Miracle-dz/UniFAR-FTUs huggingface dataset:
Is simplification of immunosuppressive medication a way to promote medication adherence of kidney transplant recipients? Findings from a randomized controlled trial

After kidney transplantation, a strict immunosuppressive medication regimen is necessary for graft survival. However, nonadherence to medication has been shown to occur early after transplantation and to increase over time. Weaning the recipient off dual therapy onto monotherapy in order to reduce immunosuppressive burden may also be a way to promote adherence, although little is known about the impact of such a regimen on fear of rejection. We performed a cohort study on medication adherence and fear of rejection in a randomized, investigator‐driven, open‐label, single‐centre pilot study. Recipients were randomized at 6‐months post‐transplant to either continue Tacrolimus and Mycophenolate mofetil (TAC/MMF) or to taper MMF at 6 months and discontinue MMF at 9 months (TAC monotherapy). Recipients completed questionnaires about medication adherence and fear of rejection at 6 and 12‐months post‐transplantation. Medication adherence was significantly higher in the TAC monotherapy group compared to dual TAC/MMF therapy group (χ2 (1) = 4.582; P = 0.032). We found no difference in fear of rejection between the two groups of recipients (P = 0.887). Simplification of the medication regimen is a potential tool for increasing adherence in clinical practice (Netherlands Trial Register – NL4672).
Lipid droplet structural remodeling in adipose tissue upon caloric excess

Excess calories are stored as triacylglycerols (TAG) and cholesteryl esters (CE) in lipid droplets (LD), and during obesity, LD expansion occurs. X-ray scattering of adipose tissue uncovered that LDs comprise two TAG packing domains: a disordered core and a multilamellar shell. The number of TAG layers increases upon diet-induced obesity and is adipose depot-specific. Further, collagen was highly oriented in brown but randomly dispersed in white fat. We discovered that the body’s surfactant, bile acids (BAs) stimulate remodeling of LD size. Deleting the BA receptor, Farnesoid X receptor (FXR) reduced a hydrophilic BA, β muricholic acid (β-MCA), and enlarged the adipocytes. BA composition is a critical determinant of overall hydrophobicity index and solubilization ability. Accordingly, we found that the obesogenic diet reduced a hydrophobic BA, chenodeoxycholic acid (CDCA). Taken together, these findings implicate that BAs, tissue niches, and diet influence LD structural remodeling. Summary Lipid droplets (LDs) pack triacylglycerols (TAGs) with altered dimensions and exhibit distinct collagen orientation between the white and brown fat depots and are remodeled by bile acids (BAs) such that deletion of BA-receptor, Farnesoid X receptor (FXR) results in adipocyte hypertrophy.
Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption

COVID-19 patients transmitted SARS-CoV-2 to minks in the Netherlands in April 2020. Subsequently, the mink-associated virus (miSARS-CoV-2) spilled back over into humans. Genetic sequences of the miSARS-CoV-2 identified a new genetic variant known as “Cluster 5” that contained mutations in the spike protein. However, the functional properties of these “Cluster 5” mutations have not been well established. In this study, we found that the Y453F mutation located in the RBD domain of miSARS-CoV-2 is an adaptive mutation that enhances binding to mink ACE2 and other orthologs of Mustela species without compromising, and even enhancing, its ability to utilize human ACE2 as a receptor for entry. Structural analysis suggested that despite the similarity in the overall binding mode of SARS-CoV-2 RBD to human and mink ACE2, Y34 of mink ACE2 was better suited to interact with a Phe rather than a Tyr at position 453 of the viral RBD due to less steric clash and tighter hydrophobic-driven interaction. Additionally, the Y453F spike exhibited resistance to convalescent serum, posing a risk for vaccine development. Thus, our study suggests that since the initial transmission from humans, SARS-CoV-2 evolved to adapt to the mink host, leading to widespread circulation among minks while still retaining its ability to efficiently utilize human ACE2 for entry, thus allowing for transmission of the miSARS-CoV-2 back into humans. These findings underscore the importance of active surveillance of SARS-CoV-2 evolution in Mustela species and other susceptible hosts in order to prevent future outbreaks.
Spontaneous emergence of non-convertible cell states with CD24-High phenotype results in phenotypic heterogeneity that associates with poor prognosis in oral cancer

Cancer cells within individual tumors often exist in distinct phenotypic states contributing to intratumoral heterogeneity (ITH). However, studies on cell state dynamics among oral cancer cells are largely missing. Here, we have multiplexed phenotypic markers of putative oral-stem-like cancer cells (SLCCs) and characterized diversity among CD44-positive oral cancer cell subpopulations with respect to distinct expression of CD24 and aldehyde dehydrogenase (ALDH)-activity. Our in vitro experimental observations were explained by a Markov model where subpopulations followed two distinct patterns of spontaneous repopulation dynamics. Cells showed stochastic inter-conversions on ALDH-axis, harnessed by cancer cells to enrich ALDHHigh subpopulations in response to Cisplatin treatment. However, these cells followed a strict non-interconvertible transition of CD24Low to CD24High subpopulations, even in response to chemotherapy-induced stress. Using phenotype-specific RNAseq, we suggest the organization of subpopulations into hierarchical structure with possible maintenance of intermediate alternate states of stemness within the differentiating oral cancer cells. We also show that the population dynamics described here may influence tumor behaviour by increasing ITH in aggressive oral tumors. Overall, the described phenotypic subgroups not only reliably exhibited spontaneous or Cisplatin-driven cellular dynamics but also the distinct transcription states of oral cancer cells. Most importantly, our in vitro model system derived observations emphasized the prognostic power which may be translated for betterment of oral cancer patients.We have characterized diversity among CD44-positive oral cancer cells lines with respect to distinct expression of CD24 and ALDH-activity. Cells showed stochastic inter-conversions on ALDH-axis but a strict non-interconvertible transition of CD24Low to CD24High phenotype, even in response to chemotherapy-induced stress. RNAseq study suggested the organization of subpopulations into hierarchical structure with possible maintenance of intermediate alternate states of stemness within the differentiating oral cancer cells. The described population dynamics may influence tumor behaviour by increasing intratumoral heterogeneity in aggressive oral tumors.
Long-read and chromosome-scale assembly of the hexaploid wheat genome achieves high resolution for research and breeding

The sequencing of the wheat (Triticum aestivum) genome has been a methodological challenge for many years due to its large size (15.5 Gb), repeat content, and hexaploidy. Many initiatives aiming at obtaining a reference genome of cultivar Chinese Spring have been launched in the past years and it was achieved in 2018 as the result of a huge effort to combine short-read sequencing with many other resources. Reference-quality genome assemblies were then produced for other accessions but the rapid evolution of sequencing technologies offers opportunities to reach high-quality standards at lower cost. Here, we report on an optimized procedure based on long-reads produced on the ONT (Oxford Nanopore Technology) PromethION device to assemble the genome of the French bread wheat cultivar Renan. We provide the most contiguous and complete chromosome-scale assembly of a bread wheat genome to date. Coupled with an annotation based on RNA-Seq data, this resource will be valuable for the crop community and will facilitate the rapid selection of agronomically important traits. We also provide a framework to generate high-quality assemblies of complex genomes using ONT.
Force-Induced Changes of PilY1 Drive Surface Sensing by Pseudomonas aeruginosa

Most bacteria live on abiotic and biotic surfaces in surface-attached communities known as biofilms. Surface sensing and increased levels of the second-messenger molecule c-di-GMP are crucial to the transition from planktonic to biofilm growth. ABSTRACT During biofilm formation, the opportunistic pathogen Pseudomonas aeruginosa uses its type IV pili (TFP) to sense a surface, eliciting increased second-messenger production and regulating target pathways required to adapt to a surface lifestyle. The mechanisms whereby TFP detect surface contact are still poorly understood, although mechanosensing is often invoked, with few data supporting this claim. Using a combination of molecular genetics and single-cell analysis, with biophysical, biochemical, and genomics techniques, we show that force-induced changes mediated by the von Willebrand A (vWA) domain-containing, TFP tip-associated protein PilY1 are required for surface sensing. Atomic force microscopy shows that TFP/PilY1 can undergo force-induced, sustained conformational changes akin to those observed for mechanosensitive proteins like titin. We show that mutation of a single cysteine residue in the vWA domain of PilY1 results in modestly lower surface adhesion forces, reduced sustained conformational changes, and increased nanospring-like properties, as well as reduced c-di-GMP signaling and biofilm formation. Mutating this cysteine has allowed us to genetically separate a role for TFP in twitching motility from surface-sensing signaling. The conservation of this Cys residue in all P. aeruginosa PA14 strains and its absence in the ∼720 sequenced strains of P. aeruginosa PAO1 may contribute to explaining the observed differences in surface colonization strategies observed for PA14 versus PAO1. IMPORTANCE Most bacteria live on abiotic and biotic surfaces in surface-attached communities known as biofilms. Surface sensing and increased levels of the second-messenger molecule c-di-GMP are crucial to the transition from planktonic to biofilm growth. The mechanism(s) underlying TFP-mediated surface detection that triggers this c-di-GMP signaling cascade is unclear. Here, we provide key insight into this question; we show that the eukaryote-like vWA domain of the TFP tip-associated protein PilY1 responds to mechanical force, which in turn drives the production of a key second messenger needed to regulate surface behaviors. Our studies highlight a potential mechanism that may account for differing surface colonization strategies.
Prior Expectations in Visual Speed Perception Predict Encoding Characteristics of Neurons in Area MT

Bayesian inference provides an elegant theoretical framework for understanding the characteristic biases and discrimination thresholds in visual speed perception. However, the framework is difficult to validate because of its flexibility and the fact that suitable constraints on the structure of the sensory uncertainty have been missing. Here, we demonstrate that a Bayesian observer model constrained by efficient coding not only well explains human visual speed perception but also provides an accurate quantitative account of the tuning characteristics of neurons known for representing visual speed. Specifically, we found that the population coding accuracy for visual speed in area MT (“neural prior”) is precisely predicted by the power-law, slow-speed prior extracted from fitting the Bayesian observer model to psychophysical data (“behavioral prior”) to the point that the two priors are indistinguishable in a cross-validation model comparison. Our results demonstrate a quantitative validation of the Bayesian observer model constrained by efficient coding at both the behavioral and neural levels. SIGNIFICANCE STATEMENT Statistical regularities of the environment play an important role in shaping both neural representations and perceptual behavior. Most previous work addressed these two aspects independently. Here we present a quantitative validation of a theoretical framework that makes joint predictions for neural coding and behavior, based on the assumption that neural representations of sensory information are efficient but also optimally used in generating a percept. Specifically, we demonstrate that the neural tuning characteristics for visual speed in brain area MT are precisely predicted by the statistical prior expectations extracted from psychophysical data. As such, our results provide a normative link between perceptual behavior and the neural representation of sensory information in the brain.
Influence of condensation domains on activity and specificity of adenylation domains

Many clinically used natural products are produced by non-ribosomal peptide synthetases (NRPSs), which due to their modular nature should be accessible to modification and engineering approaches. While the adenylation domain (A) plays the key role in substrate recognition and activation, the condensation domain (C) which is responsible for substrate linkage and stereochemical filtering recently became the subject of debate - with its attributed role as a “gatekeeper” being called into question. Since we have thoroughly investigated different combinations of C-A didomains in a series of in vitro, in vivo, and in situ experiments suggesting an important role to the C-A interface for the activity and specificity of the downstream A domain and not the C domain as such, we would like to contribute to this discussion. The role of the C-A interface, termed ‘extended gatekeeping’, due to structural features of the C domains, can also be transferred to other NRPSs by engineering, was finally investigated and characterised in an in silico approach on 30 wild-type and recombinant C-A interfaces. With these data, we not only would like to offer a new perspective on the specificity of C domains, but also to revise our previously established NRPS engineering and construction rules.
Proteomic pipeline to identify age-related compositional and structural changes of the human dentin extracellular matrix

Objective Devise a pipeline to investigate the protein composition of the human root dentin extracellular matrix (ECM) from single individuals of different age cohorts. Design Individual cervical root dentin of sound human molars from two age brackets, young (18-25 years old; n=3) and old (75-85 years old; n=3), were cut and pulverized. Protein extraction and fractionation were completed by sequential demineralization with EDTA buffer, chaotropic extraction with guanidine hydrochloride, and urea. The resulting protein extracts of differential solubility were digested into peptides and peptides were analyzed by mass spectrometry. Data generated for this study are available via ProteomeXchange, identifier PXD018320. Results We found that protein extracts of different solubilities present distinct biochemical compositions. We further define the matrisome of young (48 proteins) and old (50 proteins) human root dentin and report the identification of compositional and structural differences in ECM proteins from young and old teeth. Conclusion Our study provides a rigorous pipeline, from sample preparation to data analysis, to investigate the ECM composition – or matrisome – of the dentin. This pipeline has the potential to lead to the discovery of biomarkers of tooth aging and health.
Eye movements elevate crowding in idiopathic infantile nystagmus syndrome

Idiopathic infantile nystagmus syndrome is a disorder characterised by involuntary eye movements, which leads to decreased acuity and visual function. One such function is visual crowding; a process whereby objects that are easily recognised in isolation become impaired by nearby flankers. Crowding typically occurs in the peripheral visual field, though elevations in foveal vision have been reported in congenital nystagmus, similar to those found with amblyopia. Here we examine whether the elevated foveal crowding with nystagmus is driven by similar mechanisms to those documented in amblyopia - long-term neural changes associated with a sensory deficit - or by the momentary displacement of the stimulus through nystagmus eye movements. We used a Landolt-C orientation identification task to measure threshold gap sizes with and without either horizontally or vertically placed pairs of flanking Landolt-Cs. Because nystagmus is predominantly horizontal, crowding should be stronger with horizontal flankers if eye movements cause the interference, whereas a sensory deficit would more likely be equivalent for the two dimensions. Consistent with an origin in eye movements, we observe elevations in nystagmic crowding that are above that of typical vision, and stronger with horizontal than vertical flankers and not found in amblyopic or typical vision. We further demonstrate the same pattern of performance can be obtained in typical vision with stimulus movement that simulates nystagmus. Consequently, we propose that the origin of nystagmic crowding lies in the eye movements, either through image smear of the target and flanker elements or through relocation of the stimulus into peripheral retina.
Electrolyte Optimization for Enhancing Electrochemical Performance of Antimony Sulfide/Graphene Anodes for Sodium-Ion Batteries–Carbonate-Based and Ionic Liquid Electrolytes

The electrolyte is a key component in determining the performance of sodium-ion batteries. A systematic study is conducted to optimize the electrolyte formulation for a Sb2S3/graphene anode, which is synthesized via a facile solvothermal method. The effects of solvent composition and fluoroethylene carbonate (FEC) additive on the electrochemical properties of the anode are examined. The propylene carbonate (PC)-based electrolyte with FEC can ensure the formation of a reliable solid-electrolyte interphase layer, resulting in superior charge–discharge performance, compared to that found in the ethylene carbonate (EC)/diethyl carbonate (DEC)-based electrolyte. At 60 °C, the carbonate-based electrolyte cannot function properly. At such an elevated temperature, however, the use of an N-propyl-N-methylpyrrolidinium bis(fluorosulfonyl)imide ionic liquid electrolyte is highly promising, enabling the Sb2S3/graphene electrode to deliver a high reversible capacity of 760 mAh g–1 and retain 95% of its initial perform.
A PLSR model to predict soil salinity using Sentinel-2 MSI data

Abstract Salinization is one of the most widespread environmental threats in arid and semi-arid regions that occur either naturally or artificially within the soil. When exceeding the thresholds, salinity becomes a severe danger, damaging agricultural production, water and soil quality, biodiversity, and infrastructures. This study used spectral indices, including salinity and vegetation indices, Sentinel-2 MSI original bands, and DEM, to model soil salinity in the Great Hungarian Plain. Eighty-one soil samples in the upper 30 cm of the soil surface were collected from vegetated and nonvegetated areas by the Research Institute for Soil Sciences and Agricultural Chemistry (RISSAC). The sampling campaign of salinity monitoring was performed in the dry season to enhance salt spectral characteristics during its accumulation in the subsoil. Hence, applying a partial least squares regression (PLSR) between salt content (g/kg) and remotely sensed data manifested a highly moderate correlation with a coefficient of determination R 2 of 0.68, a p-value of 0.000017, and a root mean square error of 0.22. The final model can be deployed to highlight soil salinity levels in the study area and assist in understanding the efficacy of land management strategies.
Comparison of single- and triple-port VATS for lung cancer: A meta-analysis

Abstract Objective To compare the perioperative parameters between single- and triple-port video-assisted thoracoscopic surgery (VATS) lobectomy in the treatment of lung cancer. Methods The Pubmed, Embase, Cochrane library, and the Web of Science databases were electronically searched from inception to September 2019 for all relevant studies. Study quality was evaluated using the Jadad scale or the Newcastle-Ottawa scale. The results were pooled using the generic inverse-variance method and expressed as mean differences or risk ratios, with 95% confidence intervals. Results Three randomized controlled trials (RCTs) and ten cohort studies with 2,278 subjects were included in the meta-analysis. Whether based on RCTs or cohort studies, the pooled results showed no significant difference in the operation time, chest tube duration, intraoperative blood loss, postoperative hospital stays, lymph node dissection number, postoperative drainage volume, and postoperative complications between single- and triple-port VATS lobectomy (P > 0.05). Single-port VATS could relieve postoperative pain better than triple-port VATS, especially in the first day and fifth day (P < 0.05). No evidence of significant publication bias was found (P > 0.05). Conclusion Single-port VATS lobectomy can yield similar perioperative results to those of triple-port VATS lobectomy and is more effective in relieving postoperative pain.
Influence of COVID-19 pandemic on stress levels of urologic patients

Abstract Introduction Several studies have shown the consequences of COVID-19 pandemic on perceived stress of different populations, but none of them analyzed urological patients who underwent elective surgery. Methods We enrolled prospectively patients who underwent elective surgery between March and October 2020. A survey on COVID-19 and the 4-item Perceived Stress Scale (PPS-4) questionnaire were administered at hospital admission. Demographic and medical history data were also collected. Uni- and multivariate analyses were performed to identify independent predictors of higher PSS-4 values (≥7). Results A total of 200 patients were enrolled. Mean PSS-4 value resulted 6.04. Patients with PSS-4 value ≥7 resulted 43.5% (87/200). In multivariate analysis, PSS-4 value ≥7 was independently associated (p < 0.05) with female gender (OR 6.42), oncological disease (OR 2.87), high (>5 in a range between 0 and 10) fear of intrahospital transmission of SARS-CoV-2 infection (OR 4.75), history of bladder instillation (OR 0.26), and current smokers (OR 0.27) Conclusion High PSS-4 values at hospital admission in urologic surgical patients are positively correlated with female gender, fear of intrahospital transmission of SARS-CoV-2 infection, and oncological disease. PSS-4 questionnaire could be useful to select patients for whom a preadmission counselling is necessary to improve the management of their high stress level.
miR-496 inhibits proliferation via LYN and AKT pathway in gastric cancer

Abstract MicroRNAs (miRNAs) operate as tumor suppressor or carcinogen to regulate cell proliferation, metastasis, invasion, differentiation, apoptosis, and metabolic process. In the present research, we investigated the effect and mechanism of miR-496 in human gastric cancer cells. miR-496 was downregulated in two gastric cancer cell lines, AGS and MKN45, compared with normal gastric epithelial cell line GES-1. miR-496 mimics inhibited the proliferation of AGS cells after the transfection for 48 and 72 h. The migration and invasion of AGS cells were also inhibited by the transfection of miR-496 mimics. miR-496 mimics induced the apoptosis through upregulating the levels of Bax and Active Caspase 3 and downregulating the levels of Bcl-2 and Total Caspase 3. Bioinformatics analysis showed that there was a binding site between miR-496 and Lyn kinase (LYN). miR-496 mimics could inhibit the expression of LYN in AGS cells. LYN overexpression blocked the inhibition of tumor cell growth, as well as the inhibition of AKT/mTOR signaling pathway induced by miR-496. In conclusion, miR-496 inhibited the proliferation through the AKT/mTOR signaling pathway via targeting LYN in gastric cancer cells. Our research provides a new potential target for clinical diagnosis and targeted treatment for gastric cancer.