Miracle-dz/UniFAR-FTUs huggingface dataset:
Fluctuating NMDA Receptor Subunit Levels in Perirhinal Cortex Relate to Their Dynamic Roles in Object Memory Destabilization and Reconsolidation

Reminder cues can destabilize consolidated memories, rendering them modifiable before they return to a stable state through the process of reconsolidation. Older and stronger memories resist this process and require the presentation of reminders along with salient novel information in order to destabilize. Previously, we demonstrated in rats that novelty-induced object memory destabilization requires acetylcholine (ACh) activity at M1 muscarinic receptors. Other research predominantly has focused on glutamate, which modulates fear memory destabilization and reconsolidation through GluN2B- and GluN2A-containing NMDARs, respectively. In the current study, we demonstrate the same dissociable roles of GluN2B- and N2A-containing NMDARs in perirhinal cortex (PRh) for object memory destabilization and reconsolidation when boundary conditions are absent. However, neither GluN2 receptor subtype was required for novelty-induced destabilization of remote, resistant memories. Furthermore, GluN2B and GluN2A subunit proteins were upregulated selectively in PRh 24 h after learning, but returned to baseline by 48 h, suggesting that NMDARs, unlike muscarinic receptors, have only a temporary role in object memory destabilization. Indeed, activation of M1 receptors in PRh at the time of reactivation effectively destabilized remote memories despite inhibition of GluN2B-containing NMDARs. These findings suggest that cholinergic activity at M1 receptors overrides boundary conditions to destabilize resistant memories when other established mechanisms are insufficient.
Time-Lapse Flow Cytometry: A Robust Tool to Assess Physiological Parameters Related to the Fertilizing Capability of Human Sperm

Plasma membrane (PM) hyperpolarization, increased intracellular pH (pHi), and changes in intracellular calcium concentration ([Ca2+]i) are physiological events that occur during human sperm capacitation. These parameters are potential predictors of successful outcomes for men undergoing artificial reproduction techniques (ARTs), but methods currently available for their determination pose various technical challenges and limitations. Here, we developed a novel strategy employing time-lapse flow cytometry (TLFC) to determine capacitation-related membrane potential (Em) and pHi changes, and progesterone-induced [Ca2+]i increases. Our results show that TLFC is a robust method to measure absolute Em and pHi values and to qualitatively evaluate [Ca2+]i changes. To support the usefulness of our methodology, we used sperm from two types of normozoospermic donors: known paternity (subjects with self-reported paternity) and no-known paternity (subjects without self-reported paternity and no known fertility problems). We found relevant differences between them. The incidences of membrane hyperpolarization, pHi alkalinization, and increased [Ca2+]i were consistently high among known paternity samples (100%, 100%, and 86%, respectively), while they varied widely among no-known paternity samples (44%, 17%, and 45%, respectively). Our results indicate that TLFC is a powerful tool to analyze key physiological parameters of human sperm, which pending clinical validation, could potentially be employed as fertility predictors.
Effects of a Paediatric Antimicrobial Stewardship Program on Antimicrobial Use and Quality of Prescriptions in Patients with Appendix-Related Intraabdominal Infections

The effectiveness of antimicrobial stewardship programs (ASP) in reducing antimicrobial use (AU) in children has been proved. Many interventions have been described suitable for different institution sizes, priorities, and patients, with surgical wards being one of the areas that may benefit the most. We aimed to describe the results on AU and length of stay (LOS) in a pre-post study during the three years before (2014–2016) and the three years after (2017–2019) implementation of an ASP based on postprescription review with feedback in children and adolescents admitted for appendix-related intraabdominal infections (AR-IAI) in a European Referral Paediatric University Hospital. In the postintervention period, the quality of prescriptions (QP) was also evaluated. Overall, 2021 AR-IAIs admissions were included. Global AU, measured both as days of therapy/100 patient days (DOT/100PD) and length of therapy (LOT), and global LOS remained unchanged in the postintervention period. Phlegmonous appendicitis LOS (p = 0.003) and LOT (p < 0.001) significantly decreased, but not those of other AR-IAI diagnoses. The use of piperacillin–tazobactam decreased by 96% (p = 0.044), with no rebound in the use of other Gram-negative broad-spectrum antimicrobials. A quasisignificant (p = 0.052) increase in QP was observed upon ASP implementation. Readmission and case fatality rates remained stable. ASP interventions were safe, and they reduced LOS and LOT of phlegmonous appendicitis and the use of selected broad-spectrum antimicrobials, while increasing QP in children with AR-IAI.
In-Series U-Net Network to 3D Tumor Image Reconstruction for Liver Hepatocellular Carcinoma Recognition

Cancer is one of the common diseases. Quantitative biomarkers extracted from standard-of-care computed tomography (CT) scan can create a robust clinical decision tool for the diagnosis of hepatocellular carcinoma (HCC). According to the current clinical methods, the situation usually accounts for high expenditure of time and resources. To improve the current clinical diagnosis and therapeutic procedure, this paper proposes a deep learning-based approach, called Successive Encoder-Decoder (SED), to assist in the automatic interpretation of liver lesion/tumor segmentation through CT images. The SED framework consists of two different encoder-decoder networks connected in series. The first network aims to remove unwanted voxels and organs and to extract liver locations from CT images. The second network uses the results of the first network to further segment the lesions. For practical purpose, the predicted lesions on individual CTs were extracted and reconstructed on 3D images. The experiments conducted on 4300 CT images and LiTS dataset demonstrate that the liver segmentation and the tumor prediction achieved 0.92 and 0.75 in Dice score, respectively, by as-proposed SED method.
Detoxication versus Bioactivation Pathways of Lapatinib In Vitro: UGT1A1 Catalyzes the Hepatic Glucuronidation of Debenzylated Lapatinib

O-Dealkylation of the tyrosine kinase inhibitor lapatinib by cytochrome P450 3A enzymes is implicated in the development of lapatinib-induced hepatotoxicity. Conjugative metabolism of debenzylated lapatinib (M1) via glucuronidation and sulfation is thought to be a major detoxication pathway for lapatinib in preclinical species (rat and dog), limiting formation of the quinoneimine reactive metabolite. Glucuronidation of M1 by human recombinant UDP-glucuronosyltransferases (UGTs) has been reported in vitro; however, the relative UGT enzyme contributions are unknown, and the interspecies differences in the conjugation versus bioactivation pathways of M1 have not been fully elucidated. In the present study, reaction phenotyping experiments using human recombinant UGT enzymes and enzyme-selective chemical inhibitors demonstrated that UGT1A1 was the major hepatic UGT enzyme involved in lapatinib M1 glucuronidation. Formation of the M1-glucuronide by human liver microsomes from UGT1A1-genotyped donors was significantly correlated with UGT1A1 activity as measured by 17β-estradiol 3-glucuronidation (R2 = 0.90). Interspecies differences were found in the biotransformation of M1 in human, rat, and dog liver microsomal and 9000g supernatant (S9) fractions via glucuronidation, sulfation, aldehyde oxidase–mediated oxidation, and bioactivation to the quinoneimine trapped as a glutathione (GSH) conjugate. Moreover, we demonstrated the sequential metabolism of lapatinib in primary human hepatocytes to the M1-glucuronide, M1-sulfate, and quinoneimine-GSH conjugate. M1 glucuronidation was highly correlated with the rates of M1 formation, suggesting that O-dealkylation may be the rate-limiting step in lapatinib biotransformation. Interindividual variability in the formation and clearance pathways of lapatinib M1 likely influences the hepatic exposure to reactive metabolites and may affect the risk for hepatotoxicity. SIGNIFICANCE STATEMENT We used an integrated approach to examine the interindividual and interspecies differences in detoxication versus bioactivation pathways of lapatinib, which is associated with idiosyncratic hepatotoxicity. In addition to cytochrome P450 (P450)-mediated bioactivation, we report that multiple non-P450 pathways are involved in the biotransformation of the primary phenolic metabolite of lapatinib in vitro, including glucuronidation, sulfation, and aldehyde oxidase mediated oxidation. UGT1A1 was identified as the major hepatic enzyme involved in debenzylated lapatinib glucuronidation, which may limit hepatic exposure to the potentially toxic quinoneimine.
Norditerpenoid alkaloids from the aerial parts of Aconitum cochleare WOROSCHIN

From the aerial parts of Aconitum cochleareWoroschin, two new norditerpenoid alkaloids named aconitilearine (1) and N-deethylmethyllycaconitine (2) were isolated along with the eight known norditerpenoid alkaloids 3–10. The structures for the new compounds were established on the basis of 1H, 13C, DEPT, homonuclear 1H,1H-COSY, NOESY, HSQC, and HMBC NMR studies.
Variation of Pulegone Content in Pennyroyal (Mentha pulegium L.) Plants Growing Wild in Greece

Abstract The study of the essential oils obtained from 10 wild Mentha pulegium L. populations scattered all over Greece has shown that the content of pulegone varies greatly, ranging from <0.1–90.7% of tin total oil. Only two populations have oils rich in pulegone (42.9% and 90.7%), whereas the rest have a low pulegone content (up to 35.6%). The latter are rich either in menthone/isomenthone or in piperitone/piperitenone or in piperitone (up to 97.2% of the total oil).
Influence of the β− Radiation/Cold Atmospheric-Pressure Plasma Surface Modification on the Adhesive Bonding of Polyolefins

The goal of this research was to examine the effect of two surface modification methods, i.e., radiation cross-linking and plasma treatment, on the adhesive properties and the final quality of adhesive bonds of polypropylene (PP), which was chosen as the representative of the polyolefin group. Polymer cross-linking was induced by beta (accelerated electrons—β−) radiation in the following dosages: 33, 66, and 99 kGy. In order to determine the usability of β− radiation for these applications (improving the adhesive properties and adhesiveness of surface layers), the obtained results were compared with values measured on surfaces treated by cold atmospheric-pressure plasma with outputs 2.4, 4, and 8 W. The effects of both methods were compared by several parameters, namely wetting contact angles, free surface energy, and overall strength of adhesive bonds. Furthermore, Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) were conducted. According to our findings the following conclusion was reached; both tested surface modification methods significantly altered the properties of the specimen’s surface layer, which led to improved wetting, free surface energy, and bond adhesion. Following the β− radiation, the free surface energy of PP rose by 80%, while the strength of the bond grew in some cases by 290% in comparison with the non-treated surface. These results show that when compared with cold plasma treatment the beta radiation appears to be an effective tool capable of improving the adhesive properties and adhesiveness of PP surface layers.
Types of 23S Ribosomal RNA Point Mutations and Therapeutic Outcomes for Helicobacter pylori

Background/Aims Point mutations in the 23S ribosomal RNA gene have been associated with Helicobacter pylori clarithromycin resistance. This study aimed to detect the prevalence of these point mutations and to investigate the role of different point mutations in the success of eradication therapy. Methods We retrospectively investigated a total of 464 consecutive patients who underwent an endoscopic examination and dual-priming oligonucleotide-based multiplex polymerase chain reaction for H. pylori between June 2014 and October 2019. For 289 patients with negative point mutations, standard triple therapy was used in 287 patients, and the bismuth-quadruple regimen was used in two patients. For 175 patients with positive point mutations (A2142G, A2143G, and both mutations), standard triple and bismuth-quadruple therapies were used in 37 patients and 138 patients, respectively. Results The eradication rates of standard triple and bismuth-quadruple therapies showed no significant difference in mutation-negative patients or those with the A2142G point mutation. However, the eradication rate with bismuth-quadruple therapy was significantly higher than that with standard triple therapy in the group with the A2143G mutation or with the double mutation. The eradication rates for standard triple and bismuth-quadruple therapies, respectively, were 25.8% and 92.1% in the per-protocol group (p<0.001) and 24.2% and 85.2% in the intention-to-treat analysis (p<0.001). Conclusions The A2143G point mutation is the most prevalent cause of clarithromycin resistance. Bismuth-quadruple therapy is superior to standard triple therapy in patients with the A2143G or double point mutation.
Electrochemical Determination of Glucose in Human Serum Utilizing a Novel Nanocomposite Composed of Copper Nanoparticles in a Hollow Carbon Shell

A novel nanocomposite composed of copper nanoparticles encapsulated in a hollow carbon shell was prepared. The thin, porous carbon shell ensured efficient mass and electron transport and provided a confined environment for electrochemical reactions. The Cu@C nanocomposite exhibited favorable electrocatalytic activity toward glucose and superior electrochemical sensing performance toward glucose, with a low limit of detection (1 µM) and a wide linear dynamic range (0.0–6.1 mM). Good selectivity, reproducibility, and stability were obtained. The application of the sensor for the determination of glucose in human serum demonstrated its use for practical analysis.
Deep Brain Stimulation for Alzheimer's Disease: Tackling Circuit Dysfunction

Treatments for Alzheimer's disease are urgently needed given its enormous human and economic costs and disappointing results of clinical trials targeting the primary amyloid and tau pathology. On the other hand, deep brain stimulation (DBS) has demonstrated success in other neurological and psychiatric disorders leading to great interest in DBS as a treatment for Alzheimer's disease.
Correlation between total homocysteine and cerebral small vessel disease: A Mendelian randomization study

Cerebral small vessel disease (CSVD) is a clinical imaging syndrome with diverse etiology. Total homocysteine (HCY) level might increase the risk of myocardial and cerebral infarction by damaging the vascular endothelium. We aimed to explore the correlation between total HCY and CSVD imaging burden, based on Mendelian randomization methods.
Relationship between School Integration, Psychosocial Adjustment and Cyber-Aggression among Adolescents

The aim of this study was to analyze the relationships between sociometric types in the classroom—rejected, preferred, neglected, controversial and average—and psychological discomfort, life satisfaction and cyber-aggression, based on the adolescent’s gender. 2398 adolescents of both sexes participated in the study (49.8% girls), aged between 12 and 18 years (M = 16.03, SD = 1.91). Multivariate analyses of variance were performed. The results showed significant relationships between sociometric types, life satisfaction and cyber-aggression. Rejected adolescents also showed less satisfaction with life and greater cyber-aggression. Furthermore, the boys, regardless of their sociometric type in the classroom, displayed less psychological distress and less involvement in cyber-aggression. Controversial adolescents also showed greater involvement in cyber-aggression. Finally, programs should be promoted for the prevention of social difficulties in the school, based on the promotion of social integration, not only in the classroom, but also on the Internet.
Establishment and validation of nomogram model for survival predicting in patients with spinal metastases secondary to lung cancer

ABSTRACT Objectives To evaluate the prognostic effect of pre-treatment factors in patients with spinal metastases secondary to lung cancer, and establish a novel predicting nomogram for predicting the survival probability. Methods A total of 209 patients operated for spinal metastases from lung cancer were consecutively enrolled, and divided into the training and validation samples with a ratio of 7:3, for model establishing and validating, respectively. Basing on the training sample, univariate and multivariate COX proportional hazard models were used for identifying the prognostic effect of pre-treatment factors, following which significant prognostic factors would be listed as items in nomogram to calculate the survival probabilities at 3, 6, 12 and 18 months. Then, the C-indexes and the calibration curves would be figured out to evaluate the discrimination ability and accuracy of the model both for the training and validation samples. Results In the multivariate COX analysis, the gender, smoking history, location of spinal metastasis, visceral metastasis, Karnofsky performance status (KPS), adjuvant therapy, lymphocyte percentage and globulin were found to be significantly associated with the overall survival, and a novel nomogram was generated basing on these independent predictors. The C-indexes for the training and validation samples were 0.761 and 0.732, respectively. Favorable consistencies between the predicted and actual survival rates were demonstrated both in the internal and external validations. Discussion Pre-treatment characteristics, including gender, smoking history, location of spinal metastasis, visceral metastasis, KPS, adjuvant therapy, percentage of lymphocyte, and serum globulin level, were identified to be significantly associated with overall survival of patients living with spinal metastases derived from lung cancer, and a user-friendly nomogram was established using these independent predictors.
Bayesian Spatial Survival Analysis of Duration to Cure among New Smear-Positive Pulmonary Tuberculosis (PTB) Patients in Iran, during 2011–2018

Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), and pulmonary TB is the most prevalent form of the disease worldwide. One of the most concrete actions to ensure an effective TB control program is monitoring TB treatment outcomes, particularly duration to cure; but, there is no strong evidence in this respect. Thus, the primary aim of this study was to examine the possible spatial variations of duration to cure and its associated factors in Iran using the Bayesian spatial survival model. All new smear-positive PTB patients have diagnosed from March 2011 to March 2018 were included in the study. Out of 34,744 patients, 27,752 (79.90%) patients cured and 6992 (20.10%) cases were censored. For inferential purposes, the Markov chain Monte Carlo algorithms are applied in a Bayesian framework. According to the Bayesian estimates of the regression parameters in the proposed model, a Bayesian spatial log-logistic model, the variables gender (male vs. female, TR = 1.09), altitude (>750 m vs. ≤750 m, TR = 1.05), bacilli density in initial smear (3+ and 2+ vs. 1–9 Basil & 1+, TR = 1.09 and TR = 1.02, respectively), delayed diagnosis (>3 months vs. <1 month, TR = 1.02), nationality (Iranian vs. other, TR = 1.02), and location (urban vs. rural, TR = 1.02) had a significant influence on prolonging the duration to cure. Indeed, pretreatment weight (TR = 0.99) was substantially associated with shorter duration to cure. In summary, the spatial log-logistic model with convolution prior represented a better performance to analyze the duration to cure of PTB patients. Also, our results provide valuable information on critical determinants of duration to cure. Prolonged duration to cure was observed in provinces with low TB incidence and high average altitude as well. Accordingly, it is essential to pay a special attention to such provinces and monitor them carefully to reduce the duration to cure while maintaining a focus on high-risk provinces in terms of TB prevalence.
Numerical and Experimental Investigation of the Opposite Influence of Dielectric Anisotropy and Substrate Bending on Planar Radiators and Sensors

The simultaneous influences of the substrate anisotropy and substrate bending are numerically and experimentally investigated in this paper for planar resonators on flexible textile and polymer substrates. The pure bending effect has been examined by the help of well-selected flexible isotropic substrates. The origin of the anisotropy (direction-depended dielectric constant) of the woven textile fabrics has been numerically and then experimentally verified by two authorship methods described in the paper. The effect of the anisotropy has been numerically divided from the effect of bending and for the first time it was shown that both effects have almost comparable but opposite influences on the resonance characteristics of planar resonators. After the selection of several anisotropic textile fabrics, polymers, and flexible reinforced substrates with measured anisotropy, the opposite influence of both effects, anisotropy and bending, has been experimentally demonstrated for rectangular resonators. The separated impacts of the considered effects are numerically investigated for more sophisticated resonance structures—with different types of slots, with defected grounds and in fractal resonators for the first three fractal iterations. The bending effect is stronger for the slotted structures, while the effect of anisotropy predominates in the fractal structures. Finally, useful conclusions are formulated and the needs for future research are discussed considering effects in metamaterial wearable patches and antennas.
JZL184 protects hippocampal neurons from oxygen-glucose deprivation-induced injury via activating Nrf2/ARE signaling pathway

JZL184 is a selective inhibitor of monoacylglycerol lipase (MAGL) that has neuroprotective effect. However, the role of JZL184 in cerebral ischemia/reperfusion (I/R) injury and the exact mechanism have not been fully understood. This study was designed to elucidate the role of JZL184 in cerebral I/R injury induced by oxygen-glucose deprivation/reoxygenation (OGD/R) in hippocampal neurons. Hippocampal neurons were pretreated with various concentrations of JZL184 for 2 h, followed by OGD for 3 h and reoxygen for 24 h. Our results showed that JZL184 improved cell viability in hippocampal neurons in response to OGD/R. JZL184 treatment significantly inhibited the production of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as increased superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities in OGD/R-induced hippocampal neurons. The increased TNF-α, IL-1β, and IL-6 productions in OGD/R-induced hippocampal neurons were decreased after treatment with JZL184. Moreover, the OGD/R-caused intense TUNEL staining in hippocampal neurons was attenuated by JZL184. JZL184 treatment prevented OGD/R-caused increases in bax and cleaved caspase-3 expression and a decrease in bcl-2 expression. Furthermore, JZL184 treatment significantly promoted the activation of Nrf2/ARE signaling pathway in OGD/R-induced hippocampal neurons. Additionally, silencing of Nrf2 reversed the protective effect of JZL184 on hippocampal neurons under OGD/R condition. Taken together, these findings suggested that JZL184 exerted protective effect against OGD/R-induced injury in hippocampal neurons via activating Nrf2/ARE signaling pathway, which provided in vitro experimental support for the therapeutic benefit of JZL184 in cerebral ischemia.