Miracle-dz/UniFAR-FTUs huggingface dataset:
Age-Related Regeneration of Osteochondral and Tibial Defects by a Fibrin-Based Construct in vivo

Tissue–biomaterial interactions in different microenvironments influence significantly the repair and regeneration outcomes when a scaffold or construct is implanted. In order to elucidate this issue, a fibrin gel filled macroporous fibrin scaffold (fibrin-based scaffold) was fabricated by loading fibrinogen via a negative pressure method, following with thrombin crosslinking. The macroporous fibrin scaffold exhibited a porous structure with porosity of (88.1 ± 1.3)%, and achieved a modulus of 19.8 ± 0.4 kPa at a wet state after fibrin gel filling, providing a suitable microenvironment for bone marrow-derived mesenchymal stem cells (BMSCs). The in vitro cellular culture revealed that the fibrin-based scaffold could support the adhesion, spreading, and proliferation of BMSCs in appropriate cell encapsulation concentrations. The fibrin-based scaffolds were then combined with BMSCs and lipofectamine/plasmid deoxyribonucleic acid (DNA) encoding mouse-transforming growth factor β1 (pDNA-TGF-β1) complexes to obtain the fibrin-based constructs, which were implanted into osteochondral and tibial defects at young adult rabbits (3 months old) and aged adult rabbits (12 months old) to evaluate their respective repair effects. Partial repair of osteochondral defects and perfect restoration of tibial defects were realized at 18 weeks post-surgery for the young adult rabbits, whereas only partial repair of subchondral bone and tibial bone defects were found at the same time for the aged adult rabbits, confirming the adaptability of the fibrin-based constructs to the different tissue microenvironments by tissue-biomaterial interplays. Graphical Abstract A fibrin-based construct was fabricated to investigate its repair effects in different tissue microenvironments, namely, osteochondral tissue and tibia in young adult rabbits and aged adult rabbits. Influenced by the interactions between the implanted fibrin-based construct and respective tissue microenvironment, the osteochondral defects and tibial defects were partially or completely repaired, confirming the adaptability of the construct to different tissue microenvironments.
Rbfox1 Is Expressed in the Mouse Brain in the Form of Multiple Transcript Variants and Contains Functional E Boxes in Its Alternative Promoters

The RNA-binding protein RBFOX1 is an important regulator of neuron development and neuronal excitability. Rbfox1 is a dosage-sensitive gene and in both mice and humans, decreased expression of Rbfox1 has been linked to neurodevelopmental disorders. Alternative promoters drive expression of Rbfox1 transcript isoforms that encode an identical protein. The tissue- and developmental stage-specific expression of these isoforms, as well as the underlying regulatory mechanisms, are, however, unclear. Here, we set out to capture all of the Rbfox1 transcript isoforms and identify transcriptional mechanisms that regulate brain-specific Rbfox1 expression. Isoform sequencing identified multiple alternative Rbfox1 transcript variants in the mouse cerebral cortex, including transcripts with novel first exons, alternatively spliced exons and 3′-truncations. Quantitative RT-PCR determined the expression of the alternative first exons in the developing cerebral cortex and different subregions of the juvenile brain. Alternative first exons were found to be highly stage- and subregion specific in their expression patterns suggesting that they fulfill specific functions during cortex development and in different brain regions. Using reporter assays we found that the promoter regions of the two first exons E1B and E1C/E1C.1 contain several functional E-boxes. Together, we provide an extensive picture of Rbfox1 isoform expression. We further identified important regulatory mechanisms that drive neuron-specific Rbfox1 expression. Thus, our study forms the basis for further research into the mechanisms that ensure physiological Rbfox1 expression in the brain. It also helps to understand why, in patients with neurodevelopmental disorders deletion of individual RBFOX1 transcript isoforms could affect brain function.
Long-Lasting Rituximab-Induced Reduction of Specific—But Not Total—IgG4 in MuSK-Positive Myasthenia Gravis

The use of rituximab (RTX), an anti-CD20 monoclonal antibody (Ab), in refractory myasthenia gravis (MG) is associated with a better response in patients with Abs to the muscle-specific tyrosine kinase (MuSK) than in other MG subgroups. Anti-MuSK Abs are mostly IgG4 with proven pathogenicity and positive correlation with clinical severity. The rapid and sustained response to RTX may be related to MuSK Ab production by short-lived Ab-secreting cells derived from specific CD20+ B cells. Here, we investigated the long-term effects of RTX in nine refractory MuSK-MG patients with a follow-up ranging from 17 months to 13 years. In patients’ sera, we titrated MuSK-specific IgG (MuSK-IgG) and MuSK-IgG4, along with total IgG and IgG4 levels. Optimal response to RTX was defined as the achievement and maintenance of the status of minimal manifestations (MM)-or-better together with a ≥ 50% steroid reduction, withdrawal of immunosuppressants, and no need for plasma-exchange or intravenous immunoglobulin. After a course of RTX, eight patients improved, with optimal response in six, while only one patient did not respond. At baseline, MuSK-IgG and MuSK-IgG4 serum titers were positive in all patients, ranging from 2.15 to 49.5 nmol/L and from 0.33 to 46.2 nmol/L, respectively. MuSK Abs mostly consisted of IgG4 (range 63.80–98.86%). RTX administration was followed by a marked reduction of MuSK Abs at 2–7 months and at 12–30 months (p < 0.02 for MuSK-IgG and p < 0.01 for MuSK-IgG4). In patients with a longer follow-up, MuSK Ab titers remained suppressed, paralleling clinical response. In the patient who achieved long-term complete remission, MuSK-IgG4 was no longer detectable within 2 years, while MuSK-IgG remained positive at very low titers up to 10 years after RTX. In the patient who did not respond, MuSK-IgG and MuSK-IgG4 remained unchanged. In this patient series, total IgG and IgG4 transiently decreased (p < 0.05) at 2–7 months after RTX. The different trends of reduction between MuSK-IgG4 and total IgG4 after RTX support the view that short-lived Ab-secreting cells are the main producers of MuSK Abs. The ratio between short-lived Ab-secreting cells and long-lived plasma cells may influence the response to RTX, and B-cell severe depletion may reduce self-maintaining autoimmune reactivity.
Changes in Social Network Size Are Associated With Cognitive Changes in the Oldest-Old

Objectives Social isolation is increasing in aging societies and several studies have shown a relation with worse cognition in old age. However, less is known about the association in the oldest-old (85+); the group that is at highest risk for both social isolation and dementia. Methods Analyses were based on follow-up 5 to 9 of the longitudinal German study on aging, cognition, and dementia in primary care patients (AgeCoDe) and the study on needs, health service use, costs, and health-related quality of life in a large sample of oldest-old primary care patients (AgeQualiDe), a multi-center population-based prospective cohort study. Measurements included the Lubben Social Network Scale (LSNS-6), with a score below 12 indicating social isolation, as well as the Mini-Mental Status Examination (MMSE) as an indicator of cognitive function. Results Dementia-free study participants (n = 942) were M = 86.4 (SD = 3.0) years old at observation onset, 68.2% were women. One third (32.3%) of them were socially isolated. Adjusted linear hybrid mixed effects models revealed significantly lower cognitive function in individuals with smaller social networks (β = 0.5, 95% CI = 0.3–0.7, p < .001). Moreover, changes in an individual’s social network size were significantly associated with cognitive changes over time (β = 0.2, 95% CI = 0.1–0.4, p = .003), indicating worse cognitive function with shrinking social networks. Conclusion Social isolation is highly prevalent among oldest-old individuals, being a risk factor for decreases in cognitive function. Consequently, it is important to maintain a socially active lifestyle into very old age. Likewise, this calls for effective ways to prevent social isolation.
Non-stationary Group-Level Connectivity Analysis for Enhanced Interpretability of Oddball Tasks

Neural responses of oddball tasks can be used as a physiological biomarker to evaluate the brain potential of information processing under the assumption that the differential contribution of deviant stimuli can be assessed accurately. Nevertheless, the non-stationarity of neural activity causes the brain networks to fluctuate hugely in time, deteriorating the estimation of pairwise synergies. To deal with the time variability of neural responses, we have developed a piecewise multi-subject analysis that is applied over a set of time intervals within the stationary assumption holds. To segment the whole stimulus-locked epoch into multiple temporal windows, we experimented with two approaches for piecewise segmentation of EEG recordings: a fixed time-window, at which the estimates of FC measures fulfill a given confidence level, and variable time-window, which is segmented at the change points of the time-varying classifier performance. Employing the weighted Phase Lock Index as a functional connectivity metric, we have presented the validation in a real-world EEG data, proving the effectiveness of variable time segmentation for connectivity extraction when combined with a supervised thresholding approach. Consequently, we performed a piecewise group-level analysis of electroencephalographic data that deals with non-stationary functional connectivity measures, evaluating more carefully the contribution of a link node-set in discriminating between the labeled oddball responses.
Systemic Long-Distance Signaling and Communication Between Rootstock and Scion in Grafted Vegetables

Grafting is widely used in fruit, vegetable, and flower propagation to improve biotic and abiotic stress resistance, yield, and quality. At present, the systemic changes caused by grafting, as well as the mechanisms and effects of long-distance signal transport between rootstock and scion have mainly been investigated in model plants (Arabidopsis thaliana and Nicotiana benthamiana). However, these aspects of grafting vary when different plant materials are grafted, so the study of model plants provides only a theoretical basis and reference for the related research of grafted vegetables. The dearth of knowledge about the transport of signaling molecules in grafted vegetables is inconsistent with the rapid development of large-scale vegetable production, highlighting the need to study the mechanisms regulating the rootstock-scion interaction and long-distance transport. The rapid development of molecular biotechnology and “omics” approaches will allow researchers to unravel the physiological and molecular mechanisms involved in the rootstock–scion interaction in vegetables. We summarize recent progress in the study of the physiological aspects (e.g., hormones and nutrients) of the response in grafted vegetables and focus in particular on long-distance molecular signaling (e.g., RNA and proteins). This review provides a theoretical basis for studies of the rootstock–scion interaction in grafted vegetables, as well as provide guidance for rootstock breeding and selection to meet specific demands for efficient vegetable production.
Pathological and Incidental Findings in 403 Taiwanese Girls With Central Precocious Puberty at Initial Diagnosis

Background: Whether girls with central precocious puberty (CPP) should undergo routine brain magnetic resonance imaging (MRI) to identify potential intracranial pathologies is controversial. Aims: To evaluate the brain MRI results of girls with CPP and identify the clinical and endocrine predictors of brain abnormalities. Methods: This retrospective study obtained data from pediatric endocrine clinics at Chang Gung Children's Hospital. From 1997 and 2017, 403 girls were consecutively diagnosed with CPP. After the exclusion of patients with a history of central nervous system (CNS) insults or associated neuropsychiatric symptom or signs, we studied the prevalence of brain abnormalities in 251 girls with CPP who received detailed MRI examinations of the hypothalamus and pituitary area. We also recorded the demographic data of the participants, including the onset of puberty; initial pubertal status; height; weight; uterus and ovary sizes; and basal luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol levels, and the response to GnRH stimulation test. Results: Among the 251 girls with CPP, we observed no brain alterations in 190 (75.70%), abnormalities in the hypothalamic-pituitary (H-P) area in 54 (21.51%), and abnormalities in the non-H-P area in 7 (2.79%). Among the 54 patients that had H-P lesions, we noted pathological findings related to CPP (hypothalamic hamartoma) in only one (0.4%) girl aged below 6 years old. We also identified incidental findings in the other girls with H-P lesions, including non-functioning pituitary microadenomas (12.35%), pituitary pars intermedia cysts (4.38%), Rathke's pouch cysts (1.99%), pituitary hypoplasia (1.59%), and pineal gland cysts (0.8%). The patients that had non-H-P lesions were found to have arachnoid cysts (1.59%), Chiari I malformation (0.4%), prepontine nodule (0.4%), and choroidal fissure cyst (0.4%). Of all the patients with brain lesions, 45 (73.77%) underwent regular MRI follow-up. While none of the H-P and non-H-P lesions showed progression, 19.67% of these regressed during the follow-up. None of the participants exhibited other hormonal abnormalities or underwent surgery. Conclusion: The prevalence of true pathological brain lesions related to CPP in girls without prior symptoms or signs of CNS lesions was low (0.4%). None of the girls with intracranial lesions required further intervention besides the GnRH agonist treatment. These data question the routine use of brain MRI in all girls with CPP, especially in those who are healthy without neurologic symptoms.
First Molecular Identification of Canine Parvovirus Type 2 (CPV2) in Chile Reveals High Occurrence of CPV2c Antigenic Variant

Canine parvovirus type 2 (CPV2) is one of the most important intestinal pathogens in dogs and puppies. CPV2 has been evolved into three genetic and antigenic variants (2a, 2b, and 2c), which are distributed worldwide. We reported the first study of genetic diversity of CPV2 in Chile. Sixty-five samples were collected from puppies presenting with severe gastroenteritis and different vaccination statuses. PCR, restriction fragment length polymorphism (RFLP), and partial sequencing of the coding region of the structural viral protein VP2 was performed. Thirty of a total of 65 samples tested positive by PCR out of which 19 were further classified as CPV2c and one as CPV2a using RFLP and Sanger sequencing. The phylogeny was in concordance with the RFLP analysis. This is the first report of the genetic characterization of CPV2 in Chile and reveals a high occurrence of CPV2c.
Effects of Drought-Tolerant Ea-DREB2B Transgenic Sugarcane on Bacterial Communities in Soil

Drought is a major abiotic stress affecting plant growth and development. Sugarcane, a sugar crop planted in warmer climate, suffers dramatically from drought stress. Bacterial communities colonizing the rhizosphere, where roots sense drought stress initially, have been well studied for their beneficial effects on plant growth and health. The Ea-DREB2B gene cloned from the sugarcane, Saccharum arundinaceum, belongs to the DREB2 subgroup of the DREB gene family, which is involved in drought response regulation. Here, we present a detailed characterization of the rhizoplane, rhizosphere, and bulk soil bacterial communities determined using a high-sequencing approach with the transgenic (TG) sugarcane variety GN18 harboring the drought-tolerant Ea-DREB2B gene and its isogenic wild-type (WT) variety FN95-1702 under the same environmental conditions. In addition, the total carbon (TC), total nitrogen (TN), and total phosphorus (TP) contents in each soil area were compared to explore the relationship between bacterial alteration in the TG and WT plants and environmental factors (TC, TN, TP, C:N, C:P, and N:P). Our results showed that the bacterial communities in the rhizosphere and rhizoplane of TG sugarcane were more similar and perfectly correlated with the environmental factors than those of the WT. This suggested that the bacterial communities of the TG plants were altered in response to the changes in root exudates. The results of our study suggest that the change in soil environment caused by transgenic sugarcane alters soil bacterial communities.
Clustering Analysis of Aging Diseases and Chronic Habits With Multivariate Time Series Electrocardiogram and Medical Records

Background With recent technology, multivariate time-series electrocardiogram (ECG) analysis has played an important role in diagnosing cardiovascular diseases. However, discovering the association of wide range aging disease and chronic habit with ECG analysis still has room to be explored. This article mainly analyzes the possible relationship between common aging diseases or chorionic habits of medical record and ECG, such as diabetes, obesity, and hypertension, or the habit of smoking. Methods In the research, we first conducted different ECG features, such as those of reduced binary pattern, waveform, and wavelet and then performed a k-means clustering analysis on the correlation between ECGs and the aforementioned diseases and habits, from which it is expected to find a firm association between them and the best characteristics that can be used for future research. Results In summary, we discovered a weak and strong evidence between ECG and medical records. For strong evidence, most patients with diabetes are always assigned into a specified group no matter the number of classes in the k-means clustering, which means we can find their association between them. For weak evidence, smokers, obesity, and hypertension have less unique ECG feature vector, enabling clustering them into specific groups, so the ECGs might be used to identify smokers, obesity, and hypertension. It is also interesting that we found obesity and hypertension, which are thought to be related to cardiovascular system. However, they are not highly correlated in our clustering analysis, which might indirectly tell us that the impact of obesity and hypertension to our body is various. In addition, the clustering effect of waveform feature is better than the other two methods.
Farmer Mental Models of Biological Pest Control: Associations With Adoption of Conservation Practices in Blueberry and Cherry Orchards

Conservation practices in agriculture—such as biological pest control, provision of pollinator habitat and cover cropping—may provide ecosystem services that are beneficial to both farmers and wildlife. Despite these benefits, however, their use is not yet widespread and the factors that may limit adoption are not well-understood. In this study we tested potential associations between farmers' beliefs about ecosystem services and their management practices using data collected from questionnaires and cognitive maps from 31 Michigan blueberry and cherry farmers describing their farming systems. We found that farmers who included key biological pest control concepts in their mental model representations reported the use of more conservation practices, and/or participation in conservation programs, than those who did not. In addition, the timing of management practices was a more central factor in the mental models of farmers who included both natural predators and beneficial insects than those omitting these factors. Finally, the farmers who included those two factors showed higher degrees of systems thinking based on mental model metric analysis. We suggest that outreach emphasizing the relationships between ecosystem services and the factors farmers view as most important may positively influence communication and potential of adoption of conservation practices and preventative pest management strategies.
MarA, RamA, and SoxS as Mediators of the Stress Response: Survival at a Cost

To survive and adapt to changing environments, bacteria have evolved mechanisms to express appropriate genes at appropriate times. Exposure to antimicrobials triggers a global stress response in Enterobacteriaceae, underpinned by activation of a family of transcriptional regulators, including MarA, RamA, and SoxS. These control a program of altered gene expression allowing a rapid and measured response to improve fitness in the presence of toxic drugs. Increased expression of marA, ramA, and soxS up regulates efflux activity to allow detoxification of the cell. However, this also results in trade-offs in other phenotypes, such as impaired growth rates, biofilm formation and virulence. Here, we review the current knowledge regarding the trade-offs that exist between drug survival and other phenotypes that result from induction of marA, ramA, and soxS. Additionally, we present some new findings linking expression of these regulators and biofilm formation in Enterobacteriaceae, thereby demonstrating the interconnected nature of regulatory networks within the cell and explaining how trade-offs can exist between important phenotypes. This has important implications for our understanding of how bacterial virulence and biofilms can be influenced by exposure to antimicrobials.
The Quality of Clinical Practice Guidelines and Consensuses on the Management of Primary Aldosteronism: A Critical Appraisal

Background: Several guidelines and expert consensuses have been developed for management of primary aldosteronism (PA). It is important to understand the detailed recommendations and quality of these guidelines to help physicians make informed and reliable decision. Methods: PubMed, EMBASE, and three websites were searched for practice guidelines or consensuses of PA from inception to January 24, 2019. We summarized the major recommendations on the management of PA from these guidelines and consensuses. The Appraisal of Guidelines for Research and Evaluation II was used to assess quality of the included guidelines and consensuses. Results: We identified three clinical practice guidelines and three consensus statements. Most of the recommendations on the diagnosis and treatment of PA from these guidelines and consensuses were consistent. Some minor conflicts were recorded for patient's screen and confirmation test. All included guideline documents have a good quality (score, >70%) on the scope and purpose (mean score, 81.02%) and clarity of presentation of the recommendations (mean score, 86.88%). However, the reporting for the stakeholder involvement (mean score, 54.32%) and applicability (mean score, 47.92%) were insufficient. There was an insufficient rigorousness in most of the guideline documents (mean score, 45.56%) on the development process. The Endocrine Society practice guideline 2016 ranked highest in quality (score, 81.13%). Conclusions: Existing guideline documents provided valuable recommendations on the management of PA, but further efforts are needed to improve the methodological quality. The Endocrine Society practice guideline 2016 was recommended for use.