Miracle-dz/UniFAR-FTUs huggingface dataset:
Global Warming, Advancing Bloom and Evidence for Pollinator Plasticity from Long-Term Bee Emergence Monitoring

Simple Summary Common experience has it that natural seasonal events are earlier in some years and later in others. In temperate zones, these events often seem to be timed by some combination of winter chill hours followed by cumulative warmth, variables which vary with a year’s weather. Over the course of decades, monitored annual bloom dates of a variety of wildflower species varies over 4–8-week ranges. This study reports annual emergence dates of four wild species of ground-nesting bees recorded over 12–24 years. Their first emergence ranged over 4–6 weeks, comparable to wildflowers and in part relatable to the same thermal cues used by plants. Global warming is advancing seasonal events, notably flowering, but it appears that native bees have the phenological flexibility to maintain their floral associations and critical pollination services both in wild and agricultural settings. Abstract Global warming is extending growing seasons in temperate zones, yielding earlier wildflower blooms. Short-term field experiments with non-social bees showed that adult emergence is responsive to nest substrate temperatures. Nonetheless, some posit that global warming will decouple bee flight and host bloom periods, leading to pollination shortfalls and bee declines. Resolving these competing scenarios requires evidence for bees’ natural plasticity in their annual emergence schedules. This study reports direct observations spanning 12–24 years for annual variation in the earliest nesting or foraging activities by 1–4 populations of four native ground-nesting bees: Andrena fulva (Andrenidae), Halictus rubicundus (Halictidae), Habropoda laboriosa and Eucera (Peponapis) pruinosa (Apidae). Calendar dates of earliest annual bee activity ranged across 25 to 45 days, approximating reported multi-decadal ranges for published wildflower bloom dates. Within a given year, the bee H. rubicundus emerged in close synchrony at multiple local aggregations, explicable if meteorological factors cue emergence. Emergence dates were relatable to thermal cues, such as degree day accumulation, soil temperature at nesting depth, and the first pulse of warm spring air temperatures. Similar seasonal flexibilities in bee emergence and wildflower bloom schedules bodes well for bees and bloom to generally retain synchrony despite a warming climate. Future monitoring studies can benefit from several simple methodological improvements.
Efficacy of BRAF and MEK Inhibition in Patients with BRAF-Mutant Advanced Melanoma and Germline CDKN2A Pathogenic Variants

Simple Summary In our study, we retrospectively collected data of patients with germline CDKN2A pathogenic variants who received targeted therapy for advanced melanoma across four European centers. Since loss of CDKN2A function may intrinsically limit the activity of MAPK-directed targeted therapy, we decided to assess whether patients with germline CDKN2A pathogenic variants may achieve suboptimal results with BRAF and MEK inhibitors. To the best of our knowledge, this is the first study reporting on patients with BRAF-mutant advanced melanoma and a germline CDKN2A pathogenic variant who received treatment with BRAF with or without MEK inhibitors. Despite the limitations of our study, mostly due to the rare frequency of CDKN2A pathogenic variants, a challenge for the conduction of prospective trials with proper sample size, our results support treatment with targeted therapy in this subset of patients. Abstract Inherited pathogenic variants (PVs) in the CDKN2A tumor suppressor gene are among the strongest risk factors for cutaneous melanoma. Dysregulation of the p16/RB1 pathway may intrinsically limit the activity of MAPK-directed therapy due to the interplay between the two pathways. In our study, we assessed, for the first time, whether patients with germline CDKN2A PVs achieve suboptimal results with BRAF inhibitors (BRAFi)+/−MEK inhibitors (MEKi). We compared the response rate of nineteen CDKN2A PVs carriers who received first-line treatment with BRAFi+/−MEKi with an expected rate derived from phase III trials and “real-world” studies. We observed partial response in 16/19 patients (84%), and no complete responses. The overall response rate was higher than that expected from phase III trials (66%), although not statistically significant (p-value = 0.143; 95% CI = 0.60–0.97); the difference was statistically significant (p-value = 0.019; 95% CI = 0.62–0.97) in the comparison with real-world studies (57%). The clinical activity of BRAFi+/−MEKi in patients with germline CDKN2A PV was not inferior to that of clinical trials and real-world studies, which is of primary importance for clinical management and genetic counseling of this subgroup of patients.
Cellular Senescence in Human Aldosterone-Producing Adrenocortical Cells and Related Disorders

In situ cortisol excess was previously reported to promote cellular senescence, a cell response to stress, in cortisol-producing adenomas (CPA). The aim of this study was to explore senescence pathways in aldosterone-producing cells and related disorders, and the influence of aldosterone overproduction on in situ senescence. We analyzed 30 surgical cases of aldosterone-producing adenoma (APA), 10 idiopathic hyperaldosteronism (IHA) and 19 normal adrenals (NA). CYP11B2 and senescence markers p16 and p21 were immunolocalized in all those cases above and results were correlated with histological/endocrinological findings. In the three cohorts examined, the zona glomerulosa (ZG) was significantly more senescent than other corticosteroid-producing cells. In addition, the ZG of adjacent non-pathological adrenal glands of APA and IHA had significantly higher p16 expression than adjacent non-pathological zona fasciculata (ZF), reticularis (ZR) and ZG of NA. In addition, laboratory findings of primary aldosteronism (PA) were significantly correlated with p21 status in KCNJ5-mutated tumors. Results of our present study firstly demonstrated that non-aldosterone-producing cells in the ZG were the most senescent compared to other cortical zones and aldosterone-producing cells in PA. Therefore, aldosterone production, whether physiological or pathological, could be maintained by suppression of cell senescence in human adrenal cortex.
Association of Organizational Behavior with Work Engagement and Work-Home Conflicts of Physician in China

This study aimed to examine how organizational behavior is associated with work engagement (WE) and work-home conflicts (WHCs) of physicians. The data were from a national cross-sectional survey of 3255 Chinese physicians. We examined organizational fairness, leadership attention, and team interaction for organizational behavior. The results indicate that greater organizational fairness is associated with higher WE and lower WHCs. High task fairness was associated with greater pride, and more enjoyment in work, lower sense of guilt towards their family, and less complaints from family members. Physicians reporting higher levels of leaders’ attention to their opinions reported experiencing more enjoyment of their work, and less effects on their care for family. A greater number of dinners with colleagues per month was associated with higher WE and lower WHCs, whilst a greater number of clinical case meetings per month was associated with higher WE and higher WHCs. The results suggest that the behavior of organizations could be an important intervention to improve the wellbeing of physicians.
On the Effectiveness of Oxygen Plasma and Alkali Surface Treatments to Modify the Properties of Polylactic Acid Scaffolds

Surface modification of 3D-printed PLA structures is a major issue in terms of increasing the biofunctionality and expanding the tissue engineering applications of these parts. In this paper, different exposure times were used for low-pressure oxygen plasma applied to PLA 3D-printed scaffolds. Alkali surface treatments were also evaluated, aiming to compare the modifications introduced on the surface properties by each strategy. Surface-treated samples were characterized through the quantification of carboxyl groups, energy-dispersive X-ray spectroscopy, water contact angle measurements, and differential scanning calorimetry analysis. The change in the surface properties was studied over a two-week period. In addition, an enzymatic degradation analysis was carried out to evaluate the effect of the surface treatments on the degradation profile of the 3D structures. The physicochemical characterization results suggest different mechanism pathways for each type of treatment. Alkali-treated scaffolds showed a higher concentration of carboxyl groups on their surface, which enhanced the enzymatic degradation rate, but were also proven to be more aggressive towards 3D-printed structures. In contrast, the application of the plasma treatments led to an increased hydrophilicity of the PLA surface without affecting the bulk properties. However, the changes on the properties were less steady over time.
Development of Mucoadhesive Buccal Film for Rizatriptan: In Vitro and In Vivo Evaluation

The reduced therapeutic efficacy of rizatriptan in migraine treatment is primarily due to low oral bioavailability and extensive first pass metabolism. The purpose of this investigation was to optimize the thin mucoadhesive buccal film of rizatriptan and assess the practicability of its development as a potential substitute for conventional migraine treatment. Buccal films (FR1–FR10) were fabricated by a conventional solvent casting method utilizing a combination of polymers (Proloc, hydroxypropyl methylcellulose and Eudragit RS 100). Drug-loaded buccal films (F1–F4) were examined for mechanical, mucoadhesive, swelling and release characteristics. In vivo pharmacokinetics parameters of selected buccal film (F1) in rabbits were compared to oral administration. Films F1–F4 displayed optimal physicomechanical properties including mucoadhesive strength, which can prolong the buccal residence time. A biphasic, complete and higher drug release was seen in films F1 and F4, which followed Weibull model kinetics. The optimized film, F1, exhibited significantly higher (p < 0.005) rizatriptan buccal flux (71.94 ± 8.26 µg/cm2/h) with a short lag time. Film features suggested the drug particles were in an amorphous form, compatible with the polymers used and had an appropriate surface morphology suitable for buccal application. Pharmacokinetic data indicated a significantly higher rizatriptan plasma level (p < 0.005) and Cmax (p < 0.0001) upon buccal film application as compared to oral solution. The observed AUC0–12h (994.86 ± 95.79 ng.h/mL) in buccal treatment was two-fold higher (p < 0.0001) than the control, and the relative bioavailability judged was 245%. This investigation demonstrates the prospective of buccal films as a viable and alternative approach for effective rizatriptan delivery.
Tasty but Nasty? The Moderating Effect of Message Appeals on Food Neophilia/Neophobia as a Personality Trait: A Case Study of Pig Blood Cake and Meatballs

Given the development of food tourism, food culture has become an important motivation for tourists. This study focuses on food tourism and examines the effects of message appeal and personality traits (food neophilia or neophobia) on tourists’ willingness to consume pig blood cake (PBC) and meatballs, two rice-based Taiwanese street foods. A total of 181 valid questionnaires were administered to foreign tourists in Taiwan (the majority of subjects were Europeans and Americans) through snowball sampling. The questionnaires were analysed using the AMOS 6.0 statistical software package. Foreign tourists’ food neophobia or neophilia was found to significantly affect their willingness to consume rice-based Taiwanese street food (PBC and meatballs) and to strongly regulate the effect of message appeal on their willingness to consume the two delicacies. Past studies on food neophobia/neophilia traits have mostly focused on Western and European foods and have rarely investigated the effect of message appeal on the consumption of traditional rice-based street food in Eastern Asia (e.g., Taiwanese special delicacies). This study’s most important contribution is that food neophilia or neophobia moderates the message appeal effect on foreign tourists’ intention to consume local delicacies. This finding has implications for the hospitality industry and relevant government agencies in Asia for the marketing and promotion of food tourism.
Measurement of Iris Thickness at Different Regions in Healthy Chinese Adults

Purpose To study the variation of iris thicknesses in different regions and explore the possible correlations with age and gender. Methods Healthy Chinese adults were recruited; the anterior segment of their eyes was imaged by swept-source optical coherence tomography (SS-OCT). The horizontal scan of the right eye was selected, and the thicknesses of both the nasal and temporal irises were measured at 199 evenly spaced points. Results A total of 233 subjects with an average age of 36.79 ± 10.04 years (range 19 to 62) were included in the final analysis. The mean iris thicknesses of the temporal and nasal sides were 364.79 ± 47.58 μm and 372.44 ± 43.75 μm, respectively. The mean nasal iris thickness was positively correlated with age (β = 0.9 μm/year; P = 0.002), but the temporal one was not (β = 0.077 μm/year; P = 0.806). At 139 points of the nasal iris and 146 points of the temporal iris, the iris thickness was significantly correlated with age (P < 0.05). The thicknesses of the peripheral and pupillary parts were positively correlated with age, while the middle part was negatively correlated with age. No significant difference was observed in the mean iris thickness between genders (temporal: t = 1.597, P = 0.112; nasal: t = 1.870, P = 0.063), but females had a thicker iris than males at 50 points in the temporal side and 49 points in the nasal side (P < 0.05); no point in males was observed to have thicker iris compared to females. Conclusion Using SS-OCT and the novel method, thicknesses of the iris at different regions were measured. The thicknesses of the peripheral and pupillary irises increase with age, while the thicknesses of the middle part decrease.
Curcumin Attenuated Neurotoxicity in Sporadic Animal Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases leading to dementia. Despite research efforts, currently there are no effective pharmacotherapeutic options for the prevention and treatment of AD. Recently, numerous studies highlighted the beneficial effects of curcumin (CUR), a natural polyphenol, in the neuroprotection. Especially, its dual antioxidant and anti-inflammatory properties attracted the interest of researchers. In fact, besides its antioxidant and anti-inflammatory properties, this biomolecule is not degraded in the intestinal tract. Additionally, CUR is able to cross the blood–brain barrier and could therefore to be used to treat neurodegenerative pathologies associated with oxidative stress, inflammation and apoptosis. The present study aimed to assess the ability of CUR to induce neuronal protective and/or recovery effects on a rat model of neurotoxicity induced by aluminum chloride (AlCl3), which mimics the sporadic form of Alzheimer’s disease. Our results showed that treatment with CUR enhances pro-oxidant levels, antioxidant enzymes activities and anti-inflammatory cytokine production and decreases apoptotic cells in AlCl3-exposed hippocampus rats. Additionally, histopathological analysis of hippocampus revealed the potential of CUR in decreasing the hallmarks in the AlCl3-induced AD. We also showed that CUR post-treatment significantly improved the behavioral, oxidative stress and inflammation in AlCl3-exposed rats. Taken together, our data presented CUR as a nutraceutical potential through its protective effects that are more interesting than recovery ones in sporadic model of AD.
Mapping of Metabolic Heterogeneity of Glioma Using MR-Spectroscopy

Simple Summary Radiomics is a research field that integrates radiological and genetic information, but the application of the techniques that have been developed to this purpose have not been widely established in daily clinical practice. The purpose of our study is the development of a straightforward tool that can easily be used to preoperatively predict and correlate the metabolic signature of different CNS-lesions. Particularly in gliomas, we hope to integrate the molecular profile of these tumors into our prediction model. Our goal is to deliver an open-software tool with the intention of advancing the diagnostic work-up of gliomas to the latest standards. Abstract Proton magnetic resonance spectroscopy (1H-MRS) delivers information about the non-invasive metabolic landscape of brain pathologies. 1H-MRS is used in clinical setting in addition to MRI for diagnostic, prognostic and treatment response assessments, but the use of this radiological tool is not entirely widespread. The importance of developing automated analysis tools for 1H-MRS lies in the possibility of a straightforward application and simplified interpretation of metabolic and genetic data that allow for incorporation into the daily practice of a broad audience. Here, we report a prospective clinical imaging trial (DRKS00019855) which aimed to develop a novel MR-spectroscopy-based algorithm for in-depth characterization of brain lesions and prediction of molecular traits. Dimensional reduction of metabolic profiles demonstrated distinct patterns throughout pathologies. We combined a deep autoencoder and multi-layer linear discriminant models for voxel-wise prediction of the molecular profile based on MRS imaging. Molecular subtypes were predicted by an overall accuracy of 91.2% using a classifier score. Our study indicates a first step into combining the metabolic and molecular traits of lesions for advancing the pre-operative diagnostic workup of brain tumors and improve personalized tumor treatment.
Blue mussel (Mytilus spp.) cultivation in mesohaline eutrophied inner coastal waters: mitigation potential, threats and cost effectiveness

The EU-water framework directive (WFD) focuses on nutrient reductions to return coastal waters to the good ecological status. As of today, many coastal waters have reached a steady state of insufficient water quality due to continuous external nutrient inputs and internal loadings. This study focuses first on the current environmental status of mesohaline inner coastal waters to illustrate their needs of internal measures to reach demanded nutrient reductions and secondly, if mussel cultivation can be a suitable strategy to improve water quality. Therefore, nitrogen, phosphorus, chlorophyll a, and Secchi depth of nine mesohaline inner coastal waters in north east Germany were analyzed from 1990 to 2018. Two pilot mussel farms were used to evaluate their effectiveness as a mitigation measure and to estimate potential environmental risks, including the interactions with pathogenic vibrio bacteria. Further, estimated production and mitigation potential were used to assess economic profitability based on the sale of small sized mussels for animal feed and a compensation for nutrient mitigation. The compensation costs were derived from nutrient removal costs of a waste water treatment plant (WWTP). Results show that currently all nine water bodies do not reach the nutrient thresholds demanded by the WFD. However, coastal waters differ in nutrient pollution, indicating that some can reach the desired threshold values if internal measures are applied. The mitigation potential of mussel cultivation depends on the amount of biomass that is cultivated and harvested. However, since mussel growth is closely coupled to the salinity level, mussel cultivation in low saline environments leads to lower biomass production and inevitably to larger cultivation areas. If 50% of the case study area Greifswald Bay was covered with mussel farms the resulting nitrogen reduction would increase Secchi depth by 7.8 cm. However, high chlorophyll a values can hamper clearance rates (<20 mg m−3 = 0.43 l h−1 dry weight g−1) and therefore the mitigation potential. Also, the risk of mussel stock loss due to high summer water temperatures might affect the mitigation potential. The pilot farms had no significant effect on the total organic content of sediments beneath. However, increased values of Vibrio spp. in bio deposits within the pilot farm (1.43 106 ± 1.10 106CFU 100 ml−1 (reference site: 1.04 106 ± 1.45 106 CFU 100 ml−1) were measured with sediment traps. Hence, mussel farms might act as a sink for Vibrio spp. in systems with already high vibrio concentrations. However, more research is required to investigate the risks of Vibrio occurrence coupled to mussel farming. The economic model showed that mussel cultivation in environments below 12 PSU cannot be economic at current market prices for small size mussels and compensations based on nutrient removal cost of WWTPs.
Mentoring for Improving the Self-Esteem, Resilience, and Hope of Unaccompanied Migrant Youth in the Barcelona Metropolitan Area

In the last few years, the number of unaccompanied youths arriving in Europe has increased steadily. During their settlement in host countries, they are exposed to a great variety of vulnerabilities, which have an impact on their mental health. This research examines the effects of participation in a mentoring programme on the psychological and educational outcomes among unaccompanied migrant youths who live in the Barcelona metropolitan area. Data in this mixed-methods study were obtained from 44 surveys with mentored (treatment group) and non-mentored (control group) male youths who had recently turned 18, as well as through thirty semi-structured interviews with mentored youths, their adult mentors, and non-mentored youths. Our findings indicated that participation in the mentoring programme improved the mentored youths’ self-esteem, resilience, and hope, as well as their desired or expected educational outcomes in this new context. We conclude that well-targeted and problem-specific mentoring programmes have positive and marked effects on unaccompanied migrant youths’ mental health. The social and political implications of these outcomes are also discussed, providing information on how interventions can offer effective networks of support for the settlement and social inclusion of unaccompanied migrant youths.