Miracle-dz/UniFAR-FTUs huggingface dataset:
Ethical Considerations in Dementia Diagnosis and Care

Alzheimer disease and other dementias present unique practical challenges for patients, their families, clinicians, and health systems. These challenges reflect not only the growing public health effect of dementia in an aging global population, but also more specific ethical complexities including early loss of patients' capacity to make decisions regarding their own care, the stigma often associated with a dementia diagnosis, the difficulty of balancing concern for patients' welfare with respect for patients' remaining independence, and the effect on the physical, emotional, and financial well-being of family caregivers. Caring for patients with dementia requires respecting patient autonomy while acknowledging progressively diminishing decisional capacity and continuing to provide care in accordance with other core ethical principles (beneficence, justice, and nonmaleficence). Whereas these ethical principles remain unchanged, neurologists must reconsider how to apply them given changes across multiple domains including our understanding of disease, clinical and legal tools for addressing manifestations of illness, our expanding awareness of the crucial role of family caregivers in providing care and maintaining patient quality of life, and societal conceptions of dementia and individuals' personal expectations for aging. This revision to the American Academy of Neurology's 1996 position statement summarizes ethical considerations that often arise in caring for patients with dementia; although it addresses how such considerations influence patient management, it is not a clinical practice guideline.
Preparation of cypress (Cupressus sempervirens L.) essential oil loaded poly(lactic acid) nanofibers

Abstract This study investigated the production of poly(lactic acid) (PLA) nanofibers containing cypress (CUP) essential oil (EO) via electrospinning. The nanofibers were produced from polymer solution prepared with different percentages of cypress EO. Cypress EO-containing PLA nanofibers were characterized and some mechanical and thermal properties were examined using thermogravimetric analysis, scanning electron microscopy, Fourier-transform infrared spectroscopy, and dynamic mechanical analysis. The thermal stability of the nanofibers was reduced depending on the percentage of the cypress EO. As the ratio of the cypress EO to polymer matrices was increased, it was observed that the glassy transition temperatures of the nanofibers decreased and their flexibility increased. The T g value was determined to be 53.74°C for the neat PLA nanofiber, while 51.83°C for the PLA-CUP nanofiber (containing 15% cypress EO). According to the results of releasing trial, the increased amount of cypress EO resulted in less cypress EO releasing from polymer matrices. The nanofibers were observed to exhibit antibacterial activity against Escherichia coli and Staphylococcus aureus. The inhibition zone diameter of the nanofibers containing 10% cypress EO was 20 mm for S. aureus and 16 mm for E. coli, while 10 mm in the presence of Kanamycin.
The Influence of Servant Leadership on Organizational Citizenship Behavior: the Mediating Effect of Organizational Commitment

Abstract The main aim of the study to find out whether organizational commitment has any mediation effect on the relationship between servant leadership and organizational citizenship behavior. Data was collected from 432 managers and staff of private commercial banks in Bangladesh. The respondents were selected using the convenience sampling technique. Structural equation modeling was used for analyzing the collected data. The study reveals that servant leadership has a direct influence on organizational commitment and organizational citizenship behavior, as well as organizational commitment has a direct impact on organizational citizenship behavior. It is also revealed that the relationship between servant leadership and organizational commitment is partially mediated by organizational commitment. The main implication of the study is that employees’ organizational citizenship behavior can be improved by servant leadership of managers through the indirect effect of organizational commitment of employees. The study also pinpoints some limitations as well as future research directions.
International Conference KNOWLEDGE-BASED ORGANIZATION Vol. XXVII No 3 2021 STUDY ON THE STUDENTS’ APTITUDE AND OPENNESS FOR THE USE OF VIRTUAL REALITY AND AUGMENTED REALITY TECHNOLOGIES IN EDUCATION AND INSTRUCTION

This paper is designed to quantitatively measure the level of aptitude and availability of the students from the “Nicolae Bălcescu” Land Forces Academy in Sibiu for the use of virtual reality (VR) and augmented reality (AR) technologies as teaching tools in the process of education and instruction. The paper is a first stage of a broader research topic, the results of which will be addressed to both teachers and researchers, as well as students and other categories of trainees. The introductory part of the paper analyses the importance of VR and AR technologies as learning environments for the military education system in particular and the advantages of using them for the cadets’ combat training. Also, the main characteristics of the three types of reality, environmental, virtual and augmented, are highlighted, which allow a better understanding of the structure and operation of AR and VR. The research methodology was then developed, establishing a survey by applying a questionnaire on a sample of 300 students from the academy and then processing and interpreting the results obtained. The conclusions of the paper show the general predisposition of students to understand and use the two technologies both as tools of learning in didactic teaching and as instruments of improving the skills of fighters in modelling and simulating military actions.
The potential for mobile demersal fishing to reduce carbon storage and sequestration in seabed sediments

Subtidal marine sediments are one of the planet’s primary carbon stores and strongly influence the oceanic sink for atmospheric CO2. By far the most pervasive human activity occurring on the seabed is bottom trawling and dredging for fish and shellfish. A global first-order estimate suggested mobile demersal fishing activities may cause 160-400 Mt of organic carbon (OC) to be remineralised annually from seabed sediment carbon stores. There are, however, many uncertainties in this calculation. Here, we discuss the potential drivers of change in seabed OC stores due to mobile demersal fishing activities and conduct a systematic review, synthesising studies where this interaction has been directly investigated. Mobile demersal fishing would be expected to reduce OC in seabed stores, albeit with site-specific variability. Reductions would occur due to lower production of flora and fauna, the loss of fine flocculent material, increased sediment resuspension, mixing and transport, and increased oxygen exposure. This would be offset to some extent by reduced faunal bioturbation and respiration, increased off-shelf transport and increases in primary production from the resuspension of nutrients. Studies which directly investigated the impact of demersal fishing on OC stocks had mixed results. A finding of no significant effect was reported in 51% of 59 experimental contrasts; 41% reported lower OC due to fishing activities, with 8% reporting higher OC. In relation to remineralisation rates within the seabed, 14 experimental contrasts reported that demersal fishing activities decreased remineralisation, with four reporting higher remineralisation rates. The direction of effects was related to sediment type, impact duration, study design and local hydrography. More evidence is urgently needed to accurately quantify the impact of anthropogenic physical disturbance on seabed carbon in different environmental settings, and incorporate full evidence-based carbon considerations into global seabed management.
Protein structural features predict responsiveness to pharmacological chaperone treatment for three lysosomal storage disorders

Three-dimensional structures of proteins can provide important clues into the efficacy of personalized treatment. We perform a structural analysis of variants within three inherited lysosomal storage disorders, comparing variants responsive to pharmacological chaperone treatment to those unresponsive to such treatment. We find that predicted ΔΔG of mutation is higher on average for variants unresponsive to treatment, in the case of datasets for both Fabry disease and Pompe disease, in line with previous findings. Using both a single decision tree and an advanced machine learning approach based on the larger Fabry dataset, we correctly predict responsiveness of three Gaucher disease variants, and we provide predictions for untested variants. Many variants are predicted to be responsive to treatment, suggesting that drug-based treatments may be effective for a number of variants in Gaucher disease. In our analysis, we observe dependence on a topological feature reporting on contact arrangements which is likely connected to the order of folding of protein residues, and we provide a potential justification for this observation based on steady-state cellular kinetics. Author summary Pharmacological chaperones are small molecule drugs that bind to proteins to help stabilize the folded state. One set of diseases for which this treatment has been effective is the lysosomal storage disorders, which are caused by defective lysosomal enzymes. However, not all genotypes are equally responsive to treatment. For instance, missense mutants that are particularly destabilized relative to WT are less likely to respond. The availability of datasets containing responsiveness data for large numbers of mutants, along with crystal structures of the protein involved in each disease, make machine learning methods incorporating sequence-based and structural data feasible. We hypothesize that data from two diseases, Fabry and Pompe disease, may be useful for predicting responsiveness of variants in the related Gaucher disease. Results suggest that many rare variants in Gaucher disease could be amenable to existing drugs. Results suggest that drug responsiveness depends on protein topology is such a way that mutations in early-to-fold residues are more likely to be non-responsive to pharmacological chaperone treatment, which is consistent with a simple kinetic model of stability rescue. This study provides an example of how machine learning can be used to inform further studies towards personalized treatment in medicine.
Pharmacokinetic Effects of Combined Exposure to Nicotine and THC via E-Cigarettes in Pregnant Rats

Nicotine and cannabis are two of the most commonly consumed licit and illicit drugs during pregnancy, often consumed together via e-cigarettes. Vaping is assumed to be a safer alternative than traditional routes of consumption, yet the potential consequences of prenatal e-cigarette exposure are largely unknown, particularly when these two drugs are co-consumed. In a novel co-exposure model, pregnant Sprague-Dawley rats received nicotine (36 mg/mL), THC (100 mg/mL), the combination, or the vehicle via e-cigarettes daily from gestational days 5-20, mimicking the first and second human trimesters. Maternal blood samples were collected throughout pregnancy to measure drug and metabolite levels, and core body temperatures before and after exposure were also measured. Pregnant dams exposed to combined nicotine and THC had lower plasma nicotine and cotinine levels than those exposed to nicotine alone; similarly, the combined exposure group also had lower plasma THC and THC metabolite (THC-OH and THC-COOH) levels than those exposed to THC alone. Prenatal nicotine exposure gradually decreased basal core body temperatures each day, with chronic exposure, whereas exposure to THC alone decreased temperatures during the individual sessions. Despite these physiological effects, no changes were observed in food or water intake, weight gain, or basic litter outcomes. These data suggest that combined exposure to nicotine and THC elicits both separate and interactive physiological effects of nicotine and THC on pregnant dams. These data and use of this model can help improve education for pregnant mothers about prenatal e-cigarette use and has important implications for public policy. HIGHLIGHTS Repeated prenatal nicotine exposure via e-cigarettes gradually decreased temperatures Prenatal THC exposure via e-cigarettes decreased temperatures during intoxication Combined prenatal exposure via e-cigarettes altered plasma drug and metabolite levels This co-exposure model elicits separate and interactive effects of nicotine and THC
Recruitment of Scc2/4 to double strand breaks depends on yH2A and DNA end resection

Homologous recombination (HR) enables cells to overcome the threat of DNA double strand breaks (DSB), allowing for repair without the loss of genetic information. Central to the HR repair process is the de novo loading of Cohesin around a DSB by its loader complex Scc2/4. Although Cohesin’s accumulation at these sites has been well studied, the prerequisites leading to Scc2/4 recruitment during the repair process are still elusive. Here we investigate which factors are required for recruitment of Scc2 around DSBs in Saccharomyces cerevisiae. To address this question, we combined ChIP-qPCR with a GAL-inducible HO-endonuclease system to generate a site specific DSB in vivo. We find that Scc2 recruitment relies on yH2A and Tel1, but as opposed to Cohesin, not on Mec1. We further demonstrate that binding of Scc2 depends on and coincides with DNA end resection. Although affected by the impact on resection, this recruitment of Scc2 is not directly facilitated by the RSC, SWR1 or INO80 complexes. Our results shed light on the intricate DSB repair cascade leading to the recruitment of Scc2/4 and the subsequent loading of Cohesin.
Cerebellar control of a unitary head direction sense

Head direction (HD) cells, key neuronal elements in the mammalian’s navigation system, are hypothesized to act as a continuous attractor network, in which temporal coordination between cell members is maintained under different brain states or external sensory conditions, resembling a unitary neural representation of direction. Whether and how multiple identified HD signals in anatomically separate HD cell structures are part of a single and unique attractor network is currently unknown. By manipulating the cerebellum, we identified pairs of thalamic and retrosplenial HD cells that lose their temporal coordination in the absence of external sensory drive, while the neuronal coordination within each of these brain regions remained intact. Further, we show that distinct cerebellar mechanisms are involved in the stability of direction representation depending on external sensory conditions. These results put forward a new role for the cerebellum in mediating stable and coordinated HD neuronal activity toward a unitary thalamocortical representation of direction.
Dimensionality reduction and data integration for scRNA-seq data based on integrative hierarchical Poisson factorisation

Single-cell RNA sequencing (scRNA-seq) data sets consist of high-dimensional, sparse and noisy feature vectors, and pose a challenge for classic methods for dimensionality reduction. Such problems are compounded when dealing with composite data sets formed by different batches. We introduce Integrative Hierarchical Poisson Factorisation (IHPF), an extension of HPF that makes use of a noise ratio hyper-parameter to tune the variability attributed to batches vs. biological sources (cell phenotypes). We exemplify the application of IHPF under different data integration scenarios with varying alignments of batches and cell diversity, and show that IHPF produces latent factors that can be advantageously applied for cell clustering and visualisation. In addition, the extracted factors have a dual block structure in both cell and gene spaces with enhanced biological interpretability.
Myths and mechanisms: RecBCD and Chi hotspots as determinants of self vs. non-self

Bacteria face a challenge when DNA enters their cells by transformation, mating, or phage infection. Should they treat this DNA as an invasive foreigner and destroy it, or consider it one of their own and potentially benefit from incorporating new genes or alleles to gain useful functions? It is frequently stated that the short nucleotide sequence Chi (5’ GCTGGTGG 3’) recognized by RecBCD helicase-nuclease allows Escherichia coli to distinguish self (i.e., E. coli) DNA from non-self (i.e., any other) DNA and to destroy non-self DNA, and that Chi is “over-represented” in the E. coli genome. We show here that these dogmas are incorrect and apparently based on false assumptions. We note Chi’s wide-spread occurrence and activity in distantly related species. We illustrate multiple, highly non-random features of the genomes of coli and coliphage P1 that account for Chi’s high frequency and genomic position, leading us to propose that P1 selects for Chi’s enhancement of recombination, whereas E. coli selects for the preferred codons in Chi. We discuss other, substantiated mechanisms for self vs. non-self determination involving RecBCD and for RecBCD’s destruction of DNA that cannot recombine, whether foreign or domestic.
An Empirical Bayes Approach to Estimating Dynamic Models of Co-regulated Gene Expression

Time-course gene expression datasets provide insight into the dynamics of complex biological processes, such as immune response and organ development. It is of interest to identify genes with similar temporal expression patterns because such genes are often biologically related. However, this task is challenging due to the high dimensionality of such datasets and the nonlinearity of gene expression time dynamics. We propose an empirical Bayes approach to estimating ordinary differential equation (ODE) models of gene expression, from which we derive similarity metrics that can be used to identify groups of genes with co-moving or time-delayed expression patterns. These metrics, which we call the Bayesian lead-lag R2 values, can be used to construct clusters or networks of functionally-related genes. A key feature of this method is that it leverages biological databases that document known interactions between genes. This information is automatically used to define informative prior distributions on the ODE model’s parameters. We then derive data-driven shrinkage parameters from Stein’s unbiased risk estimate that optimally balance the ODE model’s fit to both the data and external biological information. Using real gene expression data, we demonstrate that our biologically-informed similarity metrics allow us to recover sparse, interpretable gene networks. These networks reveal new insights about the dynamics of biological systems.
Microbiome divergence of marine gastropod species separated by the Isthmus of Panama

The rise of the Isthmus of Panama ~3.5 mya separated populations of many marine organisms, which then diverged into new geminate sister species currently living in the Eastern Pacific Ocean and Caribbean Sea. However, we know very little about how such evolutionary divergences of host species have shaped their microbiomes. Here, we compared the microbiomes of whole-body and shell-surface samples of geminate species of marine gastropods in the genera Cerithium and Cerithideopsis to those of congeneric outgroups. Our results show that the effects of the Isthmus on microbiome composition varied among host genera and between sample types within the same hosts. In the whole-body samples, microbiome compositions of geminate species pairs in the focal genera tended to be similar, likely due to host filtering, although the strength of this relationship varied among the two groups and across similarity metrics. Shell-surface communities showed contrasting patterns, with co-divergence between the host taxa and a small number of microbial clades evident in Cerithideopsis, but not Cerithium. These results suggest that (i) the rise of the Isthmus of Panama affected microbiomes of geminate hosts in a complex and clade-specific manner and (ii) host-associated microbial taxa respond differently to vicariance events than the hosts themselves.
Non-invasive imaging of gene expression and protein secretion dynamics in living mice: identification of ectopic prothrombin expression as driver of thrombosis in cancer

The topology of gene expression and protein localization is a crucial characteristic of life, where the spatiotemporal dynamic of secretory proteins instruct higher order organization, including the orchestration of developmental and adaptive programs. However tools to non-invasively interrogate the fate of secretory proteins in vivo are scarce. Here we introduce a genetic tagging strategy for in vivo imaging of the secretion and expression dynamics of secretory proteins in living animals. Applying this to a prototypical liver-derived secretory protein, we demonstrate that this approach, combined with optical in-vivo imaging, uncovers extrahepatic prothrombin expression in multiple novel anatomical sites (including testes, placenta, brain, kidney, heart and lymphatic system) and in emerging tumors, resulting in significant amounts of tumor-derived prothrombin in the blood with procoagulant properties. Syngeneic cell lines from this mouse model enable unravelling regulatory mechanisms in high resolution, and in a scalable format ex vivo. Beyond discovering new functions of proteins in a targeted manner, this model allows identifying rheostats in the cross-talk between gene expression and availability of a secretory protein. It is also a valuable resource for uncovering novel (tissue-specific) therapeutic vulnerabilities.
Experiencing Surprise: The Temporal Dynamics of Its Impact on Memory

To efficiently process information, the brain shifts between encoding and retrieval states, prioritizing bottom-up or top-down processing accordingly. Expectation violation before or during learning has been shown to trigger an adaptive encoding mechanism, resulting in better memory for unexpected events. Using fMRI, we explored (1) whether this encoding mechanism is also triggered during retrieval, and if so, (2) what the temporal dynamics of its mnemonic consequences are. Male and female participants studied object images, then, with new objects, they learned a contingency between a cue and a semantic category. Rule-abiding (expected) and violating (unexpected) targets and similar foils were used at test. We found interactions between previous and current similar events' expectation, such that when an expected event followed a similar but unexpected event, its performance was boosted, underpinned by activation in the hippocampus, midbrain, and occipital cortex. In contrast, a sequence of two unexpected similar events also triggered occipital engagement; however, this did not enhance memory performance. Taken together, our findings suggest that when the goal is to retrieve, encountering surprising events engages an encoding mechanism, supported by bottom-up processing, that may enhance memory for future related events. SIGNIFICANCE STATEMENT Optimizing the balance between new learning and the retrieval of existing knowledge is an ongoing process, at the core of human cognition. Previous research into memory encoding suggests experiencing surprise leads to the prioritization of the learning of new memories, forming an adaptive encoding mechanism. We examined whether this mechanism is also engaged when the current goal is to retrieve information. Our results demonstrate that an expectation-driven shift toward an encoding state, supported by enhanced perceptual processing, is beneficial for the correct identification of subsequent expected similar events. These findings have important implications for our understanding of the temporal dynamics of the adaptive encoding of information into memory.