Miracle-dz/UniFAR-FTUs huggingface dataset:
The High Osmolarity Glycerol Mitogen-Activated Protein Kinase regulates glucose catabolite repression in filamentous fungi

The utilization of different carbon sources in filamentous fungi underlies a complex regulatory network governed by signaling events of different protein kinase pathways, including the high osmolarity glycerol (HOG) and protein kinase A (PKA) pathways. This work unraveled cross-talk events between these pathways in governing the utilization of preferred (glucose) and non-preferred (xylan, xylose) carbon sources in the reference fungus Aspergillus nidulans. An initial screening of a library of 103 non-essential protein kinase (NPK) deletion strains identified several mitogen-activated protein kinases (MAPKs) to be important for carbon catabolite repression (CCR). We selected the MAPKs Ste7, MpkB, and PbsA for further characterization and show that they are pivotal for HOG pathway activation, PKA activity, CCR via regulation of CreA cellular localization and protein accumulation, as well as for hydrolytic enzyme secretion. Protein-protein interaction studies show that Ste7, MpkB, and PbsA are part of the same protein complex that regulates CreA cellular localization in the presence of xylan and that this complex dissociates upon the addition of glucose, thus allowing CCR to proceed. Glycogen synthase kinase (GSK) A was also identified as part of this protein complex and shown to potentially phosphorylate two serine residues of the HOG MAPKK PbsA. This work shows that carbon source utilization is subject to cross-talk regulation by protein kinases of different signaling pathways. Furthermore, this study provides a model where the correct integration of PKA, HOG, and GSK signaling events are required for the utilization of different carbon sources.
Can Playfulness be Stimulated? A Randomised Placebo-Controlled Online Playfulness Intervention Study on Effects on Trait Playfulness, Well-Being, and Depression.

BACKGROUND While there are numerous applications of play-based interventions, there is little research on playfulness-based interventions. We applied interventions that aim at stimulating playfulness and test effects on happiness and depressive symptoms. METHOD In a randomised placebo-controlled online intervention, N = 533 participants were assigned to one of three 1-week playfulness conditions (i.e. three playful things, using playfulness in a new way, and counting playfulness) or a placebo condition. Participants reported on global playfulness, facets of playfulness, well-being, and depression at pretest, posttest, and at follow-ups after 2, 4, and 12 weeks. RESULTS All interventions increased expressions in all facets of playfulness, had short-term effects on well-being, and ameliorated depression. CONCLUSION Overall, findings suggest that playfulness can be stimulated by short self-administered interventions.
A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1

Primary Ovarian Insufficiency (POI) is a major cause of infertility, but its etiology remains poorly understood. Using whole-exome sequencing in a family with three cases of POI, we identified the candidate missense variant S167L in HSF2BP, an essential meiotic gene. Functional analysis of the HSF2BP-S167L variant in mouse showed that it behaves as a hypomorphic allele compared to a new loss-of-function (knock-out) mouse model. Hsf2bpS167L/S167L females show reduced fertility with smaller litter sizes. To obtain mechanistic insights, we identified C19ORF57/BRME1 as a strong interactor and stabilizer of HSF2BP and showed that the BRME1/HSF2BP protein complex co-immunoprecipitates with BRCA2, RAD51, RPA and PALB2. Meiocytes bearing the HSF2BP-S167L variant showed a strongly decreased staining of both HSF2BP and BRME1 at the recombination nodules and a reduced number of the foci formed by the recombinases RAD51/DMC1, thus leading to a lower frequency of crossovers. Our results provide insights into the molecular mechanism of HSF2BP-S167L in human ovarian insufficiency and sub(in)fertility.
Introducing the Tactual Span: A New Task for Assessing Working Memory in the Teactile Modality

The span paradigm is commonly used to assess working memory (WM), predominantly through the visual and auditory routes and less often through the tactile modality. The current study aimed to validate the “Tactual Span”, a new task developed to evaluate WM in the tactile modality. Participants were 140 healthy young adults, who performed the Tactual Span alongside span tasks in three additional modalities (auditory, visual, and visuospatial), as well as a selective attention task and a semantic verbal fluency task. The Tactual Span and other span tasks were found to correlate, while correlations with the selective attention and semantic fluency tasks were largely nonsignificant, indicating good construct validity. Cronbach’s alpha for both stages as well as skewness and kurtosis were also adequate. An exploratory factor analysis for the forward stage showed that the Tactual Span and Visuospatial Span were loaded on one factor, whereas the Auditory and Visual Spans were loaded on another factor. In the backward stage, all span tasks were loaded on a single factor. The findings provide an initial indication that the Tactual Span task is a feasible and valid tool for assessing WM in the tactile modality.
Increased First Pass Success with C-MAC Videolaryngoscopy in Prehospital Endotracheal Intubation—A Randomized Controlled Trial

Endotracheal intubation (ETI) with direct view laryngoscopy (DL) is the gold standard for airway management. Videolaryngoscopy (VL) can improve glottis visualization, thus facilitating ETI. The aim of this monocentric, randomized, prospective study on a physician staffed German air ambulance is to compare DL and VL for ETI in terms of number of attempts and time as well as visualization of the glottis in a prehospital setting in a physician-based rescue system in adult patients. A power analysis was performed à priori. We used consecutive on-scene randomization with a sealed envelope system for the DL and VL-group. Successful ETI with first pass success was significantly more frequent with VL than DL and three seconds faster. The percentage of glottis opening and the Cormack & Lehane classification were significantly better with VL than DL. Regarding improved first pass success in ETI with the VL, we would recommend the use of VL for prehospital airway management in physician-based rescue systems.
Performance of the New 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus in Children and Young Adults

To compare the diagnostic usefulness of the 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for systemic lupus erythematosus (SLE) to that of the 1997 ACR classification criteria for SLE when applied to youths (age ≤21 years) with SLE.
Non-support of species complex hypothesis of Cordyceps sinensis by targeted rDNA-ITS sequence analysis

Cordyceps sinensis is a well-known traditional Chinese herb commonly used as a tonic drug for hundreds of years.It is mainly distributed in Asian high-altitude grasslands,growing parasitically on buried larvae of Lepidoptera.Hirsutella sinensis is the only anamorph of C.sinensis that has been supported by several reports especially at rDNA-ITS level.However,the rDNA-ITS sequences of C.sinensis available from the NCBI database are still significantly divergent,except for the apparently erroneous-accessioned sequences.Based on the GenBank sequences,a hypothesis of three cryptic species involved in C.sinensis species complex was proposed before.In order to examine this hypothesis,we carried out the experiment by designing specific primers for targeted rDNA-ITS sequences using the DNA sample from individual C.sinensis fruiting body.Specimens of C.sinensis were collected from Sichuan and Qinghai of China,respectively.Our results suggested that only the C.sinensis-group A is the authentic C.sinensis. The so-called C.sinensis-group B and C.sinensis-group C are most likely different fungal species rather than the cryptic species of C.sinensis.
Microbial Composition of Oral Biofilms after Visible Light and Water-Filtered Infrared a Radiation (VIS+wIRA) in Combination with Indocyanine Green (ICG) as Photosensitizer

In view of increasing antibiotic resistance, antimicrobial photodynamic therapy (aPDT) is an alternative treatment method used to eradicate the microbial community of oral biofilms that can be responsible for different oral infections. In order to investigate changes in the microbial composition after application of aPDT with visible light and water-filtered infrared A (VIS+wIRA) in combination with indocyanine green (ICG), oral microorganisms of the initial and mature biofilm were evaluated by mass spectrometry (MALDI-TOF-MS). To determine surviving microorganisms using MALDI-TOF-MS, an in situ biofilm was irradiated with VIS+wIRA for five minutes in the presence of ICG (300 and 450 µg/mL, respectively). Treatment with chlorhexidine (0.2%) served as positive control. Identified microorganisms of the initial biofilm treated with ICG showed a clear reduction in diversity. The microbial composition of the mature oral biofilm also showed changes after the implementation of aPDT, which mainly resulted in a shift in the percentage of bacterial species. The resulting destruction of the microbial balance within the oral biofilm by aPDT using VIS+wIRA and ICG can be seen as an advantageous supplementary approach in the adjunctive treatment of periodontitis and peri-implantitis.
The Duration of Breastfeeding and Attention-Deficit Hyperactivity Disorder in School-Aged Children

ABSTRACT Attention-deficit hyperactivity disorder (ADHD) is one of the most common childhood-onset neurodevelopmental disorders. In some recent studies breastfeeding had positive effects on physical health and mental development of children and these studies have recommended further studies in this issue. This study evaluated the relationship between duration of breastfeeding and ADHD. This case-control study was carried out in 2017 on 404 children aged 7–12 (196 children with ADHD and 208 children without ADHD). The questionnaire included items on the risk factors such as the child’s sex, age, delivery method, birth weight, birth rank, gestational age, age of mother, duration of breastfeeding, history of neonatal hospitalization, history of drug use in neonatal period, history of drug use in pregnancy, history of hypothyroidism and hyperthyroidism in pregnancy, history of neonatal icter, history of neonatal blood exchange. Data were analyzed using t-test, chi-square and logistic regression. The mean of breastfeeding duration in children with ADHD was 17.05 ± 7.52 months compared with 18.59 ± 6.74 months in control group (p = .03). A stepwise logistic regression that included the variables was found to be significant in univariate analysis, demonstrating a significant association between ADHD and breastfeeding duration (p = .01), male gender (OR = 2.8), mother hypothyroidism(OR = 4.5) and history of drug use in neonatal period (OR = 1.9). Long-term duration of breastfeeding (more than 12 months) could be a protective factor in ADHD. However, further studies are required.
Biochemical Evaluation of the Antioxidant Effects of Hydroxytyrosol on Pancreatitis-Associated Gut Injury

Acute pancreatitis is a severe abdominal pathology often associated with several complications including gut dysfunction. Oxidative stress is one of the most important pathways involved in this pathology. Hydroxytyrosol (HT), a phenolic compound obtained from olive oil, has shown anti-inflammatory and antioxidant properties. We evaluated the effects of HT administration on pancreatic and intestinal injury induced by caerulein administration. CD1 female mice were administered caerulein (50 μg/kg) for 10 h. HT treatment (5 mg/kg) was performed 30 min after the first caerulein injection and for two consecutive hours afterwards. One hour after the last caerulein injection, mice were sacrificed and serum, colon and pancreatic tissue samples were collected. HT was able to reduce the serum hallmarks of pancreatitis (amylase and lipase), histological damage score in both pancreas and colon tissue, inflammatory cells recruitment (mast cells) in both injured tissues, intrapancreatic trypsin activity and overexpression of the adhesion molecules (Intercellular Adhesion Molecule-1 (ICAM-1) and P-selectin) in colon. Additionally, HT reduced cytokine (interleukin 1 beta (IL- 1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)) levels in serum, pancreas and colon tissue and chemokine release (monocyte chemotactic protein-1 (MCP1/CCL2)) in pancreas and colon tissue. HT decreased lipid peroxidation and oxidative stress (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activity) by enhancing the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in both injured tissues. Moreover, HT preserved intestinal barrier integrity, as shown by the diamine oxidase (DAO) serum levels and tight junction (zonula occludens (ZO) and occludin) expression in pancreas and colon. Our findings demonstrated that HT would be an important therapeutic tool against pancreatitis-induced injuries in the pancreas and gut.
Association Between Generalized Anxiety Disorder Scores and Online Activity Among US Adults During the COVID-19 Pandemic: Cross-Sectional Analysis

Background Evidence from past pandemics suggests that fear, uncertainty, and loss of control during large-scale public health crises may lead to increased pandemic-related information seeking, particularly among persons predisposed to high anxiety. In such groups, a greater consumption of information pertaining to the COVID-19 pandemic may increase anxiety. Objective In this study, we examine the association between online activity and Generalized Anxiety Disorder 7 (GAD-7) scores in the United States. Methods We recruited participants for an online survey through advertisements on various platforms such as Google, Facebook, and Reddit. A total of 406 adult US participants with moderate to severe (≥10) GAD-7 scores met the inclusion criteria and completed the survey. Anxiety levels measured using the GAD-7 scale formed our primary outcome. Our key independent variables were average daily time spent online and average daily time spent online searching about COVID-19 within the past 14 days. We used as controls potential confounders of the relation between our key independent variables and GAD-7 scores, namely, sleep quality, the COVID-19 Fear Inventory scale, binge drinking, substance use, prescription drug abuse, and sociodemographic attributes. Results Linear multivariate regression analyses showed that GAD-7 scores were higher among those who spent >4 hours online (per day) searching for information about COVID-19 (coefficient 1.29, P=.002), controlling for all other covariates. The total time spent online was not statistically associated with GAD-7 scores. Conclusions Results from this study indicate that limiting pandemic-related online information seeking may aid anxiety management in our study population.
Effectiveness and Impact of the 4CMenB Vaccine against Group B Meningococcal Disease in Two Italian Regions Using Different Vaccination Schedules: A Five-Year Retrospective Observational Study (2014–2018)

Background: A few years after the introduction in Italy of a four-component anti-meningococcal B vaccine (4CMenB), we evaluated the effectiveness and impact of vaccination in two regions using different schedules (2, 4, 6, 12 months in Tuscany vs. 7, 9, 15 months in Veneto) through an observational retrospective study. Methods: Vaccination started in 2014 in Tuscany and in 2015 in Veneto; the data collected referred to the period 2006–2018 for Tuscany and 2007–2018 for Veneto. Cases of invasive meningococcal disease due to N. Meningitidis B were identified by culture and/or real-time PCR. Results: In Tuscany, pre-vaccine incidence was 1.96 (95% CL 1.52; 2.40) and dropped to 0.62 (95% CL 0.60; 0.64) in the post-4CMenB era. Evaluating only vaccinated children, post-4CMenB incidence was 0.12 (95% CL 0.08; 0.15). In Veneto pre-vaccine incidence was 1.94 (95% CL 1.92; 1.96) and dropped to 1.34 (95% CL 1.31; 1.38) in the post-4CMenB era. In the vaccinated population, MenB incidence was 0.53 (95% CL 0.50; 0.56). Vaccine effectiveness was 93.6% (95% CL 55.4; 99.1) in Tuscany and 91.0% (95% CL 59.9; 97.9) in Veneto, with mean vaccine coverages of 83.9% and 81.7%, respectively. The overall impact (evaluating both vaccinated and unvaccinated children) was 0.68 (95% CL 0.10; 0.89) in Tuscany and 0.31 (95% CL −0.56; 0.69) in Veneto; the total impact (evaluating only vaccinated children) was 0.94 (95% CL 0.56; 0.99) and 0.90 (95% CL 0.57; 0.97), respectively. The relative case reduction (RCR) was 65% in Tuscany and 31% in Veneto. Considering the vaccinated population, the RCR was equal to 91% and 80%, respectively. Conclusion: In conclusion, 4CMenB appears to have a very high effectiveness in Italy; the impact of vaccination appears greater where the immunization program is started early.
Performance of Legiolert Test vs. ISO 11731 to Confirm Legionella pneumophila Contamination in Potable Water Samples

Detection and enumeration of Legionella in water samples is of great importance for risk assessment analysis. The plate culture method is the gold standard, but has received several well-known criticisms, which have induced researchers to develop alternative methods. The purpose of this study was to compare Legionella counts obtained by the analysis of potable water samples through the plate culture method and through the IDEXX liquid culture Legiolert method. Legionella plate culture, according to ISO 11731:1998, was performed using 1 L of water. Legiolert was performed using both the 10 mL and 100 mL Legiolert protocols. Overall, 123 potable water samples were analyzed. Thirty-seven (30%) of them, positive for L. pneumophila, serogroups 1 or 2–14 by plate culture, were used for comparison with the Legiolert results. The Legiolert 10 mL test detected 34 positive samples (27.6%) and the Legiolert 100 mL test detected 37 positive samples, 27.6% and 30% respectively, out of the total samples analyzed. No significant difference was found between either the Legiolert 10 mL and Legiolert 100 mL vs. the plate culture (p = 0.9 and p = 0.3, respectively) or between the Legiolert 10 mL and Legiolert 100 mL tests (p = 0.83). This study confirms the reliability of the IDEXX Legiolert test for Legionella pneumophila detection and enumeration, as already shown in similar studies. Like the plate culture method, the Legiolert assay is also suitable for obtaining isolates for typing purposes, relevant for epidemiological investigations.
Complex assessment of relationship quality within dyads.

Higher quality relationships have been linked to improved outcomes; however, the measurement of relationship quality often ignores its complexity and the possibility of co-occurring positivity and negativity across different contexts. The goal of this study is to test the added benefit of including multiple dimensions, contexts, and perspectives of relationship quality from both individuals in predicting marital functioning. The Social Relationships Index assessed positive and negative dimensions of relationship quality under neutral, positive, and support-seeking contexts for 183 heterosexual married couples. Models showed that the inclusion of multiple dimensions of relationship quality across all three contexts improved prediction of marital functioning for both women and men. The use of multidimensional multicontextual relationship quality assessments is highly recommended.
Metabolic profiling of aromatic compounds in cerebrospinal fluid of neurosurgical patients using microextraction by packed sorbent and liquid-liquid extraction with the following gas chromatography-mass spectrometry analysis.

A new approach to the quantitative analysis of aromatic metabolites in cerebrospinal fluid samples of neurosurgical patients based on microextraction by packed sorbent coupled with derivatization and GC-MS was developed. The analytical characteristics such as recoveries (40-90%), LOD (0.1-0.3 μM) and LOQ (0.4-0.7 μM) values, accuracy less than ±20% and precision less than 20%, linear correlations (R2 ≥ 0.99) over 0.4-10 μM range of concentrations demonstrated that microextraction by packed sorbent provides the results for the quantitative analysis of target compounds comparable with those for liquid-liquid extraction. Similar results were achieved using 40 μL of sample for microextraction by packed sorbent instead of 200 μL for liquid-liquid extraction. Benzoic, 3-phenylpropionic, 3-phenyllactic, 4-hydroxybenzoic, 2-(4-hydroxyphenyl)acetic, homovanillic, and 3-(4-hydroxyphenyl)lactic acids were found in cerebrospinal fluid samples (n=138) of neurosurgical patients in lower concentrations than in serum samples (n=110) of critically ill patients. Analysis of the cerebrospinal fluid and serum samples taken at the same time from neurosurgical patients (n=5) revealed the similar results for patients without infection and multidirectional results for patients with the central nervous system infection. Our preliminary results demonstrate the necessity for the further evaluating the aromatic compound profile in cerebrospinal fluid for its subsequent verification as potential diagnostic markers.
Age-Associated Salivary MicroRNA Biomarkers for Oculopharyngeal Muscular Dystrophy

Small non-coding microRNAs (miRNAs) are involved in the regulation of mRNA stability. Their features, including high stability and secretion to biofluids, make them attractive as potential biomarkers for diverse pathologies. This is the first study reporting miRNA as potential biomarkers for oculopharyngeal muscular dystrophy (OPMD), an adult-onset myopathy. We hypothesized that miRNA that is differentially expressed in affected muscles from OPMD patients is secreted to biofluids and those miRNAs could be used as biomarkers for OPMD. We first identified candidate miRNAs from OPMD-affected muscles and from muscles from an OPMD mouse model using RNA sequencing. We then compared the OPMD-deregulated miRNAs to the literature and, subsequently, we selected a few candidates for expression studies in serum and saliva biofluids using qRT-PCR. We identified 126 miRNAs OPMD-deregulated in human muscles, but 36 deregulated miRNAs in mice only (pFDR < 0.05). Only 15 OPMD-deregulated miRNAs overlapped between the in humans and mouse studies. The majority of the OPMD-deregulated miRNAs showed opposite deregulation direction compared with known muscular dystrophies miRNAs (myoMirs), which are associated. In contrast, similar dysregulation direction was found for 13 miRNAs that are common between OPMD and aging muscles. A significant age-association (p < 0.05) was found for 17 OPMD-deregulated miRNAs (13.4%), whereas in controls, only six miRNAs (1.4%) showed a significant age-association, suggesting that miRNA expression in OPMD is highly age-associated. miRNA expression in biofluids revealed that OPMD-associated deregulation in saliva was similar to that in muscles, but not in serum. The same as in muscle, miRNA expression levels in saliva were also found to be associated with age (p < 0.05). Moreover, the majority of OPMD-miRNAs were found to be associated with dysphagia as an initial symptom. We suggest that levels of specific miRNAs in saliva can mark muscle degeneration in general and dysphagia in OPMD.