Miracle-dz/UniFAR-FTUs huggingface dataset:
Longitudinal Circulating Tumor DNA Analysis in Blood and Saliva for Prediction of Response to Osimertinib and Disease Progression in EGFR-Mutant Lung Adenocarcinoma

Simple Summary ctDNA assay is a promising non-invasive method to detect genomic alterations associated with lung cancer. In this prospective study of 25 patients with EGFR-mutant lung adenocarcinoma receiving osimertinib, ctDNA progression predated radiographic progression by 118 days in 11 of 20 patients with disease progression. Saliva-based ctDNA analysis and plasma NGS detected additional patients with ctDNA progression preceding clinical progression, suggesting the potential complementary roles of different ctDNA detection methodologies. Baseline mutant ctDNA level predicted progression-free survival while tumor volume measurements by volumetric CT did not. Serial ctDNA analysis of plasma and saliva is a clinically useful tool to monitor response and resistance to osimertinib. Abstract Background: We assessed whether serial ctDNA monitoring of plasma and saliva predicts response and resistance to osimertinib in EGFR-mutant lung adenocarcinoma. Three ctDNA technologies—blood-based droplet-digital PCR (ddPCR), next-generation sequencing (NGS), and saliva-based EFIRM liquid biopsy (eLB)—were employed to investigate their complementary roles. Methods: Plasma and saliva samples were collected from patients enrolled in a prospective clinical trial of osimertinib and local ablative therapy upon progression (NCT02759835). Plasma was analyzed by ddPCR and NGS. Saliva was analyzed by eLB. Results: A total of 25 patients were included. We analyzed 534 samples by ddPCR (n = 25), 256 samples by NGS (n = 24) and 371 samples by eLB (n = 22). Among 20 patients who progressed, ctDNA progression predated RECIST 1.1 progression by a median of 118 days (range: 61–272 days) in 11 (55%) patients. Of nine patients without ctDNA progression by ddPCR, two patients had an increase in mutant EGFR by eLB and two patients were found to have ctDNA progression by NGS. Levels of ctDNA measured by ddPCR and NGS at early time points, but not volumetric tumor burden, were associated with PFS. EGFR/ERBB2/MET/KRAS amplifications, EGFR C797S, PIK3CA E545K, PTEN V9del, and CTNNB1 S45P were key resistance mechanisms identified by NGS. Conclusion: Serial assessment of ctDNA in plasma and saliva predicts response and resistance to osimertinib, with each assay having supplementary roles.
Can Transcranial Direct Current Stimulation Enhance Functionality in Older Adults? A Systematic Review

Transcranial direct current stimulation (tDCS) is a non-invasive, easy to administer, well-tolerated, and safe technique capable of affecting brain excitability, both at the cortical and cerebellum levels. However, its effectiveness has not been sufficiently assessed in all population segments or clinical applications. This systematic review aimed at compiling and summarizing the currently available scientific evidence about the effect of tDCS on functionality in older adults over 60 years of age. A search of databases was conducted to find randomized clinical trials that applied tDCS versus sham stimulation in the above-mentioned population. No limits were established in terms of date of publication. A total of 237 trials were found, of which 24 met the inclusion criteria. Finally, nine studies were analyzed, including 260 healthy subjects with average age between 61.0 and 85.8 years. Seven of the nine included studies reported superior improvements in functionality variables following the application of tDCS compared to sham stimulation. Anodal tDCS applied over the motor cortex may be an effective technique for improving balance and posture control in healthy older adults. However, further high-quality randomized controlled trials are required to determine the most effective protocols and to clarify potential benefits for older adults.
Effect of Short-Term Cold Treatment on Carbohydrate Metabolism in Potato Leaves

Plants are often challenged by an array of unfavorable environmental conditions. During cold exposure, many changes occur that include, for example, the stabilization of cell membranes, alterations in gene expression and enzyme activities, as well as the accumulation of metabolites. In the presented study, the carbohydrate metabolism was analyzed in the very early response of plants to a low temperature (2 °C) in the leaves of 5-week-old potato plants of the Russet Burbank cultivar during the first 12 h of cold treatment (2 h dark and 10 h light). First, some plant stress indicators were examined and it was shown that short-term cold exposure did not significantly affect the relative water content and chlorophyll content (only after 12 h), but caused an increase in malondialdehyde concentration and a decrease in the expression of NDA1, a homolog of the NADH dehydrogenase gene. In addition, it was shown that the content of transitory starch increased transiently in the very early phase of the plant response (3–6 h) to cold treatment, and then its decrease was observed after 12 h. In contrast, soluble sugars such as glucose and fructose were significantly increased only at the end of the light period, where a decrease in sucrose content was observed. The availability of the monosaccharides at constitutively high levels, regardless of the temperature, may delay the response to cold, involving amylolytic starch degradation in chloroplasts. The decrease in starch content, observed in leaves after 12 h of cold exposure, was preceded by a dramatic increase in the transcript levels of the key enzymes of starch degradation initiation, the α-glucan, water dikinase (GWD-EC 2.7.9.4) and the phosphoglucan, water dikinase (PWD-EC 2.7.9.5). The gene expression of both dikinases peaked at 9 h of cold exposure, as analyzed by real-time PCR. Moreover, enhanced activities of the acid invertase as well as of both glucan phosphorylases during exposure to a chilling temperature were observed. However, it was also noticed that during the light phase, there was a general increase in glucan phosphorylase activities for both control and cold-stressed plants irrespective of the temperature. In conclusion, a short-term cold treatment alters the carbohydrate metabolism in the leaves of potato, which leads to an increase in the content of soluble sugars.
Plasmid-mediated quinolone resistance genes transfer among enteric bacteria isolated from human and animal sources

This research investigates the transferability of plasmid-mediated quinolone resistance (PMQR) genes among enteric bacteria isolates in human and animal samples, as well as its implication on resistance of recipient cells. A total of 1,964 strains of five different enteric bacteria species (Escherichia coli, Salmonella sp., Shigella sp., Klebsiella sp. and Aeromonas sp.) were screened for plasmid-mediated quinolone resistance (PMQR) genes from a population of quinolone resistant (Q-r) isolates. Screening for PMQR isolates was achieved by plasmid curing using sub-lethal concentration of Sodium Dodecyl Sulphate and PMQR genes (qnrA, qnrB, qnrS, Aac(6′)-Ib-crand Qep A) were detected by polymerase chain reaction (PCR). Conjugation and transformation experiments were attempted to ascertain transfer of genes from the Q-r isolates to a susceptible, standard recipient, E. coli J53-2. The minimum inhibitory concentration (MIC) was determined before and after gene transfer, using E-test strips. Results indicate that percentage resistance to the quinolones (Qs): Nalidixic acid, Ciprofloxacin, Pefloxacin and Ofloxacin determined by agar plate diffusion technique stood at 52.6, 47.3, 50.5, 70.6 and 46.0% for Escherichia coli, Salmonella sp. , Shigellasp. , Klebsiella sp. and Aeromonas sp. respectively. Analysis of variance indicated the occurrence of significant differences (F, 46.77–613.30; 0.00) in the resistance to each tested Qs. Generally, Human isolates showed greater resistance than Animal isolates (57.4 vs 47.2%). Investigation with specific primers indicated 11, 15, 7, 1 and 0 for qnrA, qnrB, qnrS, qepA and Aac(6′)-Ib-cr genes respectively, out of 1018 Q-r and 29 PMQR isolates. Gene transfer experiments indicated the transfer of all genes except qepA either by conjugation or transformation. The MIC of tested Qs on recipient bacterium before gene transfer greatly increased from 0.0625 to 0.25 µg/mL, after transfer. This study demonstrates that PMQR genes amongst enteric bacteria in the Niger delta of Nigeria were transferable and transfer conferred a higher Q- resistance on recipient bacterium.
Proteus mirabilis Urease: Unsuspected Non-Enzymatic Properties Relevant to Pathogenicity

Infection by Proteus mirabilis causes urinary stones and catheter incrustation due to ammonia formed by urease (PMU), one of its virulence factors. Non-enzymatic properties, such as pro-inflammatory and neurotoxic activities, were previously reported for distinct ureases, including that of the gastric pathogen Helicobacter pylori. Here, PMU was assayed on isolated cells to evaluate its non-enzymatic properties. Purified PMU (nanomolar range) was tested in human (platelets, HEK293 and SH-SY5Y) cells, and in murine microglia (BV-2). PMU promoted platelet aggregation. It did not affect cellular viability and no ammonia was detected in the cultures’ supernatants. PMU-treated HEK293 cells acquired a pro-inflammatory phenotype, producing reactive oxygen species (ROS) and cytokines IL-1β and TNF-α. SH-SY5Y cells stimulated with PMU showed high levels of intracellular Ca2+ and ROS production, but unlike BV-2 cells, SH-SY5Y did not synthesize TNF-α and IL-1β. Texas Red-labeled PMU was found in the cytoplasm and in the nucleus of all cell types. Bioinformatic analysis revealed two bipartite nuclear localization sequences in PMU. We have shown that PMU, besides urinary stone formation, can potentially contribute in other ways to pathogenesis. Our data suggest that PMU triggers pro-inflammatory effects and may affect cells beyond the renal system, indicating a possible role in extra-urinary diseases.
Comparison of the Effect of Oral Versus Intravenous Bisphosphonate Administration on Osteoclastogenesis in Advanced-Stage Medication-Related Osteonecrosis of the Jaw Patients

It is yet unknown whether the intravenous administration route alone can fully account for the exacerbation of medication-related osteonecrosis of the jaw (MRONJ). The purpose of this retrospective study was to identify the potential role of the bisphosphonate (BP) administration route as an independent prognostic factor for non-cancerous, stage III MRONJ patients. Bone samples were retrospectively obtained from two groups of osteoporosis patients who underwent surgery for the treatment of stage III MRONJ. Among the subjects, 10 had a history of only oral BP consumption and 10 of intravenous (IV) BP administration. The samples were assessed for osteoclast morphology and immunohistochemical expression of the receptor activator of NF-κB ligand (RANKL), osteoprotegerin (OPG), and potassium calcium-activated channel subfamily N member 4 (Kcnn4). Although the osteoclasts derived from both groups exhibited no significant differences in the mean quantity, diameter, and nuclearity, significantly attenuated tartrate-resistant acid phosphatase activity was noted among the IV BP-induced MRONJ bones compared to those of the oral BP group. Significant suppression of the RANKL/OPG ratio and Kcnn4 expression among the retrieved bones of IV BP group patients was also noted. Our results indicate the potential of the BP administration route as an independent prognostic factor for advanced-stage MRONJ, regardless of the dosage or indication for which the BP was prescribed.
Functional traits predict resident plant response to Reynoutria japonica invasion in riparian and fallow communities in southern Poland

Abstract Reynoutria japonica is one of the most harmful invasive species in the world, dramatically reducing the diversity of resident vegetation. To mitigate the impact of R. japonica on ecosystems and properly manage affected areas, understanding the mechanisms behind this plant’s invasive success is imperative. This study aimed to comprehensively analyse plant communities invaded by R. japonica, taking into account species traits, habitat conditions and seasonal variability, and to determine the ecological profile of species that withstand the invader’s pressure. The study was performed in fallow and riparian areas in southern Poland. Pairs of adjacent plots were established at 25 sites with no obvious signs of recent human disturbance. One plot contained R. japonica, and the other contained only resident vegetation. For each plot, botanical data were collected and soil physicochemical properties were determined. Twelve sites were surveyed four times, in two springs and two summers, to capture seasonal variability. The presence of R. japonica was strongly associated with reduced resident plant species diversity and/or abundance. In addition to the ability to quickly grow and form a dense canopy that shades the ground, the success of the invader likely resulted from the production of large amounts of hard-to-decompose litter. The indirect impact of R. japonica by controlling the availability of nutrients in the soil might also play a role. A few species coexisted with R. japonica. They can be classified into three groups: (i) spring ephemerals – geophytic forbs with a mixed life history strategy, (ii) lianas with a competitive strategy and (iii) hemicryptophytic forbs with a competitive strategy. Species from the first two groups likely avoided competition for light by temporal or spatial niche separation (they grew earlier than or above the invasive plant), whereas the high competitive abilities of species from the third group likely enabled them to survive in R. japonica patches.
From Affinity to Proximity Techniques to Investigate Protein Complexes in Plants

The study of protein–protein interactions (PPIs) is fundamental in understanding the unique role of proteins within cells and their contribution to complex biological systems. While the toolkit to study PPIs has grown immensely in mammalian and unicellular eukaryote systems over recent years, application of these techniques in plants remains under-utilized. Affinity purification coupled to mass spectrometry (AP-MS) and proximity labeling coupled to mass spectrometry (PL-MS) are two powerful techniques that have significantly enhanced our understanding of PPIs. Relying on the specific binding properties of a protein to an immobilized ligand, AP is a fast, sensitive and targeted approach used to detect interactions between bait (protein of interest) and prey (interacting partners) under near-physiological conditions. Similarly, PL, which utilizes the close proximity of proteins to identify potential interacting partners, has the ability to detect transient or hydrophobic interactions under native conditions. Combined, these techniques have the potential to reveal an unprecedented spatial and temporal protein interaction network that better understands biological processes relevant to many fields of interest. In this review, we summarize the advantages and disadvantages of two increasingly common PPI determination techniques: AP-MS and PL-MS and discuss their important application to plant systems.
Clusteromics II: Methanesulfonic Acid–Base Cluster Formation

The role of methanesulfonic acid (MSA) in atmospheric new particle formation remains highly uncertain. Using state-of-the-art computational methods, we study the electrically neutral (MSA)0–2(base)0–2 clusters, with base = ammonia (A), methylamine (MA), dimethylamine (DMA), trimethylamine (TMA), and ethylenediamine (EDA). The cluster configurations are obtained using the ABCluster program and the number of initial cluster configurations is reduced based on PM7 calculations. Thermochemical parameters are calculated using the quasi-harmonic approximation based on the ωB97X-D/6-31++G(d,p) cluster structures and vibrational frequencies. The single point energies are calculated at the DLPNO-CCSD(T0)/aug-cc-pVTZ level of theory. We find that MSA shows a different interaction pattern with the bases compared to sulfuric acid and does not simply follow the basicity of the bases for these small clusters. In all cases, we find that the MSA-base clusters show very low cluster formation potential, indicating that electrically neutral clusters consisting solely of MSA as the clustering acid are most likely not capable of forming and growing under realistic atmospheric conditions.
Hierarchical Gold Flower with Sharp Tips from Controlled Galvanic Replacement Reaction for High Surface Enhanced Raman Scattering Activity

Highly branched Au flowers (AuFs) with sharp tips have been synthesized in high yield by controlling the kinetics of nanocrystal growth via galvanic replacement reaction. Controlled galvanic replacement takes place on appropriately chosen commercially available polystyrene bead supported Cu nanoparticles with HAuCl4. Such a reaction is thermodynamically driven through the exploitation of a Cu(II)/Cu(0) redox couple during nanocrystal formation. The hierarchical morphology of the resulting naked Au flowers (AuFs) depends on the galvanic exchange rate, which increases with increasing HAuCl4 concentration but over a specific concentration range. The formation of AuF is carefully studied, and a spontaneous assembly mechanism is proposed. The time-course experimental results show that the influence of electrostatic field force (EFF) of the charged resin beads is held responsible for prickly tipped AuF formation. Then the fabrication of AuF morphology becomes a large-scale free-standing synthetic protocol for a.
Antibacterial activity of honeys and potential synergism of honeys with antibiotics and alkaloid extract of Sophora alopecuroides plant against antibiotic-resistant Escherichia coli mutant

Objective(s): The increase in multidrug-resistant Escherichia coli strains with an overactivated AcrAB-TolC efflux pump has reduced the effectiveness of synthetic antibiotics, such as ciprofloxacin. The activity of this efflux pump can be reduced by using natural products. This study aimed to use a combination of ciprofloxacin, honey, and alkaloid extract of Sophora alopecuroides against an E. coli mutant with an overactivated AcrAB-TolC pump. Materials and Methods: First the physicochemical properties, total alkaloid content, antioxidant activity, and the minimum inhibitory concentration (MIC) of three local honey samples: Konar (lotus), Avishan (Thyme), and Gavan (Astragalus) were evaluated. Then, the MIC of different combinations of honey, ciprofloxacin, and plant alkaloid extract and expression of acrA and soxS genes were carried out using the agar dilution method and quantitative RT- PCR methods. Results: The net absorbance, total alkaloid content, and DPPH radical scavenging activity of Konar honey were significantly higher than those of Avishan and Gavan honeys (P<0.05). However, the MIC of lotus honey was nearly similar to other honey types, and all honey (30% w/v)-ciprofloxacin combinations decreased the viability of mutant more than ciprofloxacin alone. A synergistic interaction (FICI =0.48) was observed in triplex complex of ciprofloxacin (10 µg/ml), honey (20% w/v), and plant extract (1 mg/ml). A significant decrease (P<0.05) in the expression level of genes was seen in the presence of the triplex complex. Conclusion: It is concluded that the interaction between honey and plant alkaloid extract enhanced the anti-pump activity and reduced the oxidative stress response of the E. coli mutant.
Medium Optimization for the Production of Phytase by Recombinant Pichia pastoris Grown on Glycerol

Based on statistical designs, minimal salts medium, commonly used for yeast cultivation, was optimized to maximize GAP promoter-mediated phytase production by recombinant Pichia pastoris grown on glycerol. A Plackett-Burman design was followed to screen medium components to determine those that significantly affected phytase production. Of the 8 components studied, the concentrations of K2SO4, CaSO4•2H2O and MgSO4•7H2O were identified as having a significant effect. These three components were subsequently optimized by response surface methodology using a central composite design. The optimal concentrations of the three components, leading to a maximal extracellular phytase activity of 161.64 U/ml, were K2SO4 13.25g/l, CaSO4•2H2O 1.03g/l and MgSO4•7H2O 17.94g/l. The activity measured in cultures using optimized growth medium is significantly higher than the 73.31 U/ml measured in cultures using standard minimal salts media. The theoretical phytase yields predicted by the developed model were very close to experimentally obtained values.
Special quasirandom structure modeling of fluorite-structured oxide solid solutions with aliovalent cation substitutions

The accuracy of the special quasirandom structure (SQS) approach for modeling the structure and energetics of fluorite-structured oxide solid solutions with aliovalent cation substitutions is assessed in an ionic-pair potential study of urania and ceria based systems mixed with trivalent rare-earth ions. Mixing enthalpies for SQS supercells containing 96 and 324 lattice sites were calculated using ionic pair potentials for U0.5La0. 5O1.75, U0.5Y0. 5O1.75, Ce0.5La0. 5O1.75, Ce0.5Y0. 5O1.75, and Ce0.5Gd0. 5O1.75, which all have stoichiometries of pyrochlores. The SQS results were compared to benchmark values for random substitutional disorder obtained using large supercell models. The calculations show significant improvement of the mixing enthalpy for the larger 324 site SQS, which is attributed to a better description of the structural distortions, as characterized by the radial distribution functions in relaxed systems.
Screen time and physical activity in children and adolescents aged 10–15 years

Background Previous research studies have demonstrated a relationship between low levels of physical activity and high amounts of screen time in children and adolescents. However, this is usually based on self-reported data. Therefore, the aim of this cross-sectional study was to investigate the association between objectively measured smartphone screen time and physical activity among children and adolescents aged 10–15 years. Methods During seven consecutive days, we objectively assessed smartphone screen time, using the SCRIIN smartphone application, and physical activity, using the SCRIIN activity tracker, in children and adolescents recruited from two schools in Stockholm County, Sweden. Moreover, the children/adolescents and their parents responded to a questionnaire, obtaining among other things: self-reported screen time, physical activity, sleep and health-related quality of life. Results A total of 121 children and adolescents (mean age: 12.1 ± 1.5) were included in the study. Objectively measured smartphone screen time was 161.2 ± 81.1 min/day. Mean physical activity, measured with the SCRIIN activity tracker, was 32.6 ± 16.5 active min/day. Minutes of screen time and physical activity did not differ between the children and adolescents from the two schools, despite located in different socioeconomic areas. Further, we found no association between smartphone screen time and physical activity. However, girls aged 14–15 years, had more smartphone screen time (p<0.01) and were significantly more physically active (p<0.01) than girls aged 10–12 years. In addition, boys reported more than five times more time spent on computer and video games than girls did. Conclusion Smartphone screen time was not associated with physical activity level among children and adolescents aged 10–15 years.