Miracle-dz/UniFAR-FTUs huggingface dataset:
Niches and Seasonal Changes, Rather Than Transgenic Events, Affect the Microbial Community of Populus × euramericana ‘Neva’

Exploring the complex spatiotemporal changes and colonization mechanism of microbial communities will enable microbial communities to be better used to serve agricultural and ecological operations. In addition, evaluating the impact of transgenic plants on endogenous microbial communities is necessary for their commercial application. In this study, microbial communities of Populus × euramericana ‘Neva’ carrying Cry1Ac-Cry3A-BADH genes (ECAA1 line), Populus × euramericana ‘Neva’ carrying Cry1Ac-Cry3A-NTHK1 genes (ECAB1 line), and non-transgenic Populus × euramericana ‘Neva’ from rhizosphere soil, roots, and phloem collected in different seasons were compared and analyzed. Our analyses indicate that the richness and diversity of bacterial communities were higher in the three Populus × euramericana ‘Neva’ habitats than in those of fungi. Bacterial and fungal genetic-distance-clustering results were similar; rhizosphere soil clustered in one category, with roots and phloem in another. The diversity and evenness values of the microbial community were: rhizosphere soil > phloem > root system. The bacterial communities in the three habitats were dominated by the Proteobacteria, and fungal communities were dominated by the Ascomycota. The community composition and abundance of each part were quite different; those of Populus × euramericana ‘Neva’ were similar among seasons, but community abundance fluctuated. Seasonal fluctuation in the bacterial community was greatest in rhizosphere soil, while that of the fungal community was greatest in phloem. The transgenic lines ECAA1 and ECAB1 had a bacterial and fungal community composition similar to that of the control samples, with no significant differences in community structure or diversity among the lines. The abundances of operational taxonomic units (OTUs) were low, and differed significantly among the lines. These differences did not affect the functioning of the whole specific community. Sampling time and location were the main driving factors of changes in the Populus × euramericana ‘Neva’ microbial community. Transgenic events did not affect the Populus × euramericana ‘Neva’ rhizosphere or endophytic microbial communities. This study provides a reference for the safety evaluation of transgenic plants and the internal colonization mechanism of microorganisms in plants.
Soil and Vegetation Drive Sesquiterpene Lactone Content and Profile in Arnica montana L. Flower Heads From Apuseni-Mountains, Romania

Arnica montana L. (AM, Asteraceae) is a perennial, herbaceous vascular plant species of commercial importance. The flower heads’ pharmacological properties are attributed mainly to sesquiterpene lactones (SLs), with phenolic acids and flavonoids also considered of relevance. The botanical drug is still partly collected in different European mountain regions. The SL content can be influenced by genetic factors and environmental conditions (altitude, temperature and rainfall). Surprisingly, the influence of the soil on SL-content have rarely been investigated. However, the soil determines the occurrence, distribution and overall fitness of AM. Equally, environmental factors are crucial determinants for the biosynthesis and fluctuations in plant secondary metabolites. Therefore, different abiotic (pH, C/N ratio, base saturation, cation exchange capacity) and biotic (species richness, vegetation cover) parameters need to be assessed as potential drivers of the variable content of AM’s secondary metabolites. Consequently, we developed an in situ experimental design aiming to cover a wide range of soil pH conditions. We detected and investigated different AM populations growing in grassland on acidic soils, on siliceous as well as calcareous geologies within the same geographical region and altitudinal belt. The total SL content and most single SL contents of the AM flower heads differed significantly between the two geologies. AM flower heads of plants growing on loam on limestone showed a significant higher total SL content than the flower heads of plants growing in siliceous grasslands. Furthermore, the SL contents were significantly correlated with geobotanical species richness and vegetation cover pointing toward an effect of species interactions on the production of SLs. Moreover, the ratios of the main SLs helenalin to dihydrohelenalin esters were significantly correlated to environmental parameters indicating that SL composition might be a function of habitat conditions. The findings of this study shed light upon the often ignored, complex interactions between environmental conditions and plant secondary metabolites. We highlight the importance of both abiotic and biotic habitat parameters for SLs in AM.
The SARS-CoV-2 Pandemic Impacts the Management of Swiss Pediatric Intensive Care Units

The impact of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic on pediatric intensive care units (PICUs) is difficult to quantify. We conducted an observational study in all eight Swiss PICUs between 02/24/2020 and 06/15/2020 to characterize the logistical and medical aspects of the pandemic and their impact on the management of the Swiss PICUs. The nine patients admitted to Swiss PICUs during the study period suffering from pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) and constituting 14% (9/63) of all SARS-CoV-2 positive hospitalized patients in Swiss children's hospitals caused a higher workload [total Nine Equivalents of nursing Manpower use Score (NEMS) points, p = 0.0008] and were classified to higher workload categories (p < 0.0001) than regular PICU patients (n = 4,881) admitted in 2019. The comparison of the characteristics of the eight Swiss PICUs shows that they were confronted by different organizational issues arising from temporary regulations put in place by the federal council. These general regulations had different consequences for the eight individual PICUs due to the differences between the PICUs. In addition, the temporal relationship of these different regulations influenced the available PICU resources, dependent on the characteristics of the individual PICUs. As pandemic continues, reflecting and learning from experience is essential to reduce workload, optimize bed occupancy and manage resources in each individual PICU. In a small country as Switzerland, with a relatively decentralized health care local differences between PICUs are considerable and should be taken into account when making policy decisions.
RIBEYE B-Domain Is Essential for RIBEYE A-Domain Stability and Assembly of Synaptic Ribbons

Synaptic ribbons are presynaptic specializations that define eponymous ribbon synapses. Synaptic ribbons are largely composed of RIBEYE, a protein containing an N-terminal A-domain and a carboxyterminal B-domain that is identical with CtBP2, a NAD(H)-binding transcriptional co-repressor. Previously we showed that synaptic ribbons are completely absent in RIBEYE knockout mice in which the RIBEYE A-domain-encoding exon had been deleted, but CtBP2 is still made, demonstrating that the A-domain is required for synaptic ribbon assembly. In the present study, we asked whether the RIBEYE B-domain also has an essential role in the assembly of synaptic ribbons. For this purpose, we made use of RIBEYE knockin mice in which the RIBEYE B-domain was replaced by a fluorescent protein domain, whereas the RIBEYE A-domain was retained unchanged. We found that replacing the RIBEYE B-domain with a fluorescent protein module destabilizes the resulting hybrid protein and causes a complete loss of synaptic ribbons. Our results thus demonstrate an essential role of the RIBEYE B-domain in enabling RIBEYE assembly into synaptic ribbons, reinforcing the notion that RIBEYE is the central organizer of synaptic ribbons.
Changes in Loss Sensitivity During Treatment in Concurrent Disorders Inpatients: A Computational Model Approach to Assessing Risky Decision-Making

Background Recent studies have employed computational modeling to characterize deficits in aspects of decision-making not otherwise detected using traditional behavioral task outcomes. While prospect utility-based modeling has shown to differentiate decision-making patterns between users of different drugs, its relevance in the context of treatment has yet to be examined. This study investigated model-based decision-making as it relates to treatment outcome in inpatients with co-occurring mental health and substance use disorders. Methods 50 patients (Mage = 38.5, SD = 11.4; 16F) completed the Cambridge Gambling Task (CGT) within 2 weeks of admission (baseline) and 6 months into treatment (follow-up), and 50 controls (Mage = 31.9, SD = 10.0; 25F) completed CGT under a single outpatient session. We evaluated 4 traditional CGT outputs and 5 decisional processes derived from the Cumulative Model. Psychiatric diagnoses and discharge data were retrieved from patient health records. Results Groups were similar in age, sex, and premorbid IQ. Differences in years of education were included as covariates across all group comparisons. All patients had ≥1 mental health diagnosis, with 80% having >1 substance use disorder. On the CGT, patients showed greater Deliberation Time and Delay Aversion than controls. Estimated model parameters revealed higher Delayed Reward Discounting, and lower Probability Distortion and Loss Sensitivity in patients relative to controls. From baseline to follow-up, patients (n = 24) showed a decrease in model-derived Loss Sensitivity and Color Choice Bias. Lastly, poorer Quality of Decision-Making and Choice Consistency, and greater Color Choice Bias independently predicted higher likelihood of treatment dropout, while none were significant in relation to treatment length of stay. Conclusion This is the first study to assess a computational model of decision-making in the context of treatment for concurrent disorders. Patients were more impulsive and slower to deliberate choice than controls. While both traditional and computational outcomes predicted treatment adherence in patients, findings suggest computational methods are able to capture treatment-sensitive aspects of decision-making not accessible via traditional methods. Further research is needed to confirm findings as well as investigate the relationship between model-based decision-making and post-treatment outcomes.
Diversity of Dysregulated Long Non-Coding RNAs in HBV-Related Hepatocellular Carcinoma

Infection with the hepatitis B virus (HBV) continues to pose a major threat to public health as approximately 292 million people worldwide are currently living with the chronic form of the disease, for which treatment is non-curative. Chronic HBV infections often progress to hepatocellular carcinoma (HCC) which is one of the world’s leading causes of cancer-related deaths. Although the process of hepatocarcinogenesis is multifaceted and has yet to be fully elucidated, several studies have implicated numerous long non-coding RNAs (lncRNAs) as contributors to the development of HCC. These host-derived lncRNAs, which are often dysregulated as a consequence of viral infection, have been shown to function as signals, decoys, guides, or scaffolds, to modulate gene expression at epigenetic, transcriptional, post-transcriptional and even post-translational levels. These lncRNAs mainly function to promote HBV replication and oncogene expression or downregulate tumor suppressors. Very few lncRNAs are known to suppress tumorigenesis and these are often downregulated in HCC. In this review, we describe the mechanisms by which lncRNA dysregulation in HBV-related HCC promotes tumorigenesis and cancer progression.
Mediating Effect of Body Mass Index and Dyslipidemia on the Relation of Uric Acid and Type 2 Diabetes: Results From China Health and Retirement Longitudinal Study

Objective This study assessed temporal relationships of serum uric acid (SUA) with blood glucose and determine the mediating effects of body mass index (BMI) and dyslipidemia on the relation of SUA and risk of type 2 diabetes. Methods Participants aged ≥ 45 years were participated in 2011 and followed up until 2015. Cox proportional hazards regression with a robust variance estimator was performed to explore the association of SUA with the risk of diabetes, and crosslagged path analysis was introduced to examine the temporal relationships between SUA and blood glucose. A mediation analysis was finally used to identify the mediating effect of BMI and dyslipidemia on the relation of SUA and the future risk of diabetes. Results A total of 9,020 participants were included with an average age of 58.59 years at baseline in 2011, and 53.6% of them were women. Linear dose–response relationship was identified by restricted spline cubic analysis between baseline SUA and follow-up blood glucose (the non-linear trend for fasting plasma glucose (FPG): β2 = −0.71, p = 0.52; for HbA1c: β2 = 0.05, p = 0.07; for risk of diabetes: β2 = 0.12, p = 0.39). Additionally, compared with the lowest quartiles of SUA, the adjusted risk ratios of diabetes were 1.00 (95% CI: 0.82–1.23), 1.08 (95% CI: 0.89–1.31), and 1.37 (95% CI: 1.11–1.96) for quartile 2–4 (p-trend < 0.01), respectively. Further additional adjustments for BMI or dyslipidemia, these ratios were not statistically significant. In addition, a unidirectional relationship from baseline SUA to follow-up FPG (ρ1 = 0.24, p = 0.03) was further confirmed using crosslagged path analysis. After stratifying by genders, the above results were only significant in the women subgroup, and we thus conducted a mediation analysis in women and found that the BMI and dyslipidemia partially mediated the effect of SUA on diabetes with a 23.05 and 18.82% mediating effect, respectively. Conclusions These findings provide strong evidence that hyperuricemia preceded diabetes, and the effect of baseline SUA on follow-up type 2 diabetes was more pronounced among middle-aged and elderly Chinese women, especially in postmenopausal women, and this effect is partly mediated by BMI and dyslipidemia at baseline.
Plant-Derived Cell-Free Biofactories for the Production of Secondary Metabolites

Cell-free expression systems enable the production of proteins and metabolites within a few hours or days. Removing the cellular context while maintaining the protein biosynthesis apparatus provides an open system that allows metabolic pathways to be installed and optimized by expressing different numbers and combinations of enzymes. This facilitates the synthesis of secondary metabolites that are difficult to produce in cell-based systems because they are toxic to the host cell or immediately converted into downstream products. Recently, we developed a cell-free lysate derived from tobacco BY-2 cell suspension cultures for the production of recombinant proteins. This system is remarkably productive, achieving yields of up to 3 mg/mL in a one-pot in vitro transcription–translation reaction and contains highly active energy and cofactor regeneration pathways. Here, we demonstrate for the first time that the BY-2 cell-free lysate also allows the efficient production of several classes of secondary metabolites. As case studies, we synthesized lycopene, indigoidine, betanin, and betaxanthins, which are useful in the food, cosmetic, textile, and pharmaceutical industries. Production was achieved by the co-expression of up to three metabolic enzymes. For all four products, we achieved medium to high yields. However, the yield of betanin (555 μg/mL) was outstanding, exceeding the level reported in yeast cells by a factor of more than 30. Our results show that the BY-2 cell-free lysate is suitable not only for the verification and optimization of metabolic pathways, but also for the efficient production of small to medium quantities of secondary metabolites.
Impact of Body Composition on Prognosis and Dose-Limiting Toxicities on Metastatic Colorectal Cancer

Sarcopenia is a progressive skeletal muscle disease, often present in oncological patients, that is associated with multiple adverse events such as worse prognosis, physical performance, and quality of life. Body composition evaluation by CT cross-section at the L3 vertebrae region appears to be a precise method to quantify skeletal muscle. The optimal cut-off for the definition of sarcopenia is not yet established, therefore the incidence of sarcopenia varies according to different studies. The main goal was to evaluate the presence of sarcopenia in patients with metastatic colorectal cancer (mCRC) and its impact on overall survival (OS) and dose-limiting toxicities (DLT). A retrospective cohort study of 178 patients with mCRC under first-line chemotherapy (ChT) in association with target therapy, in two hospital units, between January 2015 and December 2018. Skeletal mass area (SMA) was quantified with the NIH ImageJ software in CT cross-sectional images at the L3 vertebrae region. Statistical analysis was performed with IBM SPSS v25 software https://www.ibm. com/analytics/spss-statistics-software. The median age was 62 (SD ± 11) years old, 65% were men and 62.9% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0. The cut-off value was established based on ROC analysis, with sarcopenia defined as SMI < 49.12 cm2/m2 for men and < 35.85 cm2/m2 for women. Despite the mean body mass index (BMI) of 25.71 (± 4.71) kg/m2, half of the patients presented sarcopenia. In a multivariate analysis using a Cox regression model, an association was observed between OS and higher ECOG PS (p = 0.014; HR 5.46, CI 95% [1.42–21.10]), neutrophil-to-lymphocyte ratio (NLR) >2.80 (p = 0.038; HR 2.20, CI 95% [1,05–4.62]), and sarcopenia (p = 0.01; HR 4.73, CI 95% [1.85–12.09]). Additionally, in a logistic regression model, age (p = 0.014; OR 1.09, IC 95% [1.02–1.16]) and sarcopenia (p= 0.030, OR 4.13, IC 95% [1.15-14.8]) were associated with higher incidence of DLT. The CT evaluation of the body composition at the L3 region allows for the quantification of sarcopenia, providing prognostic information and predictive value of DLT in patients with mCRC, although the establishment of optimal cut-off values are required for implementation in clinical practice. A multimodal strategy to delay muscle waste should be considered in these patients.
Apolipoprotein E Genotype Moderation of the Association Between Physical Activity and Brain Health. A Systematic Review and Meta-Analysis

Introduction Possession of one or two e4 alleles of the apolipoprotein E (APOE) gene is associated with cognitive decline and dementia risk. Some evidence suggests that physical activity may benefit carriers of the e4 allele differently. Method We conducted a systematic review and meta-analysis of studies which assessed APOE differences in the association between physical activity and: lipid profile, Alzheimer's disease pathology, brain structure and brain function in healthy adults. Searches were carried out in PubMed, SCOPUS, Web of Science and PsycInfo. Results Thirty studies were included from 4,896 papers screened. Carriers of the e4 allele gained the same benefit from physical activity as non-carriers on most outcomes. For brain activation, e4 carriers appeared to gain a greater benefit from physical activity on task-related and resting-state activation and resting-state functional connectivity compared to non-carriers. Post-hoc analysis identified possible compensatory mechanisms allowing e4 carriers to maintain cognitive function. Discussion Though there is evidence suggesting physical activity may benefit e4 carriers differently compared to non-carriers, this may vary by the specific brain health outcome, perhaps limited to brain activation. Further research is required to confirm these findings and elucidate the mechanisms.
Whole-Exome Sequencing Implicates Neuronal Calcium Channel with Familial Atrial Fibrillation

Background: Atrial Fibrillation (AF) is the most prevalent sustained cardiac arrhythmia, responsible for considerable morbidity and mortality. The heterogenic and complex pathogenesis of AF remains poorly understood, which contributes to the current limitation in effective treatments. We aimed to identify rare genetic variants associated with AF in patients with familial AF. Methods and results: We performed whole exome sequencing in a large family with familial AF and identified a rare variant in the gene CACNA1A c.5053G > A which co-segregated with AF. The gene encodes for the protein variants CaV2.1-V1686M, and is important in neuronal function. Functional characterization of the CACNA1A, using patch-clamp recordings on transiently transfected mammalian cells, revealed a modest loss-of-function of CaV2.1-V1686M. Conclusion: We identified a rare loss-of-function variant associated with AF in a gene previously linked with neuronal function. The results allude to a novel link between dysfunction of an ion channel previously associated with neuronal functions and increased risk of developing AF.
The Efficacy and Safety of Celecoxib for Pain Management After Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background This study aimed to determine the efficacy and safety of celecoxib for pain management after total knee arthroplasty (TKA). Methods PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched to identify eligible randomized controlled trials (RCTs) that compared celecoxib with a placebo in term of pain control efficacy after TKA. Primary outcomes included pain scores at 24, 48, and 72 h after TKA. Secondary outcomes included the active range of motion (ROM) at 24, 48,72 h, and 7 days postoperatively, morphine consumption over 72 h after TKA, incidence of postoperative nausea and vomiting (PONV), and total blood loss after surgery. Data analysis was conducted using RevMan version 5.3. Results Five RCTs involving 593 participants were included in the study. Compared with a placebo, celecoxib significantly reduced visual analog scale (VAS) scores at rest at 24 h [mean difference (MD) = −0.72; 95% confidence interval (CI), −1.27 to −0.17; I2 = 82%; P = 0.01], 48 h (MD = −1.51; 95% CI, −2.07 to −0.95; I2 = 0%; P < 0.00001), and 72 h (MD = −1.30; 95% CI, −2.07 to −0.54; I2 = 82%; P = 0.0009) after TKA, decreased morphine consumption over postoperative 72 h (MD = −0.73; 95% CI, −0.96 to −0.51; I2 = 96%; P < 0.00001), and increased active ROM at 48 h (MD = 13.23; 95% CI, 7.79 to 18.67; I2 = 0%; P < 0.00001), 72 h (MD = 6.52; 95% CI, 4.95 to 8.10; I2 = 68%; P < 0.00001), and 7 days (MD = 7.98; 95% CI, 3.64 to 12.31; I2 = 68%; P = 0.0003) after the operation. No significant difference was found in the active ROM at 24 h (MD = 7.60; 95% CI, −6.14 to 21.34; I2 = 94%; P = 0.28) and the incidence of PONV after surgery [risk ratio (RR) = 0.66; 95% CI, 0.40 to 1.09; I2 = 0%; P = 0.11]. Conclusion The administration of celecoxib is an effective and safe strategy for postoperative analgesia after TKA.