44 mice, but not from 12-month-old FVB mice, coincubated with aortic rings from FVB mice, induced impaired endothelium-dependent vasodilation and this effect was partially reversed by an arginase inhibitor [2(S)-amino-6-boronohexanoic acid]. Conclusion In the Tgαq*44 murine model of HF, systemic ED accelerates erythropathy and, conversely, erythropathy may contribute to ED. These results suggest that erythropathy may be regarded as a marker and a mediator of systemic ED in HF. RBC arginase and possibly other RBC-mediated mechanisms may represent novel therapeutic targets for systemic ED in HF.
Neighborhood poverty, allostatic load, and changes in cellular aging in African American young adults: the moderating role of attachment

ABSTRACT Attachment experiences are thought to contribute to physical health across the lifespan. Evidence suggests that attachment style may serve as a protective factor for individuals’ physical health by mitigating the negative effects of social and environmental risk factors. In the present study, we evaluated how attachment styles may moderate the link between African American adolescents’ exposure to neighborhood poverty and accelerated cellular aging in young adulthood. Analyses revealed that allostatic load at age 19 mediated the association between neighborhood poverty in adolescence and changes in cellular aging from age 20 to 27. Notably, attachment avoidance (but not attachment anxiety) moderated this association, such that allostatic load was only associated with faster cellular aging for individuals who were high in avoidance. These findings suggest that allostatic load may give rise to faster cellular aging, but these detrimental effects of allostatic load can be offset by young adults’ effective use of attachment figures.
Fulvestrant-Palbociclib vs Letrozole-Palbociclib as Initial Therapy for Endocrine-Sensitive, Hormone Receptor-Positive, ERBB2-Negative Advanced Breast Cancer: A Randomized Clinical Trial.

Importance The cyclin-dependent kinase 4 and 6 inhibitor palbociclib in combination with letrozole has become a standard first-line treatment for patients with endocrine-sensitive, hormone receptor-positive, ERBB2-negative advanced breast cancer. Meanwhile, the antiestrogen fulvestrant was shown to be superior to anastrozole in the absence of cyclin-dependent kinase 4 and 6 inhibition for this patient population. Objective To assess whether fulvestrant is superior to letrozole when combined with palbociclib in the first-line scenario. Design, Setting, and Participants In this international, randomized, open-label, phase 2 clinical study conducted from July 30, 2015, to January 8, 2018, patients with hormone receptor-positive, ERBB2-negative advanced breast cancer with no prior therapy in the metastatic setting and endocrine-sensitive criteria were recruited from 47 centers in 7 countries. Data were analyzed from February 11 to May 15, 2020. Interventions Patients were randomly assigned (1:1 ratio) to receive palbociclib with either fulvestrant or letrozole. Stratification factors were type of disease presentation (de novo vs recurrent) and the presence of visceral involvement (yes vs no). Main Outcomes and Measures The primary end point was investigator-assessed progression-free survival determined by Response Evaluation Criteria in Solid Tumors, version 1.1. Results A total of 486 women (median age, 63 years [range, 25-90 years]; 3 Asian women [0.6%]; 4 Black women [0.8%]; 461 White women [94.9%]; 18 women of unknown race [3.7%]) were randomized (243 to fulvestrant-palbociclib and 243 to letrozole-palbociclib). Median investigator-assessed progression-free survival was 27.9 months (95% CI, 24.2-33.1 months) in the fulvestrant-palbociclib group vs 32.8 months (95% CI, 25.8-35.9 months) in the letrozole-palbociclib group (hazard ratio, 1.13; 95% CI, 0.89-1.45; P = .32). This result was consistent across the stratification factors. No significant differences were observed in objective response rate (46.5% vs 50.2%) and 3-year overall survival rate (79.4% vs 77.1%) for fulvestrant-palbociclib and letrozole-palbociclib, respectively. Grade 3-4 adverse events were comparable among treatment groups, and no new safety signals were identified. No treatment-related deaths were reported. Conclusions and Relevance Although fulvestrant-palbociclib demonstrated significant antitumor activity, this randomized clinical trial failed to identify an improvement in progression-free survival with this regimen over letrozole-palbociclib in patients with endocrine-sensitive, hormone receptor-positive, ERBB2-negative advanced breast cancer. Trial Registration ClinicalTrials.gov Identifier: NCT02491983.
Comparative Evaluation of 4-Dimensional Computed Tomography and 4-Dimensional Magnetic Resonance Imaging to Delineate the Target of Primary Liver Cancer

Purpose: To evaluate the feasibility of 4-dimensional magnetic resonance imaging (4DMRI) in establishing the target of primary liver cancer in comparison with 4-dimensional computed tomography (4DCT). Methods and Materials: A total of 23 patients with primary liver cancer who received radiotherapy were selected, and 4DCT and T2w-4DMRI simulations were conducted to obtain 4DCT and T2w-4DMRI simulation images. The 4DCT and T2w-4DMRI data were sorted into 10 and 8 respiratory phase bins, respectively. The liver and gross tumor volumes (GTVs) were delineated in all images using programmed clinical workflows under tumor delineation guidelines. The internal organs at risk volumes (IRVs) and internal target volumes (ITVs) were the unions of all the phase livers and GTVs, respectively. Then, the artifacts, liver volume, GTV, and motion range in 4DCT and T2w-4DMRI were compared. Results: The mean GTV volume based on 4DMRI was 136.42 ± 231.27 cm3, which was 25.04 cm3 (15.5%) less than that of 4DCT (161.46 ± 280.29 cm3). The average volume of ITV determined by 4DMRI was 166.12 ± 270.43 cm3, which was 22.44 cm3 (11.9%) less than that determined by 4DCT (188.56 ± 307.57 cm3). Liver volume and IRV in 4DMRI increased by 4.0% and 6.6%, respectively, compared with 4DCT. The difference in tumor motion by T2w-4DMRI based on the centroid was greater than that of 4DCT in the L/R, A/P, and S/I directions, and the average displacement differences were 2.6, 2.8, and 6.9 mm, respectively. The severe artifacts in 4DCT were 47.8% (11/23) greater than in 4DMRI 17.4% (4/23). Conclusions: Compared with 4DCT, T2-weighted and navigator-triggered 4DMRI produces fewer artifacts and larger motion differences in hepatic intrafraction tumors, which is a feasible technique for primary liver cancer treatment planning.
Using Feasibility Data and Codesign to Refine a Group-Based Health Literacy Intervention for New Parents

Few health literacy interventions exist for new parents. We developed a group-based health literacy program (“Parenting Plus”), which was initially tested in a feasibility study in 2018. In this brief report, we describe how feasibility findings were incorporated into the Parenting Plus program. Using a codesign process with patient partners (feasibility study participants) and health staff to revise the program, version 2 was tested in a single-site pilot using pre- and post-intervention testing. Parents older than age 16 years whose child was between ages 4 and 26 weeks were recruited from nurse home visits in western Sydney, Australia. Interested participants attended the free 4-week health literacy program (four 2-hour sessions) delivered by a trained facilitator. Piloting suggested the revised program is acceptable to new parents, has good retention (93% over the course of 4 weeks), and can improve health literacy skills, including access to reliable health information and services. Our iterative development and codesign approach integrated learnings from various sources to inform the design of an evidence-based health literacy intervention. We now move to an effectiveness implementation hybrid trial to test intervention effectiveness (health literacy skill development) and support translation of research findings into routine practice. [HLRP: Health Literacy Research and Practice. 2021;5(4):e276–e282. ]
Evaluation of Protective Effects of Curcumin and Nanocurcumin on Aluminium Phosphide‑Induced Subacute Lung Injury in Rats: Modulation of Oxidative Stress through SIRT1/FOXO3 Signalling Pathway

Abstract Objective Aluminum phosphide (AlP) is widely used to protect stored food products and grains from pests and rodents. The availability of AlP, especially in Asian countries it has become a desirable factor to commit suicide. The phosphine produced from ALP is a very reactive radical and a respiratory inhibitor that causes oxidative damage. There is no dedicated antidote or effective drug to manage AlP-induced lung toxicity. The present study aims to evaluate and compare the protective effects of curcumin and nanocurcumin on ALP‑induced subacute lung injury and determine the underlying mechanism. Methods Rats were exposed to AlP (2 mg/kg/day, orally)+curcumin or nanocurcumin (100 mg/kg/day, orally) for 7 days. Then rats were anesthetized and lung tissues were collected. Oxidative stress biomarkers, genes expression of antioxidant enzymes, participated genes in the SIRT1/FOXO3 pathway, and lung histopathology were assessed by biochemical and ELISA methods, Real-Time PCR analysis, and H&E staining. Results Curcumin and nanocurcumin produced a remarkable improvement in AlP-induced lung damage through reduction of MDA, induction of antioxidant capacity (TAC, TTG) and antioxidant enzymes (CAT, GPx), modulation of histopathological changes, and up-regulation of genes expression of SIRT1, FOXO3, FOXO1 in lung tissue. Conclusion Nanocurcumin had a significantly more protective effect than curcumin to prevent AlP-induced lung injury via inhibition of oxidative stress. Nanocurcumin could be considered a suitable therapeutic choice for AlP poisoning.
NIN-like protein7 and PROTEOLYSIS6 functional interaction enhances tolerance to sucrose, ABA, and submergence

Abstract Nitrate (NO3) assimilation and signaling regulate plant growth through the relevant function of the transcription factor NIN-like Protein7 (NLP7). NO3 is also the main source for plants to produce nitric oxide (NO), which regulates growth and stress responses. NO-mediated regulation requires efficient sensing via the PROTEOLYSIS6 (PRT6)-mediated proteasome-triggered degradation of group VII of ethylene response transcription factors through the Cys/Arg N-degron pathway. The convergence of NO3 signaling and N-degron proteolysis on NO-mediated regulation remains largely unknown. Here, we investigated the functional interaction between NLP7 and PRT6 using Arabidopsis (Arabidopsis thaliana) double prt6 nlp7 mutant plants as well as complementation lines overexpressing NLP7 in different mutant genetic backgrounds. prt6 nlp7 mutant plants displayed several potentiated prt6 characteristic phenotypes, including slower vegetative growth, increased NO content, and diminished tolerance to abiotic stresses such as high-sucrose concentration, abscisic acid, and hypoxia–reoxygenation. Although NLP7 has an N-terminus that could be targeted by the N-degron proteolytic pathway, it was not a PRT6 substrate. The potential PRT6- and NO-regulated nucleocytoplasmic translocation of NLP7, which is likely modulated by posttranslational modifications, is proposed to act as a regulatory loop to control NO homeostasis and action.
Post-licensure safety monitoring of quadrivalent human papillomavirus vaccine using the national adverse event following immunization surveillance system from Zhejiang province, 2018-2020

ABSTRACT Objectives To evaluate the reporting rate of adverse events following immunization (AEFI) of the quadrivalent human papillomavirus vaccine (4vHPV) and to compare the reporting rate of AEFI following 4vHPV with those following other vaccines. Methods Review and describe the AEFI reported to national adverse event following immunization surveillance system (NAEFISS) in Zhejiang province from 2018 to 2020. Reporting rates of AEFI were calculated by age, city, severity of AEFI, categories of AEFI, and reaction categories. The data mining algorithm used in this study was reporting odds ratio (ROR). A value of ROR‑1.96SE >1 (standard error [SE]) was considered as positive signal. Results NAEFISS received 238 reports after receipt of 4vHPV and 899,282 doses of 4vHPV were administered during the study period, with a crude reporting rate of 2.7/10000 doses. Fever/redness/induration (101 reports) was the most common event reported (1.12/10000 doses). Two cases of anaphylactic shock, three cases of Guillain Barre Syndrome and two cases of acute disseminated encephalomyelitis were reported. ROR showed positive signals for seizure (ROR‑1.96SE: 2.1), syncope (ROR‑1.96SE: 1.3), allergic rash (ROR‑1.96SE: 1.6) and headache (ROR‑1.96SE: 2.1). Conclusion The present analysis did not identify new/unexpected safety concerns. Further epidemiological studies are required to systematically validate the data provided by NAEFISS.
Understanding professional identity in occupational therapy: A scoping review

Abstract Introduction A strong professional identity helps occupational therapists maintain professional values and thrive when facing work-related challenges and opportunities including generic, blurred or emerging roles, funding pressures and a push for outcome evidence. A scoping review will build understanding of professional identity and how to maintain it in such circumstances. Objectives To scope what is currently understood of professional identity in occupational therapy and factors which influence ability to maintain this and adapt in challenging work environments. Methods Using Arksey and O’Malley’s scoping review framework three databases were searched using the terms ‘occupational therap*’ and ‘professional identity’. Data extraction and thematic analysis highlighted the extent and nature of current literature and mapped key concepts. Results 89 papers were included. Professional identity was revealed as a multidimensional construction. Four themes emerged: developing a shared ontology, embracing the culture, enacting occupational therapy, and believing in occupational therapy. Factors which influenced development and maintenance of professional identity included occupation-centred practice, ontological reflexivity, linking theory to practice and professional socialization. Conclusions and significance The enhanced understanding of professional identity and factors which preserve or enhance it can help the profession identify how to position itself to remain resilient and adaptive in an ever-changing environment.
Surveillance of Listeria monocytogenes: Early Detection, Population Dynamics, and Quasimetagenomic Sequencing during Selective Enrichment

We showed that a combination of a short primary enrichment combined with MDA and Nanopore sequencing can accelerate the traditional process of cultivation and identification of L. monocytogenes. The use of Illumina MiSeq sequencing additionally allowed us to predict the presence of cooccurring L. monocytogenes strains. ABSTRACT In this study, we addressed different aspects regarding the implementation of quasimetagenomic sequencing as a hybrid surveillance method in combination with enrichment for early detection of Listeria monocytogenes in the food industry. Different experimental enrichment cultures were used, comprising seven L. monocytogenes strains of different sequence types (STs), with and without a background microbiota community. To assess whether the proportions of the different STs changed over time during enrichment, the growth and population dynamics were assessed using dapE colony sequencing and dapE and 16S rRNA amplicon sequencing. There was a tendency of some STs to have a higher relative abundance during the late stage of enrichment when L. monocytogenes was enriched without background microbiota. When coenriched with background microbiota, the population dynamics of the different STs was more consistent over time. To evaluate the earliest possible time point during enrichment that allows the detection of L. monocytogenes and at the same time the generation of genetic information that enables an estimation regarding the strain diversity in a sample, quasimetagenomic sequencing was performed early during enrichment in the presence of the background microbiota using Oxford Nanopore Technologies Flongle and Illumina MiSeq sequencing. The application of multiple displacement amplification (MDA) enabled detection of L. monocytogenes (and the background microbiota) after only 4 h of enrichment using both applied sequencing approaches. The MiSeq sequencing data additionally enabled the prediction of cooccurring L. monocytogenes strains in the samples. IMPORTANCE We showed that a combination of a short primary enrichment combined with MDA and Nanopore sequencing can accelerate the traditional process of cultivation and identification of L. monocytogenes. The use of Illumina MiSeq sequencing additionally allowed us to predict the presence of cooccurring L. monocytogenes strains. Our results suggest quasimetagenomic sequencing is a valuable and promising hybrid surveillance tool for the food industry that enables faster identification of L. monocytogenes during early enrichment. Routine application of this approach could lead to more efficient and proactive actions in the food industry that prevent contamination and subsequent product recalls and food destruction, economic and reputational losses, and human listeriosis cases.
Is there collaboration specific neurophysiological activation during collaborative task activity? An analysis of brain responses using electroencephalography and hyperscanning

Collaboration between two individuals is thought to be associated with the synchrony of two different brain activities. Indeed, prefrontal cortical activation and alpha frequency band modulation has been widely reported, but little is known about interbrain synchrony (IBS) changes occurring during social interaction such as collaboration or competition. In this study, we assess the dynamic of IBS variation in order to provide novel insights into the frequency band modulation underlying collaboration. To address this question, we used electroencephalography (EEG) to simultaneously record the brain activity of two individuals playing a computer‐based game facing four different conditions: collaboration, competition, single participation, and passive observation. The computer‐based game consisted of a fast button response task. Using data recorded in sensor space, we calculated an IBS value for each frequency band using both wavelet coherence transform and phase‐locking value and performed single‐subject analysis to compare each condition. We found significant IBS in frontal electrodes only present during collaboration associated with alpha frequency band modulation. In addition, we observed significant IBS in the theta frequency band for both collaboration and competition conditions, along with a significant single‐subject cortical activity. Competition is distinguishable through single‐subject activity in several regions and frequency bands of the brain. Performance is correlated with single‐subject frontal activation during collaboration in the alpha and beta frequency band.