Miracle-dz/UniFAR-FTUs huggingface dataset:
A New Laccase Biosensor For Polyphenols Determination

Abstract: The relevance of polyphenols in human health is a well known fact. Prompted by that, very intensive research has been directed to get a method to detect them, which will improve the current ones. Laccase (p-diphenol:dioxygen oxidoreductase, EC 1.10.3.2) is a multi-copper oxidase, which couples catalytic oxidation of phenolic substrates with four electron reduction of dioxygen to water [1] . A maximum catalytic response in oxygenated electrolyte was observed between 4.5 and 5.5 [2], while for pH > 6.9 the laccase was found to be inactive [3]. We prepared a biosensor with laccase immobilised on a polyether sulphone membrane, at pH 4.5, which was applied at Universal Sensors base electrode. Reduction of the product of oxidation of several polyphenols, catalysed by laccase, was done at a potential for which the polyphenol of interest was found to respond. Reduction of catechol was found to occur at a potential of –200mV, which is often referred to in the literature for polyphenolic biosensors. However other polyphenols did not respond at that potential. It was observed that (+)- catechin produced a very large cathodic current when +100mV were applied to the laccase biosensor, both in aqueous acetate and 12% ethanol acetate buffer , whereas caffeic acid responded at –50mV. Other polyphenols tested were gallic acid, malvidin, quercetin, rutin,
Investigation on Potential Correlation Between Small Nuclear Ribonucleoprotein Polypeptide A and Lung Cancer

SNRPA (small nuclear ribonucleoprotein polypeptide A) gene is essential for the pre-mRNA splicing process. Using the available datasets of TCGA or GEO, we aimed at exploring the potential association between the SNRPA gene and lung cancer by several online tools (such as GEIPA2, MEXPRESS, Oncomine) and bioinformatics analysis software (R or GSEA). SNRPA was highly expressed in the tissues of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma tissue (LUSC), compared with control tissues. The high SNRPA expression was associated with a poor survival prognosis of LUAD cases, while the genetic alteration within SNRPA was linked to the overall survival prognosis of LUSC cases. There was a potential correlation between promoter methylation and the expression of SNRPA for LUAD. Compared with normal tissues, we observed a higher phosphorylation level at the S115 site of SNRPA protein (NP_004587.1) (p = 0.002) in the primary LUAD tissues. The potential ATR kinase of the S115 site was predicted. Besides, SNRPA expression in lung cancer was negatively correlated with the infiltration level of M2 macrophage but positively correlated with that of Follicular B helper T cells, in both LUAD and LUSC. The enrichment analysis of SNRPA-correlated genes showed that cell cycle and ubiquitin mechanism-related issues were mainly observed for LUAD; however, RNA splicing-related cellular issues were mainly for LUSC. In summary, the SNRPA gene was identified as a potential prognosis biomarker of lung cancer, especially lung adenocarcinoma, which sheds new light on the association between the spliceosomal complex component and tumorigenesis.
Effect of Tumor Size on Long-Term Survival After Resection for Solitary Intrahepatic Cholangiocarcinoma

Background The relationship between tumor size and survival in intrahepatic cholangiocarcinoma (ICC) is still controversial. This study aimed to evaluate the prognostic ability of tumor size for solitary ICC after resection and explore optimal cut-off values in different subgroups. Methods Patients with solitary ICC who underwent liver resection from the Surveillance, Epidemiology, and End Results Program and Shandong Provincial Hospital were retrospectively analyzed. Kaplan-Meier and Cox regression analysis were used to assess the prognostic ability of tumor size. The log-rank test was used to determine the optimal cut-off values, and a minimum P was regarded as the optimal one in different subgroups. Results Large tumor size groups had worse overall survival (OS) than small tumor size groups. Cox regression analysis suggested that tumor size was an independent prognostic factor for OS for solitary ICC after resection. Subgroup analysis showed tumor size was associated with OS for both solitary ICC with and without vascular invasion (VI). Furthermore, the optimal cut-off values for solitary ICC with and without VI were found to be 8 and 3 cm, respectively, which could divide the patients into two groups with significant differences in OS. Conclusion Tumor size was an independent prognostic factor for solitary ICC after resection. The existing American Joint Committee on Cancer (AJCC) staging system could be improved if the cut-off value of the T1 stage was changed to 8 cm and if the T2 stage incorporated a tumor size with a cut-off value of 3 cm. Further studies with more cases are needed to validate these findings.
Behavioral and Developmental Changes in Brown Trout After Exposure to the Antidepressant Venlafaxine

During the last decades, depression has been diagnosed in increasing numbers, accompanied by rising prescription rates of antidepressants. Concomitantly, these pharmaceuticals are frequently detected in surface waters. Serotonin and noradrenalin reuptake inhibitors such as venlafaxine form the second largest group of antidepressants worldwide, and venlafaxine is the second most prescribed antidepressant in Germany. As drug targets are evolutionary highly conserved, venlafaxine can potentially change not only behavior and related physiological processes in humans but also in non-target species, especially aquatic organisms. In order to test this hypothesis for fish, we exposed brown trout larvae and juveniles to venlafaxine at concentrations ranging from 1 to 1,000 μg/L. Larvaewere exposed for 5 months from the eyed ova stage until 8 weeks post yolk-sac consumption at 7 and 11 °C. Juveniles were exposed for 4 weeks at 7 °C. Mortality, weight, length, behavior during exposure and behavior in a stressful environment were recorded in both experiments. For larvae, additionally, hatching rate and heart rate were analyzed. In juvenile fish, tissue cortisol levels were determined. Our results clearly showed, that brown trout, irrespective of their life stage, change their behavior when being exposed to venlafaxine: During exposure, venlafaxine at 7 °C caused larvae to sojourn in the upper part of the aquaria for a longer time, with a lowest observed effect concentration of 100 μg/L. In a stressful environment with limited space, fish exposed to ≥10 μg/L venlafaxine were less active than controls. Furthermore, venlafaxine reduced the growth of larvae (length at ≥10 μg/L, weight at 1mg/L) and their survival after 5 months (at 1mg/L). Hatching rate and heart rate of larvae as well as tissue cortisol concentration of juveniles were not affected by venlafaxine treatment.
Laparoscopic Proximal Gastrectomy Versus Laparoscopic Total Gastrectomy for Proximal Gastric Cancer: A Systematic Review and Meta−Analysis

Background To compare laparoscopic proximal gastrectomy (LPG) and laparoscopic total gastrectomy (LTG) with regard to outcomes, including efficacy and safety, in patients with proximal gastric cancer. Methods Original English-language articles comparing LPG and LTG for proximal gastric cancer up to November 2019 were systematically searched in the Embase, PubMed, Cochrane Library, Web of Knowledge, and ClinicalTrials.gov databases by two independent reviewers. Our main endpoints were surgery-related features (operation time, blood loss, harvested lymph nodes, and postoperative hospital stay), postoperative complications (anastomotic leakage, anastomotic bleeding, anastomotic stenosis, and reflux esophagitis), and oncologic outcomes (5-year overall survival and recurrent cancer). Results Fourteen studies including a total of 1,282 cases (510 LPG and 772 LTG) were enrolled. Fewer lymph nodes were harvested (WMD = −13.33, 95% CI: −15.66 to −11.00, P < 0.00001) and more postoperative anastomotic stenosis (OR = 2.03, 95% CI: 1.21 to 3.39, P = 0.007) observed in LPG than LTG. There were no significant differences in other explored parameters between the two methods. However, based on a subgroup analysis of digestive tract reconstruction, LPG with esophagogastrostomy (LPG-EG) had shorter operative time (WMD = −42.51, 95% CI: −58.99 to −26.03, P < 0.00001), less intraoperative blood loss (WMD = −79.52, 95% CI: −116.63 to −42.41, P < 0.0001), and more reflux esophagitis (OR = 3.92, 95% CI: 1.56 to 9.83, P = 0.004) than was observed for LTG. There was no difference between LPG performed with the double tract anastomosis/double-flap technique (DT/DFT) and LTG. Conclusion LPG can be performed as an alternative to LTG for proximal gastric cancer, especially LPG-DT/DFT, with comparable safety and efficacy.
Accurate Neuronal Soma Segmentation Using 3D Multi-Task Learning U-Shaped Fully Convolutional Neural Networks

Neuronal soma segmentation is a crucial step for the quantitative analysis of neuronal morphology. Automated neuronal soma segmentation methods have opened up the opportunity to improve the time-consuming manual labeling required during the neuronal soma morphology reconstruction for large-scale images. However, the presence of touching neuronal somata and variable soma shapes in images brings challenges for automated algorithms. This study proposes a neuronal soma segmentation method combining 3D U-shaped fully convolutional neural networks with multi-task learning. Compared to existing methods, this technique applies multi-task learning to predict the soma boundary to split touching somata, and adopts U-shaped architecture convolutional neural network which is effective for a limited dataset. The contour-aware multi-task learning framework is applied to the proposed method to predict the masks of neuronal somata and boundaries simultaneously. In addition, a spatial attention module is embedded into the multi-task model to improve neuronal soma segmentation results. The Nissl-stained dataset captured by the micro-optical sectioning tomography system is used to validate the proposed method. Following comparison to four existing segmentation models, the proposed method outperforms the others notably in both localization and segmentation. The novel method has potential for high-throughput neuronal soma segmentation in large-scale optical imaging data for neuron morphology quantitative analysis.
Deafness Weakens Interareal Couplings in the Auditory Cortex

The function of the cerebral cortex essentially depends on the ability to form functional assemblies across different cortical areas serving different functions. Here we investigated how developmental hearing experience affects functional and effective interareal connectivity in the auditory cortex in an animal model with years-long and complete auditory deprivation (deafness) from birth, the congenitally deaf cat (CDC). Using intracortical multielectrode arrays, neuronal activity of adult hearing controls and CDCs was registered in the primary auditory cortex and the secondary posterior auditory field (PAF). Ongoing activity as well as responses to acoustic stimulation (in adult hearing controls) and electric stimulation applied via cochlear implants (in adult hearing controls and CDCs) were analyzed. As functional connectivity measures pairwise phase consistency and Granger causality were used. While the number of coupled sites was nearly identical between controls and CDCs, a reduced coupling strength between the primary and the higher order field was found in CDCs under auditory stimulation. Such stimulus-related decoupling was particularly pronounced in the alpha band and in top–down direction. Ongoing connectivity did not show such a decoupling. These findings suggest that developmental experience is essential for functional interareal interactions during sensory processing. The outcomes demonstrate that corticocortical couplings, particularly top-down connectivity, are compromised following congenital sensory deprivation.
Neuromuscular Adaptations and Enhancement of Physical Performance in Female Basketball Players After 8 Weeks of Plyometric Training

The aim of this study was to examine the effects of an 8-week in-season plyometric training (PT) program on the physical performance and neuromuscular adaptations of female basketball players. Twenty-seven elite female basketball players (aged 21.0 ± 2.6 years) were assigned between an experimental group (n = 15) who substituted a part of their usual training with biweekly PT, and a control group (n = 12) who maintained their standard basketball training. Analyses of variance and co-variance assessed changes in 10, 20, and 30 m sprint times, ability to change direction (T-test) and jumping ability [squat jump (SJ) and countermovement jump (CMJ)] with electromyographic assessment of the vastus lateralis, vastus medialis, and rectus femoris muscles during jumping and meassurement of the isokinetic strength of the knee muscles. After 8 weeks of the plyometric program the experimental group enhanced change of direction performance (Δ = −3.90%, d = 0.67) and showed a greater thigh cross sectional area (Δ = 9.89%, d = 0.95) relative to controls. Neural adaptations included significant improvements of EMG parameters for the vastus medialis muscle during Squat Jumping (Δ = 109.3%, d = 0.59). However, trends to improvements of sprinting times and jumping performances did not reach statistical significance. In addition, there were no gains in the peak torque and the average power of the quadriceps and hamstring muscles at either slow or moderate test speeds. We conclude that 8-weeks of PT (72–126 jumps) was insufficient to improve many of the variables associated with basketball performance in our subject-group. Further studies of female basketball players, extending the program period and increasing the intensity and speed of jumps are recommended in the search for more significant results.
A Putative Serine Protease is Required to Initiate the RIPK3-MLKL—Mediated Necroptotic Death Pathway in Neutrophils

Adhesion receptors, such as CD44, have been shown to activate receptor interacting protein kinase-3 (RIPK3)—mixed lineage kinase-like (MLKL) signaling, leading to a non-apoptotic cell death in human granulocyte/macrophage colony-stimulating factor (GM-CSF) – primed neutrophils. The signaling events of this necroptotic pathway, however, remain to be investigated. In the present study, we report the design, synthesis, and characterization of a series of novel serine protease inhibitors. Two of these inhibitors, compounds 1 and 3, were able to block CD44-triggered necroptosis in GM-CSF-primed neutrophils. Both inhibitors prevented the activation of MLKL, p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3’—kinase (PI3K), hence blocking the increased levels of reactive oxygen species (ROS) required for cell death. Although compounds one and three partially inhibited isolated human neutrophil elastase (HNE) activity, we obtained no pharmacological evidence that HNE is involved in the initiation of this death pathway within a cellular context. Interestingly, neither serine protease inhibitor had any effect on FAS receptor-mediated apoptosis. Taken together, these results suggest that a serine protease is involved in non-apoptotic CD44-triggered RIPK3-MLKL-dependent neutrophil cell death, but not FAS receptor-mediated caspase-dependent apoptosis. Thus, a pharmacological block on serine proteases might be beneficial for preventing exacerbation of disease in neutrophilic inflammatory responses.
Evaluation of dissociation constants of ammonium ions in aqueous ammonium chloride and potassium chloride solutions and of pertinent higher-order parameters according to the Pitzer approach

Dissociation constants of NH+4 at 298.15 K in NH4Cl solutions, calculated in terms of Pitzer's equations, have been compared with observed ones. The values in up to 3 mol kg–1 solutions of NH4Cl, calculated with reported values for the higher-order terms θH N H4(both ionic strength-dependent and -independent) and ψH N H4Cl, agreed with the observed ones within experimental uncertainties, while the calculated values showed large deviations from the observed ones in solutions of NH4Cl more concentrated than 3 mol kg–1. Thus, the values for the higher-order terms were re-evaluated by fitting the dissociation constants observed in those solutions to the values calculated with Pitzer's equations. Values for higher-order terms θN H4K and ψN H4KCl pertaining to the dissociation of NH+4 in KCl solutions were determined by the same procedures. Activity coefficients of NH3 in NH4Cl and KCl solutions at 298.15 K, which were required for the calculation of the dissociation constants, were obtained by a transpiration method.
Combining Miconazole and Domiphen Bromide Results in Excess of Reactive Oxygen Species and Killing of Biofilm Cells

Fungal biofilm-related infections are increasingly occurring. We previously identified a fungicidal antibiofilm combination, consisting of miconazole (MCZ) and the quaternary ammonium compound domiphen bromide (DB). DB eliminates tolerance rather than altering the susceptibility to MCZ of various Candida spp. Here we studied the mode of action of the MCZ-DB combination in more detail. We found that DB's action increases the permeability of the plasma membrane as well as that of the vacuolar membrane of Candida spp. Furthermore, the addition of DB affects the intracellular azole distribution. MCZ is a fungicidal azole that, apart from its well-known inhibition of ergosterol biosynthesis, also induces accumulation of reactive oxygen species (ROS). Interestingly, the MCZ-DB combination induced significantly more ROS in C. albicans biofilms as compared to single compound treatment. Co-administration of the antioxidant ascorbic acid resulted in abolishment of the ROS generated by MCZ-DB combination as well as its fungicidal action. In conclusion, increased intracellular MCZ availability due to DB's action results in excess of ROS and enhanced fungal cell killing.
Development and Validation of a Sepsis Mortality Risk Score for Sepsis-3 Patients in Intensive Care Unit

Background: Many severity scores are widely used for clinical outcome prediction for critically ill patients in the intensive care unit (ICU). However, for patients identified by sepsis-3 criteria, none of these have been developed. This study aimed to develop and validate a risk stratification score for mortality prediction in sepsis-3 patients. Methods: In this retrospective cohort study, we employed the Medical Information Mart for Intensive Care III (MIMIC III) database for model development and the eICU database for external validation. We identified septic patients by sepsis-3 criteria on day 1 of ICU entry. The Least Absolute Shrinkage and Selection Operator (LASSO) technique was performed to select predictive variables. We also developed a sepsis mortality prediction model and associated risk stratification score. We then compared model discrimination and calibration with other traditional severity scores. Results: For model development, we enrolled a total of 5,443 patients fulfilling the sepsis-3 criteria. The 30-day mortality was 16.7%. With 5,658 septic patients in the validation set, there were 1,135 deaths (mortality 20.1%). The score had good discrimination in development and validation sets (area under curve: 0.789 and 0.765). In the validation set, the calibration slope was 0.862, and the Brier value was 0.140. In the development dataset, the score divided patients according to mortality risk of low (3.2%), moderate (12.4%), high (30.7%), and very high (68.1%). The corresponding mortality in the validation dataset was 2.8, 10.5, 21.1, and 51.2%. As shown by the decision curve analysis, the score always had a positive net benefit. Conclusion: We observed moderate discrimination and calibration for the score termed Sepsis Mortality Risk Score (SMRS), allowing stratification of patients according to mortality risk. However, we still require further modification and external validation.
The “C3aR Antagonist” SB290157 is a Partial C5aR2 Agonist

Innate immune complement activation generates the C3 and C5 protein cleavage products C3a and C5a, defined classically as anaphylatoxins. C3a activates C3aR, while C5a activates two receptors (C5aR1 and C5aR2) to exert their immunomodulatory activities. The non-peptide compound, SB290157, was originally reported in 2001 as the first C3aR antagonist. In 2005, the first report on the non-selective nature of SB290157 was published, where the compound exerted clear agonistic, not antagonistic, activity in variety of cells. Other studies also documented the non-selective activities of this drug in vivo. These findings severely hamper data interpretation regarding C3aR when using this compound. Unfortunately, given the dearth of C3aR inhibitors, SB290157 still remains widely used to explore C3aR biology (>70 publications to date). Given these issues, in the present study we aimed to further explore SB290157's pharmacological selectivity by screening the drug against three human anaphylatoxin receptors, C3aR, C5aR1 and C5aR2, using cell models. We identified that SB290157 exerts partial agonist activity at C5aR2 by mediating β-arrestin recruitment at higher compound doses. This translated to a functional outcome in both human and mouse primary macrophages, where SB290157 significantly dampened C5a-induced ERK signaling. We also confirmed that SB290157 acts as a potent agonist at human C3aR in transfected cells, but as an antagonist in primary human macrophages. Our results therefore provide even more caution against using SB290157 as a research tool to explore C3aR function. Given the reported immunomodulatory and anti-inflammatory activities of C5aR2 agonism, any function observed with SB290157 could be due to these off-target activities.
DICER1 Syndrome and Cancer Predisposition: From a Rare Pediatric Tumor to Lifetime Risk

DICER1 syndrome is a rare genetic condition predisposing to hereditary cancer and caused by variants in the DICER1 gene. The risk to present a neoplasm before the age of 10 years is 5.3 and 31.5% before the age of 60. DICER1 variants have been associated with a syndrome involving familial pleuropulmonary blastoma (PPB), a rare malignant tumor of the lung, which occurs primarily in children under the age of 6 years and represents the most common life-threatening manifestation of DICER1 syndrome. Type I, II, III, and Ir (type I regressed) PPB are reported with a 5-year overall survival ranging from 53 to 100% (for type Ir). DICER1 gene should be screened in all patients with PPB and considered in other tumors mainly in thyroid neoplasms (multinodular goiter, thyroid cancer, adenomas), ovarian tumors (Sertoli-Leydig cell tumor, sarcoma, and gynandroblastoma), and cystic nephroma. A prompt identification of this syndrome is necessary to plan a correct follow-up and screening during lifetime.