Miracle-dz/UniFAR-FTUs huggingface dataset:
Megalencephalic Leukoencephalopathy: Insights Into Pathophysiology and Perspectives for Therapy

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare genetic disorder belonging to the group of vacuolating leukodystrophies. It is characterized by megalencephaly, loss of motor functions, epilepsy, and mild mental decline. In brain biopsies of MLC patients, vacuoles were observed in myelin and in astrocytes surrounding blood vessels. It is mainly caused by recessive mutations in MLC1 and HEPACAM (also called GLIALCAM) genes. These disease variants are called MLC1 and MLC2A with both types of patients sharing the same clinical phenotype. Besides, dominant mutations in HEPACAM were also identified in a subtype of MLC patients (MLC2B) with a remitting phenotype. MLC1 and GlialCAM proteins form a complex mainly expressed in brain astrocytes at the gliovascular interface and in Bergmann glia at the cerebellum. Both proteins regulate several ion channels and transporters involved in the control of ion and water fluxes in glial cells, either directly influencing their location and function, or indirectly regulating associated signal transduction pathways. However, the MLC1/GLIALCAM complex function and the related pathological mechanisms leading to MLC are still unknown. It has been hypothesized that, in MLC, the role of glial cells in brain ion homeostasis is altered in both physiological and inflammatory conditions. There is no therapy for MLC patients, only supportive treatment. As MLC2B patients show an MLC reversible phenotype, we speculated that the phenotype of MLC1 and MLC2A patients could also be mitigated by the re-introduction of the correct gene even at later stages. To prove this hypothesis, we injected in the cerebellar subarachnoid space of Mlc1 knockout mice an adeno-associated virus (AAV) coding for human MLC1 under the control of the glial-fibrillary acidic protein promoter. MLC1 expression in the cerebellum extremely reduced myelin vacuolation at all ages in a dose-dependent manner. This study could be considered as the first preclinical approach for MLC. We also suggest other potential therapeutic strategies in this review.
Adaptive Time-Dependent Priors and Bayesian Inference to Evaluate SARS-CoV-2 Public Health Measures Validated on 31 Countries

With the rapid spread of the SARS-CoV-2 virus since the end of 2019, public health confinement measures to contain the propagation of the pandemic have been implemented. Our method to estimate the reproduction number using Bayesian inference with time-dependent priors enhances previous approaches by considering a dynamic prior continuously updated as restrictive measures and comportments within the society evolve. In addition, to allow direct comparison between reproduction number and introduction of public health measures in a specific country, the infection dates are inferred from daily confirmed cases and confirmed death. The evolution of this reproduction number in combination with the stringency index is analyzed on 31 European countries. We show that most countries required tough state interventions with a stringency index equal to 79.6 out of 100 to reduce their reproduction number below one and control the progression of the pandemic. In addition, we show a direct correlation between the time taken to introduce restrictive measures and the time required to contain the spread of the pandemic with a median time of 8 days. This analysis is validated by comparing the excess deaths and the time taken to implement restrictive measures. Our analysis reinforces the importance of having a fast response with a coherent and comprehensive set of confinement measures to control the pandemic. Only restrictions or combinations of those have shown to effectively control the pandemic.
Psychological Resilience as a Protective Factor for Depression and Anxiety Among the Public During the Outbreak of COVID-19

Background Psychological resilience may reduce the impact of psychological distress to some extent. We aimed to investigate the mental health status of the public during the outbreak of coronavirus disease 2019 (COVID-19) and explore the level and related factors of anxiety and depression. Methods From February 8 to March 9, 2020, 3,180 public completed the Zung’s Self-Rating Anxiety Scale (SAS) for anxiety, Zung’s Self-Rating Depression Scale (SDS) for depression, the Connor–Davidson resilience scale (CD-RISC) for psychological resilience, and the Simplified Coping Style Questionnaire (SCSQ) for the attitudes and coping styles. Results The number of people with depressive symptoms (SDS > 53) was 1,303 (the rate was 41.0%). The number of people with anxiety symptoms (SAS > 50) was 1,184 (the rate was 37.2%). The depressed group and anxiety group had less education, more unmarried and younger age, as well as had significant different in SDS total score (P < 0.001), SAS total score (P < 0.001), CD-RISC total score (P < 0.001), and SCSQ score (P < 0.001). The binary logistic regression showed that female (B = -0.261, P = 0.026), strength (B = -0.079, P = 0.000), and the subscales of active coping style in SCSQ (B = -0.983, P = 0.000) remained protective factors and passive coping style (B = 0.293, P = 0.003) and higher SAS score (B = 0.175, P = 0.000) were risk factors for depression. Optimism (B = -0.041, P = 0.015) in CD-RISC was a protective factor, and passive coping styles (B = 0.483, P = 0.000) and higher SDS score (B = 0.134, P = 0.000) were risk factors for anxiety. Limitations This study adopted a cross-sectional design and used self-report questionnaires. Conclusion The mental health of the public, especially females, the younger and less educational populations, and unmarried individuals, should be given more attention. Individuals with high level of mental resilience and active coping styles would have lower levels of anxiety and depression during the outbreak of COVID-19.
Pressure Injury Prevention in COVID-19 Patients With Acute Respiratory Distress Syndrome

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in China in December 2019 and became a pandemic in a short period of time. While most infected people might have mild symptoms, older people and people with chronic illnesses may develop acute respiratory distress syndrome (ARDS). Patients with ARDS with worsening hypoxemia require prone positioning to improve the respiratory mechanics and oxygenation. Intubated patients may stay in a prone position up to 12–16 h, increasing the risk of pressure injury (PI). Frequent skin inspections and PI risk assessment in COVID-19 patients will be challenging due to hospital infection control measures aimed to reduce the risk for health professionals. In this perspective article, we summarize the best practice recommendations for prevention of PI in SARS-CoV-2-infected ARDS patients in prone positioning. Prior to positioning patients in prone position, the main recommendations are to (1) conduct a skin assessment, (2) use pressure redistribution devices, (3) select an appropriate mattress or an overlay, (4) ensure that the endotracheal tube securing device is removed and the endotracheal tube is secured with tapes, (5) use a liquid film-forming protective dressing, and (6) lubricate the eyes and tape them closed. Once a patient is in prone position, it is recommended to (1) use the swimmer's position, (2) reposition the patient every 2 h, and (3) keep the skin clean. When the patient is repositioned to supine position, healthcare professionals are advised to (1) assess the pressure points and (2) promote early mobilization.
Short-Term Exposure to Sterile Seawater Reduces Bacterial Community Diversity in the Sea Anemone, Exaiptasia diaphana

The global decline of coral reefs heightens the need to understand how corals may persist under changing environmental conditions. Restructuring of the coral-associated bacterial community, either through natural or assisted strategies, has been suggested as a means of adaptation to climate change. A low complexity microbial system would facilitate testing the efficacy of microbial restructuring strategies. We used the model organism for corals, Exaiptasia diaphana, and determined that short-term (3 weeks) exposure to filter-sterilized seawater conditions alone reduced the complexity of the microbiome. Metabarcoding of the V5–V6 region of the bacterial 16S rRNA gene revealed that alpha diversity was approximately halved in anemones reared in filter-sterilized seawater compared to controls reared in unfiltered seawater and that the composition (beta diversity) differed significantly between the two. By reducing the complexity of the E. diaphana microbiome, the development of a system for testing assisted strategies such as probiotics, is more feasible.
A Meaning-Aware Cultural Tourism Intelligent Navigation System Based on Anticipatory Calculation

To improve the personalized service of cultural tourism, anticipatory calculation has become an essential technology in the content design of intelligence navigation system. Culture tourism, as a form of leisure activity, is being favored by an increasing number of people, which calls for further improvements in the cultural consumption experience. An important component of cultural tourism is for tourists to experience intangible cultural heritage projects with local characteristics. However, from the perspective of user needs and the content adaptive system, there are few suitable intelligent navigation and user demand anticipatory systems for intangible cultural heritage content. Purple clay culture is one of the first batches of national intangible cultural heritage protection projects in China. Therefore, taking purple clay culture exhibition as an example, this paper attempts to analyze the personalized information demand of tourism consumption experience in intangible cultural heritage communication activities with affective computing and meaning-driven innovative design method, by taking the content design in the navigation system as the research object. This paper uses the theory of planned behavior to calculate the relationship between tourists’ attitude, experience behavior, and display information demand. The findings indicate two issues. First, tourists’ demand for the entertainment and leisure attributes of intangible cultural heritage is greater than the demand for educational function attributes. Second, the meaning elements of information can change tourists’ beliefs in intangible cultural heritage and affect their attitude and behavior toward such heritage. According to the research results, strengthening the meaning elements of specific group information can improve people’s cultural identity and tourism satisfaction. The research results provide the basis for the content design direction of future museum intelligent navigation systems.
Independent Validation of Genomic Prediction in Strawberry Over Multiple Cycles

The University of Florida strawberry (Fragaria × ananassa) breeding program has implemented genomic prediction (GP) as a tool for choosing outstanding parents for crosses over the last five seasons. This has allowed the use of some parents 1 year earlier than with traditional methods, thus reducing the duration of the breeding cycle. However, as the number of breeding cycles increases over time, greater knowledge is needed on how multiple cycles can be used in the practical implementation of GP in strawberry breeding. Advanced selections and cultivars totaling 1,558 unique individuals were tested in field trials for yield and fruit quality traits over five consecutive years and genotyped for 9,908 SNP markers. Prediction of breeding values was carried out using Bayes B models. Independent validation was carried out using separate trials/years as training (TRN) and testing (TST) populations. Single-trial predictive abilities for five polygenic traits averaged 0.35, which was reduced to 0.24 when individuals common across trials were excluded, emphasizing the importance of relatedness among training and testing populations. Training populations including up to four previous breeding cycles increased predictive abilities, likely due to increases in both training population size and relatedness. Predictive ability was also strongly influenced by heritability, but less so by changes in linkage disequilibrium and effective population size. Genotype by year interactions were minimal. A strategy for practical implementation of GP in strawberry breeding is outlined that uses multiple cycles to predict parental performance and accounts for traits not included in GP models when constructing crosses. Given the importance of relatedness to the success of GP in strawberry, future work could focus on the optimization of relatedness in the design of TRN and TST populations to increase predictive ability in the short-term without compromising long-term genetic gains.
Pivotal Role of Tenascin-W (-N) in Postnatal Incisor Growth and Periodontal Ligament Remodeling

The continuously growing mouse incisor provides a fascinating model for studying stem cell regulation and organ renewal. In the incisor, epithelial and mesenchymal stem cells assure lifelong tooth growth. The epithelial stem cells reside in a niche known as the cervical loop. Mesenchymal stem cells are located in the nearby apical neurovascular bundle and in the neural plexus. So far, little is known about extracellular cues that are controlling incisor stem cell renewal and guidance. The extracellular matrix protein tenascin-W, also known as tenascin-N (TNN), is expressed in the mesenchyme of the pulp and of the periodontal ligament of the incisor, and is closely associated with collagen 3 fibers. Here, we report for the first time the phenotype of tenascin-W/TNN deficient mice, which in a C57BL/6N background exhibit a reduced body weight and lifespan. We found major defects in the alveolar bone and periodontal ligament of the growing rodent incisors, whereas molars were not affected. The alveolar bone around the incisor was replaced by a dense scar-like connective tissue, enriched with newly formed nerve fibers likely leading to periodontal pain, less food intake and reduced body weight. Using soft food to reduce mechanical load on the incisor partially rescued the phenotype. In situ hybridization and Gli1 reporter mouse experiments revealed decreased hedgehog signaling in the incisor mesenchymal stem cell compartment, which coordinates the development of mesenchymal stem cell niche. These results indicate that TNN deficiency in mice affects periodontal remodeling and increases nerve fiber branching. Through periodontal pain the food intake is reduced and the incisor renewal and the neurovascular sonic hedgehog secretion rate are reduced. In conclusion, tenascin-W/TNN seems to have a primary function in rapid periodontal tissue remodeling and a secondary function in mechanosensation.
Chinese Herbal Medicine for Psoriasis: Evidence From 11 High-Quality Randomized Controlled Trials

Background: Chinese herbal medicine (CHM) provides a theoretical basis for the treatment of psoriasis with considerable benefits and a low toxicity. The purpose of this quantitative study was to show high-quality evidence of the efficacy and safety of CHM for the treatment of psoriasis to promote its clinical application. Methods: Several databases were systematically searched including PubMed, Embase, Cochrane Central Register of Controlled Trials, China Network Knowledge Infrastructure, Chinese Scientific Journals Database, and Wan Fang Database. High-quality randomized controlled trials that compared CHM with non-CHM interventions were included. The RevMan5.3 software was used to calculate risk ratios (RR) at 95% confidence intervals (CI) and conduct the meta-analysis. Results: Altogether, 1,215 patients participated in this study, including 711 in the experimental group and 504 in the control group. The psoriasis area severity index (PASI) score of the CHM group was significantly lower than that of the placebo group (MD, −4.02; 95% CI, −6.71 to −1.34; p = 0.003). To achieve PASI-60 and PASI-75, the arrival rate of the CHM group was higher than that of the placebo group (PASI-60: RR, 3.52; 95% CI, 1.17 to 10.61; p = 0.03; PASI-75: RR, 9.87; 95% CI, 3.11 to 31.31; p = 0.0001). Furthermore, the efficacy rate was higher in patients receiving CHM than in those receiving placebo (RR, 1.72; 95% CI, 1.01 to 2.93; p = 0.04). The results suggested a greater impact of CHM in improving the dermatology life quality index (DLQI) of patients (MD, −2.12; 95% CI, −3.75 to −0.49; p = 0.01). Regarding pruritus severity, there was no significant difference between the two groups (MD, −1.90; 95% CI, −3.79 to −0.01; p = 0.05). The meta-analysis revealed that the recurrence rate (RR, 0.74; 95% CI, 0.32 to 1.71; p = 0.48) and proportion of adverse events (RR, 1.36; 95% CI, 0.95 to 1.93; p = 0.09) associated with using CHM were similar to those associated with using a placebo. Conclusion: CHM appears safe and effective in the treatment of psoriasis and has a great positive impact on the DQLI of patients; however, CHM could not completely eliminate skin lesions, improve pruritus severity, and reduce the recurrence rate.
Visual Abnormalities Associate With Hippocampus in Mild Cognitive Impairment and Early Alzheimer's Disease

Background and Objective: Alzheimer's disease (AD) has been shown to affect vision in human patients and animal models. This study was conducted to explore ocular abnormalities in the primary visual pathway and their relationship with hippocampal atrophy in patients with AD and mild cognitive impairment (MCI). The aim of this study was to investigate the potential value of ocular examinations as a biomarker during the AD progression. Methods: Patients with MCI (n = 23) or AD (n = 17) and age-matched cognitively normal controls (NC; n = 19) were enrolled. Pattern visual-evoked potentials (PVEP), flash electroretinogram (FERG) recordings and optical coherence tomography (OCT) were performed for all participants. Hippocampal volumes were measured by 3T magnetic resonance imaging. Cognitive function was assessed by Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog). Pearson correlation was employed to analyze the potential associations between ocular abnormalities and hippocampal volumes. Hierarchical regression models were conducted to determine associations between cognitive performances and ocular abnormalities as well as hippocampal volumes after adjusting for confounding factors including age, sex, cognitive reserve, and APOE4 status. Results: PVEP amplitude of P100 waveform was significantly decreased in AD patients compared to MCI and normal individuals. In FERG test, delayed latencies of rod response, rod cone response and 3.0 flicker time were found in cognitively impaired groups, indicating dysfunctions of both the rod and cone systems in the disease progression. OCT test revealed reduced macular retinal nerve fiber layer (m-RNFL) thickness in MCI and AD patients, which significantly correlated with brain structure of hippocampus particularly vulnerable during the progression of AD. Interestingly, P100 amplitude showed a significant association with hippocampal volumes even after adjusting confounding factors including age, sex, and cognitive reserve. Hierarchical regression analysis further demonstrated that m-RNFL thickness, as well as hippocampal volumes, significantly associated with ADAS-cog scores. Conclusion: P100 amplitude and m-RNFL thickness showed significant correlations with brain structure involved in AD-related neurodegeneration, and therefore proved to be potential indicators of brain imaging pathologies.
Chronic Hyperglycemia Drives Functional Impairment of Lymphocytes in Diabetic INSC94Y Transgenic Pigs

People with diabetes mellitus have an increased risk for infections, however, there is still a critical gap in precise knowledge about altered immune mechanisms in this disease. Since diabetic INSC94Y transgenic pigs exhibit elevated blood glucose and a stable diabetic phenotype soon after birth, they provide a favorable model to explore functional alterations of immune cells in an early stage of diabetes mellitus in vivo. Hence, we investigated peripheral blood mononuclear cells (PBMC) of these diabetic pigs compared to non-diabetic wild-type littermates. We found a 5-fold decreased proliferative response of T cells in INSC94Y tg pigs to polyclonal T cell mitogen phytohemagglutinin (PHA). Using label-free LC-MS/MS, a total of 3,487 proteins were quantified, and distinct changes in protein abundances in CD4+ T cells of early-stage diabetic pigs were detectable. Additionally, we found significant increases in mitochondrial oxygen consumption rate (OCR) and higher basal glycolytic activity in PBMC of diabetic INSC94Y tg pigs, indicating an altered metabolic immune cell phenotype. Thus, our study provides new insights into molecular mechanisms of dysregulated immune cells triggered by permanent hyperglycemia.
Working While Ill Is Not Always Bad—Positive Effects of Presenteeism

Presenteeism—going to work while ill—is a widespread phenomenon worldwide. Previous research has concentrated mainly on its negative effects. This study investigates the positive consequences of presenteeism derived from a comprehensive content model of presenteeism that was developed on the basis of negative effects. In a quantitative online-survey employees (N = 181) rated the degree of experienced or potential positive effects depending on whether they had worked while ill (75%) or not (25%) during the previous year. Results revealed that all postulated positive effects described in the content model were relevant. Most positive effects were rated significantly higher by participants who had shown presenteeism in comparison to those who had not. The positive effects significantly predicted presenteeism propensity (adjusted R2 = 0.20) for participants having shown presenteeism. In addition, an overall rating of positive effects was significantly related to presenteeism, however, to a lesser degree. Overall, the results demonstrate the applicability of the content model to positive effects of presenteeism. They point to the need for further investigation of them and their consideration for the management of presenteeism.