Miracle-dz/UniFAR-FTUs huggingface dataset:
Proof Theory of Partially Normal Skew Monoidal Categories

The skew monoidal categories of Szlach\'anyi are a weakening of monoidal categories where the three structural laws of left and right unitality and associativity are not required to be isomorphisms but merely transformations in a particular direction. In previous work, we showed that the free skew monoidal category on a set of generating objects can be concretely presented as a sequent calculus. This calculus enjoys cut elimination and admits focusing, i.e. a subsystem of canonical derivations, which solves the coherence problem for skew monoidal categories. In this paper, we develop sequent calculi for partially normal skew monoidal categories, which are skew monoidal categories with one or more structural laws invertible. Each normality condition leads to additional inference rules and equations on them. We prove cut elimination and we show that the calculi admit focusing. The result is a family of sequent calculi between those of skew monoidal categories and (fully normal) monoidal categories. On the level of derivability, these define 8 weakenings of the (unit,tensor) fragment of intuitionistic non-commutative linear logic.
Postprandial Apolipoprotein B48 is Associated with Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis

Objective: To describe postprandial lipemia in patients with rheumatoid arthritis (RA) and to analyze its association with subclinical atherosclerosis measured as carotid intima-media thickness (cIMT). Methods: We performed an observational study of 40 patients with RA and 40 sex and age-matched controls. Patients with dyslipidemia were excluded. Pathologically increased cIMT was defined as a carotid thickness greater than the 90th percentile (>p90) for age and sex. Fasting and postprandial plasma lipids, cholesterol, triglycerides, apolipoprotein B48 (ApoB48), and total ApoB were evaluated. The other variables included were clinical and laboratory values, Framingham score, and the 28-joint Disease Activity Score (DAS28). Two multivariate models were constructed to identify factors associated with pathologic cIMT in patients with RA. Results: Fasting lipid values were similar in patients with RA and controls, although those of postprandial ApoB48 were higher (median (IQR), 14.4 (10.8–12.1) vs. 12.1 (2.3–9,8); p = 0.042). Pathologic cIMT was recorded in 10 patients with RA (25%) and nine controls (22.5%). In patients with RA, pathologic cIMT was associated with postprandial ApoB48 (OR (95% CI), 1.15 (1.0–1.3)) and total ApoB (OR [95% CI], 1.12 [1.1–1.2]). The second model revealed a mean increase of 0.256 mm for cIMT in patients with elevated anticitrullinated protein antibodies (ACPAs). Conclusion: Postprandial ApoB48 levels in patients with RA are higher than in controls. Postprandial ApoB48 and total ApoB levels and markers of severity, such as ACPAs, are associated with pathologic cIMT in patients with RA. Our findings could indicate that these atherogenic particles have a negative effect on the endothelium.
Comparison of In Vitro and In Vivo Antioxidant Activities of Six Flavonoids with Similar Structures

The in vitro and in vivo antioxidant activities of six flavonoids with similar structures, including epicatechin (EC), epigallocatechin (EGC), procyanidin B2 (P), quercetin (Q), taxifolin (T), and rutin (R) were compared. The structures of the six flavonoids and their scavenging activities for 2,2-diphenyl-1-picrylhydrazyl (DPPH•) and 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) radicals were closely related. The flavonoids decreased serum contents of malondialdehyde (MDA) and nitric oxide (NO), and increased serum total antioxidative capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) levels to different degrees in d-galactose-treated mice. The changes in mRNA expression of liver GSH-Px1, CAT, SOD1, and SOD2 by d-galactose were dissimilarly restored by the six flavonoids. Moreover, the six flavonoids differentially prevented the inflammatory response caused by oxidative stress by inhibiting interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels, and restoring IL-10 levels. These six flavonoids from two subclasses revealed the following antioxidant capability: P > EC, EGC > EC, Q > T, Q > R. Our results indicate that (1) the pyrogallol, dimerization, and C2=C3 double bonds of flavonoids enhanced antioxidant activity and (2) the C3 glycosylation of flavonoids attenuated antioxidant capacity.
The use of microsatellite markers for parentage analysis in the Pacific cupped oyster, Crassostrea gigas (Thunberg)

Highly polymorphic genetic markers can be useful tools for the analysis of parental contributions. The present paper reports 3 experiments using microsatellite markers to analyse parental contributions in controlled in vitro factorial crosses of the cupped oyster Crassostrea gigas. Parentage analysis was eased by the large polymorphism observed at the 3 loci studied. In a cross between 20 males and 20 females, a quarter of the progeny could be assigned to a given parent using a single microsatellite locus showing 28 alleles. In 3 crosses between 5 males and females, all the progeny could be assigned to a family by using 3 loci. In all cases, the combined genotyping at 2 loci allowed parentage to be detennined unambiguously. Despite the balanced gametic contribution of each parent before fertilisation, unbalanced parental contributions are observed in the progeny, both at larval and juvenile stages. Evidence of gametic and zygotic competition is given to explain the observed unbalanced parental contributions.
Fluorescence Spectroscopy of Recoverin Function and Conformation

Recoverin is a neuronal calcium sensor protein (NCS protein) from the vertebrate photoreceptor which is involved in light adaptation. Recoverin changes its conformation upon sequential binding of two calcium ions. This conformational change induces the extrusion of a covalently attached myristoyl residue from a hydrophobic binding pocket which enables Recoverin to interact with lipid membranes (calcium myristoyl switch). In this thesis, I report on my investigation of Recoverin�s calcium myristoyl switch, using a recently developed modification of fluorescence correlation spectroscopy (FCS) that is called dual focus FCS (2fFCS). This method allows for measuring absolute diffusion coefficients with an accuracy of better than a few percent. Recoverin, and the Recoverin mutants E85Q and E121Q which bind only one or no Ca2+, respectively, were labeled with the fluorescent dye Alexa647. Differences in the hydrodynamic radius due to conformational changes of Recoverin and its mutants upon calcium binding were monitored by measuring the diffusion coefficient of these molecules as a function of free calcium concentration. The calcium dependent interaction of Recoverin with lipid membranes was measured in solutions of small unilamellar vesicles (SUVs) of different lipid composition. Again, diffusion measurements were used to determine the fraction of free and lipid bound Recoverin using the strongly different diffusion coefficients of both fractions. To account for the fluorescence brightness difference of the dye label when in solution and close to a lipid membrane, a new three photon correlation analysis was developed and tested.
Role of Smoking in the Pathogenesis of Multiple Sclerosis: A Review Article

Multiple sclerosis (MS) is a complex and unpredictable neurological condition. It is the most commonly seen autoimmune disorder. The incidence of disease and its prevalence are growing worldwide. Early identification of the disease and accurate diagnosis is important to prevent further complications and disability. The etiology remains unclear, and it is believed that complex gene-environment interactions play an essential role. Genetic predisposition only describes a portion of the disease risk, whereas lifestyle and environmental factors are significant contributors. Smoking was identified as an important risk factor for MS. The main objectives of this review were to examine the underlying mechanisms of immune dysregulation in the development of MS, explore the association between smoking and MS, and identify other genetic and environmental factors that alter the risk of developing the disease. We searched PubMed for articles relevant to the study topic published between 2000 and 2020 using the search terms “multiple sclerosis,” “cigarette smoking,” “risk factors,” and, “epigenetics. ” Studies reveal a marked association between smoking and the risk of MS. Unlike genetic risk factors, many lifestyles and environmental factors can be adjusted, with potential for prevention, particularly for people at the highest risk, such as families of individuals with MS.
Cytokinesis-blocked micronucleus assay in a group of Egyptian patients with Fanconi anemia

IntroductionFanconi anemia (FA) is one of the chromosomal instability syndromes characterized by a DNA repair defect. Cells derived from patients are hypersensitive to DNA cross-linking agents. In addition to the chromosomal breakages as a manifestation of the genomic instability, a few studies have detected elevated levels of micronuclei (MN) in patients with FA. The cytokinesis-blocked micronucleus (CBMN) assay was originally developed as a comprehensive test for measuring MN; however, it can also be used to measure nucleoplasmic bridges and nuclear buds. AimThe aim of this work is to determine the value of CBMN as a biomarker of genomic instability in patients with FA and its relation to their hematological findings. Patients and methodsCBMN assay was performed to analyze leukocytes from 12 patients with FA and eight normal individuals as controls to determine the sensitivity of this technique for the evaluation of genomic instability in patients with FA. The CBMN assay was performed for cultures with and without diepoxybutane. The patients with FA showed significantly high frequencies of MN, nuclear buds, and dicentric bridges. ConclusionFrom the results of this study, we can conclude that the CBMN assay in fact represents a comprehensive method to evaluate the genomic instability of patients with FA. It can also be used as an indicator for the hematological condition of the patients.
Campylomma verbasci (Heteroptera: Miridae): Pheromone-Based Seasonal Flight Patterns and Prediction of Nymphal Densities in Apple Orchards

Weekly catches of adult male Campylomma verbasci (Meyer) in sex pheromone-baited wing traps provided a seasonal record of Right activity during 1991 in apple orchards and patches of mullein in the interior of British Columbia. The first of two periods of flight activity reflected migration from apple to mullein, and the second probably represented two generations on mullein followed by migration back to apple. Monitoring of adult male C. verbasci using sex pheromone-baited traps in fall of 1990 and 1991 followed by limb-tap samples for first-generation nymphs the following years showed a significant positive relationship between fall catches and density of nymphs in conventional apple orchards. This result suggests that a pheromone-based monitoring system during fall could be developed to predict the density of nymphs the following spring. There was no such relationship in organic orchards, where adult populations in the fall were similar to those in conventional orchards, but mean counts of nymphs in the spring were 20 times lower. Two probable hypotheses could account for this disparity. Either female C. verbasci lay fewer overwintering eggs in organic orchards or mortality is higher, possibly resulting from biological-control agents acting in some organic orchards.
Clinical and Pre-Clinical Evidence of Carbonic Anhydrase IX in Pancreatic Cancer and Its High Expression in Pre-Cancerous Lesions

Hypoxia is a common phenomenon that occurs in most solid tumors. Regardless of tumor origin, the evolution of a hypoxia-adapted phenotype is critical for invasive cancer development. Pancreatic ductal adenocarcinoma is also characterized by hypoxia, desmoplasia, and the presence of necrosis, predicting poor outcome. Carbonic anhydrase IX (CAIX) is one of the most strict hypoxia regulated genes which plays a key role in the adaptation of cancer cells to hypoxia and acidosis. Here, we summarize clinical data showing that CAIX expression is associated with tumor necrosis, vascularization, expression of Frizzled-1, mucins, or proteins involved in glycolysis, and inevitably, poor prognosis of pancreatic cancer patients. We also describe the transcriptional regulation of CAIX in relation to signaling pathways activated in pancreatic cancers. A large part deals with the preclinical evidence supporting the relevance of CAIX in processes leading to the aggressive behavior of pancreatic tumors. Furthermore, we focus on CAIX occurrence in pre-cancerous lesions, and for the first time, we describe CAIX expression within intraductal papillary mucinous neoplasia. Our review concludes with a detailed account of clinical trials implicating that treatment consisting of conventionally used therapies combined with CAIX targeting could result in an improved anti-cancer response in pancreatic cancer patients.
Space Flight Diet-Induced Deficiency and Response to Gravity-Free Resistive Exercise

Immune system dysregulation is among the many adverse effects incurred by astronauts during space flights. Omega-3 fatty acids, β-alanine, and carnosine are among the many nutrients that contribute to immune system health. For space flight, crewmembers are prescribed a diet with a macronutrient composition of 55% carbohydrate, 30% fat, and 15% protein. To quantify omega-3 fatty acid, β-alanine and carnosine intakes from such a diet, and to examine each nutrient’s impact on exercise performance, 21 participants adhered to the aforementioned macronutrient ratio for 14 days which was immediately followed by a workout performed on gravity-independent resistive exercise hardware. Results included daily omega-3 fatty acid intakes below the suggested dietary intake. Daily omega-3 fatty acid, β-alanine and carnosine intakes each correlated with non-significant amounts of variance from the workout’s volume of work. Given the nutritional requirements to maintain immune system function and the demands of in-flight exercise countermeasures for missions of increasingly longer durations current results, in combination with previously published works, imply in-flight supplementation may be a prudent approach to help address the physiological and mental challenges incurred by astronauts on future space flights.
Electrosprayed Alginate Nanoparticles as CRISPR Plasmid DNA Delivery Carrier: Preparation, Optimization, and Characterization

Therapeutic gene editing is becoming more feasible with the emergence of the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein (Cas) system. However, the successful implementation of CRISPR/Cas9-based therapeutics requires a safe and efficient in vivo delivery of the CRISPR components, which remains challenging. This study presents successful preparation, optimization, and characterization of alginate nanoparticles (ALG NPs), loaded with two CRISPR plasmids, using electrospray technique. The aim of this delivery system is to edit a target gene in another plasmid (green fluorescent protein (GFP)). The effect of formulation and process variables were evaluated. CRISPR ALG NPs showed mean size and zeta potential of 228 nm and −4.42 mV, respectively. Over 99.0% encapsulation efficiency was achieved while preserving payload integrity. The presence of CRISPR plasmids in the ALG NPs was confirmed by Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy. The tests revealed that the nanoparticles were cytocompatible and successfully introduced the Cas9 transgene in HepG2 cells. Nanoparticles-transfected HepG2 was able to edit its target plasmid by introducing double-strand break (DSB) in GFP gene, indicating the bioactivity of CRISPR plasmids encapsulated in alginate nanoparticles. This suggests that this method is suitable for biomedical application in vitro or ex vivo. Future investigation of theses nanoparticles might result in nanocarrier suitable for in vivo delivery of CRISPR/Cas9 system.
Mining of prognosis-related genes in cervical squamous cell carcinoma immune microenvironment

Purpose The aim of this study was to explore the effective immune scoring method and mine the novel and potential immune microenvironment-related diagnostic and prognostic markers for cervical squamous cell carcinoma (CSSC). Materials and Methods The Cancer Genome Atlas (TCGA) data was downloaded and multiple data analysis approaches were initially used to search for the immune-related scoring system on the basis of Estimation of STromal and Immune cells in MAlignant Tumour tissues using Expression data (ESTIMATE) algorithm. Afterwards, the representative genes in the gene modules correlated with immune-related scores based on ESTIMATE algorithm were further screened using Weighted Gene Co-expression Network Analysis (WGCNA) and network topology analysis. Gene functions were mined through enrichment analysis, followed by exploration of the correlation between these genes and immune checkpoint genes. Finally, survival analysis was applied to search for genes with significant association with overall survival and external database was employed for further validation. Results The immune-related scores based on ESTIMATE algorithm was closely associated with other categories of scores, the HPV infection status, prognosis and the mutation levels of multiple CSCC-related genes (HLA and TP53). Eighteen new representative immune microenvironment-related genes were finally screened closely associated with patient prognosis and were further validated by the independent dataset GSE44001. Conclusion Our present study suggested that the immune-related scores based on ESTIMATE algorithm can help to screen out novel immune-related diagnostic indicators, therapeutic targets and prognostic predictors in CSCC.
Content Validation of the ATTR Amyloidosis Patient Symptom Survey: Findings from Patient and Clinician Cognitive Debriefing Interviews

Purpose Amyloid transthyretin (ATTR) amyloidosis is a rare, progressive, and fatal disease. The ATTR Patient Symptom Survey (ATTR-PSS) was previously developed through literature review and concept elicitation input from clinicians and patients and revised after evaluation by a patient focus group. This study further evaluated the content validity of the ATTR-PSS through qualitative cognitive debriefing interviews with clinicians and patients. Methods Seven clinicians and 10 patients with ATTR amyloidosis were interviewed individually regarding their overall impressions, the clarity and appropriateness of the survey, relevance of concepts measured, and comprehensiveness and comprehensibility of items and response choice sets. Results Clinicians acknowledged the usefulness of the ATTR-PSS in research and clinical settings. They suggested minor modifications to the survey instructions, the addition of 3 symptoms, and the transfer of 10 conditions from the symptom list to 2 separate items. Patients found the ATTR-PSS to be easy to complete and relevant to their experiences. Their feedback resulted in modification to instruction text, edits to the description of 4 symptoms, removal of 1 symptom, and addition of 2 diagnoses. Conclusion The findings support the content validity of the ATTR-PSS as an appropriate measure of symptom frequency, severity, and impact in patients with wild-type and hereditary ATTR amyloidosis.
Decreased Expression of the High Mobility Group Box 1 (HMGB1) Gene in Peripheral Blood in Patients with Mild or Moderate Clostridioides difficile Infection

Cytokines are mediators of inflammation induced in the course of Clostridioides difficile infection (CDI). High Mobility Group Box 1 (HMGB1) is a cytokine playing an important role in the pathogenesis of numerous inflammatory and autoimmune diseases. The aim of the study was to assess the HMGB1 gene expression in the course of CDI. We have performed a prospective case-control study- including 55 adult patients, among them 27 with CDI, who were hospitalized from October 2018 to February 2020 and 28 healthy volunteers. We assessed: a complete blood count with differential leukocyte count, blood creatinine, albumin, and C-reactive protein (CRP) levels. Then, the expression of the HMGB1 gene was evaluated using quantitative Real-Time PCR. Patients with CDI were found to have a significant increase in white blood cells (WBC), neutrophil count, and CRP levels, they also exhibited decreased levels of albumin compared with controls. The HMGB1 gene expression was significantly lower among patients with CDI compared with the control group and significantly, inversely correlated with CRP level in blood. In conclusion, we have observed a decreased expression of the HMGB1 gene in peripheral blood of patients with mild or moderate CDI, which hypothetically could reflect their diminished capability to fight the pathogen.
Effect of in situ aspartame mouthwash to prevent intrinsic and extrinsic erosive tooth wear

Background The aim was to evaluate whether aspartame regular mouthwash prior to erosive challenges with citric or hydrochloric acids would be able to prevent erosive enamel wear. Material and Methods This randomized, single blind in situ study was conducted with 3 crossover phases of 5 days. Polished bovine enamel blocks (n=252) were randomly divided among 6 groups/ 3 phases/ 21 volunteers. The groups under study were: aspartame solution (0.024% of aspartame in deionized water - experimental group), deionized water (negative-control) and stannous-containing solution (Elmex® Erosion Protection Dental Rinse; positive-control); subjected to erosion on citric acid or hydrochloric acid. Four times per day the volunteers rinsed the intraoral appliance with the respective solutions (in situ) prior to immersion of half of the appliance in 0.05M citric acid and the other half in 0.01M hydrochloric acid for 120 seconds (extraoral). The response variable was enamel loss by profilometry. Data were analyzed by ANOVA and Tukey’s test (p<0.05). Results No difference on enamel loss was found between aspartame solution and deionized water. Stannous-solution resulted in less enamel loss compared to deionized water. Hydrochloric acid resulted in higher enamel loss than citric acid. Conclusions In this model, aspartame was not able to prevent erosive tooth wear against citric or hydrochloric acids. Key words:Dental erosion, aspartame, stannous fluoride, citric acid, hydrochloric acid.
The Effect of UV Irradiation on Vitamin D2 Content and Antioxidant and Antiglycation Activities of Mushrooms

Mushroom irradiation has been considered a sustainable process to generate high amounts of vitamin D2 due to the role of this vitamin for human health and of the global concerns regarding its deficient or inadequate intake. Mushrooms are also receiving increasing interest due to their nutritional and medicinal properties. However, there is still a knowledge gap regarding the effect of UV irradiation on mushroom bioactive compounds. In this study, two of the most cultivated mushroom species worldwide, Agaricus bisporus and Pleurotus ostreatus, were irradiated with UV-B, and the effect of processing was investigated on the contents of vitamin D2 as well as on antioxidant and antiglycation activities. UV irradiation increased vitamin D2 up to 57 µg/g d.w, which is an adequate level for the fortification of a number of target foods. UV irradiation decreased the antioxidant activity when measured by the Folin–Ciocalteu reagent, the 2,2-diphenyl-1-(2,4,6 trinitrophenyl) hydrazyl radical assay and the ferric ion-reducing antioxidant power assay, but did not decrease the mushroom’s ability to inhibit glycation of a target protein. These results open up a new area of investigation aimed at selecting mushroom species with high nutraceutical benefits for irradiation in order to maintain their potential properties to inhibit oxidative and glycation processes responsible for human diseases.