Miracle-dz/UniFAR-FTUs huggingface dataset:
MPK3/6‐induced degradation of ARR1/10/12 promotes salt tolerance in Arabidopsis

Cytokinins are phytohormones that regulate plant development, growth, and responses to stress. In particular, cytokinin has been reported to negatively regulate plant adaptation to high salinity; however, the molecular mechanisms that counteract cytokinin signaling and enable salt tolerance are not fully understood. Here, we provide evidence that salt stress induces the degradation of the cytokinin signaling components Arabidopsis (Arabidopisis thaliana) response regulator 1 (ARR1), ARR10 and ARR12. Furthermore, the stress‐activated mitogen‐activated protein kinase 3 (MPK3) and MPK6 interact with and phosphorylate ARR1/10/12 to promote their degradation in response to salt stress. As expected, salt tolerance is decreased in the mpk3/6 double mutant, but enhanced upon ectopic MPK3/MPK6 activation in an MKK5DD line. Importantly, salt hypersensitivity phenotypes of the mpk3/6 line were significantly alleviated by mutation of ARR1/12. The above results indicate that MPK3/6 enhance salt tolerance in part via their negative regulation of ARR1/10/12 protein stability. Thus, our work reveals a new molecular mechanism underlying salt‐induced stress adaptation and the inhibition of plant growth, via enhanced degradation of cytokinin signaling components.
Using Infodemiology Metrics to Assess Public Interest in Liver Transplantation: Google Trends Analysis

Background Liver transplantation (LT) is the only curative treatment for end-stage liver disease. Less than 10% of global transplantation needs are met worldwide, and the need for LT is still increasing. The death rates on the waiting list remain too high. Objective It is, therefore, critical to raise awareness among the public and health care providers and in turn increasingly acquire donors. Methods We performed a Google Trends search using the search terms liver transplantation and liver transplant on October 15, 2020. On the basis of the resulting monthly data, the annual average Google Trends indices were calculated for the years 2004 to 2018. We not only investigated the trend worldwide but also used data from the United Network for Organ Sharing (UNOS), Spain, and Eurotransplant. Using pairwise Spearman correlations, Google Trends indices were examined over time and compared with the total number of liver transplants retrieved from the respective official websites of UNOS, the Organización Nacional de Trasplantes, and Eurotransplant. Results From 2004 to 2018, there was a significant decrease in the worldwide Google Trends index from 78.2 in 2004 to 20.5 in 2018 (–71.2%). This trend was more evident in UNOS than in the Eurotransplant group. In the same period, the number of transplanted livers increased worldwide. The waiting list mortality rate was 31% for Eurotransplant and 29% for UNOS. However, in Spain, where there are excellent awareness programs, the Google Trends index remained stable over the years with comparable, increasing LT numbers but a significantly lower waiting list mortality (15%). Conclusions Public awareness in LT has decreased significantly over the past two decades. Therefore, novel awareness programs should be initialized.
Ecology and Function of the Transmissible Locus of Stress Tolerance in Escherichia coli and Plant-Associated Enterobacteriaceae

The transmissible locus of stress tolerance (tLST) is a genomic island comprising 10 core genes that occurs in diverse Enterobacteriaceae and confers resistance to heat and chlorine. Experimentation described in the manuscript describes the physiological function of the core genes by characterization of the resistance of 13 single-knockout (KO) mutants and by characterization of protein and membrane oxidation in these strains after chlorine challenge. ABSTRACT The transmissible locus of stress tolerance (tLST) is a genomic island which confers resistance to heat and chlorine. In this study, we determined that the tLST is frequent in genomes of those Enterobacteriaceae that occur in association with plants as well as the intestines of humans and animals and are relevant as nosocomial pathogens, e.g., Klebsiella and Cronobacter species. The tLST is more frequent in environmental and clinical isolates of Klebsiella pneumoniae than in animal isolates, and heat and chlorine resistance of tLST-positive strains of K. pneumoniae matched the resistance of tLST-positive strains of Escherichia coli. The function of 13 tLST genes was determined by assessing the heat and chlorine resistance of E. coli MG1655 mutants. The deletion of sHsp20, clpKGI, sHspGI, pscA, pscB, and hdeDGI reduced both heat and chlorine resistance; deletion of kefB reduced only chlorine resistance. Genes coding for heat shock proteins sHsp20, clpKGI, and sHspGI decreased the oxidation of cytoplasmic proteins, while kefB decreased the oxidation of membrane lipids. The fitness cost of the tLST for E. coli MG1655 was assessed by pairwise competition experiments with isogenic tLST-positive or tLST-negative strains. The tLST imposes a fitness cost that is compensated for by frequent and lethal challenges with chlorine. All core genes need to be present to maintain the ecological advantage relative to the fitness cost. Taken together, core tLST genes are necessary to provide protection for E. coli against heat and chlorine stress, and the selective pressure for the tLST maintains core genes. IMPORTANCE The transmissible locus of stress tolerance (tLST) is a genomic island comprising 10 core genes that occurs in diverse Enterobacteriaceae and confers resistance to heat and chlorine. Experimentation described in the manuscript describes the physiological function of the core genes by characterization of the resistance of 13 single-knockout (KO) mutants and by characterization of protein and membrane oxidation in these strains after chlorine challenge. Results identify tLST resistance as a genomic island that is specific for those Enterobacteriaceae that occur in plant-associated habitats as well in the intestines of vertebrates. In addition, the ecological function of the genomic island was characterized by large-scale genomic analysis and competition experiments of wild-type and mutant strains. Results suggest that tLST-mediated resistance to chlorine may contribute to the persistence of nosocomial pathogens in hospitals.
Lifelong reductions of PKMζ in ventral hippocampus of nonhuman primates exposed to early-life adversity due to unpredictable maternal care

Protein kinase Mζ (PKMζ) maintains long-term potentiation (LTP) and long-term memory through persistent increases in kinase expression. Early-life adversity is a precursor to adult mood and anxiety disorders, in part, through persistent disruption of emotional memory throughout life. Here we subjected 10- to 16-wk-old male bonnet macaques to adversity by a maternal variable-foraging demand paradigm. We then examined PKMζ expression in their ventral hippocampi as 7- to 12-yr-old adults. Quantitative immunohistochemistry reveals decreased PKMζ in dentate gyrus, CA1, and subiculum of subjects who had experienced early-life adversity due to the unpredictability of maternal care. Adult animals with persistent decrements of PKMζ in ventral hippocampus express timid rather than confrontational responses to a human intruder. Persistent down-regulation of PKMζ in the ventral hippocampus might reduce the capacity for emotional memory maintenance and contribute to the long-lasting emotional effects of early-life adversity.
The importance of health literacy for self-management: A scoping review of reviews

Objectives Self-management of chronic diseases is rather complex, especially for patients with limited health literacy. In this review, we aim to disentangle the specific difficulties patients with limited health literacy face in relation to self-management and their associated needs with respect to self-management support. Methods We performed a literature search in five databases. We used a broad definition of health literacy and self-management was categorized into four types of activities: medical management, changing lifestyle, communicating and navigating through the health care system and coping. Included reviews described the relationship between health literacy and different domains of self-management and were published after 2010. Results A total of 28 reviews were included. Some clear difficulties of patients with limited health literacy emerged, predominantly in the area of medical management (especially adherence), communication and knowledge. Other associations between health literacy and self-management were inconclusive. Barriers from the patients’ perspective described mainly medical management and the communication and navigation of the health care system. Discussion Patients with limited health literacy experience difficulties with specific domains of self-management. For a better understanding of the relationship between health literacy and self-management, a broader conceptualization of health literacy is warranted, including both cognitive and behavioural aspects.
Clinical Applications of Myelin Plasticity for Remyelinating Therapies in Multiple Sclerosis

Central nervous system demyelination in multiple sclerosis (MS) and subsequent axonal degeneration represent a major cause of clinical morbidity. Learning, salient experiences, and stimulation of neuronal activity induce new myelin formation in rodents, and in animal models of demyelination, remyelination can be enhanced via experience‐ and activity‐dependent mechanisms. Furthermore, preliminary studies in MS patients support the use of neuromodulation and rehabilitation exercises for symptomatic improvement, suggesting that these interventions may represent nonpharmacological strategies for promoting remyelination. Here, we review the literature on myelin plasticity processes and assess the potential to leverage these mechanisms to develop remyelinating therapies. ANN NEUROL 2021;90:558–567
MiR-20b-5p modulates inflammation, apoptosis and angiogenesis in severe acute pancreatitis through autophagy by targeting AKT3

Abstract Background Severe acute pancreatitis (SAP) is a common acute abdominal disease with high morbidity and mortality. However, the mechanism underlying SAP is still unclear. Methods Cerulean and LPS (Cer-LPS) was used to establish a rat model and an in vitro model of SAP. qRT-PCR, western blot and IHC were determined to analyse the expression of mRNA and proteins. IL-1β, TNF-α and IL-6 levels were measured applying ELISA. H&E staining was determined to observe the pathological changes. Apoptosis was tested by AV-PI staining using flow cytometry. CCK8 assay was taken to detect cell viability. Cell migration was assessed by transwell assay. Tube formation assay was conducted to evaluate angiogenesis. Luciferase assay was used to detect relationship of miR-20b-5p and AKT3. Results MiR-20b-5p was lowly expressed in SAP models both in vivo and in vitro. Overexpression of miR-20b-5p restrained inflammation and apoptosis in Cer-LPS treated pancreatic acinar cells. Furthermore, miR-20b-5p promoted the angiogenesis of vascular endothelial cells, since the viability, migration and the capability of tube formation were increased by miR-20b-5p. Mechanically, miR-20b-5p directly targeted AKT3 to promote autophagy. Furthermore, miR-20b-5p could prevent the inflammation, apoptosis and enhance angiogenesis via enhancing autophagy, which was verified in vivo. Conclusion This study demonstrated miR-20b-5p attenuates SAP through directly targeting AKT3 to regulate autophagy, subsequently inhibit inflammation and apoptosis, and promote angiogenesis. Our findings suggested a novel target of miR-20b-5p for the therapy of SAP.
The pharmacotherapeutic management of pulmonary tuberculosis: an update of the state-of-the-art

ABSTRACT Introduction Pulmonary tuberculosis (TB) remains an important global health challenge of the 21st century, and the emerging resistance against anti-TB drugs is still a growing concern. And while there was a significant cumulative reduction in the incidence of TB between 2015 and 2019, 2.8% of all TB cases in 2019 were reported to be drug resistant. Area covered This review provides the reader with an update on pharmacotherapy for patients with TB susceptible or resistant to drug therapy. The authors also include promising investigational drugs herein. Finally, the authors share with the reader their expert opinions on the current state of the art and their future perspectives. Expert opinion The current pharmacotherapeutic management aims to enhance favorable treatment outcomes and reduce treatment-related adverse events. One approach is to use shorter and all-oral regimens for eligible patients. Traditional longer regimens for most patients are also optimized to lower incidence of treatment failure and serious adverse events.
Use of Quantitative Vertebral Bone Marrow Fat Fraction to Assess Disease Activity and Chronicity in Patients with Ankylosing Spondylitis

Objective We quantitatively measured the fat fraction (FF) in the vertebrae of patients with ankylosing spondylitis (AS) using magnetic resonance imaging (MRI) and investigated the role of FF as an indicator of both active inflammation and chronicity. Materials and Methods A total of 52 patients with AS who underwent spinal MRI were retrospectively evaluated. The FF values of the anterosuperior and anteroinferior corners of the bone marrow in the L1-S1 spine were assessed using the modified Dixon technique. AS activity was measured using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), AS Disease Activity Score (ASDAS), and serum inflammatory marker levels. AS disease chronicity was assessed by AS disease duration and the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). Univariable and multivariable regression analyses were conducted to investigate the correlation between FF and other clinical characteristics. Results The mean FF ± standard deviation of the total lumbar spine was 43.0% ± 11.3%. At univariable analysis, spinal FF showed significant negative correlation with BASDAI (β = −0.474, p = 0.002) and ASDAS with C-reactive protein (ASDAS-CRP; β = −0.478, p = 0.002) and a significant positive correlation with AS disease duration (β = 0.440, p = 0.001). After adjusting for patient age, sex, and total mSASSS score, spinal FF remained significantly negatively correlated with BASDAI (β = −0.543, p < 0.001), ASDAS-CRP (β = −0.568, p < 0.001), and ASDAS with erythrocyte sedimentation rate (β = −0.533, p = 0.001). Spinal FF was significantly lower in patients with very high disease activity (ASDAS-CRP > 3.5) than in those with only high disease activity (2.1 ≤ ASDAS-CRP ≤ 3.5) (p = 0.010). Conclusion Spinal FF may help assess both AS disease activity and chronicity.
Functional capacity and walking speed reserve in individuals with chronic stroke: A cross-sectional study

ABSTRACT Introduction Individuals with stroke experience residual walking disabilities, as the inability to increase walking speed (walking speed reserve – WSR), and frequently present decreasing in functional capacity. The relation between functional capacity and walking ability may contribute to more specific functional management of stroke. Objective To investigate the association between WSR and functional capacity in individuals with chronic stroke and compare functional capacity between individuals who can increase walking speed or not. Methods Cross-sectional study, where functional capacity was assessed with the Duke Activity Status Index (DASI), in metabolic equivalent (METS). WSR was assessed through the difference between fast and self-selected speed (in m/s). The individuals were assigned into two groups: able (WSR ≥ 0.2 m/s) and unable (WSR<0.2 m/s) to increase speed. Pearson’s correlation and t test were used for analysis. Results Fifty-five individuals (functional capacity 23 ± 13 METS and WSR 0.3 ± 0.2 m/s) were included. The association between functional capacity and WSR was positive and statistically significant, with moderate magnitude (r = 0.56) (p < .001). Individuals who were unable to increase their walking speed have less functional capacity (17.5 versus 31.3) (p = .003). Conclusion Functional capacity has a positive association with WSR in individuals with chronic stroke. The individuals who are unable to increase walking speed present lower functional capacity.
Sodium/glucose cotransporter 2 inhibitors for the treatment of type 1 diabetes: what are the latest developments?

ABSTRACT Despite the improvements in insulin therapy, many patients with type 1 diabetes mellitus (T1DM) do not achieve glycemic targets. Hypoglycemia and weight gain are important barriers in reaching these targets. Sodium/glucose cotransporter 2 (SGLT2) inhibitors lack these side effects and have an insulin-independent mechanism of action. Therefore, they might be useful in patients with T1DM. The authors discuss the safety and efficacy of SGLT2 inhibitors in T1DM. Several randomized controlled trials have evaluated dapagliflozin, sotagliflozin and empagliflozin in this population whereas fewer data are available for other members of this class. In these studies, SGLT2 inhibitors reduced HbA1c levels and body weight without a greater risk of hypoglycemia. However, a higher incidence of diabetic ketoacidosis (DKA) was observed in patients treated with these agents. SGLT2 inhibitors improve glycemic control in patients with T1DM but this effect is modest. Even though weight loss and the neutral effect on the incidence of hypoglycemia are advantages of these agents, the increased risk of DKA is a cause of concern. Overall, SGLT2 inhibitors should be used with caution and only in carefully selected patients with T1DM who are motivated, adherent to treatment, well-trained in recognizing DKA and are closely followed-up.
High historical variability weakens the effects of current climate differentiation on microbial community dissimilarity and assembly

Understanding the influences of global climate change on soil microbial communities is essential in evaluating the terrestrial biosphere's feedback to this alarming anthropogenic disturbance. However, little is known about how intra‐site historical climate variability can mediate the influences of current climate differences on community dissimilarity and assembly. To fill this gap, we examined and disentangled the interactive effects of historical climate variability and current climate differences on the soil bacterial community dissimilarity and stochasticity of community assembly among 143 sites from 28 forests across eastern China. We hypothesize that the relative importance of stochasticity and community dissimilarity are related to historical climate variability and that an increasing sum of intra‐site historical variability enhances stochasticity while reduces dissimilarity between two communities. To test our hypothesis, we statistically controlled for covariates between sites including differences in soil chemistry, plant diversity, spatial distance, and seasonal climate variations at annual timescales. We observed that an increase in inter‐site current climate differences led to a reduced impact of stochasticity in community assembly and a pronounced divergence between communities. In stark contrast, when communities were subjected to a high level of intra‐site historical climate fluctuation, the observed impact incurred from current climate differences was substantially weakened. Moreover, the influence of increased historical variability was consistent along the gradient of current temperature differences between sites. However, effects induced by historical fluctuation in precipitation were disproportional and only evident when small inter‐site differences were observed. Consequently, if the prior climate variability is ignored, especially regarding environmental factors like temperature, we assert that the influence current climate differentiation has on regulating community dissimilarity and assembly stochasticity will be underestimated. Together, our findings highlight the importance and need of explicitly controlling the mean and the historical variability of climate factors for the next “generation” of climate change experiments to come.
Mothers' Experiences with Antenatal Milk Expression

Abstract Background: Antenatal milk expression is a milk expression intervention beginning at either 36 or 37 weeks of gestation for the purpose of potential colostrum collection and storage prior to birth for postnatal infant feeding. Research on antenatal milk expression is limited and originates outside the United States. Methods: Women who used antenatal milk expression were interviewed about their experiences. A conventional, inductive approach to qualitative content analysis was used to analyze participants' responses. Results: Three women participated in interviews. They reported learning and performing antenatal milk expression for various postpartum needs including avoidance of formula, milk available for potential infant hypoglycemia, and to support human milk feeding during surrogate mother–infant separation. These mothers obtained education and information on antenatal milk expression primarily on their own. Clinical Implications: Greater awareness and understanding of antenatal milk expression is needed in the professional community caring for childbearing women. Perinatal nurses need to be aware of all breastfeeding practices including antenatal milk expression. Knowledge of the practice and advocacy for more research on antenatal milk expression will improve lactation support and ensure expectant mothers reach their personal breastfeeding goals. Antenatal milk expression may be a way to avoid formula supplementation for infants with hypoglycemia after birth, but more data are needed on efficacy, safety, and outcomes for mothers and babies. In this study women who practiced antenatal milk expression share their rationale and experiences.
Association of EEG-fMRI Responses and Outcome After Epilepsy Surgery

Background and Objectives To assess the utility of EEG-fMRI for epilepsy surgery, we evaluated surgical outcome in relation to the resection of the most significant EEG-fMRI response. Methods Patients with postoperative neuroimaging and follow-up of at least 1 year were included. In EEG-fMRI responses, we defined as primary the cluster with the highest absolute t value located in the cortex and evaluated 3 levels of confidence for the results. The threshold for low confidence was t ≥ 3.1 (p < 0.005); the one for medium confidence corresponded to correction for multiple comparisons with a false discovery rate of 0.05; and a result reached high confidence when the primary cluster was much more significant than the next highest cluster. Concordance with the resection was determined by comparison to postoperative neuroimaging. Results We evaluated 106 epilepsy surgeries in 84 patients. An increasing association between concordance and surgical outcome with higher levels of confidence was demonstrated. If the peak response was not resected, the surgical outcome was likely to be poor: for the high confidence level, no patient had a good outcome; for the medium and low levels, only 18% and 28% had a good outcome. The positive predictive value remained low for all confidence levels, indicating that removing the maximum cluster did not ensure seizure freedom. Discussion Resection of the primary EEG-fMRI cluster, especially in high confidence cases, is necessary to obtain a good outcome but not sufficient. Classification of Evidence This study provides Class II evidence that failure to resect the primary EEG-fMRI cluster is associated with poorer epilepsy surgery outcomes.