Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluations of Quality by Design (QbD) Elements Impact for Developing Niosomes as a Promising Topical Drug Delivery Platform

Topical corticosteroids are used to treat a variety of skin conditions such as allergic reactions, eczema, and psoriasis. Niosomes are a novel surfactant-based delivery system that may be used to deliver desoximetasone via topical product application in order to mitigate common side effects associated with traditional oral delivery routes. The aim of this research was to identify the critical material attributes (CMAs) and critical process parameters (CPPs) that impact key characteristics of drug-loaded niosomes using a systematic quality by design (QbD) approach. An organic phase injection method was developed and used to manufacture the niosomes. The CMAs were identified to be drug amount, concentrations of surfactant and cholesterol, and types of lipids. The CPPs were phase volumes, temperature, mixing parameters, and addition rate based on previous research. The quality attributes measured were entrapment efficiency, particle size distribution, PDI, and zeta potential. These were used to determine the quality target product profile (QTPP) of niosomes. The experimental data indicate that the critical impacting variables for niosomes are: surfactant and cholesterol concentrations, mixing parameters, and organic-phase addition rate. Based on the experimental results of this study methanol:diethyl ether (75:25) as the organic system, drug:surfactant:cholesterol in 1:2:1 concentration, stearic acid as the charge-inducing material, 20 mL external phase and 10 mL internal phase volume, 65 °C external phase temperature, 60 min mixing time, 650 RPM mixing speed and 1 mL/ml addition rate is the ideal combination to achieve desirable desoximetasone niosomes with optimum entrapment efficiency and particle size for topical application.
Prevalence and Characterization of Specific Phobia Disorder in People over 65 Years Old in a Madrid Community Sample (Spain) and its Relationship to Quality of Life

The prevalence of anxiety disorders over the last year among seniors ranged from 3.6% to 17.2%. The most prevalent disorders are specific phobias. Data are needed concerning the consequences of specific phobia disorder on the level of functioning and quality of life of older people, the age of onset of specific phobia disorder, and the duration of episodes. In total, 555 community-dwelling people aged between 65 and 84 years who lived in Madrid (Spain) were assessed (Composite International Diagnostic Interview for people over 65 years (CIDI65+), WHO Disability Assessment Schedule (WHODAS II), Health of the Nation Outcome Scales for Older Adults (HoNOS65+), World Health Organization Quality of Life Brief (WHOQOL-BREF). Prevalence rates and odds ratio, t-tests, binary logistic regression, and point-biserial correlations were calculated. A total of 12.07% of the sample suffered a specific phobia disorder over the last year. The average age at onset of the specific phobia was 38.78 (sd = 21.61) years. The mean duration of the phobia was approximately 20 (sd = 20) years. A significant effect of the specific phobia was found for the current levels of functioning and quality of life: WHOQOL-BREF total score (p < 0.05), WHODAS II overall score (p < 0.01), and HoNOS65+ total score (p < 0.001). Having specific phobia disorder decreased the level of functioning and negatively affected the quality of life. These data suggest the need for primary healthcare professionals to include the detection of specific phobia disorders in their protocols because people do not receive treatment for this problem, and they might carry it throughout their lives.
Daily use of high-potency cannabis is associated with more positive symptoms in first-episode psychosis patients: the EU-GEI case–control study

Abstract Background Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients. Method We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses. Results In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14–0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = −0.22; 95% CI −0.37 to −0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use. Conclusions Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.
Fixed bed study of nitrate removal from water by protonated cross-linked chitosan supported by biomass-derived carbon particles

Abstract In this study, a green adsorbent was synthesized for the removal of nitrate ions from water. The adsorbent consisted of carbonaceous particles with high specific surface area (1,240 m2 g−1) and porosity derived from pyrolysis of cornelian cherry stone and modified by protonated cross-linked chitosan. The adsorbent was characterized using various techniques like SEM, FTIR, BJH and zeta potential measurements. Dynamic behavior of the adsorbent in the nitrate adsorption was studied in a packed bed system at various operating conditions and in the presence of other competing anions (PO43−, HCO3−, SO42−). Based on the error analysis, the optimum operating conditions were considered at flow rate of 3.8 mL min−1, bed depth of 10 cm and nitrate concentration of 75 mg L−1. The kinetics of the adsorption process was studied using Adams–Bohart and Thomas models and the qmax was calculated to be about 12.4 mg g−1 at neutral pH and room temperature. Furthermore, the relationship between the bed height and the breakthrough time was described by bed depth service time (BDST) model. The experimental results suggested that the adsorbent possessed significant ability in nitrate removal from water due to the desired chemistry of the biopolymer and the excellent textural properties of the carbon support.
Contamination Pathways can Be Traced along the Poultry Processing Chain by Whole Genome Sequencing of Listeria innocua

Foodborne infection with Listeria causes potentially life-threatening disease listeriosis. Listeria monocytogenes is widely recognized as the only species of public health concern, and the closely related species Listeria innocua is commonly used by the food industry as an indicator to identify environmental conditions that allow for presence, growth, and persistence of Listeria spp. in general. In our study, we analyze the occurrence of Listeria spp. in a farm-to-fork approach in a poultry production chain in Egypt and identify bacterial entry gates and transmission systems. Prevalence of Listeria innocua at the three production stages (farm, slaughterhouse, food products) ranged from 11% to 28%. The pathogenic species Listeria monocytogenes was not detected, and Listeria innocua strains under study did not show genetic virulence determinants. However, the close genetic relatedness of Listeria innocua isolates (maximum 63 SNP differences) indicated cross-contamination between all stages from farm to final food product. Based on these results, chicken can be seen as a natural source of Listeria. Last but not least, sanitary measures during production should be reassessed to prevent bacterial contamination from entering the food chain and to consequently prevent human listeriosis infections. For this purpose, surveillance must not be restricted to pathogenic species.
DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels

Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7−/− mice. Although palmitoylation of barttin in kidneys of Zdhhc7−/− animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7−/− mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension.
Genetic diversity of 15 autosomal STRs in a sample of Berbers from Aurès region in the Northeast of Algeria and genetic relationships with other neighbouring samples

Abstract Background: The history of the Aurès mountains and neighbouring areas, a large region of the East of Algeria, was part of the history of the ancient independent Berber kingdoms supposed to be the ancestors of the current Berber people. The genetic background of this region has not yet been clarified. Aim: The aims of our study were to investigate the genetic characteristics of 15 autosomal short tandem repeats (STRs) in a sample from these regions, to determine the degree of heterogeneity among Algerian and North African samples and to analyse the genetic relationships with other populations. Subjects and methods: Allele frequencies, forensic parameters and Hardy–Weinberg equilibrium (HWE) of 15 autosomal STRs included in the PowerPlex® ESI 16 System were obtained from 308 individuals. Allele frequencies were used to determine the relationships with other populations. Results: All loci were highly polymorphic and no significant deviation from HWE was detected. Allele frequencies showed that the samples of Aurès region share genetic affinities with other Algerian, North African and Middle Eastern samples, with the exception of samples from Iran and Matmata. Conclusions: These markers revealed a genetic homogeneity between the Algerian and North African samples. The genetic affinities indicate that this sample could share a common ancestor with the Middle Eastern samples.
Perioperative Circulating Tumor DNA in Colorectal Liver Metastases: Concordance with Metastatic Tissue and Predictive Value for Tumor Burden and Prognosis

Background The surgical resection of colorectal cancer with liver metastases (CLM) has proven to be the most important modality for long-term survival, while effective biomarkers for outcome prediction or postoperative surveillance are still lacking. Currently, circulating biomarkers obtained from a liquid biopsy are widely used to assess the treatment response, disease recurrence and progression. In this study, we analyzed the value of the liquid biopsy, which includes circulating tumor DNA (ctDNA) and cell-free DNA (cfDNA), in patients with CLM. Methods Capture-based targeted deep sequencing was performed on matched pre-surgery, post-surgery and liver metastatic tissues of 20 CRC patients who underwent the resection of liver metastases between May and September 2017 using a panel consisting of 41 genes. Mutation landscapes obtained from pre-surgery plasma samples and metastatic tissue samples were compared. Results Collectively, we identified 47 mutations from 17 pre-surgery plasma samples (85%), and the remaining 3 patients had no mutation detected from the panel. We revealed a high by-variant concordance rate of 82.14% between pre-surgery plasma samples and liver metastatic tissue samples. We further analyzed the correlation between ctDNA, cfDNA, CEA and tumor burden and revealed a positive correlation between ctDNA and tumor burden (R=0.69, p=0.002). As of the date for data cutoff, 8/20 patients experienced relapse. Our study also demonstrated that pre-surgery ctDNA (p<0.001), cfDNA (p=0.001) and CEA (p=0.012) levels had predictive value for relapse. Patients with low pre-surgery ctDNA (p<0.001), cfDNA (p=0.001) or CEA (p=0.012) levels were more likely to experience prolonged progression-free survival. Conclusion Our data demonstrate that the genomic profile obtained from ctDNA is comparable with the genomic profile obtained from metastatic liver tumors. Furthermore, our study also show that pre-surgery ctDNA levels are positively correlated with tumor burden. In addition, pre-surgery ctDNA, cfDNA and CEA levels have predictive value for relapse.
Genomic and Transcriptomic Evidence Supports Methane Metabolism in Archaeoglobi

Current understanding of the diversity, biology, and ecology of Archaea is very limited, especially considering how few of the known phyla have been cultured or genomically explored. The reconstruction of “Ca. Methanomixophus” MAGs not only expands the known range of metabolic versatility of the members of Archaeoglobi but also suggests that the phylogenetic distribution of MCR and MTR complexes is even wider than previously anticipated. ABSTRACT Euryarchaeal lineages have been believed to have a methanogenic last common ancestor. However, members of euryarchaeal Archaeoglobi have long been considered nonmethanogenic and their evolutionary history remains elusive. Here, three high-quality metagenomic-assembled genomes (MAGs) retrieved from high-temperature oil reservoir and hot springs, together with three newly assembled Archaeoglobi MAGs from previously reported hot spring metagenomes, are demonstrated to represent a novel genus of Archaeoglobaceae, “Candidatus Methanomixophus. ” All “Ca. Methanomixophus” MAGs encode an M methyltransferase (MTR) complex and a traditional type of methyl-coenzyme M reductase (MCR) complex, which is different from the divergent MCR complexes found in “Ca. Polytropus marinifundus. ” In addition, “Ca. Methanomixophus dualitatem” MAGs preserve the genomic capacity for dissimilatory sulfate reduction. Comparative phylogenetic analysis supports a laterally transferred origin for an MCR complex and vertical heritage of the MTR complex in this lineage. Metatranscriptomic analysis revealed concomitant in situ activity of hydrogen-dependent methylotrophic methanogenesis and heterotrophic fermentation within populations of “Ca. Methanomixophus hydrogenotrophicum” in a high-temperature oil reservoir. IMPORTANCE Current understanding of the diversity, biology, and ecology of Archaea is very limited, especially considering how few of the known phyla have been cultured or genomically explored. The reconstruction of “Ca. Methanomixophus” MAGs not only expands the known range of metabolic versatility of the members of Archaeoglobi but also suggests that the phylogenetic distribution of MCR and MTR complexes is even wider than previously anticipated.
Beneficial Effects of Pulsed Electromagnetic Field during Cast Immobilization in Patients with Distal Radius Fracture

To assess whether pulsed electromagnetic field therapy during cast immobilization of distal radius fractures has beneficial effects on pain and limb function, the study included 52 patients (mean age 60.8 ± 15.0 years) with distal radius fractures treated with cast immobilization. Patients were allocated to a pulsed electromagnetic field group (n = 27) or a control group (n = 25). Pain; forearm and arm circumference; range of motion; disabilities of the arm, shoulder, and hand score; and touch sensation were evaluated on the day of the plaster cast dressing and 3 and 6 weeks after. In comparison to the control group, the pulsed electromagnetic field group reported significant changes after 3 and 6 weeks of treatment: lower pain levels (p=0.0052; p < 0.0001, respectively), greater mobility of upper-limb joints, improvement in exteroceptive sensation, and reduction in disability of the upper limb (disabilities of the arm, shoulder, and hand) (p=0.0003; p < 0.0001, respectively). Our results suggest that early addition of pulsed electromagnetic field treatment, during cast immobilization of distal radius fractures, has beneficial effects on the pain, exteroceptive sensation, range of motion, and daily functioning of patients.
N-Ethyl-n-Nitrosourea Induced Leukaemia in a Mouse Model through Upregulation of Vascular Endothelial Growth Factor and Evading Apoptosis

Chemical carcinogens are commonly used to investigate the biology and prognoses of various cancers. This study investigated the mechanism of leukaemogenic effects of n-ethyl-n-nitrosourea (ENU) in a mouse model. A total of 14 3-week-old male Institute of Cancer Research (ICR)-mice were used for the study. The mice were divided into groups A and B with seven mice each. Group A served as the control while group B received intraperitoneal (IP) injections of 80 mg/kg ENU twice with a one-week interval and were monitored monthly for 3 months for the development of leukaemia via blood smear examination. The mice were sacrificed humanely using a CO2 chamber. Blood, spleen, lymph nodes, liver, kidney and lung samples were collected for blood smear examination and histopathological evaluation. The expression of angiogenic protein (VEGF), and pro and anti-apoptotic proteins (BCL2 and BAX), was detected and quantified using Western blot technique. Leukaemia was confirmed by the presence of numerous blast cells in the peripheral blood smear in group B. Similarly, the VEGF and BCL2 proteins were significantly (p < 0.05) upregulated in group B compared to A. It is concluded that IP administration of 80 mg/kg ENU induced leukaemia in ICR-mice 12 weeks post administration through upregulation of angiogenic and anti-apoptotic proteins: VEGF and BCL2.
Hypothesized Mechanisms Through Which Exercise May Attenuate Memory Interference

In this paper we introduce a mechanistic model through which exercise may enhance episodic memory, specifically via attenuating proactive and retroactive memory interference. We discuss the various types of memory, different stages of memory function, review the mechanisms behind forgetting, and the mechanistic role of exercise in facilitating pattern separation (to attenuate memory interference).
Recellularized Colorectal Cancer Patient-Derived Scaffolds as In Vitro Pre-Clinical 3D Model for Drug Screening

Colorectal cancer (CRC) shows highly ineffective therapeutic management. An urgent unmet need is the random assignment to adjuvant chemotherapy of high-risk stage II and stage III CRC patients without any predictive factor of efficacy. In the field of drug discovery, a critical step is the preclinical evaluation of drug cytotoxicity, efficacy, and efficiency. We proposed a patient-derived 3D preclinical model for drug evaluation that could mimic in vitro the patient’s disease. Surgically resected CRC tissue and adjacent healthy colon mucosa were decellularized by a detergent-enzymatic treatment. Scaffolds were recellularized with HT29 and HCT116 cells. Qualitative and quantitative characterization of matched recellularized samples were evaluated through histology, immunofluorescences, scanning electron microscopy, and DNA amount quantification. A chemosensitivity test was performed using an increasing concentration of 5-fluorouracil (5FU). In vivo studies were carried out using zebrafish (Danio rerio) animal model. Permeability test and drug absorption were also determined. The decellularization protocol allowed the preservation of the original structure and ultrastructure. Five days after recellularization with HT29 and HCT116 cell lines, the 3D CRC model exhibited reduced sensitivity to 5FU treatments compared with conventional 2D cultures. Calculated the half maximal inhibitory concentration (IC50) for HT29 treated with 5FU resulted in 11.5 µM in 3D and 1.3 µM in 2D, and for HCT116, 9.87 µM in 3D and 1.7 µM in 2D. In xenograft experiments, HT29 extravasation was detected after 4 days post-injection, and we obtained a 5FU IC50 fully comparable to that observed in the 3D CRC model. Using confocal microscopy, we demonstrated that the drug diffused through the repopulated 3D CRC scaffolds and co-localized with the cell nuclei. The bioengineered CRC 3D model could be a reliable preclinical patient-specific platform to bridge the gap between in vitro and in vivo drug testing assays and provide effective cancer treatment.
Benefit of Later-Time-Point PET Imaging of HER3 Expression Using Optimized Radiocobalt-Labeled Affibody Molecules

HER3-binding affibody molecules are a promising format for visualization of HER3 expression. Cobalt-55, a positron-emitting isotope, with a half-life of 17.5 h, allows for next-day imaging. We investigated the influence of the charge of the radiocobalt–chelator complex on the biodistribution of anti-HER3 affibody molecule (HE)3-ZHER3 and compared the best radiocobalt-labeled variant with a recently optimized gallium-labeled variant. Affibody conjugates (HE)3-ZHER3-X (X = NOTA, NODAGA, DOTA, DOTAGA) were labeled with [57Co]Co (surrogate for 55Co). Affinity measurements, binding specificity and cellular processing were studied in two HER3-expressing cancer cell lines. Biodistribution was studied 3 and 24 h post-injection (pi) in mice with HER3-expressing BxPC-3 xenografts and compared to [68Ga]Ga-(HE)3-ZHER3-NODAGA. Micro-single-photon emission tomography/computed tomography (microSPECT/CT) and micro-positron emission tomography/computed tomography (microPET/CT) imaging was performed 3 and 24 h pi. Stably labeled conjugates bound to HER3 with subnanomolar affinity. [57Co]Co-(HE)3-ZHER3-DOTA had the best tumor retention and a significantly lower concentration in blood than other conjugates, leading to superior tumor-to-blood and tumor-to-liver ratios 24 h pi. Compared to [68Ga]Ga-(HE)3-ZHER3-NODAGA 3 h pi, [57Co]Co-(HE)3-ZHER3-DOTA provided superior imaging contrast in liver 24 h pi. Concluding, the composition and charge of the [57Co]Co–chelator complex influenced the uptake in tumors and normal tissue. [57Co]Co-(HE)3-ZHER3-DOTA provided the best imaging properties among the cobalt-labeled conjugates. Delayed imaging of HER3 expression with [57Co]Co-(HE)3-ZHER3-DOTA improved imaging contrast compared to early-time-point imaging with [68Ga]Ga-(HE)3-ZHER3-NODAGA.