Miracle-dz/UniFAR-FTUs huggingface dataset:
Extracellular Vesicles Derived From Citrus sinensis Modulate Inflammatory Genes and Tight Junctions in a Human Model of Intestinal Epithelium

It is widely acknowledged that mammalian exosomes (or extracellular vesicles), have a key role in intercellular communication, owing to the presence of various bioactive molecules such as lipids, proteins, and microRNAs within their inner compartment. Most recently, the discovery of extracellular vesicles isolated from edible plants (such as vegetables and fruits) and their similarity in terms of size and content with exosomes has opened new perspectives on possible intercellular communication and regulation of important biological processes in which these vesicles are involved. It is also well-known that a balanced diet rich of fruits and vegetables (i.e., the Mediterranean diet) can contribute to maintain a “healthy gut” by preserving the intestinal epithelial barrier integrity and avoid that inflammatory stimuli that can alter homeostasis. In our study, we optimized a method to isolate extracellular vesicles from the orange juice (Citrus sinensis) (CS-EVs), and we characterized their morphology and behavior when in contact with the intestinal epithelium. We showed that CS-EVs are stable in a simulated gastrointestinal environment and are absorbed by intestinal cells without toxic effects, as expected. Furthermore, we demonstrated that CS-EVs can alter the gene expression of several genes involved in inflammation (i.e., ICAM1 and HMOX-1) and tight junctions (i.e., OCLN, CLDN1, and MLCK), contributing to limit inflammatory stimuli and restore a functional barrier by increasing the tight junction OCLN protein. Therefore, our study emphasizes the relevant role of fruit-derived extracellular vesicles in modulating important biological processes and maintaining a healthy intestinal epithelium, ultimately promoting human health and well-being.
Longitudinal Quantitative MRI Evaluation of Muscle Involvement in Amyotrophic Lateral Sclerosis

Background: Biomarkers of disease progression and outcome measures are still lacking for patients with amyotrophic lateral sclerosis (ALS). Muscle MRI can be a promising candidate to track longitudinal changes and to predict response to the therapy in clinical trials. Objective: Our aim is to apply quantitative muscle MRI in the evaluation of disease progression, focusing on thigh and leg muscles of patients with ALS, and to explore the correlation between radiological and clinical scores. Methods: We enrolled newly diagnosed patients with ALS, longitudinally scored using the ALS Functional Rating Scale-Revised (ALSFRS-R), who underwent a 3T muscle MRI protocol including a 6-point Dixon gradient-echo sequence and multi-echo turbo spin echo (TSE) T2-weighted sequence for quantification of fat fraction (FF), cross-sectional area (CSA), and water T2 (wT2). A total of 12 muscles of the thigh and six muscles of the leg were assessed by the manual drawing of 18 regions of interest (ROIs), for each side. A group of 11 age-matched healthy controls (HCs) was enrolled for comparison. Results: 15 patients (M/F 8/7; mean age 62.2 years old, range 29–79) diagnosed with possible (n = 2), probable (n = 12), or definite (n = 1) ALS were enrolled. Eleven patients presented spinal onset, whereas four of them had initial bulbar involvement. All patients performed MRI at T0, nine of them at T1, and seven of them at T2. At baseline, wT2 was significantly elevated in ALS subjects compared to HCs for several muscles of the thigh and mainly for leg muscles. By contrast, FF was elevated in few muscles, and mainly at the level of the thigh. The applied mixed effects model showed that FF increased significantly in the leg muscles over time (mainly in the triceps surae) and that wT2 decreased significantly in line with worsening in the leg subscore of ALSFRS-R, mainly at the leg level and in the anterior and medial compartment of the thigh. Conclusions: Quantitative MRI represents a non-invasive tool that is able to outline the trajectory of pathogenic modifications at the muscle level in ALS. In particular, wT2 was found to be increased early in the clinical history of ALS and also tended to decrease over time, also showing a positive correlation with leg subscore of ALSFRS-R.
An Integrative Assessment Combining Deep-Sea Net Sampling, in situ Observations and Environmental DNA Analysis Identifies Cabo Verde as a Cephalopod Biodiversity Hotspot in the Atlantic Ocean

The deep sea is among the largest, most biologically diverse, yet least-explored ecosystems on Earth. Baseline information on deep-sea biodiversity is crucial for understanding ecosystem functioning and for detecting community changes. Here, we established a baseline of cephalopod community composition and distribution off Cabo Verde, an archipelago in the eastern tropical Atlantic. This baseline served to test the hypothesis that Cabo Verde is biogeographically separated from other Macaronesian archipelagos and allowed the identification of cephalopod species which may play a role in the Macaronesian carbon cycle and oceanic food web. To investigate cephalopod community composition, this study used 746 individual cephalopods obtained by nets (0–1000 m) and 52 cephalopod encounters during video surveys with either towed camera (0–2500 m) or manned submersible (0–375 m). Additionally, environmental DNA (eDNA) metabarcoding on 105 seawater samples (50–2500 m), using an 18S rRNA universal cephalopod primer pair, and a species-specific primer pair for Taningia danae resulted in the detection of 32 cephalopod taxa. When combined, the three methods detected a total of 87 taxa, including 47 distinct species. Each method contributed between 7 and 54% of taxa that were not detected by the other methods, indicating that multiple methodological approaches are needed for optimal deep-sea cephalopod biodiversity assessments. This study documents the occurrences of six species and three genera for the first time in waters surrounding Cabo Verde. Video surveys and eDNA analysis detected Taningia danae recurrently (100–2500 m). eDNA metabarcoding proved to be a powerful tool for cephalopod biodiversity monitoring and complementary to traditional sampling methods. When also including literature records, Cabo Verde hosts at least 102 cephalopod taxa including 30 families and 64 benthic and pelagic species. The total number and species composition of Cabo Verde cephalopods is similar to the Canary Islands and Azores, two known cephalopod biodiversity hotspots, but the Cabo Verde octopus fauna seems to differ. Due to a range of life history characteristics, we hypothesize that the squids Taningia danae (Octopoteuthidae) and Sthenoteuthis pteropus (Ommastrephidae) are important in the carbon cycle of Macaronesia. As a cephalopod biodiversity hotspot Cabo Verde could function as a model region to investigate cephalopod biology and ecology in a rapidly changing Atlantic Ocean.
Lenvatinib Plus PD-1 Inhibitors as First-Line Treatment in Patients With Unresectable Biliary Tract Cancer: A Single-Arm, Open-Label, Phase II Study

Objective We investigated lenvatinib plus programmed cell death-1 (PD-1) inhibitors as a first-line treatment for initially unresectable biliary tract cancer (BTC). Methods In this Phase II study, adults with initially unresectable BTC received lenvatinib (body weight ≥60 kg, 12 mg; <60 kg, 8 mg) daily and PD-1 inhibitors (pembrolizumab/tislelizumab/sintilimab/camrelizumab 200 mg or toripalimab 240 mg) every 3 weeks. Primary endpoints were objective response rate (ORR) and safety. Secondary endpoints included surgical conversion rate, disease control rate (DCR), event-free survival (EFS), overall survival (OS) and tumor biomarkers. Results Among 38 enrolled patients, the ORR was 42.1% and the DCR was 76.3%. Thirteen (34.2%) patients achieved downstaging and underwent surgery, six of whom (46.2%) achieved a major pathologic response (n=2) or partial pathologic response (n=4) in the primary tumor. In total, 84.2% of patients experienced ≥1 treatment-related adverse event (TRAE), 34.2% experienced a Grade ≥3 TRAE and no treatment-related deaths occurred. After a median follow-up of 13.7 months the median EFS was 8.0 months (95% CI: 4.6–11.4) and the median OS was 17.7 months (95% CI: not estimable). Conclusions Lenvatinib plus PD-1 inhibitors showed promising anti-tumor efficacy in patients with initially unresectable BTC and was generally well tolerated. Clinical Trial Registration www.chictr. org.cn, ChiCTR2100044476.
The Effects of Using a Nature-Sound Mobile Application on Psychological Well-Being and Cognitive Performance Among University Students

Many university students have been struggling with multiple challenges that may cause mental fatigue. Exposure to the natural environment is found to have restorative effects on mental fatigue, which can be explained by its benefits in physiological, psychological, and cognitive aspects. While the natural environment contains both visual and auditory elements, research on the effects of auditory elements, such as nature sounds, is underdeveloped and limited to laboratory settings. It remains unclear what are the effects of exposure to nature sounds in daily life settings. The study was conducted with 71 students from a university, who were randomly assigned to the experimental group using a nature-sound mobile application in daily life and the control group not using the application. After a 4-week exposure to the intervention, the students in the experimental group outperformed their counterparts in the control group on psychological well-being reflected in positive affect, as well as cognitive performance reflected in flow state, attention (in terms of alerting) and working memory (in terms of accuracy and reaction time). The findings reveal the positive impact of exposure to relaxing nature sounds on university students’ psychological well-being and cognitive performance, as well as the potential of mobile applications to provide easy exposure to nature sounds.
Performance of Noise Barriers with Absorptive Edge Treatments

The installation of sound-absorptive materials near the edge of a noise barrier is known to increase its insertion loss. First, scale-model experiments were performed to compare the performance of barriers that have absorptive edge linings with that of linearly extended, rigid uniform barriers and T-shaped barriers. The issue of effective positioning of the sound-absorptive material was also addressed. It was found that in terms of material use, an absorptive treatment was the most effective treatment for reducing the sound level in the shadow zone for a given barrier height. It was concluded that absorptive edge treatments may offer the opportunity to design effective treatments that could be retrofitted to existing barrier installations to improve their effectiveness. Preliminary field measurements were performed near South Bend, Indiana. The performance of an existing barrier was evaluated. Predictions of its performance made using the FHWA Traffic Noise Model were verified. An acoustical treatment was added to one vertical edge of the highway noise barrier. The results for the performance of the acoustical treatment measured in the field confirmed the trends of the scale-model laboratory measurements.
Effects of IRR Glazing on Radiant Heat and Thermal Comfort for On-Road Conditions

The authors tested the hypothesis that reducing radiant heat by the application of an infrared-reflective (IRR) treatment will allow occupants to maintain the same level of comfort in a warmer vehicle cabin. Participants were passengers in a mid-sized sedan that was driven for 46 minutes along a 41.5-mile route. Each participant experienced two drives: one with IRR film applied to all glazing surfaces of the vehicle, and one with no IRR treatment applied. Every two minutes, participants were asked to rate their thermal sensation at five body locations and to indicate whether, overall, they felt too hot or too cold. Cabin air temperature in the vehicle was raised or lowered depending on participants' responses. Although the IRR treatment did not have a statistically significant effect on the air temperature that participants found comfortable, the trend was in the expected direction, and a decrease in the average time required to reach thermal comfort was observed. IRR-treated drives were also associated with reductions in air conditioner compressor use and fuel consumption. While the physical effects in this study confirmed findings of previous studies, data concerning the relationship between radiant heat and comfortable air temperature were more complicated and inconclusive and would benefit from further research.
Younger and Late Middle-Aged Adults Exhibit Different Patterns of Cognitive-Motor Interference During Locomotor Adaptation, With No Disruption of Savings

It has been proposed that motor adaptation and subsequent savings (or faster relearning) of an adapted movement pattern are mediated by cognitive processes. Here, we evaluated the pattern of cognitive-motor interference that emerges when young and late middle-aged adults perform an executive working memory task during locomotor adaptation. We also asked if this interferes with savings of a newly learned walking pattern, as has been suggested by a study of reaching adaptation. We studied split-belt treadmill adaptation and savings in young (21 ± 2 y/o) and late middle-aged (56 ± 6 y/o) adults with or without a secondary 2-back task during adaptation. We found that young adults showed similar performance on the 2-back task during baseline and adaptation, suggesting no effect of the dual-task on cognitive performance; however, dual-tasking interfered with adaptation over the first few steps. Conversely, dual-tasking caused a decrement in cognitive performance in late middle-aged adults with no effect on adaptation. To determine if this effect was specific to adaptation, we also evaluated dual-task interference in late middle-aged adults that dual-tasked while walking in a complex environment that did not induce motor adaptation. This group exhibited less cognitive-motor interference than late middle-aged adults who dual-tasked during adaptation. Savings was unaffected by dual-tasking in both young and late middle-aged adults, which may indicate different underlying mechanisms for savings of reaching and walking. Collectively, our findings reveal an age-dependent effect of cognitive-motor interference during dual-task locomotor adaptation and no effect of dual-tasking on savings, regardless of age. Young adults maintain cognitive performance and show a mild decrement in locomotor adaptation, while late middle-aged adults adapt locomotion at the expense of cognitive performance.
Stress and Pain Before, During and After the First Wave of the COVID-19 Pandemic: An Exploratory Longitudinal Mixed Methods Study

Aims: This study explores the association between subjective feeling of stress and pain experience in the context of the COVID-19 pandemic with a focus on characteristics known to trigger a physiological stress response [sense of low control, threat to ego, unpredictability and novelty (STUN)]. Methods: This exploratory longitudinal convergent mixed methods design consisted of online questionnaires over three time points (before, during and after the 1st wave of the COVID-19 pandemic) (N = 49) and qualitative interviews (N = 27) during the 1st wave of the pandemic on distinct samples of individuals living with chronic pain (CP). Both types of data sources were mixed upon integration using joint display. Results: Mean pain intensity scores remained stable across time points, while pain unpleasantness and pain interference scores significantly improved. Global impression of change scores measured during the first wave of the pandemic do not entirely concord with pain scores evolution. Two thirds of participants reported a global deterioration of their pain condition at the beginning of the pandemic. Stress and pain catastrophizing before the pandemic were associated with pain scores throughout the pandemic; while most specific measures of stress due to the novel, uncontrollable, unpredictable and threatening nature of the pandemic were not. Qualitative data demonstrated that the deterioration reported in pain status reflected additional dimensions, including spatial expansion of the painful area, reduced access to treatments and challenges in adapting pain management strategies. Conclusions: Helping individuals to negotiate stressful aspects of the pandemic might help offset the negative impacts of stress on pain status in this context or other important life events.
Cognitive Process of Psoriasis and Its Comorbidities: From Epidemiology to Genetics

Psoriasis (PsO) is a chronic inflammatory skin disease that affects approximately 2% of the population all over the world. Comorbidities of PsO have increasingly garnered more interest in the past decades. Compared with the normal population, the incidences of comorbidities are higher among patients with PsO. In the last 20 years, researchers have focused on studying the genetic components of PsO, and genetic associations between PsO and its comorbidities were elucidated. This review provides an in-depth understanding and summarization of the connection between PsO and its comorbidities from the perspectives of epidemiology and genetics. Further understanding of PsO and its comorbidities will promote research on the pathogenesis, drug development, novel therapy methods, and personalized and precision treatment of PsO and its comorbidities.
Automatic Diagnosis of Schizophrenia in EEG Signals Using CNN-LSTM Models

Schizophrenia (SZ) is a mental disorder whereby due to the secretion of specific chemicals in the brain, the function of some brain regions is out of balance, leading to the lack of coordination between thoughts, actions, and emotions. This study provides various intelligent deep learning (DL)-based methods for automated SZ diagnosis via electroencephalography (EEG) signals. The obtained results are compared with those of conventional intelligent methods. To implement the proposed methods, the dataset of the Institute of Psychiatry and Neurology in Warsaw, Poland, has been used. First, EEG signals were divided into 25 s time frames and then were normalized by z-score or norm L2. In the classification step, two different approaches were considered for SZ diagnosis via EEG signals. In this step, the classification of EEG signals was first carried out by conventional machine learning methods, e.g., support vector machine, k-nearest neighbors, decision tree, naïve Bayes, random forest, extremely randomized trees, and bagging. Various proposed DL models, namely, long short-term memories (LSTMs), one-dimensional convolutional networks (1D-CNNs), and 1D-CNN-LSTMs, were used in the following. In this step, the DL models were implemented and compared with different activation functions. Among the proposed DL models, the CNN-LSTM architecture has had the best performance. In this architecture, the ReLU activation function with the z-score and L2-combined normalization was used. The proposed CNN-LSTM model has achieved an accuracy percentage of 99.25%, better than the results of most former studies in this field. It is worth mentioning that to perform all simulations, the k-fold cross-validation method with k = 5 has been used.
Combined Magnetostratigraphy From Three Localities of the Rainstorm Member of the Johnnie Formation in California and Nevada, United States Calibrated by Cyclostratigraphy: A 13 R/Ma Reversal Frequency for the Ediacaran

A combined magnetostratigraphy for the Rainstorm Member of the Ediacaran Johnnie Formation was constructed using the sediment accumulation rates determined by rock magnetic cyclostratigraphy for three localities of the Rainstorm Member to provide a high resolution, time-calibrated record of geomagnetic field reversal frequency at a critical time period in Earth history. Two previously reported magnetostratigraphy records from Death Valley, California, the Nopah Range and Winters Pass Hills (Minguez et al., 2015), were combined with new paleomagnetic and cyclostratigraphic results from the Desert Range locality of the Rainstorm Member in south central Nevada, United States . The Johnnie oolite marker bed is at the base of each of the three sections and allows their regional correlation. The Nopah Range and Desert Range localities have similar sediment accumulation rates of ∼5 cm/ka, so their stratigraphic sections can be combined directly. The Winters Pass Hills locality has a higher sediment accumulation rate of 8.4 cm/ka, therefore its stratigraphic positions are multiplied by 0.6 to combine with the Desert Range and Nopah Range magnetostratigraphy. The thermal demagnetization results from the Desert Range locality isolates characteristic remanent magnetizations that indicate two nearly antipodal east-west and shallow directions and a mean paleopole (11.7˚N, 348.4˚E) that is consistent with “shallow” Ediacaran directions. The Desert Range also yields a magnetic susceptibility rock magnetic cyclostratigraphy that records short eccentricity, obliquity, and precession astronomically-forced climate cycles in the Ediacaran. The high-resolution combined magnetostratigraphy with nearly meter-scale stratigraphic spacing (nominally 23 ka, based on the Desert Range sediment accumulation rate), indicates 11 polarity intervals in a cyclostratigraphy-calibrated duration of 849 ka, indicating a reversal frequency of 13 R/Ma. The Rainstorm Member records the Shuram carbon isotope excursion, hence its age is ∼574 Ma. Given the recent cyclostratigraphy-calibrated reversal frequency of 20 R/Ma from the Zigan Formation (Levashova et al., 2021) at 547 Ma, our results show that reversal frequency was high but fluctuated during the Ediacaran.
Neoliberal Economic Policies’ Effects on Perceptions of Social Justice and Sociopolitical Participation in Portugal

Contemporary societies challenge long-standing projects of the “good society” and social equality through neoliberal economic policies. Social forms of uncertainty generated by financial deprivation, precarity, and inequality seem to have effects on agency and coping and so socioeconomic and psychological consequences. This study aims to test these relationships, as well as a hypothesis on the potential impact of these constructs on beliefs of sociopolitical control and social dominance, which have implications for social justice. A mediation model explores the effects of financial access (the manifest benefit of work) on psychosocial uncertainty (which reflects the perception of uncertainty in the social context and the experience of its consequences within work, relationships, and the adoption of self-defeating beliefs) and on emotional coping strategies towards uncertainty, and their effects on personal agency, sociopolitical control (SPC), and social dominance orientation (SDO). Data are derived from a study of 633 participants in Portugal. Although personal agency is influenced by financial access and psychosocial uncertainty, it is not proved as a significant mediator for SPC and SDO. Nevertheless, financial access, psychosocial uncertainty, and emotional coping significantly contribute to the model, supporting the hypothesis that financial access protects against psychosocial uncertainty. Both have an impact on SPC and SDO. Therefore, financial deprivation and psychosocial uncertainty potentially contribute to extremism and populism in societies characterised by socially created forms of uncertainty. Implications of results for psychological intervention, namely in vocational/professional counselling, are discussed.