Miracle-dz/UniFAR-FTUs huggingface dataset:
A Methodological Safe-by-Design Approach for the Development of Nanomedicines

Safe-by-Design (SbD) concepts foresee the risk identification and reduction as well as uncertainties regarding human health and environmental safety in early stages of product development. The EU’s NANoREG project and further on the H2020 ProSafe initiative, NanoReg2, and CALIBRATE projects have developed a general SbD approach for nanotechnologies (e.g., paints, textiles, etc.). Based on it, the GoNanoBioMat project elaborated a methodological SbD approach (GoNanoBioMat SbD approach) for nanomedicines with a focus on polymeric nanobiomaterials (NBMs) used for drug delivery. NBMs have various advantages such as the potential to increase drug efficacy and bioavailability. However, the nanoscale brings new challenges to product design, manufacturing, and handling. Nanomedicines are costly and require the combination of knowledge from several fields. In this paper, we present the GoNanoBioMat SbD approach, which allows identifying and addressing the relevant safety aspects to address when developing polymeric NBMs during design, characterization, assessment of human health and environmental risk, manufacturing and handling, and combines the nanoscale and medicine field under one approach. Furthermore, regulatory requirements are integrated into the innovation process.
Partial Weight-Bearing in Female Rats: Proof of Concept in a Martian-Gravity Analog

Many studies have investigated the physiological response to microgravity in both astronauts and animals. However, while space agencies have sought to deploy more women on their missions; animal models rarely include females studies or comparisons between males and females. Therefore, we exposed adult female rats to 2 weeks of partial weight-bearing at either 100% of their normal loading (PWB100) or 40% of their normal loading (PWB40), corresponding to Martian gravity-analog, and assess muscle function, force and histomorphometry. Females exposed to PWB showed an 11.62% decline in hindlimb grip force associated with an 11.84% decrease in soleus myofiber size after 14 days of exposure, while maintaining normal blood oxygenation and stress levels. This pilot study represents the first experiment designed to understand the muscular disuse associated with a partial reduction in mechanical loading in female rats, and the first step needed to develop successful mitigating strategies. New and Noteworthy This research article describes the first use of quadrupedal partial weight-bearing in female rats. This study demonstrates the feasibility of partial gravity analogs in females and allows for future investigations about the impact of sex on muscle deconditioning due to reduced mechanical loading.
Sphingobacterium sp. BHU-AV3 Induces Salt Tolerance in Tomato by Enhancing Antioxidant Activities and Energy Metabolism

Salt tolerant bacteria can be helpful in improving a plant’s tolerance to salinity. Although plant–bacteria interactions in response to salt stress have been characterized, the precise molecular mechanisms by which bacterial inoculation alleviates salt stress in plants are still poorly explored. In the present study, we aimed to determine the role of a salt-tolerant plant growth-promoting rhizobacteria (PGPR) Sphingobacterium BHU-AV3 for improving salt tolerance in tomato through investigating the physiological responses of tomato roots and leaves under salinity stress. Tomato plants inoculated with BHU-AV3 and challenged with 200 mM NaCl exhibited less senescence, positively correlated with the maintenance of ion balance, lowered reactive oxygen species (ROS), and increased proline content compared to the non-inoculated plants. BHU-AV3-inoculated plant leaves were less affected by oxidative stress, as evident from a reduction in superoxide contents, cell death, and lipid peroxidation. The reduction in ROS level was associated with the increased antioxidant enzyme activities along with multiple-isoform expression [peroxidase (POD), polyphenol oxidase (PPO), and superoxide dismutase (SOD)] in plant roots. Additionally, BHU-AV3 inoculation induced the expression of proteins involved in (i) energy production [ATP synthase], (ii) carbohydrate metabolism (enolase), (iii) thiamine biosynthesis protein, (iv) translation protein (elongation factor 1 alpha), and the antioxidant defense system (catalase) in tomato roots. These findings have provided insight into the molecular mechanisms of bacteria-mediated alleviation of salt stress in plants. From the study, we can conclude that BHU-AV3 inoculation effectively induces antioxidant systems and energy metabolism in tomato roots, which leads to whole plant protection during salt stress through induced systemic tolerance.
Nb-Doped MXene With Enhanced Energy Storage Capacity and Stability

MXenes present unique features as materials for energy storage; however, limited interlayer distance, and structural stability with ongoing cycling limit their applications. Here, we have developed a unique method involving incorporating Nb atoms into MXene (Ti3C2) to enhance its ability to achieve higher ionic storage and longer stability. Computational analysis using density functional theory was performed that explained the material structure, electronic structure, band structure, and density of states in atomistic detail. Nb-doped MXene showed a good charge storage capacity of 442.7 F/g, which makes it applicable in a supercapacitor. X-ray diffraction (XRD) indicated c-lattice parameter enhancement after Nb-doping in MXene (from 19.2A° to 23.4A°), which showed the effect of the introduction of an element with a larger ionic radius (Nb). Also, the bandgap changes from 0.9 eV for pristine MXene to 0.1 eV for Nb-doped MXene, which indicates that the latter has the signature of increased conductivity due to more metallic nature, in support of the experimental results. This work presents not only the effect of doping in MXene but also helps to explain the phenomena involved in changes in physical parameters, advancing the field of energy storage based on 2D materials.
Methylglyoxal, a Reactive Glucose Metabolite, Induces Bladder Overactivity in Addition to Inflammation in Mice

Diabetic bladder dysfunction (DBD) is one of the most common complication of diabetes. Methylglyoxal (MGO), a highly reactive dicarbonyl compound formed as a by-product of glycolysis, is found at high levels in plasma of diabetic patients. Here, we explored the effects of chronic administration of MGO on micturition pattern (cystometry) and bladder contractility in vitro in healthy male C57/BL6 mice. Methylglyoxal was given at 0.5% in drinking water for 4 weeks. Exposure to MGO led to bladder tissue disorganization, edema of lamina propria, partial loss of urothelium and multiple leukocyte infiltrates. Filling cystometry revealed significant increases of micturition frequency and number of non-voiding contractions (NVCs) in the MGO group, clearly indicating an overactive bladder profile. Bladder contractions induced by electrical-field stimulation (EFS) and carbachol were significantly higher in the MGO group, while the muscarinic M2 and M3 mRNA expressions remained unchanged between groups. Additionally, MGO exposure induced upregulation of TRPA1 and down-regulation of TRPV1 and TRPV4 in bladder tissues. Methylglyoxal did not change the mRNA expression of the advanced glycation end products receptor (RAGE), but markedly increased its downstream NF-κB - iNOS signaling. The mRNA expression of cyclooxygenase-2 (COX-2) and reactive-oxygen species (ROS) levels remained unchanged. Altogether, our data show that 4-week MGO intake in mice produces an overactive bladder phenotype in addition to bladder inflammation and increased NF-kB/iNOS signaling. TRPA1 up-regulation and TRPV1/TRPV4 down-regulation may account for the MGO-induced bladder overactivity. Scavengers of MGO could be an option to ameliorate bladder dysfunction in diabetic conditions.
New Machine, Old Cough: Technology and Tuberculosis in Patna

In 2013, a new technology, GeneXpert, was introduced in India, which, in addition to testing for TB, could also diagnose whether the detected strain was drug resistant. By detecting the bacterium more effectively than other available tests and simultaneously testing for resistance, GeneXpert promised to reduce the delay in diagnosis and hence ineffective treatments. The new test was introduced to multiple cities via a coalition that included global health funding bodies, the government of India, the World Health Organization, and non-governmental organizations. Despite the concerted effort of the coalition, among formal providers (those trained in biomedicine) in the private sector, the new technology was not adopted as quickly as had been hoped. Examining formal providers' initial responses to the technology's introduction in the city of Patna reveals how the adoption of new technology can be influenced by the particularities of the local medical market such as the availability of diagnostic tests, presence of informal providers, and reputation of formal providers. While protocols and operations might seem standardized across implementation plans, the work that is required to ensure success must take into account the particular role that the market plays from site to site.
Illuminating Relationships Between the Pre- and Post-synapse

Excitatory synapses in the mammalian cortex are highly diverse, both in terms of their structure and function. However, relationships between synaptic features indicate they are highly coordinated entities. Imaging techniques, that enable physiology at the resolution of individual synapses to be investigated, have allowed the presynaptic activity level of the synapse to be related to postsynaptic function. This approach has revealed that neuronal activity induces the pre- and post-synapse to be functionally correlated and that subsets of synapses are more susceptible to certain forms of synaptic plasticity. As presynaptic function is often examined in isolation from postsynaptic properties, the effect it has on the post-synapse is not fully understood. However, since postsynaptic receptors at excitatory synapses respond to release of glutamate, it follows that they may be differentially regulated depending on the frequency of its release. Therefore, examining postsynaptic properties in the context of presynaptic function may be a useful way to approach a broad range of questions on synaptic physiology. In this review, we focus on how optophysiology tools have been utilized to study relationships between the pre- and the post-synapse. Multiple imaging techniques have revealed correlations in synaptic properties from the submicron to the dendritic level. Optical tools together with advanced imaging techniques are ideally suited to illuminate this area further, due to the spatial resolution and control they allow.
Mindfulness Mediates the Effect of a Psychological Online Intervention for Psychosis on Self-Reported Hallucinations: A Secondary Analysis of Voice Hearers From the EviBaS Trial

Background Psychological online interventions (POIs) could represent a promising approach to narrow the treatment gap in psychosis but it remains unclear whether improving mindfulness functions as a mechanism of change in POIs. For the present study, we examined if mindfulness mediates the effect of a comprehensive POI on distressing (auditory) hallucinations. Methods We conducted a secondary analysis on voice hearers (n = 55) from a randomized controlled trial evaluating a POI for psychosis (EviBaS; trial registration NCT02974400, clinicaltrials.gov). The POI includes a module on mindfulness and we only considered POI participants in our analyses who completed the mindfulness module (n = 16). Results Participants who completed the mindfulness module reported higher mindfulness (p = 0.015) and lower hallucinations (p = 0.001) at post assessment, compared to controls, but there was no effect on distress by voices (p = 0.598). Mindfulness mediated the POI’s effect on hallucinations (b = −1.618, LLCI = −3.747, ULCI = −0.054) but not on distress by voices (b = −0.057, LLCI = −0.640, ULCI = 0.915). Limitations and Discussion Completion of the mindfulness module was not randomized. Hence, we cannot draw causal inferences. Even if we assumed causality, it remains unclear which contents of the POI could have resulted in increased mindfulness and reduced hallucinations, as participants completed other modules as well. In addition, confounding variables could explain the mediation and the sample size was small. Nonetheless, the overall pattern of results indicates that the POI is likely to improve mindfulness, and that increased mindfulness could partially explain the POI’s efficacy.
More Purpose in Life and Less Novelty Seeking Predict Improvements in Self-Compassion During a Mindfulness-Based Intervention: The EXMIND Study

Objectives Recently, a 4-week mindfulness-based intervention followed by a 4-week existential approach was found to be as effective for increasing self-compassion as an 8-week mindfulness-based intervention. The purpose of the present study was to identify the factors that predicted change in self-compassion during the 8-week mindfulness-based intervention. Methods Fifty-seven of the 61 completers of the 8-week mindfulness-based intervention provided baseline, 4-week, and 8-week self-compassion scale scores. The mean age of the 47 females and 10 males was 49.6 years. Pearson’s correlation coefficients were generated on the associations between the change of total self-compassion scale scores from baseline to 8 weeks with age; gender; and the baseline scores on the Temperament Evaluation of Memphis, Pisa and San Diego Auto-questionnaire, Temperament and Character Inventory (TCI), Mini-Mental State Examination, Japanese Adult Reading Test, Young Mania Rating Scale, Hamilton Rating Scale for Depression, Parental Bonding Instrument, and purpose in life (PIL). Multiple regression analysis was performed to identify the predictors of the change in total self-compassion scale scores. Results Novelty seeking (TCI) was significantly and negatively associated with the change in total self-compassion scale scores, whereas the PIL scores were significantly and positively associated with the change in total self-compassion scale scores. Novelty seeking was not significantly associated with baseline, 4-week, or 8-week total self-compassion scale scores, whereas the PIL scores were significantly and positively associated with baseline, 4-week, and 8-week total self-compassion scale scores. The limitation of the present study was a relatively small number of subjects which deterred a more sophisticated analysis of the pathways involved. Conclusions The present findings suggest that more PIL and less novelty seeking predict improvements in self-compassion during mindfulness-based interventions, although novelty seeking might substantially predict the improvement but self-compassion scale and PIL might somewhat conceptually overlap.
Expansion Microscopy for Cell Biology Analysis in Fungi

Super-resolution microscopy has evolved as a powerful method for subdiffraction-resolution fluorescence imaging of cells and cellular organelles, but requires sophisticated and expensive installations. Expansion microscopy (ExM), which is based on the physical expansion of the cellular structure of interest, provides a cheap alternative to bypass the diffraction limit and enable super-resolution imaging on a conventional fluorescence microscope. While ExM has shown impressive results for the magnified visualization of proteins and RNAs in cells and tissues, it has not yet been applied in fungi, mainly due to their complex cell wall. Here we developed a method that enables reliable isotropic expansion of ascomycetes and basidiomycetes upon treatment with cell wall degrading enzymes. Confocal laser scanning microscopy (CLSM) and structured illumination microscopy (SIM) images of 4.5-fold expanded sporidia of Ustilago maydis expressing fluorescent fungal rhodopsins and hyphae of Fusarium oxysporum or Aspergillus fumigatus expressing either histone H1-mCherry together with Lifeact-sGFP or mRFP targeted to mitochondria, revealed details of subcellular structures with an estimated spatial resolution of around 30 nm. ExM is thus well suited for cell biology studies in fungi on conventional fluorescence microscopes.
Designing and Evaluating the Usability of a Machine Learning API for Rapid Prototyping Music Technology

To better support creative software developers and music technologists' needs, and to empower them as machine learning users and innovators, the usability of and developer experience with machine learning tools must be considered and better understood. We review background research on the design and evaluation of application programming interfaces (APIs), with a focus on the domain of machine learning for music technology software development. We present the design rationale for the RAPID-MIX API, an easy-to-use API for rapid prototyping with interactive machine learning, and a usability evaluation study with software developers of music technology. A cognitive dimensions questionnaire was designed and delivered to a group of 12 participants who used the RAPID-MIX API in their software projects, including people who developed systems for personal use and professionals developing software products for music and creative technology companies. The results from questionnaire indicate that participants found the RAPID-MIX API a machine learning API which is easy to learn and use, fun, and good for rapid prototyping with interactive machine learning. Based on these findings, we present an analysis and characterization of the RAPID-MIX API based on the cognitive dimensions framework, and discuss its design trade-offs and usability issues. We use these insights and our design experience to provide design recommendations for ML APIs for rapid prototyping of music technology. We conclude with a summary of the main insights, a discussion of the merits and challenges of the application of the CDs framework to the evaluation of machine learning APIs, and directions to future work which our research deems valuable.
The Use of Peripheral Blood-Derived Stem Cells for Cartilage Repair and Regeneration In Vivo: A Review

Background Peripheral blood (PB) is a potential source of chondrogenic progenitor cells that can be used for cartilage repair and regeneration. However, the cell types, isolation and implantation methods, seeding dosage, ultimate therapeutic effect, and in vivo safety remain unclear. Methods PubMed, Embase, and the Web of Science databases were systematically searched for relevant reports published from January 1990 to December 2019. Original articles that used PB as a source of stem cells to repair cartilage in vivo were selected for analysis. Results A total of 18 studies were included. Eight human studies used autologous nonculture-expanded PB-derived stem cells (PBSCs) as seed cells with the blood cell separation isolation method, and 10 animal studies used autologous, allogenic or xenogeneic culture-expanded PB-derived mesenchymal stem cells (PB-MSCs), or nonculture-expanded PBSCs as seed cells. Four human and three animal studies surgically implanted cells, while the remaining studies implanted cells by single or repeated intra-articular injections. 121 of 130 patients (in 8 human clinical studies), and 230 of 278 animals (in 6 veterinary clinical studies) using PBSCs for cartilage repair achieved significant clinical improvement. All reviewed articles indicated that using PB as a source of seed cells enhances cartilage repair in vivo without serious adverse events. Conclusion Autologous nonculture-expanded PBSCs are currently the most commonly used cells among all stem cell types derived from PB. Allogeneic, autologous, and xenogeneic PB-MSCs are more widely used in animal studies and are potential seed cell types for future applications. Improving the mobilization and purification technology, and shortening the culture cycle of culture-expanded PB-MSCs will obviously promote the researchers' interest. The use of PBSCs for cartilage repair and regeneration in vivo are safe. PBSCs considerably warrant further investigations due to their superiority and safety in clinical settings and positive effects despite limited evidence in humans.
Leading Teachers’ Emotions Like Parents: Relationships Between Paternalistic Leadership, Emotional Labor and Teacher Commitment in China

Emotional labor plays an essential role in school leadership and teaching, as principals and teachers undergo complex interactions with students, colleagues, and parents. Although researchers have realized the influence of leaders’ behaviors on followers’ emotions in management and educational contexts, the relationship between leadership behaviors, teachers’ emotional labor, and related organizational outcomes has been underexplored. As leadership and emotional labor are situated and influenced by cultural contexts, the current study focused on the relationship between teachers’ emotional labor strategies, multidimensional teacher commitment, and paternalistic leadership, a unique leadership type rooted in Confucianism. Paternalistic leadership is a style that combines strong authority with fatherly benevolence, which is prevalent in East Asia and the Middle East. A sample of 419 teachers was randomly selected to participate in a survey. The results showed that principals’ authoritarian leadership behaviors had negative influences on teachers’ commitment to the profession and commitment to the school. Benevolent leadership had positive effects on teachers’ commitment to students, commitment to the profession, and commitment to the school. Teachers’ deep acting played positive mediating effects, while surface acting was a negative mediator. The results imply that school leaders could properly exert parent-like leadership practices to facilitate teacher commitment through managing teachers’ emotions.
Functional and Structural Brain Alterations in Encephalitis With LGI1 Antibodies

Objective: The purpose of this study was to examine the neural substrates and mechanisms that generate memory deficits, seizures and neuropsychiatric abnormalities in encephalitis with LGI1 antibodies using a data-driven, multimodal magnetic resonance imaging (MRI) approach. Methods: Functional MRI data were acquired from 14 anti-LGI1 encephalitis patients and 14 age and gender matched normal controls. Independent component analysis with hierarchical partner matching (HPM-ICA) was used to assess the whole-brain intrinsic functional connectivity. Granger causality (GC) was applied to investigate the effective connectivity among the brain regions that identified by HPM-ICA. Diffusion tensor imaging (DTI) was utilized to investigate white matter microstructural changes of the patients. Results: Participants with LGI1 antibodies encephalitis presented reduced functional connectivity in the brain areas associated with memory, cognition and motion circuits, while increased functional connectivity in putamen and caudate in comparison to the normal controls. Moreover, the effective connectivity in patients was decreased from the frontal cortex to supplementary motor area. Finally, patients had significant reductions in fractional anisotropy (FA) for the corpus callosum, internal capsule, corona radiata and superior longitudinal fasciculus, accompanied by increases in mean diffusivity (MD) for these regions as compared to controls. Conclusion: Our findings suggest that the neural disorder and behavioral deficits of anti-LGI1 encephalitis may be associated with extensive changes in brain connectivity and microstructure. These pathological alterations affect the basal ganglia and limbic system besides the temporal and frontal lobe.