Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction Model for Bronchopulmonary Dysplasia in Preterm Newborns

OBJECTIVE: To develop a multifactorial model that allows the prediction of bronchopulmonary dysplasia (BPD) in preterm newborns. MATERIALS AND METHODS: A single-center retrospective study of infants born below 32 + 0 weeks gestational age. We created a receiver operating characteristic curve to assess the multifactorial BPD risk and calculate the BPD risk accuracy using the area under the curve (AUC). BPD risk was categorized using a multifactorial predictive model based on the weight of the evidence. RESULTS: Of the 278 analyzed preterm newborns, 127 (46%) developed BPD. The significant risk factors for BPD in the multivariate analysis were gestational age, number of red blood cell concentrate transfusions, number of surfactant administrations, and hemodynamically significant patent ductus arteriosus. The combination of these factors determined the risk of developing BPD, with an AUC value of 0.932. A multifactorial predictive model based on these factors, weighted by their odds ratios, identified four categories of newborns with mean BPD risks of 9%, 59%, 82%, and 100%. CONCLUSION: A multifactorial model based on easily available clinical factors can predict BPD risk in preterm newborns and inform potential preventive measures.
Dysfunction in the Cystic Fibrosis Transmembrane Regulator in Chronic Obstructive Pulmonary Disease as a Potential Target for Personalised Medicine

In recent years, numerous pathways were explored in the pathogenesis of COPD in the quest for new potential therapeutic targets for more personalised medical care. In this context, the study of the cystic fibrosis transmembrane conductance regulator (CFTR) began to gain importance, especially since the advent of the new CFTR modulators which had the potential to correct this protein’s dysfunction in COPD. The CFTR is an ion transporter that regulates the hydration and viscosity of mucous secretions in the airway. Therefore, its abnormal function favours the accumulation of thicker and more viscous secretions, reduces the periciliary layer and mucociliary clearance, and produces inflammation in the airway, as a consequence of a bronchial infection by both bacteria and viruses. Identifying CFTR dysfunction in the context of COPD pathogenesis is key to fully understanding its role in the complex pathophysiology of COPD and the potential of the different therapeutic approaches proposed to overcome this dysfunction. In particular, the potential of the rehydration of mucus and the role of antioxidants and phosphodiesterase inhibitors should be discussed. Additionally, the modulatory drugs which enhance or restore decreased levels of the protein CFTR were recently described. In particular, two CFTR potentiators, ivacaftor and icenticaftor, were explored in COPD. The present review updated the pathophysiology of the complex role of CFTR in COPD and the therapeutic options which could be explored.
1,5-Benzodiazepin-2(3H)-ones: In Vitro Evaluation as Antiparkinsonian Agents

A new series of twenty-three 1,5-benzodiazepin-2(3H)-ones were synthesized and evaluated in the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), ferric reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays as a new chemotype with antioxidant and good drug-like properties. All of the derivatives showed low cytotoxicity in comparison to curcumin against the human neuroblastoma SH-SY5Y and the human hepatoma HepG2 cell lines. Experimental solubility in bio-relevant media showed a good relationship with melting points in this series. Five compounds with the best antioxidant properties showed neuroprotectant activity against H2O2-induced oxidative stress in the SH-SY5Y cell line. From them, derivatives 4-phenyl-1H-1,5-benzodiazepin-2(3H)-one (18) and 4-(3,4,5-trimethoxyphenyl)-1H-1,5-benzodiazepin-2(3H)-one (20) yielded good neuroprotection activity in the same neuronal cell line under 6-OHD and MPP+ insults as in vitro models of mitochondrial dysfunction and oxidative stress in Parkinson’s disease (PD). Both compounds also demonstrated a significant reduction of intracellular Reactive Oxygen Species (ROS) and superoxide levels, in parallel with a good improvement of the Mitochondrial Membrane Potential (ΔΨm). Compared with curcumin, compound 18 better reduced lipid peroxidation levels, malondialdehyde (MDA), in SH-SY5Y cells under oxidative stress pressure and recovered intracellular glutathione synthetase (GSH) levels. Apoptosis and caspase-3 levels of SH-SY5Y under H2O2 pressure were also reduced after treatment with 18. Neuroprotection in neuron-like differentiated SH-SY5Y cells was also achieved with 18. In summary, this family of 1,5-benzodiazepin-2-ones with an interesting antioxidant and drug-like profile, with low cytotoxic and good neuroprotectant activity, constitutes a new promising chemical class with high potential for the development of new therapeutic agents against PD.
The Experiences of a Complex Arts-Based Intervention for Patients with End-Stage Kidney Disease Whilst Receiving Haemodialysis: A Qualitative Process Evaluation

The global prevalence and burden of end-stage kidney disease (ESKD) is increasing, partially as a result of an aging population. Patients with ESKD who receive haemodialysis experience a difficult, protracted treatment regimen that can negatively impact mental health and wellbeing. One way of addressing this issue could be through the provision of arts-based interventions during haemodialysis treatment. A process evaluation was conducted as part of a larger feasibility study, to explore experiences and acceptability of an intra-dialytic (during haemodialysis) arts-based intervention. Thirteen patients and nine healthcare professionals were interviewed. The interviews were transcribed verbatim and thematically analysed. Three themes related to the experience of art on dialysis included: the perception of art participation, as patients described initial anxiety around participating in art, which reduced after they experienced the intervention; the benefits of art participation on both patients and healthcare professionals; the benefits including improved self-esteem, motivation, increased social interaction and an overall improved haemodialysis experience; and the acceptability of the arts-based intervention, as the intervention was highly acceptable, even when delivered by a facilitator who was not a professional artist. This study highlights that arts-based interventions could be used to improve the mental health and wellbeing of patients with ESKD receiving haemodialysis.
Isolation of RNA from Acute Ischemic Stroke Clots Retrieved by Mechanical Thrombectomy

Mechanical thrombectomy (MT) for large vessel acute ischemic stroke (AIS) has enabled biologic analyses of resected clots. While clot histology has been well-studied, little is known about gene expression within the tissue, which could shed light on stroke pathophysiology. In this methodological study, we develop a pipeline for obtaining useful RNA from AIS clots. A total of 73 clot samples retrieved by MT were collected and stored in RNALater and in 10% phosphate-buffered formalin. RNA was extracted from all samples using a modified Chemagen magnetic bead extraction protocol on the PerkinElmer Chemagic 360. RNA was interrogated by UV–Vis absorption and electrophoretic quality control analysis. All samples with sufficient volume underwent traditional qPCR analysis and samples with sufficient RNA quality were subjected to next-generation RNA sequencing on the Illumina NovaSeq platform. Whole blood RNA samples from three patients were used as controls, and H&E-stained histological sections of the clots were used to assess clot cellular makeup. Isolated mRNA was eluted into a volume of 140 µL and had a concentration ranging from 0.01 ng/µL to 46 ng/µL. Most mRNA samples were partially degraded, with RNA integrity numbers ranging from 0 to 9.5. The majority of samples (71/73) underwent qPCR analysis, which showed linear relationships between the expression of three housekeeping genes (GAPDH, GPI, and HPRT1) across all samples. Of these, 48 samples were used for RNA sequencing, which had moderate quality based on MultiQC evaluation (on average, ~35 M reads were sequenced). Analysis of clot histology showed that more acellular samples yielded RNA of lower quantity and quality. We obtained useful mRNA from AIS clot samples stored in RNALater. qPCR analysis could be performed in almost all cases, while sequencing data could only be performed in approximately two-thirds of the samples. Acellular clots tended to have lower RNA quantity and quality.
Surveillance for Antibiotic-Resistant E. coli in the Salish Sea Ecosystem

E. coli was isolated from the Salish Sea (Puget Sound) ecosystem, including samples of marine and fresh water, and wildlife dependent on this environment. E. coli isolates were assessed for phenotypic and genotypic resistance to antibiotics. A total of 305 E. coli isolates was characterized from samples collected from: marine water obtained in four quadrants of the Salish Sea; select locations near beaches; fresh water from streams near marine beaches; and fecal samples from harbor porpoises (Phocoena phocoena), harbor seals (Phoca vitulina), river otters (Lontra canadensis), and English sole (Parophrys vetulus). Isolates were evaluated using antimicrobial susceptibility typing, whole-genome sequencing, fumC, and multilocus sequence typing. Resistance and virulence genes were identified from sequence data. Of the 305 isolates from Salish Sea samples, 20 (6.6%) of the E. coli were intermediate, and 31 (10.2%) were resistant to ≥1 class of antibiotics, with 26.9% of nonsusceptible (resistant and intermediate resistant) E. coli isolates from marine mammals and 70% from river otters. The proportion of nonsusceptible isolates from animals was significantly higher than samples taken from marine water (p < 0.0001). A total of 196 unique STs was identified including 37 extraintestinal pathogenic E. coli (ExPEC)-associated STs [ST10, ST38, ST58, ST69, ST73, ST117, ST131, and ST405]. The study suggests that animals may be potential sentinels for antibiotic-resistant and ExPEC E. coli in the Salish Sea ecosystem.
Breast Cancer Drug Approvals Issued by EMA: A Review of Clinical Trials

Simple Summary Considering the high incidence and mortality of breast cancer, a lot of trials evaluating new drugs for the treatment of this disease are currently ongoing. However, few drugs show a statistically and clinically significant improvement in the outcomes leading to the Competent Authority approval. In this review we analyzed the European Medicines Agency breast cancer drug indications issued between January 2015 and June 2021 and we evaluated the clinical trials results leading to the approval and their update. Abstract Breast cancer represents the first cause of cancer worldwide and the leading cause of cancer mortality for women. Therefore, new therapies are needed to improve the prognosis of women diagnosed with this disease. In this review, we summarize the new drug indications for the treatment of breast cancer approved by European Medicines Agency between January 2015 and June 2021. In particular, we analyzed the clinical trials results leading to approvals and their update (when available), according to setting (localized and locally advanced or metastatic) and clinical features (hormone receptor positive, HER2 positive, triple negative, BRCA 1/2 mutation). The aim of this paper is to describe the clinical benefit obtained with the new indications.
Efficacy of hyaluronic acid film on perianal wound healing in a rat model

Purpose Postoperative pain and delayed wound healing are the main complications following anal surgery associated with poor quality of life. Hyaluronic acid (HA) supports tissue regeneration and rapid wound healing by promoting cell proliferation and migration. We investigated the effects of HA on perianal wound healing in a rat model. Methods Forty-eight 8-week-old Sprague-Dawley rats with perianal wounds created by biopsy punch were divided into 3 groups: simple dressing with gauze (control), dressing with topical HA film, and dressing with topical HA gel. HA agents were not reapplied postoperatively. Wound healing was evaluated by measuring the healed area, and histological analyses were randomly performed using hematoxylin and eosin and Masson trichrome staining. Results Fewer mean days were required for complete wound healing in the HA film and HA gel groups than in the control group (11.6 vs. 11.9 vs. 13.8 days, respectively; P = 0.010). The healed area in the HA film group on day 11 was larger than that in the HA gel and control groups (80.2% vs. 61.9% vs. 53.2%, respectively; P < 0.001). Histologically, the HA film group showed accelerated reepithelialization, a rapid transition to lymphocyte-predominant inflammation, and increased fibroblastic proliferation and collagen deposition compared to the other groups. There was no treatment-related toxicity in the HA application groups. Conclusion Topical application of HA film to perianal wounds improves the wound healing rate in a rat model. This finding suggests a potential benefit of HA film application in promoting wound healing after anal surgery in humans.
Effect of External Feedback on Bimanual Coordination Control in Patients with Parkinson’s Disease

Bimanual coordination control requires task-specific control of the spatial and temporal characteristics of the coupling of both upper limbs. The present study examined the effects of external feedback (i.e., auditory signal) on bimanual coordination movement during patients with Parkinson’s disease (PD). Twelve PD patients in advanced stages and 12 early stages of untreated PD patients, and 12 age-matched normal adults were instructed to perform bimanual coordination control using preference (1 Hz) and fast (1.75 Hz) speeds with metronome auditory cue. The results demonstrated that the advanced PD patients showed reduced synchronized bimanual coordination control during the anti-phase movement compared with other two groups. Moreover, the decreased movement accuracy was exhibited not only at the preference speed, but also more particularly at the fast speed with anti-phase rather than in-phase movement. This suggests that PD results in impairments in scaling the bimanual movement speed and amplitude of limb, and these deficits were more pronounced as a function of movement control speed. Overall, the current data provide evidence of the pathophysiology of the basal ganglia on the bimanual coordination movement.
Occurrence of Sinonasal Intestinal-Type Adenocarcinoma and Non-Intestinal-Type Adenocarcinoma in Two Countries with Different Patterns of Wood Dust Exposure

Simple Summary Wood dust exposure is a reported pathogenetic factor for sinonasal intestinal-type adenocarcinoma, particularly in occupational exposure in wood-working industries. This study characterized wood dust exposure and compared the occurrence of sinonasal intestinal-type adenocarcinoma and non-intestinal-type adenocarcinoma between France with predominantly deciduous hardwood forests and Finland with mostly coniferous softwood forests. The findings indicated that sinonasal intestinal-type adenocarcinomas occur much more frequently in France than in Finland and are distinctly more common than non-intestinal adenocarcinomas, while in Finland the reverse is true. This is the first systematic comparison of the occurrence of the two tumor types in countries with distinctly different wood usage and wood dust exposure. It is also the first systematic study on differences in wood dust exposure between sinonasal intestinal-type adenocarcinoma and non-intestinal-type adenocarcinoma. The results provide important epidemiological information on pathogenetic differences between the two tumor types, highlighting the significance of the source of the wood dust. Abstract Sinonasal intestinal-type adenocarcinoma is strongly associated with hardwood dust exposure. Non-intestinal-type adenocarcinoma is a rarer and less well-known subtype considered not to be related with wood dust exposure. We determined the relative numbers of these two tumor types in 56 sinonasal adenocarcinoma patients in France and Finland, relating them with carefully assessed wood dust exposure histories. Diagnostic workup including immunohistochemistry for the intestinal markers CDX2 and CK20 indicated that the proportions of the two tumors differed significantly between France and Finland. In Finnish samples non-intestinal adenocarcinomas were more common than intestinal-type adenocarcinomas (12 non-intestinal vs. nine intestinal), while in the French samples the reverse was true (six non-intestinal vs. 29 intestinal). Such remarkably dissimilar occurrence of these tumors in France and Finland presumably reflects different pathogenetic circumstances in the two countries, and perhaps their different patterns of wood dust exposure. In France the main source of wood dust is from hardwoods. In Finland it is derived from softwoods. This is the first systematic comparison of the occurrence of intestinal-type adenocarcinoma and non-intestinal-type adenocarcinoma in two countries with different wood usage. It appears to be the first systematic study on differences in wood dust exposure between intestinal-type adenocarcinoma and non-intestinal-type adenocarcinoma.
Participation of Selected Soluble BMP-2 and BMP-7 Bone Morphogenetic Proteins and Their Soluble Type I ALK-1 and Type II BMPR2 Receptors in Formation and Development of Endometriosis

Angiogenesis is considered to be one of the key stages in the development of endometriosis. Recent studies indicate that bone morphogenetic proteins (BMPs) and their receptors (BMPR) may play an important role in the angiogenesis process. In the literature, however, there is a lack of publications concerning binding BMPs and their receptors with the pathogenesis of endometriosis. The aim of the study was to determine the role of soluble bone morphogenetic proteins, BMP-2 and BMP-7, and their receptors, ALK-1 and BMPR2, in the process of the formation and development of endometriosis. Peritoneal fluid was collected in the proliferative phase of the menstrual cycle, from 80 women aged 21–49 years (mean age 31.3 ± 6.7 years) undergoing laparoscopy to determine the causes of primary infertility. The study involved 60 women in the I, II, III, and IV stages of the disease. The reference group consisted of 20 women who did not have endometriosis or other lesions in the pelvic area. The concentration in the peritoneal fluid of women with endometriosis was compared to the concentration of this parameter in the reference group, and a statistically significant reduction in the concentration of the BMP-2 molecule was found, as well as increasing concentrations of BMP-7, ALK-1, and BMPR2. BMP-2 and BMP-7 and their soluble receptors, ALK-1 and BMPR2, are involved in the formation of endometriosis. The changes in the concentrations of most of the tested parameters demonstrated in the study, especially in the early stages of the disease, may indicate the more effective formation of new blood vessels in this period.
Equisetin Restores Colistin Sensitivity against Multi-Drug Resistant Gram-Negative Bacteria

The overuse of antibiotics and the scarcity of new drugs have led to a serious antimicrobial resistance crisis, especially for multi-drug resistant (MDR) Gram-negative bacteria. In the present study, we investigated the antimicrobial activity of a marine antibiotic equisetin in combination with colistin against Gram-negative bacteria and explored the mechanisms of synergistic activity. We tested the synergistic effect of equisetin in combination with colistin on 23 clinical mcr-1 positive isolates and found that 4 µg/mL equisetin combined with 1 µg/mL colistin showed 100% inhibition. Consistently, equisetin restored the sensitivity of 10 species of mcr-1 positive Gram-negative bacteria to colistin. The combination of equisetin and colistin quickly killed 99.9% bacteria in one hour in time-kill assays. We found that colistin promoted intracellular accumulation of equisetin in colistin-resistant E. coli based on LC-MS/MS analysis. Interestingly, equisetin boosted ROS accumulation in E. coli in the presence of colistin. Moreover, we found that equisetin and colistin lost the synergistic effect in two LPS-deficient A. baumannii strains. These findings suggest that colistin destroys the hydrophobic barrier of Gram-negative bacteria, facilitating equisetin to enter the cell and exert its antibacterial effect. Lastly, equisetin restored the activity of colistin in a G. mellonella larvae infection model. Collectively, these results reveal that equisetin can potentiate colistin activity against MDR Gram-negative bacteria including colistin-resistant strains, providing an alternative approach to address Gram-negative pathogens associated with infections in clinics.
The Effect of FATP1 on Adipocyte Differentiation in Qinchuan Beef Cattle

Simple Summary Previous research found that FATP1 plays an important role in the regulation of fatty acid metabolism and lipid accumulation in pig and chicken, but its function has not been explored in bovine adipocyte yet. In this study, we investigated the effect of FATP1 expression on preadipocyte differentiation in Qinchuan cattle using overexpression and interference assays. Our results reveal that FATP1 overexpression promoted preadipocyte differentiation, lipid droplet formation, and the expression of LPL and PPARγ, while FATP1 interference had the opposite effects on adipocyte differentiation and fat deposition. Following FATP1 overexpression and FATP1 interference in adipocytes, RNA-seq analysis identified that SLPI, STC1, SEMA6A, TNFRSF19, SLN, PTGS2, ADCYP1, FADS2, and SCD genes were differentially expressed. Pathway analysis revealed that the PPAR signaling pathway, AMPK signal pathway, and Insulin signaling pathway were enriched with differentially expressed genes. We propose that the FATP1 gene may affect the beef quality by involving adipocyte differentiation and lipid deposition, and may shed new light on the formation mechanisms of adipose tissues. Abstract FATP1 plays an important role in the regulation of fatty acid metabolism and lipid accumulation. In this study, we investigated the patterns of FATP1 expression in various tissues obtained from calf and adult Qinchuan cattle, and in differentiating adipocytes. Next, we investigated the effect of FATP1 expression on preadipocyte differentiation in Qinchuan cattle using overexpression and interference assays. We also identified the differentially expressed genes (DEGs) and pathways associated with FATP1 overexpression/interference. Our results reveal that FATP1 was broadly expressed in heart, kidney, muscle, small intestine, large intestine, and perirenal fat tissues. While FATP1 overexpression promoted preadipocyte differentiation, fat deposition, and the expression of several genes involved in fat metabolism, FATP1 interference had the opposite effects on adipocyte differentiation. Following FATP1 overexpression and FATP1 interference in adipocytes, RNA-seq analysis was performed to identify DEGs related to fat metabolism. The DEGs identified include SLPI, STC1, SEMA6A, TNFRSF19, SLN, PTGS2, ADCYP1, FADS2, and SCD. Pathway analysis revealed that the DEGs were enriched in the PPAR signaling pathway, AMPK signal pathway, and Insulin signaling pathway. Our results provide an in-depth understanding of the function and regulation mechanism of FAPT1 in fat metabolism.