Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurourology and Urodynamics

Funding information Fonds Wetenschappelijk Onderzoek, Grant/Award Number: G069715N Abstract Background: Although pelvic floor dysfunction (PFD) has a multifactorial etiology, pregnancy and childbirth are considered crucial events predisposing to urinary incontinence as well as pelvic organ prolapse, which are highly prevalent. Rats are the most frequently used animal model and pudendal nerve crush (PNC) and vaginal distension (VD) are often used to mimic vaginal delivery. Objective: To document the time course of events after simulated vaginal delivery (SVD) on the urethral sphincter and the vaginal smooth muscle layer. Materials and Methods: Virgin female Sprague‐Dawley rats were subjected to SVD (PNC+VD) or sham surgery and evaluated at 7, 14, 21, and 42 days after the injury. Urethral function was determined in vivo by microultrasound during cystometry and vaginal smooth muscle layer was harvested for in vitro pharmacologic investigation by isometric tension recording. Furthermore, vaginal and urethral samples were investigated by immunohistochemistry and real‐time quantitative polymerase chain reaction. Results: Microultrasound showed no bursting of the urethral sphincter in the SVD group at 7 days with a functional recovery starting at 14 days, and normal bursting at 21 and 42 days. Vaginal smooth muscle showed higher sensitivity to carbachol at 14 and 21 days after injury; however, at 42 days, its sensitivity decreased when compared with sham. Conclusion: SVD induces urethral dysfunction and a shift in vaginal smooth muscle contractile responses to carbachol.
PERIOD1 coordinates hippocampal rhythms and memory processing with daytime

In species ranging from flies to mammals, parameters of memory processing, like acquisition, consolidation, and retrieval are clearly molded by time of day. However, mechanisms that regulate and adapt these temporal differences are elusive, with an involvement of clock genes and their protein products suggestive. Therefore, we analyzed initially in mouse hippocampus the daytime‐dependent dynamics of parameters, known to be important for proper memory formation, like phosphorylation of the “memory molecule” cyclic adenosine monophosphate (cAMP) responsive element binding protein (CREB) and chromatin remodeling. Next, in an effort to characterize the mechanistic role of clock genes within hippocampal molecular dynamics, we compared the results obtained from wildtype (WT) ‐mice and mice deficient for the archetypical clock gene Period1 (Per1‐/‐‐mice). We detected that the circadian rhythm of CREB phosphorylation in the hippocampus of WT mice disappeared completely in mice lacking Per1. Furthermore, we found that the here for the first time described profound endogenous day/night rhythms in histone modifications in the hippocampus of WT‐mice are markedly perturbed in Per1‐/‐‐mice. Concomitantly, both, in vivo recorded LTP, a cellular correlate for long‐term memory, and hippocampal gene expression were significantly altered in the absence of Per1. Notably, these molecular perturbations in Per1‐/‐‐mice were accompanied by the loss of daytime‐dependent differences in spatial working memory performance. Our data provide a molecular blueprint for a novel role of PER1 in temporally shaping the daytime‐dependency of memory performance, likely, by gating CREB signaling, and by coupling to downstream chromatin remodeling. © 2014 Wiley Periodicals, Inc.
Neurourology and Urodynamics

Correspondence Marcio A. Averbeck, Department of Urology, Moinhos de Vento Hospital, 333 Tiradentes St, Sixth Floor— Videourodynamics, Porto Alegre 90560030, Brazil. Email: marcioaverbeck@gmail.com Abstract Aims: To review current prevention strategies for urinary incontinence among patients undergoing radical prostatectomy (RP). Methods: This is a consensus report of the proceedings of a research proposal from the annual International Consultation on Incontinence‐Research Society (ICI‐RS), 14 to 16 June 2018 (Bristol, UK): “How can we prevent postprostatectomy incontinence by patient selection, and by preoperative, peroperative, and postoperative measures? ” Results: Several baseline parameters were proposed as predicting factors for postprostatectomy urinary incontinence (PPUI), including age, tumor stage, prostate volume, preoperative lower urinary tract symptoms, maximum urethral closure pressure, and previous transurethral resection of the prostate. More recently, magnetic resonance imaging has been used to measure the membranous urethral length and sphincter volume. Peroperative techniques include preservative and reconstructive approaches. Bladder neck preservation improved early (6 months), as well as long‐term (>12 months) continence rates. Several prospective studies have reported earlier return of continence following preservation of puboprostatic ligaments, although no long‐term data are available. Preservation of the urethral length yielded controversial outcomes. Concerning postoperative strategies, it is probably optimal to remove the catheter in a window between 4 and 7 days if clinically appropriate; however, more research in this regard is still required. Postoperative PFME (preoperative pelvic floor muscle exercise) appears to speed up the recovery of continence after RP. Conclusions: Conservative strategies to prevent PPUI include proper patient selection and PFME. Peroperative techniques have largely shown benefit in the short term. Postoperative complications and timing of trial without catheter can influence continence status. Future research initiatives must assess peroperative and postoperative measures, with longer‐term follow‐up.
Repressor binding to a dorsal regulatory site traps human eIF4E in a high cap‐affinity state

Eukaryotic translation initiation involves recognition of the 5′ end of cellular mRNA by the cap‐binding complex known as eukaryotic initiation factor 4F (eIF4F). Initiation is a key point of regulation in gene expression in response to mechanisms mediated by signal transduction pathways. We have investigated the molecular interactions underlying inhibition of human eIF4E function by regulatable repressors called 4E‐binding proteins (4E‐BPs). Two essential components of eIF4F are the cap‐binding protein eIF4E, and eIF4G, a multi‐functional protein that binds both eIF4E and other essential eIFs. We show that the 4E‐BPs 1 and 2 block the interaction between eIF4G and eIF4E by competing for binding to a dorsal site on eIF4E. Remarkably, binding of the 4E‐BPs at this dorsal site enhances cap‐binding via the ventral cap‐binding slot, thus trapping eIF4E in inactive complexes with high affinity for capped mRNA. The binding contacts and affinities for the interactions between 4E‐BP1/2 and eIF4E are distinct (estimated Kd values of 10−8 and 3×10−9 for 4E‐BP1 and 2, respectively), and the differences in these properties are determined by three amino acids within an otherwise conserved motif. These data provide a quantitative framework for a new molecular model of translational regulation.
Two-Process Models of Recognition Memory: Evidence for Recall-to-Reject?

Abstract According to two-process accounts of recognition memory, a familiarity-based process is followed by a slower, more accurate, recall-like process. The dominant two-process account is the recall-to-reject account, in which this second process facilitates the rejection of similar foils. To evaluate the recall-to-reject account, we reanalyzed two experiments from Hintzman and Curran (1994) in which subjects made word recognition judgments at different response deadlines, and we conducted two new recognition experiments using pairs of similar pseudowords. The new analyses included modeling at both the group and individual subject levels. The results did not provide any distinctive evidence for recall-to-reject. In addition to discussing this two-process account, we describe a one-process account of recognition, in which the nature of similarity information varies across the course of judgment.
Isolation and Characterization of Collagen and Antioxidant Collagen Peptides from Scales of Croceine Croaker (Pseudosciaena crocea)

Acid soluble collagen (ASC) from scales of croceine croaker (ASC-C) was successfully isolated with the yield of 0.37% ± 0.08% (dry weight basis), and characterized as type I collagen on the basis of amino acid analysis and electrophoretic pattern. The antioxidant hydrolysate of ASC-C (ACH) was prepared through a two-stage in vitro digestion (4-h trypsin followed by 4-h pepsin), and three antioxidant peptides (ACH-P1, ACH-P2, and ACH-P3) were further isolated from ACH using ultrafiltration, gel chromatography, and RP-HPLC, and their amino acid sequences were identified as GFRGTIGLVG (ACH-P1), GPAGPAG (ACH-P2), and GFPSG (ACH-P3). ACH-P1, ACH-P2, and ACH-P3 showed good scavenging activities on hydroxyl radical (IC50 0.293, 0.240, and 0.107 mg/mL, respectively), DPPH radical (IC50 1.271, 0.675, and 0.283 mg/mL, respectively), superoxide radical (IC50 0.463, 0.099, and 0.151 mg/mL, respectively), and ABTS radical (IC50 0.421, 0.309, and 0.210 mg/mL, respectively). ACH-P3 was also effectively against lipid peroxidation in the model system. The antioxidant activities of three collagen peptides were due to the presence of hydrophobic amino acid residues within the peptide sequences. The collagen peptides might be used as antioxidant for the therapy of diseases associated with oxidative stress, or reducing oxidative changes during storage.
Review article: Luminex technology for HLA antibody detection in organ transplantation

Since its inception in the early 1960s, the serologically based complement‐dependent cytotoxicity (CDC) assay has been the cornerstone technique for the detection of human leucocyte antigen (HLA) antibodies, not only in pre‐transplant renal patients, but also in other forms of organ transplantation. Recently, solid phase assays have been developed and introduced for this purpose, and in particular the Flow‐based bead assays such as the Luminex system. This latter assay has proved to be far more sensitive than the CDC assay and has revealed pre‐sensitization in potential transplant recipients not detected by other methods of HLA antibody detection. However, the clinical implications of this increased sensitivity have not been convincingly demonstrated until recently. This technology for HLA antibody detection permits the evaluation of the clinical importance of antibodies directed at, for example, HLA‐DPB1 and HLA‐DQA1, which has not been possible to date. There are Luminex issues, however, requiring resolution such as the ability to distinguish between complement fixing and non‐complement fixing antibodies and determination of their relative clinical significance. Luminex technology will permit a re‐evaluation of the role of HLA antibodies in both early and late antibody‐mediated rejection.
NAC Attenuates LPS-Induced Toxicity in Aspirin-Sensitized Mouse Macrophages via Suppression of Oxidative Stress and Mitochondrial Dysfunction

Bacterial endotoxin lipopolysaccharide (LPS) induces the production of inflammatory cytokines and reactive oxygen species (ROS) under in vivo and in vitro conditions. Acetylsalicylic acid (ASA, aspirin) is a commonly used anti-inflammatory drug. Our aim was to study the effects of N-acetyl cysteine (NAC), an antioxidant precursor of GSH synthesis, on aspirin-sensitized macrophages treated with LPS. We investigated the effects of LPS alone and in conjunction with a sub-toxic concentration of ASA, on metabolic and oxidative stress, apoptosis, and mitochondrial function using J774.2 mouse macrophage cell line. Protection from LPS-induced toxicity by NAC was also studied. LPS alone markedly induced ROS production and oxidative stress in macrophage cells. When ASA was added to LPS-treated macrophages, the increase in oxidative stress was significantly higher than that with LPS alone. Similarly, alteration in glutathione-dependent redox metabolism was also observed in macrophages after treatment with LPS and ASA. The combination of LPS and ASA selectively altered the CYP 3A4, CYP 2E1 and CYP 1A1 catalytic activities. Mitochondrial respiratory complexes and ATP production were also inhibited by LPS-ASA treatment. Furthermore a higher apoptotic cell death was also observed in LPS-ASA treated macrophages. NAC pre-treatment showed protection against oxidative stress induced apoptosis and mitochondrial dysfunction. These effects are presumed, at least in part, to be associated with alterations in NF-κB/Nrf-2 mediated cell signaling. These results suggest that macrophages are more sensitive to LPS when challenged with ASA and that NAC pre-treatment protects the macrophages from these deleterious effects.
Vascular Age as a Cardiovascular Risk Marker in Asymptomatic Patients with Type 2 Diabetes Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy

Aim: There is a wide variety of cardiovascular outcomes in patients with type 2 diabetes (T2DM), even in asymptomatic individuals. Carotid intima-media thickness (CIMT) is a marker of subclinical atherosclerosis and can be considered as a predictor of cardiovascular risk (CVR). The aim of this study was to evaluate the relationship between CIMT-determined vascular age (VA), CVR scores, and thyroid function in asymptomatic patients with T2DM. Patients and Methods: Clinical laboratory and CIMT parameters were measured in 154 asymptomatic patients with T2DM. The Framingham risk score (FRS) was performed with chronological age (CA) and with VA. A multinomial logistic regression model was used to analyze variables related to CVR reclassi ﬁ cation. Results: The use of CIMT-determined VA led to the reclassi ﬁ cation of 54 (35.52%) out of 152 asymptomatic T2DM patients, being 20 (37.03%) to a lower categorical risk and 34 (62.96%) to a higher categorical risk according to FRS. The variables that were associated to reclassi ﬁ cation to a higher categorical risk were positive family history (FH) of premature coronary artery disease (p=0.046), FH of thyroid disease (p=0.010), use of statins (p=0.027), and free T4 levels (p=0.009). Conclusion: VA determined from CIMT allowed the reclassi ﬁ cation of the CVR in asymptomatic T2DM patients. FH of premature CAD, FH of known thyroid disease, use of statins, and free T4 levels were associated to a reclassi ﬁ cation into a higher risk category. The use of doppler to perform CIMT measure is currently more accessible, especially in a low-middle income country like Brazil. However, further prospective studies must be performed to establish the predictive values of CIMT on atherosclerosis and how thyroid function acts like cardiovascular risk marker on CVR scores.
Update on Targeted Therapies for Advanced Non-Small Cell Lung Cancer: Durvalumab in Context

: Immune checkpoint inhibitors (ICIs) have transformed the therapeutic strategy and prognosis of advanced non-small cell lung cancer (NSCLC) patients. Nowadays, ICIs as monotherapy or in combination with chemotherapy are the standard of care treatment in advanced NSCLC, and in stage III, durvalumab (a programmed death ligand 1 inhibitor) is the unique drug approved as consolidation treatment after chemo-radiotherapy. This article reviews the pharmacological properties, clinical activity and safety of durvalumab as monotherapy or in combination with chemotherapy or other ICIs in the therapeutic strategy of NSCLC patients.
Random-noise suppression in seismic data: What can deep learning do?

In the past few years, deep learning has gained great success in image signal and information processing. What are the challenges of seismic denoising compared to image denoising when using deep learning? First, the clean training seismic data are usually unavailable. Secondly, most of the networks are set for two-dimensional (2D) image denoising. However, seismic data denoising is mainly aiming at three-dimensional (3D) or higher dimensional data. Whether it works when expanding the network from 2D to 3D or higher dimension for seismic denoising? Finally, the most importance thing is to learn what aspects has been enhanced from deep learning compared to conventional methods for seismic denoising. This abstract takes random noise suppression in 3D poststack seismic data processing as an example to discuss the application of deep learning in seismic denoising. Except for white noise, there are imaging noise and scattered noise due to near surface non-uniformity in seismic data. This means 3D seismic random noise is usually non-Gaussian. According to the features of seismic noise, we propose 3D denoising convolutional neural networks (3D-DnCnn) incorporating sample screening. The seismic data acquired in a survey covering 700 square kilometers are used in our test. A small part of data with high signal-to-noise ratio (SNR) is selected for training. Other data are used for testing. The test results show that the network has similar random noise attenuation performance to conventional methods. Moreover, it can extract features of noise from the overall situation and thus has better suppressing performance of imaging noise. In addition, we adopt residual learning and batch normalization for accelerating training speed. And after network training is satisfactorily completed, its processing efficiency can be significantly faster than conventional denoising methods.
Chronic exposure to graphene‐based nanomaterials induces behavioral deficits and neural damage in Caenorhabditis elegans

Nanomaterials of graphene and its derivatives have been widely applied in recent years, but whose impacts on the environment and health are still not well understood. In the present study, the potential adverse effects of graphite (G), graphite oxide nanoplatelets (GO) and graphene quantum dots (GQDs) on the motor nervous system were investigated using nematode Caenorhabditis elegans as the assay system. After being characterized using TEM, SEM, XPS and PLE, three nanomaterials were chronically exposed to C. elegans for 6 days. In total, 50–100 mg l−1 GO caused a significant reduction in the survival rate, but G and GDDs showed low lethality on nematodes. After chronic exposure of sub‐lethal dosages, three nanomaterials were observed to distribute primarily in the pharynx and intestine; but GQDs were widespread in nematode body. Three graphene‐based nanomaterials resulted in significant declines in locomotor frequency of body bending, head thrashing and pharynx pumping. In addition, mean speed, bending angle‐frequency and wavelength of the crawling movement were significantly reduced after exposure. Using transgenic nematodes, we found high concentrations of graphene‐based nanomaterials induced down‐expression of dat‐1::GFP and eat‐4::GFP, but no significant changes in unc‐47::GFP. This indicates that graphene‐based nanomaterials can lead to damages in the dopaminergic and glutamatergic neurons. The present data suggest that chronic exposure of graphene‐based nanomaterials may cause neurotoxicity risks of inducing behavioral deficits and neural damage. These findings provide useful information to understand the toxicity and safe application of graphene‐based nanomaterials. Copyright © 2017 John Wiley & Sons, Ltd.
Surgical flow modification of the anterior cerebral artery-anterior communicating artery complex in the management of giant aneurysms of internal carotid artery bifurcation: An alternative for a difficult clip reconstruction

Background: Internal carotid artery bifurcation (ICAb) aneurysms account for about 2–15% of all intracranial aneurysms. In giant and complex cases, treatment may be difficult and dangerous, once some aneurysms have wide neck and anterior cerebral artery (ACA) and middle cerebral artery (MCA) may arise from the aneurysm itself. Clip reconstruction may be difficult in such cases. Whenever possible, the occlusion of ACA transform the bifurcation in a single artery reconstruction (ICA to MCA), much easier than a bifurcation reconstruction. Methods: In patients with giant and complex ICAb aneurysms, we propose routine preoperative angiography with anatomical evaluation of anterior communicating artery (ACoA) patency during cervical common carotid compression with concomitant contralateral carotid artery injection. This allowed visualization of the expected reversal of flow in the A1 segment–ACoA complex. When test is positive, we can perform ipsilateral ACA (A1 segment) clip occlusion and flow modification of the ACA-ACoA complex transforming a three vessel (ICA, ACA, and MCA) reconstruction into a two vessel (ICA and MCA) reconstruction. Results: Two patients were treated, with 100% of occlusion and good outcome. Conclusions: Surgical treatment of giant and complex ICAb may be achieved with acceptable morbidity.
Incorporating Opponent Models into Adversary Search

This work presents a generalized theoretical framework that allows incorporation of opponent models into adversary search. We present the M* algorithm, a generalization of minimax that uses an arbitrary opponent model to simulate the opponent's search. The opponent model is a recursive structure consisting of the opponent's evaluation function and its model of the player. We demonstrate experimentally the potential benefit of using an opponent model. Pruning in M* is impossible in the general case. We prove a sufficient condition for pruning and present the αβ* algorithm which returns the M* value of a tree while searching only necessary branches.
Relationship between Sociodemographic and Health-Related Factors and Sedentary Time in Middle-Aged and Older Adults in Taiwan

Background and Objectives: This study aimed to investigate the associations between sociodemographic and health-related factors and sedentary time in middle-aged and older Taiwanese adults. Materials and Methods: A total of 1031 participants (460 men, 571 women; mean age 65.0 years ± 7.8 years; range 55 to 93 years) were randomly recruited from the National Computer Assessment Telephone Interview, Taiwan, in 2013. Sedentary time, TV viewing, physical activity, and sociodemographic factors were assessed through questionnaires. Body mass index was self-reported and calculated to evaluate obesity. In 2023, the associations between sedentary time and sociodemographic and health-related factors were analyzed using Pearson’s correlation, cross tabulation, and logistic regression and were stratified by gender. Results: Over 47% of participants reported spending more than 2 h watching TV, and more than 33% reported engaging in over 6 h of total sedentary activities. Men and women with insufficient physical activity had a higher probability of prolonged sedentary time than their physically active counterparts (p = 0.032 for men, p = 0.024 for women). Both men and women who spent more than 2 h watching TV daily were more likely to have high sedentary time compared to those with shorter TV viewing durations (both p < 0.001). Highly educated and unmarried women exhibited a higher likelihood of prolonged sedentary time than their less educated and married counterparts (p = 0.021 and p = 0.01, respectively). Conclusions: Sedentary time showed significant and positive associations with both insufficient physical activity and prolonged TV viewing in both genders. Additionally, significant associations were observed between sedentary time and high education and unmarried status in women. These findings emphasize the importance of implementing gender-specific approaches in future interventions and policy initiatives aimed at reducing sedentary behavior among middle-aged and older adults.