Miracle-dz/UniFAR-FTUs huggingface dataset:
Topological Point Defects of Liquid Crystals in Quasi-Two-Dimensional Geometries

We review the interactions and dynamics of topological defects in liquid crystals (LCs) in quasi-two-dimensional (2D) geometries. Such spatial restrictions can be realized in thin freely suspended smectic C films, in thin sandwich cells filled with nematic LCs, and under specific boundary conditions in LC shells embedded in aqueous solutions. Random defect patterns can be created by thermal quenching of the samples from lower ordered into higher ordered phases. On the other hand, well-defined isolated defect configurations for the study of elementary interaction steps can be prepared by using simple mechanical techniques. Observation by polarizing microscopy is straightforward. Spatial dimensions of the experimental systems as well as time scales are convenient for observation. The continuum theory of LCs is well-developed so that, in addition to the experimental characterization, an analytical or numerical description is feasible. From interactions and dynamic features observed in these LC systems, general conclusions on defect dynamics can be drawn.
Stomata and Sporophytes of the Model Moss Physcomitrium patens

Mosses are an ancient land plant lineage and are therefore important in studying the evolution of plant developmental processes. Here, we describe stomatal development in the model moss species Physcomitrium patens (previously known as Physcomitrella patens) over the duration of sporophyte development. We dissect the molecular mechanisms guiding cell division and fate and highlight how stomatal function might vary under different environmental conditions. In contrast to the asymmetric entry divisions described in Arabidopsis thaliana, moss protodermal cells can enter the stomatal lineage directly by expanding into an oval shaped guard mother cell (GMC). We observed that when two early stage P. patens GMCs form adjacently, a spacing division can occur, leading to separation of the GMCs by an intervening epidermal spacer cell. We investigated whether orthologs of Arabidopsis stomatal development regulators are required for this spacing division. Our results indicated that bHLH transcription factors PpSMF1 and PpSCRM1 are required for GMC formation. Moreover, the ligand and receptor components PpEPF1 and PpTMM are also required for orientating cell divisions and preventing single or clustered early GMCs from developing adjacent to one another. The identification of GMC spacing divisions in P. patens raises the possibility that the ability to space stomatal lineage cells could have evolved before mosses diverged from the ancestral lineage. This would have enabled plants to integrate stomatal development with sporophyte growth and could underpin the adoption of multiple bHLH transcription factors and EPF ligands to more precisely control stomatal patterning in later diverging plant lineages. We also observed that when P. patens sporophyte capsules mature in wet conditions, stomata are typically plugged whereas under drier conditions this is not the case; instead, mucilage drying leads to hollow sub-stomatal cavities. This appears to aid capsule drying and provides further evidence for early land plant stomata contributing to capsule rupture and spore release.
A systematic review and meta-analysis protocol to compare the risk of attrition among prenatal vitamin D supplemented gestational diabetes mellitus patients with its non-recipients.

Aim: Recently, several clinical trials have tested the effect of prenatal vitamin D supplementation in gestational diabetes mellitus (GDM) patients and their newborns. However, their participant attrition, an important determinant of the internal validity, remains poorly explored. Therefore, this review protocol is proposed, which aims to compare it between prenatal vitamin D supplemented and not supplemented GDM patients. Method: Randomized clinical trials studying the above will be searched mainly in different electronic databases. It will search for the English language articles irrespective of publication date. Data concerning the reviewed trials design, population, interventions, and outcome of interest will be extracted. Subsequently, their risk of bias will be assessed. Outcome data between the interventions will be juxtaposed meta-analytically to estimate the risk ratio. Next, the statistical heterogeneity (by Chi2 and I2 statistics) and publication bias (using funnel plot and Eggers test) among the trials will be evaluated. Subgroup analysis will follow if the heterogeneity is high. Finally, a sensitivity analysis will iterate the meta-analysis using an alternative model and by eliminating a trial every time. Statistical significance will be determined at p<0.05 and 95% CI. All analyses will be done in Stata. If a meta-analysis is not possible, a narrative reporting will ensue. Results: The review will follow the PRISMA reporting guideline. Any statistically significant findings evidence quality will be graded by the GRADE approach. Conclusion: The proposed review will compare the risk of loss to follow up among GDM patients complemented and not complemented with prenatal vitamin D.
A Novel Quantitative Spasticity Evaluation Method Based on Surface Electromyogram Signals and Adaptive Neuro Fuzzy Inference System

Stroke patients often suffer from spasticity. Before treatment of spasticity, there are often practical demands for objective and quantitative assessment of muscle spasticity. However, the common quantitative spasticity assessment method, the tonic stretch reflex threshold (TSRT), is time-consuming and complicated to implement due to the requirement of multiple passive stretches. To evaluate spasticity conveniently, a novel spasticity evaluation method based on surface electromyogram (sEMG) signals and adaptive neuro fuzzy inference system (i.e., the sEMG-ANFIS method) was presented in this paper. Eleven stroke patients with spasticity and four healthy subjects were recruited to participate in the experiment. During the experiment, the Modified Ashworth scale (MAS) scores of each subject was obtained and sEMG signals from four elbow flexors or extensors were collected from several times (4–5) repetitions of passive stretching. Four time-domain features (root mean square, the zero-cross rate, the wavelength and a 4th-order autoregressive model coefficient) and one frequency-domain feature (the mean power frequency) were extracted from the collected sEMG signals to reflect the spasticity information. Using the ANFIS classifier, excellent regression performance was achieved [mean accuracy = 0.96, mean root-mean-square error (RMSE) = 0.13], outperforming the classical TSRT method (accuracy = 0.88, RMSE = 0.28). The results showed that the sEMG-ANFIS method not only has higher accuracy but also is convenient to implement by requiring fewer repetitions (4–5) of passive stretches. The sEMG-ANFIS method can help stroke patients develop proper rehabilitation training programs and can potentially be used to provide therapeutic feedback for some new spasticity interventions, such as shockwave therapy and repetitive transcranial magnetic stimulation.
Good communication is critical to supporting people living and working with a rare disease: current rare disease support perceived as inadequate.

Background Many people living and working with rare diseases describe consistent difficulties accessing appropriate information and support. In this study an evaluation of the awareness of rare diseases, alongside related information and educational resources available for patients, their families and healthcare professionals, was conducted in 2018-2019 using an online survey and semi-structured interviews with rare disease collaborative groups (charities, voluntary and community groups) active across Northern Ireland (NI). Results Ninety-nine participants engaged with the survey with 31 respondents providing detailed answers. Resources such as information, communication, registries, online services, training and improvements to support services were queried. Excellent communication is an important factor in delivering good rare disease support. Training for health professionals was also highlighted as an essential element of improving support for those with a rare disease to ensure they approach people with these unique and challenging diseases in an appropriate way. Carers were mentioned several times throughout the study; it is often felt they are overlooked in rare disease research and more support should be in place for them. Current care/support for those with a rare disease was highlighted as inadequate. Nine semi-structured interviews were conducted with rare disease collaborative groups. Reoccurring themes included a need for more effective: information and communication, training for health professionals, online presence, support for carers, and involvement in research. Conclusions All rare disease collaborative groups agreed that current services for people living and working with a rare disease are not adequate. An important finding to consider in future research within the rare disease field is the inclusion of carers perceptions and experiences in studies. Due to the unique role a carer has in the life of a person with a rare disease it is vital that their voice is heard and their needs are listened to. This research provides insight into the support available for rare diseases across Northern Ireland, highlights unmet needs in service provision, and suggests approaches to improve rare disease support prioritising improved information and communication provision, improved access to services, and tailored support for carers of people with a rare disease. Keywords Collaboratives groups; communication; Northern Ireland; online; rare disease semi-structured interview; social media; support; survey
Ultradian Secretion of Growth Hormone in Mice: Linking Physiology With Changes in Synapse Parameters Using Super-Resolution Microscopy

Neuroendocrine circuits are orchestrated by the pituitary gland in response to hypothalamic hormone-releasing and inhibiting factors to generate an ultradian and/or circadian rhythm of hormone secretion. However, mechanisms that govern this rhythmicity are not fully understood. It has been shown that synaptic transmission in the rodent hypothalamus undergoes cyclical changes in parallel with rhythmic hormone secretion and a growing body of evidence suggests that rapid rewiring of hypothalamic neurons may be the source of these changes. For decades, structural synaptic studies have been utilizing electron microscopy, which provides the resolution suitable for visualizing synapses. However, the small field of view, limited specificity and manual analysis susceptible to bias fuel the search for a more quantitative approach. Here, we apply the fluorescence super-resolution microscopy approach direct Stochastic Optical Reconstruction Microscopy (dSTORM) to quantify and structurally characterize excitatory and inhibitory synapses that contact growth hormone-releasing-hormone (GHRH) neurons during peak and trough values of growth hormone (GH) concentration in mice. This approach relies on a three-color immunofluorescence staining of GHRH and pre- and post-synaptic markers, and a quantitative analysis with a Density-Based Spatial Clustering of Applications with Noise (DBSCAN) algorithm. With this method we confirm our previous findings, using electron microscopy, of increased excitatory synaptic input to GHRH neurons during peak levels of GH. Additionally, we find a shift in synapse numbers during low GH levels, where more inhibitory synaptic inputs are detected. Lastly, we utilize dSTORM to study novel aspects of synaptic structure. We show that more excitatory (but not inhibitory) pre-synaptic clusters associate with excitatory post-synaptic clusters during peaks of GH secretion and that the numbers of post-synaptic clusters increase during high hormone levels. The results presented here provide an opportunity to highlight dSTORM as a valuable quantitative approach to study synaptic structure in the neuroendocrine circuit. Importantly, our analysis of GH circuitry sheds light on the potential mechanism that drives ultradian changes in synaptic transmission and possibly aids in GH pulse generation in mice.
An audit of uncertainty in multi-scale cardiac electrophysiology models

Models of electrical activation and recovery in cardiac cells and tissue have become valuable research tools, and are beginning to be used in safety-critical applications including guidance for clinical procedures and for drug safety assessment. As a consequence, there is an urgent need for a more detailed and quantitative understanding of the ways that uncertainty and variability influence model predictions. In this paper, we review the sources of uncertainty in these models at different spatial scales, discuss how uncertainties are communicated across scales, and begin to assess their relative importance. We conclude by highlighting important challenges that continue to face the cardiac modelling community, identifying open questions, and making recommendations for future studies. This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’.
Uncertainty quantification and sensitivity analysis of left ventricular function during the full cardiac cycle

Patient-specific computer simulations can be a powerful tool in clinical applications, helping in diagnostics and the development of new treatments. However, its practical use depends on the reliability of the models. The construction of cardiac simulations involves several steps with inherent uncertainties, including model parameters, the generation of personalized geometry and fibre orientation assignment, which are semi-manual processes subject to errors. Thus, it is important to quantify how these uncertainties impact model predictions. The present work performs uncertainty quantification and sensitivity analyses to assess the variability in important quantities of interest (QoI). Clinical quantities are analysed in terms of overall variability and to identify which parameters are the major contributors. The analyses are performed for simulations of the left ventricle function during the entire cardiac cycle. Uncertainties are incorporated in several model parameters, including regional wall thickness, fibre orientation, passive material parameters, active stress and the circulatory model. The results show that the QoI are very sensitive to active stress, wall thickness and fibre direction, where ejection fraction and ventricular torsion are the most impacted outputs. Thus, to improve the precision of models of cardiac mechanics, new methods should be considered to decrease uncertainties associated with geometrical reconstruction, estimation of active stress and of fibre orientation. This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’.
A Nitrate-Blind P. putida Strain Boosts PHA Production in a Synthetic Mixed Culture

One of the major challenges for the present and future generations is to find suitable substitutes for the fossil resources we rely on today. In this context, cyanobacterial carbohydrates have been discussed as an emerging renewable feedstock in industrial biotechnology for the production of fuels and chemicals. Based on this, we recently presented a synthetic bacterial co-culture for the production of medium-chain-length polyhydroxyalkanoates (PHAs) from CO2. This co-cultivation system is composed of two partner strains: Synechococcus elongatus cscB which fixes CO2, converts it to sucrose and exports it into the culture supernatant, and a Pseudomonas putida strain that metabolizes this sugar and accumulates PHAs in the cytoplasm. However, these biopolymers are preferably accumulated under conditions of nitrogen limitation, a situation difficult to achieve in a co-culture as the other partner, at best, should not perceive any limitation. In this article, we will present an approach to overcome this dilemma by uncoupling the PHA production from the presence of nitrate in the medium. This is achieved by the construction of a P. putida strain that is no longer able to grow with nitrate as nitrogen source -is thus nitrate blind, and able to grow with sucrose as carbon source. The deletion of the nasT gene encoding the response regulator of the NasS/NasT two-component system resulted in such a strain that has lost the ability use nitrate, but growth with ammonium was not affected. Subsequently, the nasT deletion was implemented in P. putida cscRABY, an efficient sucrose consuming strain. This genetic engineering approach introduced an artificial unilateral nitrogen limitation in the co-cultivation process, and the amount of PHA produced from light and CO2 was 8.8 fold increased to 14.8% of its CDW compared to the nitrate consuming reference strain. This nitrate blind strain, P. putidaΔnasT attTn7:cscRABY, is not only a valuable partner in the co-cultivation but additionally enables the use of other nitrate containing substrates for medium-chain-length PHA production, like for example waste-water.
Primary Categorizing and Masking Cerebral Small Vessel Disease Based on “Deep Learning System”

Objective To supply the attending doctor’s diagnosis of the persisting of cerebral small vessel disease and speed up their work effectively, we developed a “deep learning system (DLS)” for cerebral small vessel disease predication. The reliability and the disease area segmentation accuracy, of the proposed DLS, was also investigated. Methods A deep learning model based on the convolutional neural network was designed and trained on 1,010 DWI b1000 images from 1010 patients diagnosed with segmentation of subcortical infarction, 359 T2∗ images from 359 patients diagnosed with segmentation of cerebral microbleed, as well as 824 T1-weighted and T2-FLAIR images from 824 patients diagnosed with segmentation of lacune and WMH. Dicw accuracy, recall, and f1-score were calculated to evaluate the proposed deep learning model. Finally, we also compared the DLS prediction capability with that of 6 doctors with 3 to 18 years’ clinical experience (8 ± 6 years). Results The results support that an appropriately trained DLS can achieve a high-level dice accuracy, 0.598 in the training section over all these four classifications on 30 patients (0.576 for young neuroradiologists), validation accuracy is 0.496 in lacune, 0.666 in WMH, 0.728 in subcortical infarction, and 0.503 in cerebral microbleeds. It is comparable to attending doctor with a few years of experience, regardless of whether the emphasis is placed on the segmentation or detection of lesions with less time-spending compared with manual analysis, about 4.4 s/case, which is dramatically less than doctors about 634 s/case. Conclusion The results of our comparison lend support to the case that an appropriately trained DLS can be trusted to the same extent as one would trust an attending doctor with a few years of experience, regardless of whether the emphasis is placed on the segmentation or detection of lesions.
Cannibalism of parasitoid‐attacked conspecifics in a non‐carnivorous caterpillar

Cannibalism, the killing and consumption of conspecifics, can even occur in insect species typically considered to be non‐carnivorous. Of particular interest is the cannibalism of parasitoid‐attacked conspecifics, which could reduce parasitism levels in subsequent generations for that conspecific population. This study reports on the occurrence and some of the consequences of cannibalism in parasitoid‐attacked obliquebanded leafroller, Choristoneura rosaceana (Harris) (Lepidoptera: Tortricidae). We show that larvae of C. rosaceana, which is considered to be an herbivorous caterpillar species, did not prey upon live conspecifics, but readily consumed conspecifics attacked by Habrobracon gelechiae Ashmead (Hymenoptera: Braconidae). Further examination found that C. rosaceana larvae feeding on parasitoid‐attacked conspecifics, since their fourth instar, suffered a higher mortality and reduction in body size than those fed on plant material only. The cannibalism of attacked conspecifics did not appear to offer any nutrient benefits for the cannibal. To our best knowledge, this is the first empirical example of the occurrence and some of the consequences of cannibalism by a non‐carnivorous insect on its parasitoid‐attacked conspecifics. We discuss the adaptive significance of such cannibalism on parasitoid‐attacked conspecifics with respect to a trans‐generational fitness gain for the population through the killing of the parasitoids, thereby reducing parasitism in subsequent generations.
Hybrid Bioprinting of Chondrogenically Induced Human Mesenchymal Stem Cell Spheroids

To date, the treatment of articular cartilage lesions remains challenging. A promising strategy for the development of new regenerative therapies is hybrid bioprinting, combining the principles of developmental biology, biomaterial science, and 3D bioprinting. In this approach, scaffold-free cartilage microtissues with small diameters are used as building blocks, combined with a photo-crosslinkable hydrogel and subsequently bioprinted. Spheroids of human bone marrow-derived mesenchymal stem cells (hBM-MSC) are created using a high-throughput microwell system and chondrogenic differentiation is induced during 42 days by applying chondrogenic culture medium and low oxygen tension (5%). Stable and homogeneous cartilage spheroids with a mean diameter of 116 ± 2.80 μm, which is compatible with bioprinting, were created after 14 days of culture and a glycosaminoglycans (GAG)- and collagen II-positive extracellular matrix (ECM) was observed. Spheroids were able to assemble at random into a macrotissue, driven by developmental biology tissue fusion processes, and after 72 h of culture, a compact macrotissue was formed. In a directed assembly approach, spheroids were assembled with high spatial control using the bio-ink based extrusion bioprinting approach. Therefore, 14-day spheroids were combined with a photo-crosslinkable methacrylamide-modified gelatin (gelMA) as viscous printing medium to ensure shape fidelity of the printed construct. The photo-initiators Irgacure 2959 and Li-TPO-L were evaluated by assessing their effect on bio-ink properties and the chondrogenic phenotype. The encapsulation in gelMA resulted in further chondrogenic maturation observed by an increased production of GAG and a reduction of collagen I. Moreover, the use of Li-TPO-L lead to constructs with lower stiffness which induced a decrease of collagen I and an increase in GAG and collagen II production. After 3D bioprinting, spheroids remained viable and the cartilage phenotype was maintained. Our findings demonstrate that hBM-MSC spheroids are able to differentiate into cartilage microtissues and display a geometry compatible with 3D bioprinting. Furthermore, for hybrid bioprinting of these spheroids, gelMA is a promising material as it exhibits favorable properties in terms of printability and it supports the viability and chondrogenic phenotype of hBM-MSC microtissues. Moreover, it was shown that a lower hydrogel stiffness enhances further chondrogenic maturation after bioprinting.