Miracle-dz/UniFAR-FTUs huggingface dataset:
Autophagy-deficient Arabidopsis mutant atg5, which shows ultraviolet-B sensitivity, cannot remove ultraviolet-B-induced fragmented mitochondria

Mitochondria damaged by ultraviolet-B radiation (UV-B, 280-315 nm) are removed by mitophagy, a selective autophagic process. Recently, we demonstrated that autophagy-deficient Arabidopsis thaliana mutants exhibit a UV-B-sensitive phenotype like that of cyclobutane pyrimidine dimer (CPD)-specific photolyase (PHR1)-deficient mutants. To explore the relationship between UV-B sensitivity and autophagy in UV-B-damaged plants, we monitored mitochondrial dynamics and autophagy in wild-type Arabidopsis (ecotype Columbia); an autophagy-deficient mutant, atg5; a PHR1-deficient mutant, phr1; an atg5 phr1 double mutant; and AtPHR1-overexpressing (AtPHR1ox) plants following high-dose UV-B exposure (1.5 W m-2 for 1 h). At 10 h after exposure, the number of mitochondria per mesophyll leaf cell was increased and the volumes of individual mitochondria were decreased independently of UV-B-induced CPD accumulation in all genotypes. At 24 h after exposure, the mitochondrial number had recovered or almost recovered to pre-exposure levels in plants with functional autophagy (WT, phr1, and AtPHR1ox), but had increased even further in atg5. This suggested that the high dose of UV-B led to the inactivation and fragmentation of mitochondria, which were removed by mitophagy activated by UV-B. The UV-B-sensitive phenotype of the atg5 phr1 double mutant was more severe than that of atg5 or phr1. In wild-type, phr1, and AtPHR1ox plants, autophagy-related genes were strongly expressed following UV-B exposure independently of UV-B-induced CPD accumulation. Therefore, mitophagy might be one of the important repair mechanisms for UV-B-induced damage. The severe UV-B-sensitive phenotype of atg5 phr1 is likely an additive effect of deficiencies in independent machineries for UV-B protection, autophagy, and CPD photorepair.
Is the Mean Platelet Volume a Predictive Factor for Atrial Fibrillation Developing After Coronary Artery Bypass Grafting in Elderly Patients?

BACKGROUND Postoperative atrial fibrillation (PoAF) is the most common arrhythmic complication detected after coronary artery bypass grafting (CABG). It is associated with increased morbidity and mortality, especially in elderly patients. Mean platelet volume (MPV) shows the activation of platelets effective in the inflammatory and thrombotic process. The purpose of the present study was to investigate the relations between the preoperative MPV levels and development of PoAF in isolated CABG in elderly patients. METHODS A total of 103 elderly patients (aged ≥ 65 years), who underwent isolated CABG and were at preoperative sinus rhythm, were included in the study. Patients who did not have PoAF were identified as Group 1 (N = 74), and those with PoAF were identified as Group 2 (N = 29). RESULTS PoAF incidence was 28.2%. Preoperative MPV level was 8.41 ± 1.13 fL in Group 1, and 9.28 ± 1.00 fL in Group 2. The difference was statistically significant (P < .001). Multivariate logistic regression analysis revealed that age, preoperative hemoglobin, and preoperative MPV were independent predictive factors for PoAF development (OR [odds ratio]: 1.149, 95% CI [confidence interval]: 1.043-1.265, P = .005; OR: 1.334, 95% CI: 1.013-1.758, P = .040; OR: 2.103, 95% CI: 1.324-3.339, P = .002, respectively). The cut-off value for MPV as the predictor of PoAF development was found to be 8.43 (sensitivity: 82.8% and specificity: 55.4%). CONCLUSION This study showed that MPV levels are associated with PoAF development in elderly patients, and other independent predictive factors include age and preoperative hemoglobin levels for POAF development.
Comparing Mortality of Peritoneal and Hemodialysis Patients in an Era of Medicare Payment Reform

Supplemental Digital Content is available in the text. Background: Prior studies have shown peritoneal dialysis (PD) patients to have lower or equivalent mortality to patients who receive in-center hemodialysis (HD). Medicare’s 2011 bundled dialysis prospective payment system encouraged expansion of home-based PD with unclear impacts on patient outcomes. This paper revisits the comparative risk of mortality between HD and PD among patients with incident end-stage kidney disease initiating dialysis in 2006–2013. Research Design: We conducted a retrospective cohort study comparing 2-year all-cause mortality among patients with incident end-stage kidney disease initiating dialysis via HD and PD in 2006–2013, using data from the US Renal Data System and Medicare. Analysis was conducted using Cox proportional hazards models fit with inverse probability of treatment weighting that adjusted for measured patient demographic and clinical characteristics and dialysis market characteristics. Results: Of the 449,652 patients starting dialysis between 2006 and 2013, the rate of PD use in the first 90 days increased from 9.3% of incident patients in 2006 to 14.2% in 2013. Crude 2-year mortality was 27.6% for patients dialyzing via HD and 16.7% for patients on PD. In adjusted models, there was no evidence of mortality differences between PD and HD before and after bundled payment (hazard ratio, 0.96; 95% confidence interval, 0.89–1.04; P=0.33). Conclusions: Overall mortality for HD and PD use was similar and mortality differences between modalities did not change before versus after the 2011 Medicare dialysis bundled payment, suggesting that increased use of home-based PD did not adversely impact patient outcomes.
Metastatic site discriminates survival benefit of primary tumor surgery for differentiated thyroid cancer with distant metastases

Abstract The role of primary tumor surgery in the management of differentiated thyroid cancer (DTC) with distant metastases (DM) remains controversial. We aimed to explore the survival benefit of primary tumor surgery in patients with different metastatic sites. A retrospective cohort study based on the SEER database was conducted to identify DTC patients with DM diagnosed between 2010 and 2016. Patients were divided into following 2 groups: surgery and non-surgery group. Propensity score weighting was employed to balance clinicopathologic factors between the 2 groups. Of 3537 DTC patients with DM, 956 (66.0%) patients underwent primary tumor surgery while 493 (34.0%) patients did not. There were 798 all-cause deaths and 704 DTC-specific deaths over a median follow-up of 22 months. The weighted 3-year overall survival (OS) for the surgery group was 55.2%, compared to 27.8% (P < .001) for the non-surgery group. The magnitude of the survival difference of surgery was significantly correlated with metastatic sites (Pinteraction <.001). Significant survival improvements in surgery group compared with non-surgery group were observed in patients with lung-only metastasis (adjusted HR = 0.45, P < .001), bone-only metastasis (adjusted HR = 0.40, P < .001), and liver-only metastasis (adjusted HR = 0.27, P < .001), whereas no survival improvement of surgery was found for patients with brain-only metastasis (adjusted HR = 0.57, P = .059) or multiply organ distant metastases (adjusted HR = 0.81, P = .099). The survival benefit from primary tumor surgery for DTC patients with DM varies by metastatic sites. Decisions for primary tumor surgery of DTC patients with DM should be tailored according to metastatic sites.
D-glucose overflow metabolism in an evolutionary engineered high-performance D-xylose consuming Saccharomyces cerevisiae strain

ABSTRACT Co-consumption of D-xylose and D-glucose by Saccharomyces cerevisiae is essential for cost-efficient cellulosic bioethanol production. There is a need for improved sugar conversion rates to minimize fermentation times. Previously, we have employed evolutionary engineering to enhance D-xylose transport and metabolism in the presence of D-glucose in a xylose-fermenting S. cerevisiae strain devoid of hexokinases. Re-introduction of Hxk2 in the high performance xylose-consuming strains restored D-glucose utilization during D-xylose/D-glucose co-metabolism, but at rates lower than the non-evolved strain. In the absence of D-xylose, D-glucose consumption was similar to the parental strain. The evolved strains accumulated trehalose-6-phosphate during sugar co-metabolism, and showed an increased expression of trehalose pathway genes. Upon the deletion of TSL1, trehalose-6-phosphate levels were decreased and D-glucose consumption and growth on mixed sugars was improved. The data suggest that D-glucose/D-xylose co-consumption in high-performance D-xylose consuming strains causes the glycolytic flux to saturate. Excess D-glucose is phosphorylated enters the trehalose pathway resulting in glucose recycling and energy dissipation, accumulation of trehalose-6-phosphate which inhibits the hexokinase activity, and release of trehalose into the medium.
Variability in the Content of Phenolic Compounds in Plum Fruit

The aim of this study was to determine the composition and content of phenolic compounds in extracts of plum fruit. Fruit of 17 plum cultivars were analyzed. Fruit samples were collected in 2019 from fruit trees with “Myrobalan” (P. cerasifera Ehrh.) and “Wangenheim Prune” (P. domestica L.) rootstocks. The following glycosides of the flavonol group were identified: avicularin, isorhamnetin-3-O-rutinoside, isoquercitrin, hyperoside, rutin, and an aglycone quercetin. Compounds of the flavan-3-ol group were identified, such as (+)-catechin, procyanidin C1, and procyanidin A2, along with chlorogenic acid attributed to phenolic acids and a non-phenolic cyclitol–quinic acid. Of all the analytes identified in plum fruit samples, quinic acid predominated, while chlorogenic acid predominated among all the identified phenolic compounds, and rutin predominated in the flavonol group. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) revealed that fruit samples of “Kubanskaya Kometa”, “Zarechnaya Raniaya”, “Duke of Edinburgh”, “Jubileum”, and “Favorita del Sultano” cultivars had different quantitative content of phenolic compounds from that observed in other samples. The highest total amount of phenolic compounds was found in the European plum samples of the “Zarechnaya Rannyaya” cultivar, while the amount of quinic acid was the highest in plum fruit samples of the “Jubileum” cultivar.
Recent Advances on Ultrasound Contrast Agents for Blood-Brain Barrier Opening with Focused Ultrasound

The blood-brain barrier is the primary obstacle to efficient intracerebral drug delivery. Focused ultrasound, in conjunction with microbubbles, is a targeted and non-invasive way to disrupt the blood-brain barrier. Many commercially available ultrasound contrast agents and agents specifically designed for therapeutic purposes have been investigated in ultrasound-mediated blood-brain barrier opening studies. The new generation of sono-sensitive agents, such as liquid-core droplets, can also potentially disrupt the blood-brain barrier after their ultrasound-induced vaporization. In this review, we describe the different compositions of agents used for ultrasound-mediated blood-brain barrier opening in recent studies, and we discuss the challenges of the past five years related to the optimal formulation of agents.
Purification and Biochemical Characterization of a New Protease Inhibitor from Conyza dioscoridis with Antimicrobial, Antifungal and Cytotoxic Effects

The main objective of the current study was the extraction, purification, and biochemical characterization of a protein protease inhibitor from Conyza dioscoridis. Antimicrobial potential and cytotoxic effects were also examined. The protease inhibitor was extracted in 0.1 M phosphate buffer (pH 6–7). Then, the protease inhibitor, named PDInhibitor, was purified using ammonium sulfate precipitation followed by filtration through a Sephadex G-50 column and had an apparent molecular weight of 25 kDa. The N-terminal sequence of PDInhibitor showed a high level of identity with those of the Kunitz family. PDInhibitor was found to be active at pH values ranging from 5.0 to 11.0, with maximal activity at pH 9.0. It was also fully active at 50 °C and maintained 90% of its stability at over 55 °C. The thermostability of the PDInhibitor was clearly enhanced by CaCl2 and sorbitol, whereas the presence of Ca2+ and Zn2+ ions, Sodium taurodeoxycholate (NaTDC), Sodium dodecyl sulfate (SDS), Dithiothreitol (DTT), and β-ME dramatically improved the inhibitory activity. A remarkable affinity of the protease inhibitor with available important therapeutic proteases (elastase and trypsin) was observed. PDInhibitor also acted as a potent inhibitor of commercial proteases from Aspergillus oryzae and of Proteinase K. The inhibitor displayed potent antimicrobial activity against gram+ and gram- bacteria and against fungal strains. Interestingly, PDInhibitor affected several human cancer cell lines, namely HCT-116, MDA-MB-231, and Lovo. Thus, it can be considered a potentially powerful therapeutic agent.
Phenotypic Characterization and Transformation Attempts Reveal Peculiar Traits of Xylella fastidiosa Subspecies pauca Strain De Donno

Xylella fastidiosa subsp. pauca strain De Donno has been recently identified as the causal agent of a severe disease affecting olive trees in a wide area of the Apulia Region (Italy). While insights on the genetics and epidemiology of this virulent strain have been gained, its phenotypic and biological traits remained to be explored. We investigated in vitro behavior of the strain and compare its relevant biological features (growth rate, biofilm formation, cell–cell aggregation, and twitching motility) with those of the type strain Temecula1. The experiments clearly showed that the strain De Donno did not show fringe on the agar plates, produced larger amounts of biofilm and had a more aggregative behavior than the strain Temecula1. Repeated attempts to transform, by natural competence, the strain De Donno failed to produce a GFP-expressing and a knockout mutant for the rpfF gene. Computational prediction allowed us to identify potentially deleterious sequence variations most likely affecting the natural competence and the lack of fringe formation. GFP and rpfF- mutants were successfully obtained by co-electroporation in the presence of an inhibitor of the type I restriction–modification system. The availability of De Donno mutant strains will open for new explorations of its interactions with hosts and insect vectors.
The Role of the Persistent Sodium Current in Epilepsy

Voltage-gated sodium channels (VGSCs) are foundational to excitable cell function: Their coordinated passage of sodium ions into the cell is critical for the generation and propagation of action potentials throughout the nervous system. The classical paradigm of action potential physiology states that sodium passes through the membrane only transiently (1-2 milliseconds), before the channels inactivate and cease to conduct sodium ions. However, in reality, a small fraction of the total sodium current (1%-2%) remains at steady state despite prolonged depolarization. While this persistent sodium current (INaP) contributes to normal physiological functioning of neurons, accumulating evidence indicates a particularly pathogenic role for an elevated INaP in epilepsy (reviewed previously 1 ). Due to significant advances over the past decade of epilepsy research concerning the importance of INaP in sodium channelopathies, this review seeks to summarize recent evidence and highlight promising novel anti-seizure medication strategies through preferentially targeting INaP.
90Y Radiosynovectomy in Persistent Synovitis Caused by Knee Replacement

Introduction After knee replacement, therapy resistant, persistent synovitis is a common issue, which causes effusion and pain, and leads to loosing. It has been hypothesized that radiosynovectomy (RSO) is useful in these patients. Materials and Methods A cohort of 55 patients with 57 knee replacements and persistent synovitis underwent RSO using 4.9 ± 0.24 mCi (182 ± 9 MBq) of 90Y-citrate. The number of RSOs ranged from 1 to 4. Bone scans before and 3 months after every RSO were performed. Long-term follow-up ranged from 0.8 to 7.6 years with a mean of 23.2 months. For qualitative analysis, an established 4 steps scoring was used. For quantification, the uptake was determined within the 99mTc-MDP scintigraphy blood pool phase before and after therapy. Results Long-term response was in 27% with excellent, 24% good, 30% weak, and 20% no response. The duration of response was 12.0 ± 12.0 months (maximum, 54 months). In patients with repeated treatment, the effect after the first therapy was lesser than in patients who received a single treatment in total. However, 3 months after the last RSO, patients with repeated treatment showed a similar effectiveness than single treated patients. At the end of long-term follow-up, patients with repeated RSOs had a higher effectiveness at similar duration response. In bone scan, 65% of patients showed a reduction of uptake. When comparing subjective and objective response, 78% of patients showed a concordance in both symptoms and scintigraphy. Pilot histological analysis revealed that the synovitis is triggered by small plastic particles. Conclusions We concluded that RSO is an effective therapy in patients with knee replacement and persistent synovitis with high long-term response. Repeated treatment leads to a stronger long-time response.
Ketamine for the treatment of prehospital acute pain: a systematic review of benefit and harm

Background Few publications have addressed prehospital use of ketamine in analgesic doses. We aimed to assess the effect and safety profile of ketamine compared with other analgesic drugs (or no drug) in adult prehospital patients with acute pain. Methods A systematic review of clinical trials assessing prehospital administration of ketamine in analgesic doses compared with other analgesic drugs or no analgesic treatment in adults. We searched PubMed, EMBASE, Cochrane Library and Epistemonikos from inception until 15 February 2020, including relevant articles in English and Nordic languages. We used the Cochrane and Grading of Recommendations Assessment, Development and Evaluation methodologies and exclusively assessed patient-centred outcomes. Two independent authors screened trials for eligibility, extracted data and assessed risk of bias. Results We included eight studies (2760 patients). Ketamine was compared with various opioids given alone, and intranasal ketamine given with nitrous oxide was compared with nitrous oxide given alone. Four randomised controlled trials (RCTs) and one cluster randomised trial included 699 patients. One prospective cohort included 27 patients and two retrospective cohorts included 2034 patients. Five of the eight studies had high risks of bias. Pain score with ketamine is probably lower than after opioids as demonstrated in a cluster-RCT (308 patients) and a retrospective cohort (158 patients) study, Δvisual analogue scale −0.4 (−0.8 to 0.0) and Δnumeric pain rating scale −3.0 (−3.86 to −2.14), respectively. Ketamine probably leads to less nausea and vomiting (risk ratio (RR) 0.24 (0.11 to 0.52)) but more agitation (RR 7.81 (1.85 to 33)) than opioids. Conclusions This systematic literature review finds that ketamine probably reduces pain more than opioids and with less nausea and vomiting but higher risk of agitation. Risk of bias in included studies is high. Other Scandinavian society of anaesthesiology and intensive care medicine funded meetings and software. The Norwegian Air Ambulance Foundation funded publication. Otherwise this research received no grant from any agency in the public, commercial or not-for-profit sectors. PROSPERO registration number CRD42018114399.
Postsynaptic cAMP signalling regulates the antagonistic balance of Drosophila glutamate receptor subtypes

ABSTRACT The balance among different subtypes of glutamate receptors (GluRs) is crucial for synaptic function and plasticity at excitatory synapses. However, the mechanisms balancing synaptic GluR subtypes remain unclear. Herein, we show that the two subtypes of GluRs (A and B) expressed at Drosophila neuromuscular junction synapses mutually antagonize each other in terms of their relative synaptic levels and affect subsynaptic localization of each other, as shown by super-resolution microscopy. Upon temperature shift-induced neuromuscular junction plasticity, GluR subtype A increased but subtype B decreased with a timecourse of hours. Inhibition of the activity of GluR subtype A led to imbalance of GluR subtypes towards more GluRIIA. To gain a better understanding of the signalling pathways underlying the balance of GluR subtypes, we performed an RNA interference screen of candidate genes and found that postsynaptic-specific knockdown of dunce, which encodes cAMP phosphodiesterase, increased levels of GluR subtype A but decreased subtype B. Furthermore, bidirectional alterations of postsynaptic cAMP signalling resulted in the same antagonistic regulation of the two GluR subtypes. Our findings thus identify a direct role of postsynaptic cAMP signalling in control of the plasticity-related balance of GluRs. Summary: The antagonistic balance of GluR subtypes, which is associated with synaptic plasticity, is regulated by cAMP signalling in postsynaptic muscles of Drosophila NMJ synapses.
From 2D to 4D Phase‐Contrast MRI in the Neurovascular System: Will It Be a Quantum Jump or a Fancy Decoration?

Considering the crosstalk between the flow and vessel wall, hemodynamic assessment of the neurovascular system may offer a well‐integrated solution for both diagnosis and management by adding prognostic significance to the standard CT/MR angiography. 4D flow MRI or time‐resolved 3D velocity‐encoded phase‐contrast MRI has long been promising for the hemodynamic evaluation of the great vessels, but challenged in clinical studies for assessing intracranial vessels with small diameter due to long scan times and low spatiotemporal resolution. Current accelerated MRI techniques, including parallel imaging with compressed sensing and radial k‐space undersampling acquisitions, have decreased scan times dramatically while preserving spatial resolution. 4D flow MRI visualized and measured 3D complex flow of neurovascular diseases such as aneurysm, arteriovenous shunts, and atherosclerotic stenosis using parameters including flow volume, velocity vector, pressure gradients, and wall shear stress. In addition to the noninvasiveness of the phase contrast technique and retrospective flow measurement through the wanted windows of the analysis plane, 4D flow MRI has shown several advantages over Doppler ultrasound or computational fluid dynamics. The evaluation of the flow status and vessel wall can be performed simultaneously in the same imaging modality. This article is an overview of the recent advances in neurovascular 4D flow MRI techniques and their potential clinical applications in neurovascular disease.