Miracle-dz/UniFAR-FTUs huggingface dataset:
Preparation and Characterization of MUC-30-Loaded Polymeric Micelles against MCF-7 Cell Lines Using Molecular Docking Methods and In Vitro Study

MUC-30 is a hydrophobic compound which is active against the MCF-7 cancer cell line. In this study, MUC-30 was loaded in polymeric micelles to improve the water solubility and release rate. For prolonged MUC-30 release, MUC-30 was encapsulated in polymeric micelles using PEG-b-PLA and PEG-b-PCL as materials. Micelles prepared with 1 : 9 w per w ratios by film hydration achieved the highest entrapment efficiency (EE%). The EE% of MUC-30-loaded PEG-b-PCL micelles was approximately 30% greater than that of PEG-b-PLA micelles, due to the different H-bond formations between MUC-30 and the polymer membrane (PCL, 4; PLA, 3). The cytotoxic activity of MUC-30 against EGFR theoretically presented 399.31 nM (IC50 = 282.26 ng/mL) by molecular docking. In vitro cytotoxic activity of MUC-30 was confirmed by MTT assay. MUC-30 (IC50 = 11 ± 0.39 ng/mL) showed three-fold higher activity over MUC-30-loaded PEG-b-PLA micelles (IC50 = 37 ± 1.18 ng/mL) and two-fold higher over PEG-b-PCL micelles (IC50 = 75 ± 3.97 ng/mL). This was due to the higher release rate of MUC-30 from PEG-b-PLA micelles compared to PEG-b-PCL micelles. Therefore, MUC-30-loaded PEG-b-PLA micelles could be a promising candidate for breast cancer chemotherapy.
Current Opinion on Prucalopride in Gastroparesis and Chronic Constipation Treatment: A Focus on Patient Selection and Safety

Abstract Prucalopride is a third-generation, highly selective 5-hydroxytryptamine 4 (5-HT4) receptor agonist. Many recent studies indicate prucalopride may play an important role in various motility disorders. The aim of this study was to investigate safety and patient selection considerations when using prucalopride as gastroparesis and chronic constipation treatment. We systematically searched PubMed, Embase, the Cochrane Central Register and ClinicalTrials.gov, and we reviewed all studies that evaluated prucalopride for the treatment of gastroparesis and chronic idiopathic constipation in adults. Prucalopride is an effective and safe option based on all the studies currently conducted. Thus, it may be the first-line treatment in the future. Prucalopride has the potential to be useful in the treatment of functional constipation and other forms of gastrointestinal diseases (eg, gastroparesis). Through the research on this potential, prucalopride is expected to be a useful and versatile option for treating gastrointestinal diseases in the future.
Oncogenic RAS drives the CRAF‐dependent extracellular vesicle uptake mechanism coupled with metastasis

Abstract Oncogenic RAS impacts communication between cancer cells and their microenvironment, but it is unclear how this process influences cellular interactions with extracellular vesicles (EVs). This is important as intercellular EV trafficking plays a key role in cancer invasion and metastasis. Here we report that overexpression of mutant RAS drives the EV internalization switch from endocytosis (in non‐transformed cells) to macropinocytosis (in cancer cells) resulting in enhanced EV uptake. This process depends on the surface proteoglycan, fibronectin and EV engulfment mechanism regulated by CRAF. Both mutant RAS and activated CRAF expression is associated with formation of membrane ruffles to which they colocalize along with actin, sodium‐hydrogen exchangers (NHEs) and phosphorylated myosin phosphatase (pMYPT). RAS‐transformed cells internalize EVs in the vicinity of ruffled structures followed by apparent trafficking to lysosome and degradation. NHE inhibitor (EIPA) suppresses RAS‐driven EV uptake, along with adhesion‐independent clonal growth and experimental metastasis in mice. Thus, EV uptake may represent a targetable step in progression of RAS‐driven cancers.
Genomic clustering analysis identifies molecular subtypes of thymic epithelial tumors independent of World Health Organization histologic type

Further characterization of thymic epithelial tumors (TETs) is needed. Genomic information from 102 evaluable TETs from The Cancer Genome Atlas (TCGA) dataset and from the IU-TAB-1 cell line (type AB thymoma) underwent clustering analysis to identify molecular subtypes of TETs. Six novel molecular subtypes (TH1-TH6) of TETs from the TCGA were identified, and there was no association with WHO histologic subtype. The IU-TAB-1 cell line clustered into the TH4 molecular subtype and in vitro testing of candidate therapeutics was performed. The IU-TAB-1 cell line was noted to be resistant to everolimus (mTORC1 inhibitor) and sensitive to nelfinavir (AKT1 inhibitor) across the endpoints measured. Sensitivity to nelfinavir was due to the IU-TAB-1 cell line’s gain-of function (GOF) mutation in PIK3CA and amplification of genes observed from array comparative genomic hybridization (aCGH), including AURKA, ERBB2, KIT, PDGFRA and PDGFB, that are known upregulate AKT, while resistance to everolimus was primarily driven by upregulation of downstream signaling of KIT, PDGFRA and PDGFB in the presence of mTORC1 inhibition. We present a novel molecular classification of TETs independent of WHO histologic subtype, which may be used for preclinical validation studies of potential candidate therapeutics of interest for this rare disease.
Targeted axillary biopsy and sentinel lymph node biopsy for axillary restaging after neoadjuvant chemotherapy

Purpose Accurate restaging of the axilla after neoadjuvant chemotherapy (NAC) is an important issue to ensure deescalating axillary surgery in patients with initial metastatic nodes. We aimed to present our results of targeted axillary biopsy (TAB) combined with sentinel lymph node biopsy (SLNB) for axillary restaging after NAC. Methods In 64 breast cancer patients who underwent NAC, biopsy-proven positive nodes were marked with clips before NAC, and ultrasound-guided wire localization of clip-marked nodes was performed after NAC. Patients underwent TAB and SLNB for post-NAC axilla restaging. Results Identification rates of post-NAC TAB and SLNB were 98.4% and 87.5%, respectively (P = 0.033). Histopathology revealed a nodal pathologic complete response (pCR) rate of 47% in which axillary lymph node dissection (ALND) was avoided. TAB alone and SLNB alone detected residual disease in 29 (85.3%) and 20 (58.8%) patients (P = 0.029), respectively. Whereas rates of up to 97% had been achieved with a combination of TAB and SLNB. The pCR rates after NAC were 64.3% for human epidermal growth factor receptor 2 positive and triple-negative tumors and 13.6% in luminal tumors (P = 0.0002). Conclusion Pathologic analysis following TAB combined with SLNB revealed the pCR rates to NAC in a considerable number of patients that provided de-escalation of axillary surgery. A combination of SLNB and TAB was found to be an accurate procedure in establishing residual nodal disease. This combined procedure in patients with initially positive nodes was a reliable method for post-NAC axillary restaging.
Negative and Positive Bias for Emotional Faces: Evidence from the Attention and Working Memory Paradigms

Visual attention and visual working memory (VWM) are two major cognitive functions in humans, and they have much in common. A growing body of research has investigated the effect of emotional information on visual attention and VWM. Interestingly, contradictory findings have supported both a negative bias and a positive bias toward emotional faces (e.g., angry faces or happy faces) in the attention and VWM fields. We found that the classical paradigms—that is, the visual search paradigm in attention and the change detection paradigm in VWM—are considerably similar. The settings of these paradigms could therefore be responsible for the contradictory results. In this paper, we compare previous controversial results from behavioral and neuroscience studies using these two paradigms. We suggest three possible contributing factors that have significant impacts on the contradictory conclusions regarding different emotional bias effects; these factors are stimulus choice, experimental setting, and cognitive process. We also propose new research directions and guidelines for future studies.
Impact of different cooking methods on polycyclic aromatic hydrocarbons in rabbit meat

Abstract The influence of a variety of cooking methods (poaching, boiling, grilling (charcoal or gas)), frying (pan, deep frying, and stir frying) with a variety of oils (vegetable oil, extra virgin olive oil, sesame oil, extra light olive oil, and sunflower oil), microwaving, and oven roasting on polycyclic aromatic hydrocarbons (PAHs) formation in rabbit meat samples was investigated. Meat samples (including three replicates) were prepared without additives or spices. PAHs extraction was carried out by saponification method with potassium hydroxide in methanol which was followed by a silica gel column technique and the samples were quantified by using gas chromatography with mass spectrometry (GC‐MS). PAHs standards, fluorene, naphthalene, anthracene, phenanthrene, pyrene, acenaphthalene, fluoranthene, and benzopyrene, were used for this study. The other PAHs except fluorene were not observed (detection limit‐0.009 µg/g) in all the samples. Among traditional processing techniques, higher PAH contents were observed as a result of frying. Frying with vegetable oil produced higher fluorene content (0.06–0.13 µg/g) in the deep‐fried sample, although sesame oil is the best oil which produces lowest PAH contents in fried samples. Among all the processing techniques, lower fluorene (0.01–0.02 µg/g) content was noticed in poaching. Benzo(a)pyrene was not observed in all the investigated samples which is viewed as a reliable strategy of the cooking process for human consumption. After processing, the cooking loss was determined and oven roasting and grilling exhibited greater moisture loss.
Arterial Healing 10 Months After Implantation of an Ultrathin-Strut, Biodegradable-Polymer, Sirolimus-Eluting Stent　― An Angioscopic Study ―

Background: The OrsiroTM ultrathin-strut, biodegradable-polymer, sirolimus-eluting stent (O-SES) has specific characteristics regarding its components and has demonstrated comparable clinical outcomes compared with durable-polymer, drug-eluting stents (DES). However, arterial repair following deployment of the O-SES has not been elucidated to date. Methods and Results: Using data from the Kansai Rosai Hospital database between November 2010 and September 2020, we analyzed coronary angioscopy (CAS) findings a mean (±SD) of 10±2 months after implantation of an O-SES, a durable-polymer everolimus-eluting stent (XienceTM; X-EES), or a biodegradable-polymer everolimus-eluting stent (SynergyTM; S-EES). Neointimal coverage (NIC), yellow color intensity of the stented segment, and the incidence of thrombus adhesion were compared between the O-SES (66 stents from 42 patients), X-EES (119 stents from 87 patients), and S-EES (132 stents from 88 patients). NIC was significantly thinner for the O-SES than S-EES (P<0.001), but was similar between the O-SES and X-EES (P=0.25). Yellow color intensity was significantly greater for the O-SES than X-EES (P<0.001), but similar between the O-SES and S-EES (P=0.51). The incidence of thrombus adhesions was similar in all 3 groups. Conclusions: O-SES and X-EES resulted in similar inhibition of NIC and both resulted in a thinner NIC than with S-EES. In addition, O-SES exhibited a similar degree of thrombus adhesion as the other DES, suggesting similar thrombogenicity.
A Decade of Effective Dry Eye Disease Management with Systane Ultra (Polyethylene Glycol/Propylene Glycol with Hydroxypropyl Guar) Lubricant Eye Drops

Abstract Dry eye disease (DED) is a multifactorial ocular condition characterized by a loss of homeostasis of the tear film resulting in ocular symptoms of discomfort, irritation, and visual disturbance, all of which significantly impact the patients’ social and occupational quality of life. While management of DED depends on the severity of symptoms and signs, use of artificial tear products (ATPs) that replace or supplement the deficient natural tear film is the mainstay treatment option. In this review, we present a decade of evidence on Systane Ultra® (polyethylene glycol [PEG]/propylene glycol [PG] with hydroxypropyl guar [HP guar]) in effectively managing DED. The active demulcents in Systane Ultra®—PEG, PG, along with HP guar gelling technology—provide optimal ocular surface protection and lubrication to heal damaged areas of the cornea caused by DED and, therefore, are recommended for patients with both aqueous and/or mucin layer deficiencies. Over the years, several clinical studies have shown that PEG/PG with HP guar provides long-lasting relief from dry eye and has often been chosen as a standard or comparator against other ATPs. Here, we describe the salient features of PEG/PG with HP guar—its constituents and their mechanisms of action. Furthermore, we summarize results from a systematic literature search that identified 23 relevant publications further emphasizing on the effectiveness and safety of PEG/PG with HP guar in alleviating the signs and symptoms of DED.
Evaluation of the bioaccessibility of a carotenoid beadlet blend using an in vitro system mimicking the upper gastrointestinal tract

Abstract The release characteristics of a unique blend of carotenoid beadlets designed to increase bioavailability were tested using the dynamic gastrointestinal model TIM‐1. Individual carotenoid bioaccessibility peaks were observed over approximately 3–4 hr in the order of lutein and zeaxanthin first, followed by lycopene, and then finally α‐ and β‐carotene; when tested as a beadlet blend or when the beadlets were compressed into tablets. Bioaccessibility measurements of 7%–20% were similar to those previously reported in literature and comparable between the two formulations, beadlet blend and tablet formulations. Total recovery of carotenoids from all compartments ranged from 70% to 90% for all carotenoids, except lycopene where almost 50% was unrecoverable after digestion in the TIM system.
Analytical Concordance of PD-L1 Assays Utilizing Antibodies From FDA-Approved Diagnostics in Advanced Cancers: A Systematic Literature Review

PURPOSE Four programmed death ligand 1 (PD-L1) immunohistochemistry assays (28-8, 22C3, SP263, and SP142) have been approved for use by the US Food and Drug Administration (FDA). Analytical concordance between these assays has been evaluated in multiple studies. This systematic review included studies that investigated the analytical concordance of immunohistochemistry assays utilizing two or more PD-L1 antibodies from FDA-approved diagnostics for evaluation of PD-L1 expression on tumor or immune cells across a range of tumor types and algorithms. METHODS Literature searches were conducted in MEDLINE (via PubMed) and EMBASE to identify studies published between January 1, 2010, and March 31, 2019, that evaluated analytical concordance between two or more assays based on antibodies from FDA-approved assays. Proceedings of key oncology and pathology congresses that took place between January 2016 and March 2019 were searched for abstracts of studies evaluating PD-L1 assay concordance. RESULTS A total of 42 studies across a range of tumor types met the selection criteria. Concordance between 28-8-, 22C3-, and SP263-based assays in lung cancer, urothelial carcinoma, and squamous cell carcinoma of the head and neck was high when used to assess PD-L1 expression on tumor cells (TCs). SP142-based assays had overall low concordance with other approved assays when used to assess PD-L1 expression on TCs. Analytical concordance for assessment of PD-L1 expression on immune cells was variable and generally lower than for PD-L1 expression on TCs. CONCLUSION A large body of evidence supports the potential interchangeability of 28-8-, 22C3-, and SP263-based assays for the assessment of PD-L1 expression on TCs in lung cancer. Further studies are required in tumor types for which less evidence is available.
Optimization of gamma‐aminobutyric acid production by Lactobacillus brevis PML1 in dairy sludge‐based culture medium through response surface methodology

Abstract Gamma‐aminobutyric acid (GABA) is a pharmaceutical, bioactive amino acid that can produce by some species of Lactic Acid Bacteria (LAB). For the first time, we evaluated the production of GABA by Lactobacillus brevis PML1 in the medium that contain the contaminant food bio‐product like dairy sludge and soybean meal. GABA production was analyzed by chromatography (TLC, HPLC) and the features of fermented extract which contains this amino acid were evaluated. The results of Response Surface Methodology (RSM) of Central Composite Design (CCD) at p < . 05 showed 300 ppm of GABA production in optimal treatment including 14.77% dairy sludge powder, 6.27% soybean meal, and 0.49% ammonium sulfate (32°C for 120 hr fermentation). The results of fermented extract also showed the acceptable antimicrobial, antioxidant, and toxicity (against cancer cell) properties. Also, L. brevis PML1has not shown any hemolytic or DNase activity which confirm its safety aspects. According to the results, this new culture can be used as a cheap substrate to biological production of GABA, by L. brevis PML1 in various food and pharmaceutical formulations.
Protective Effects of Hydroalcoholic Extract of Rosa canina Fruit on Vancomycin-Induced Nephrotoxicity in Rats

Vancomycin-induced nephrotoxicity (VIN) has been reported to occur in 5–35% of recipient patients. The aims of the study were to evaluate protective effects of Rosa canina (RC) on VIN in rats. Rats were randomly divided into five groups as follows: control group I, group II (received VAN 400 mg/kg/day, every 12 h at doses of 200 mg/kg/day, for 7 consecutive days), group III (VAN + RC 250 mg/kg/day, for 7 consecutive days), group IV (VAN + RC 500 mg/kg/day, for consecutive days), and group V (received RC 500 mg/kg/day, for consecutive 7 days). On the eighth day after anesthetizing the animals, blood samples were taken from the heart, and then, the kidneys were removed to investigate kidney function, oxidative stress, and histopathological marker. Also, the chemical composition of RC extract was identified by GC-MS analysis. Oral dose of 500 mg/kg RC extract significantly reduced the serum levels of blood urea nitrogen (BUN), creatinine (Cr), malondialdehyde (MDA), and nitric oxide (NO) and also the kidney tissue MDA, protein carbonyl, and NO metabolites (nitrite) levels compared to the VAN-treated group (P < 0.05). Based on histopathological analysis, RC extract at the dose of 500 mg/kg inhibited the destructive effects of VAN on kidney tissues. GC-MS analysis indicated that the main compositions were found to be lactose (21.96%), 3-t-butyloxaziridine (20.91%), and 5-oxymethylfurfurole (16.75%). The results indicated that oral administration of RC was able to reduce VAN-induced nephrotoxicity in rats, possibly through antioxidant pathways.
Association between serum 25‐hydroxyvitamin D concentrations and obesity in one‐year‐old Chinese infants

Abstract Recent studies suggested that vitamin D is linked with obesity, but evidence in infants is scarce. Therefore, we aimed to make an exploration in infants. A total of 414 infants at one year old who visited Maternity and Child Health Care Hospital of Wuxi in China were recruited. Finger‐stick blood sampling was conducted in all the subjects, and serum 25‐hydroxyvitamin D [25(OH)D] concentrations were measured. Maternal characteristics during pregnancy and infantile information were collected by questionnaires or extracting from medical records. Multivariable linear models were performed to assess the relationship between 25(OH)D and body mass index (BMI), while multivariable logistic regression models were used to examine the association between 25(OH)D and obesity. Among the 414 infants, 69 (16.67%) and 81 (19.57%) infants were defined as obesity and vitamin D deficiency [25(OH)D < 50 nmol/L], respectively. The mean (SD) of 25(OH)D concentration was 68.05 (19.05) in infants without obesity, which was significantly higher than that of obese infants [60.36(18.49), p = . 002]. Inverse linear relationships were observed between 25(OH)D level and BMI (β = −0.017, p = .004) as well as BMI Z‐score (β = −0.010, p = .004). Furthermore, vitamin D deficiency was associated with an increased risk of obesity of infants (adjusted odds ratio = 2.74, 95% confidence interval = 1.20–6.25, with 25(OH)D ≥ 75 nmol/L as a reference). The results showed that serum 25(OH)D concentrations were significantly lower in infants with obesity, suggesting vitamin D deficiency may be an independent risk factor for obesity among one‐year‐old Chinese infants.
Antibody Responses to SARS-CoV-2 mRNA Vaccines Are Detectable in Saliva

The approved Pfizer and Moderna mRNA vaccines are well known to induce serum antibody responses to the SARS-CoV-2 Spike (S)-protein. However, their abilities to elicit mucosal immune responses have not been reported. Saliva antibodies represent mucosal responses that may be relevant to how mRNA vaccines prevent oral and nasal SARS-CoV-2 transmission. Here, we describe the outcome of a cross-sectional study on a healthcare worker cohort (WELCOME-NYPH), in which we assessed whether IgM, IgG, and IgA antibodies to the S-protein and its receptor-binding domain (RBD) were present in serum and saliva samples. Anti-S-protein IgG was detected in 14/31 and 66/66 of saliva samples from uninfected participants after vaccine doses-1 and -2, respectively. IgA antibodies to the S-protein were present in 40/66 saliva samples after dose 2. Anti-S-protein IgG was present in every serum sample from recipients of 2 vaccine doses. Vaccine-induced antibodies against the RBD were also frequently present in saliva and sera. These findings may help our understanding of whether and how vaccines may impede SARS-CoV-2 transmission, including to oral cavity target cells.
Prevalence and Associated Factors of Methicillin Resistance Staphylococcus aureus (MRSA) Among Urinary Tract Infection Suspected Patients Attending at Arba Minch General Hospital, Southern Ethiopia

Background Urinary tract infection (UTI) is a very frequent infection both in the community and hospital patients, and the emergence of methicillin-resistant Staphylococcus aureus (MRSA) in the community setting and infections with this pathogen become a prevalent problem among UTI patients. Therefore, the aim of this study was to determine prevalence and associated factors of methicillin resistance staphylococcus aureus (MRSA) among urinary tract infection suspected patients attending at Arba Minch General Hospital. Methods Facility-based cross-sectional study was done at Arba Minch General Hospital from July to October 2020. Midstream urine specimen was collected from outpatients, cultured and biochemical tests were performed to identify the intended pathogen, finally the antibiotic susceptibility pattern of MRSA was done and possible associated factors were determined. The cleaned data were entered and analyzed using SPSS version 21. Results Four hundred and twenty two (422) adult outpatients were enrolled in this study, of which males accounted for 238 (56.4%) of the participants. The mean and standard deviation age of the participants was 27.4 (SD 27.4 ± 15.6) years. A total of 54 S. aureus isolates were recovered from urine specimen. The prevalence of MRSA among the isolated S. aureus was 23/54 (42.59% (95% CI (35.0, 47.0)). Participants who had previous exposure to UTI (p < 0.002), presence of chronic disease (p < 0.029), and hospitalization (p < 0.006) were statically associated with the prevalence of MRSA. From all the MRSA isolates, 53.7% were resistant against Nitrofurantoin. Conclusion This study revealed that MRSA could be prevalent in isolates from patients suspected of urinary tract infection and exhibiting different resistance pattern for antibiotics commonly used for treatment of staphylococcal infections.