Miracle-dz/UniFAR-FTUs huggingface dataset:
The Role of Sphingolipids in Regulating Vascular Permeability in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a disease that causes scarring and fibrotic transformation of the lung parenchyma, resulting in the progressive loss of respiratory function and, often, death. Current treatments that target profibrotic factors can slow the rate of progression but are unable to ultimately stop it. In the past decade, many studies have shown that increased vascular permeability may be both a predictive and perpetuating factor in fibrogenesis. Consequently, there is a search for therapeutic targets to try and modulate vascular permeability in fibrotic lungs. One such class of targets that show great promise is sphingolipids. Sphingolipids are common in cell membranes and are increasingly recognized as critical to many cell signaling pathways, including those that affect the integrity of the vascular endothelial barrier. In this focused review we look at sphingolipids, particularly the sphingosine-1-phosphate (S1P) axis and its effects on vascular permeability, and how those effects may affect the pathogenesis of IPF. We further examine existing S1P modulators and their potential efficacy as therapeutics for IPF.
Low- and Negative-Pressure Hydrocephalus: New Report of Six Cases and Literature Review

Low- or very-low-pressure hydrocephalus is a serious and rare phenomenon, which is becoming better known since it was first described in 1994 by Pang and Altschuler. Forced drainage at negative pressures can, in most cases, restore the ventricles to their original size, thus achieving neurological recovery. We present six new cases that suffered this syndrome from 2015 to 2020: two of them after medulloblastoma surgery; a third one as a consequence of a severe head trauma that required bifrontal craniectomy; another one after craniopharyngioma surgery; a fifth one with leptomeningeal glioneuronal tumor; and, finally, a patient with a shunt for normotensive hydrocephalus. Before the development of this condition, four of them had mid-low-pressure cerebrospinal fluid (CSF) shunts. Four patients required cerebrospinal fluid (CSF) drainage at negative pressures oscillating from zero to −15 mmHg by external ventricular drainage until ventricular size normalized, followed by the placement of a new definitive low-pressure shunt, one of them to the right atrium. The duration of drainage in negative pressures through external ventricular drainage (EVD) ranged from 10 to 40 days with concomitant intracranial pressure monitoring at the neurointensive care unit. Approximately 200 cases of this syndrome have been described in the literature. The causes are varied and superimposable to those of high-pressure hydrocephalus. Neurological impairment is due to ventricular size and not to pressure values. Subzero drainage is still the most commonly used method, but other treatments have been described, such as neck wrapping, ventriculostomy of the third ventricle, and lumbar blood patches when associated with lumbar puncture. Its pathophysiology is not clear, although it seems to involve changes in the permeability and viscoelasticity of the brain parenchyma together with an imbalance in CSF circulation in the craniospinal subarachnoid space.
Functional Analysis of GSTK1 in Peroxisomal Redox Homeostasis in HEK-293 Cells

Peroxisomes serve as important centers for cellular redox metabolism and communication. However, fundamental gaps remain in our understanding of how the peroxisomal redox equilibrium is maintained. In particular, very little is known about the function of the nonenzymatic antioxidant glutathione in the peroxisome interior and how the glutathione antioxidant system balances with peroxisomal protein thiols. So far, only one human peroxisomal glutathione-consuming enzyme has been identified: glutathione S-transferase 1 kappa (GSTK1). To study the role of this enzyme in peroxisomal glutathione regulation and function, a GSTK1-deficient HEK-293 cell line was generated and fluorescent redox sensors were used to monitor the intraperoxisomal GSSG/GSH and NAD+/NADH redox couples and NADPH levels. We provide evidence that ablation of GSTK1 does not change the basal intraperoxisomal redox state but significantly extends the recovery period of the peroxisomal glutathione redox sensor po-roGFP2 upon treatment of the cells with thiol-specific oxidants. Given that this delay (i) can be rescued by reintroduction of GSTK1, but not its S16A active site mutant, and (ii) is not observed with a glutaredoxin-tagged version of po-roGFP2, our findings demonstrate that GSTK1 contains GSH-dependent disulfide bond oxidoreductase activity.
Excitation-Inhibition Imbalance in Migraine: From Neurotransmitters to Brain Oscillations

Migraine is among the most common and debilitating neurological disorders typically affecting people of working age. It is characterised by a unilateral, pulsating headache often associated with severe pain. Despite the intensive research, there is still little understanding of the pathophysiology of migraine. At the electrophysiological level, altered oscillatory parameters have been reported within the alpha and gamma bands. At the molecular level, altered glutamate and GABA concentrations have been reported. However, there has been little cross-talk between these lines of research. Thus, the relationship between oscillatory activity and neurotransmitter concentrations remains to be empirically traced. Importantly, how these indices link back to altered sensory processing has to be clearly established as yet. Accordingly, pharmacologic treatments have been mostly symptom-based, and yet sometimes proving ineffective in resolving pain or related issues. This review provides an integrative theoretical framework of excitation–inhibition imbalance for the understanding of current evidence and to address outstanding questions concerning the pathophysiology of migraine. We propose the use of computational modelling for the rigorous formulation of testable hypotheses on mechanisms of homeostatic imbalance and for the development of mechanism-based pharmacological treatments and neurostimulation interventions.
Radiomics from Mesorectal Blood Vessels and Lymph Nodes: A Novel Prognostic Predictor for Rectal Cancer with Neoadjuvant Therapy

The objective of our study is to investigate the predictive value of various combinations of radiomic features from intratumoral and different peritumoral regions of interest (ROIs) for achieving a good pathological response (pGR) following neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC). This retrospective study was conducted using data from LARC patients who underwent nCRT between 2013 and 2021. Patients were divided into training and validation cohorts at a ratio of 4:1. Intratumoral ROIs (ROIITU) were segmented on T2–weighted imaging, while peritumoral ROIs were segmented using two methods: ROIPTU_2mm, ROIPTU_4mm, and ROIPTU_6mm, obtained by dilating the boundary of ROIITU by 2 mm, 4 mm, and 6 mm, respectively; and ROIMR_F and ROIMR_BVLN, obtained by separating the fat and blood vessels + lymph nodes in the mesorectum. After feature extraction and selection, 12 logistic regression models were established using radiomics features derived from different ROIs or ROI combinations, and five–fold cross–validation was performed. The average area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of the models. The study included 209 patients, consisting of 118 pGR and 91 non–pGR patients. The model that integrated ROIITU and ROIMR_BVLN features demonstrated the highest predictive ability, with an AUC (95% confidence interval) of 0.936 (0.904–0.972) in the training cohort and 0.859 (0.745–0.974) in the validation cohort. This model outperformed models that utilized ROIITU alone (AUC = 0.779), ROIMR_BVLN alone (AUC = 0.758), and other models. The radscore derived from the optimal model can predict the treatment response and prognosis after nCRT. Our findings validated that the integration of intratumoral and peritumoral radiomic features, especially those associated with mesorectal blood vessels and lymph nodes, serves as a potent predictor of pGR to nCRT in patients with LARC. Pending further corroboration in future research, these insights could provide novel imaging markers for refining therapeutic strategies.
Cellular Senescence, Inflammation, and Cancer in the Gastrointestinal Tract

Due to modern medical advancements, greater proportions of the population will continue to age with longer life spans. Increased life span, however, does not always correlate with improved health span, and may result in an increase in aging-related diseases and disorders. These diseases are often attributed to cellular senescence, in which cells become disengaged from the cell cycle and inert to cell death. These cells are characterized by a proinflammatory secretome. The proinflammatory senescence-associated secretory phenotype, although part of a natural function intended to prevent further DNA damage, creates a microenvironment suited to tumor progression. This microenvironment is most evident in the gastrointestinal tract (GI), where a combination of bacterial infections, senescent cells, and inflammatory proteins can lead to oncogenesis. Thus, it is important to find potential senescence biomarkers as targets of novel therapies for GI diseases and disorders including cancers. However, finding therapeutic targets in the GI microenvironment to reduce the risk of GI tumor onset may also be of value. This review summarizes the effects of cellular senescence on GI aging, inflammation, and cancers, and aims to improve our understanding of these processes with a goal of enhancing future therapy.
Effect of the Freeze-Dried Mullein Flower Extract (Verbascum nigrum L.) Addition on Oxidative Stability and Antioxidant Activity of Selected Cold-Pressed Oils

The aim of the study was to analyze the influence of mullein flower extract addition on the oxidative stability and antioxidant activity of cold-pressed oils with a high content of unsaturated fatty acids. The conducted research has shown that the addition of mullein flower extract increases the oxidative stability of oils, but its addition depends on the type of oil and should be selected experimentally. In rapeseed and linseed oil, the best stability was found for samples with 60 mg of extract/kg of oil, while in chia seed oil and hemp oil, it was found with 20 and 15 mg of extract/kg of oil, respectively. The hemp oil exhibited the highest antioxidant properties, as evidenced by an increase in the induction time at 90 °C from 12.11 h to 14.05 h. Additionally, the extract demonstrated a protective factor of 1.16. Oils (rapeseed, chia seed, linseed, and hempseed) without and with the addition of mullein extract (2–200 mg of extract/kg of oil) were analyzed for oxidative stability, phenolic compounds content, and antioxidant activity using DPPH• and ABTS•+ radicals. After the addition of the extract, the oils had from 363.25 to 401.24 mg GAE/100 g for rapeseed oil and chia seed oil, respectively. The antioxidant activity of the oils after the addition of the extract ranged from 102.8 to 221.7 and from 324.9 to 888.8 µM Trolox/kg for the DPPH and ABTS methods, respectively. The kinetics parameters were calculated based on the oils’ oxidative stability results. The extract increased the activation energy (Ea) and decreased the constant oxidation rate (k).
Trait Depression and Subjective Well-Being: The Chain Mediating Role of Community Feeling and Self-Compassion

Although subjective well-being has been widely discussed as being one of the important indicators of clinical depression, few studies have explored how it relates to trait depression. In particular, increasing the number of positive experiences has long been a potential goal for depression-related clinical interventions, but the mechanisms by which such interventions work in countering depression have been poorly studied. Grounded in the cognitive theory of depression, the current study aimed to address this specific gap by testing the mediating effects of community feeling and self-compassion between trait depression and subjective well-being. A survey of 783 college students found that trait depression was not only able to directly and negatively predict individual subjective well-being but also indirectly predict individual subjective well-being through the mediating role of community feeling and self-compassion alone and through the chain mediating role of self-compassion from community feeling. These findings reveal the internal mechanisms of trait depression that, to some extent, impede subjective well-being and offer certain guiding significance for the self-regulation of interventions for clinical and non-clinical individuals with trait depression.
Specific Methyl-CpG Configurations Define Cell Identity through Gene Expression Regulation

Cell identity is determined by the chromatin structure and profiles of gene expression, which are dependent on chromatin accessibility and DNA methylation of the regions critical for gene expression, such as enhancers and promoters. These epigenetic modifications are required for mammalian development and are essential for the establishment and maintenance of the cellular identity. DNA methylation was once thought to be a permanent repressive epigenetic mark, but systematic analyses in various genomic contexts have revealed a more dynamic regulation than previously thought. In fact, both active DNA methylation and demethylation occur during cell fate commitment and terminal differentiation. To link methylation signatures of specific genes to their expression profiles, we determined the methyl-CpG configurations of the promoters of five genes switched on and off during murine postnatal brain differentiation by bisulfite-targeted sequencing. Here, we report the structure of significant, dynamic, and stable methyl-CpG profiles associated with silencing or activation of the expression of genes during neural stem cell and brain postnatal differentiation. Strikingly, these methylation cores mark different mouse brain areas and cell types derived from the same areas during differentiation.
Dental Caries in Adult Patients with Rheumatoid Arthritis—A Systematic Review

Patients suffering from rheumatoid arthritis (RA) are repeatedly affected by oral diseases or complaints, including xerostomia, periodontitis and dental caries. The aim of this systematic review was the evaluation of caries prevalence and/or incidence in patients with RA. Within this review, there is a systematic search of the literature based on PubMed, Web of Science and Scopus. Two independent researchers performed the search in February 2023. The search terms were “dental caries” AND “rheumatoid arthritis”. Additionally, a manual search completed the review process. Studies on adult patients (age ≥ 18 years) only suffering from RA were included. Studies had to explicitly report on the prevalence or incidence of dental caries. The respective studies were checked regarding suitability and, if they were eligible, analyzed qualitatively. A quality appraisal was performed for all of the analyzed studies. A total of 336 studies were detected, of which 16 studies met the in- and exclusion criteria. The sample sizes of the clinical investigations ranged between 13 and 1337 participants. Twelve studies evaluated a healthy control group. In 8/12 studies, a significant difference in the prevalence/incidence of caries was found between RA patients and controls. The majority of the studies applied the decayed (DT), missing and filled teeth index (DMFT) for the diagnosis of caries. On average (mean value), 0.8 to 5.79 carious teeth per patient were reported across the studies. There was no information on the stadium, activity or location of caries (e.g., root caries) in any study. Quality appraisal revealed a moderate quality for most studies. In conclusion, caries prevalence was heterogeneous across studies, while a higher caries prevalence was repeatedly reported in RA patients against controls. Further research regarding dental caries in RA appears recommendable; multidisciplinary, patient-centered dental care for patients with RA should be fostered to improve patients’ dental health status.
Salen-like Chromium and Aluminum Complexes as Catalysts in the Copolymerization of Epoxides with Cyclic Anhydrides for the Synthesis of Polyesters

Chromium and aluminum complexes bearing salalen ligands were explored as catalysts for the ring-opening copolymerization (ROCOP) of succinic (SA), maleic (MA), and phthalic (PA) anhydrides with several epoxides: cyclohexene oxide (CHO), propylene oxide (PO), and limonene oxide (LO). Their behavior was compared with that of traditional salen chromium complexes. A completely alternating enchainment of monomers to provide pure polyesters was achieved with all the catalysts when used in combination with 4-(dimethylamino)pyridine (DMAP) as the cocatalyst. Poly(propylene maleate-block-polyglycolide), a diblock polyester with a precise composition, was obtained by switch catalysis, in which the same catalyst was able to combine the ROCOP of propylene oxide and maleic anhydride with the ring-opening polymerization (ROP) of glycolide (GA) through a one-pot procedure, starting from an initial mixture of the three different monomers.
The Relationship between Nursing Practice Environment and Pressure Ulcer Care Quality in Portugal’s Long-Term Care Units

Background: The morbidity associated with ageing has contributed to an increase in the prevalence of Pressure Ulcers (PUs) in all care settings. The impact of these on people’s quality of life and the extent of the associated economic and social burden constitutes today, by their importance, a serious public health problem. This study aims to describe the nursing work environment in Portuguese long-term care (LTC) units and to assess how this environment relates to the quality of PU care. Methods: A longitudinal study among inpatients with PUs was conducted in LTC units. The Nursing Work Index-Revised Scale (NWI-R) was sent to all nurses in these units. Cox proportional hazard models were used to relate the satisfaction degree with the service (measured by the NWI-R-PT items) to the healing time of the PUs, adjusting for confounders. Results: A total of 165 of 451 invited nurses completed the NWI-R-PT. Most were women (74.6%) and had 1 to 5 years of professional experience. Less than half (38.4%) had education in wound care. Of the 88 patients identified with PUs, only 63 had their PU documented, highlighting the difficulties in updating electronic records. The results showed that the level of concordance with Q28 “Floating so that staffing is equalised among units” is strongly associated with a shorter PU healing time. Conclusion: A good distribution of nursing staff over the units will likely improve the quality of wound care. We found no evidence for possible associations with the questions on participation in policy decisions, salary level, or staffing educational development and their relationship with PUs healing times.
Association between Facebook Addiction, Depression, and Emotional Regulation among Women

Facebook has grown to be one of the most widely used communication platforms. A new condition linked with widespread use has emerged with its expanding popularity: Facebook addiction. A descriptive cross-sectional research design was used in the current study, in two randomly selected villages (Elmanial and Batra) and one town (Talkha city) affiliated with Dakahlia Governorate, Egypt. Data were collected from women only through using a self-administered socio-demographic questionnaire, Facebook addiction scale, Beck depression inventory-II, and emotional regulation scale. The study found 83.7% of the studied women reported moderate emotional regulation; 27.9% had moderate Facebook addiction, and 23.9% reported mild depression. The study concluded there was a significant negative correlation between Facebook addiction and emotional regulation.
Association of Inflammatory and Oxidative Status Markers with Metabolic Syndrome and Its Components in 40-to-45-Year-Old Females: A Cross-Sectional Study

Oxidative stress and sterile inflammation play roles in the induction and maintenance of metabolic syndrome (MetS). This study cohort included 170 females aged 40 to 45 years who were categorized according to the presentation of MetS components (e.g., central obesity, insulin resistance, atherogenic dyslipidemia, and elevated systolic blood pressure) as controls not presenting a single component (n = 43), those with pre-MetS displaying one to two components (n = 70), and females manifesting MetS, e.g., ≥3 components (n = 53). We analyzed the trends of seventeen oxidative and nine inflammatory status markers across three clinical categories. A multivariate regression of selected oxidative status and inflammatory markers on the components of MetS was performed. Markers of oxidative damage (malondialdehyde and advanced-glycation-end-products-associated fluorescence of plasma) were similar across the groups. Healthy controls displayed lower uricemia and higher bilirubinemia than females with MetS; and lower leukocyte counts, concentrations of C-reactive protein, interleukine-6, and higher levels of carotenoids/lipids and soluble receptors for advanced glycation end-products than those with pre-MetS and MetS. In multivariate regression models, levels of C-reactive protein, uric acid, and interleukine-6 were consistently associated with MetS components, although the impacts of single markers differed. Our data suggest that a proinflammatory imbalance precedes the manifestation of MetS, while an imbalance of oxidative status accompanies overt MetS. Further studies are needed to elucidate whether determining markers beyond traditional ones could help improve the prognosis of subjects at an early stage of MetS.
Increasing Antibody Responses to Five Doses of SARS-CoV-2 mRNA Vaccine in Lung Transplant Patients

Purpose: COVID-19 causes high mortality in Lung Transplant (LTx) patients, therefore vaccination in this population is potentially life-saving. However, the antibody response is impaired after three vaccinations in LTx patients. We questioned whether this response might be increased, and therefore studied the serological IgG antibody response across up to five doses of the SARS-CoV-2 vaccine. In addition, risk factors for non-response were investigated. Methods: In this large retrospective cohort study, antibody responses were assessed after 1–5 mRNA-based SARS-CoV-2 vaccines in all LTx patients between February 2021 and September 2022. A positive vaccine response was defined as an IgG level ≥ 300 BAU/mL. Positive antibody responses due to COVID-19 infection were excluded from the analysis. Outcome and clinical parameters were compared between responders and non-responders, and multivariable logistic regression analysis was performed to determine the risk factors for vaccine-response failure. Results: The antibody responses of 292 LTx patients were analyzed. Positive antibody response to 1–5 SARS-CoV-2 vaccinations occurred in 0%, 15%, 36%, 46%, and 51%, respectively. During the study period, 146/292 (50%) of the vaccinated individuals tested positive for SARS-CoV-2 infection. The COVID-19-related mortality was 2.7% (4/146), and all four patients were non-responders. Risk factors associated with non-response to SARS-CoV-2 vaccines in univariable analyses were age (p = 0.004), chronic kidney disease (CKD) (p = 0.006), and shorter time since transplantation (p = 0.047). In the multivariable analysis, they were CKD (p = 0.043), and shorter time since transplantation (p = 0.028). Conclusion: A two- to five-dose regime of SARS-CoV-2 vaccines in LTx patients increases the probability of vaccine response and results in a cumulative vaccine response in 51% of the LTx population. LTx patient antibody response to SARS-CoV-2 vaccinations is therefore impaired, especially in patients shortly after LTx, patients with CKD, and the elderly.