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Background: Our recent analyses of miRNA expression signatures showed that miR-1 and miR-133a were significantly reduced in several types of cancer. Interestingly, miR-1 and miR-133a are located on the same chromosomal locus in the human genome. We examined the functional significance of miR-1 and miR-133a in prostate cancer (PCa) cells and identified the novel molecular targets regulated by both miR-1 and miR-133a.Methods and Results: The expression levels of miR-1 and miR-133a were significantly downregulated in PCa compared with non-PCa tissues. Restoration of miR-1 or miR-133a in PC3 and DU145 cells revealed significant inhibition of proliferation, migration, and invasion. Molecular target identification by genome-wide gene expression analysis and luciferase reporter assay showed that purine nucleoside phosphorylase (PNP) was directly regulated by both miRNAs. Silencing of the PNP gene inhibited proliferation, migration, and invasion in both PC3 and DU145 cells. Immunohistochemistry detected positive staining of PNP in PCa specimens.Conclusions: Downregulation of miR-1 and miR-133a was a frequent event in PCa and both function as tumour suppressors. The PNP is a novel target gene of both miRNAs and potentially functions as an oncogene. Therefore, identification of novel molecular networks regulated by miRNAs may provide new insights into the underlying causes of PCa oncogenesis. [ABSTRACT FROM AUTHOR]

Understanding how knotted proteins fold is a challenging problem in biology. Researchers have proposed several models for their folding pathways, based on theory, simulations and experiments. The geometry of proteins with the same knot type can vary substantially and recent simulations reveal different folding behaviour for deeply and shallow knotted proteins. We analyse proteins forming open-ended trefoil knots by introducing a topologically inspired statistical metric that measures their entanglement. By looking directly at the geometry and topology of their native states, we are able to probe different folding pathways for such proteins. In particular, the folding pathway of shallow knotted carbonic anhydrases involves the creation of a double-looped structure, contrary to what has been observed for other knotted trefoil proteins. We validate this with Molecular Dynamics simulations. By leveraging the geometry and local symmetries of knotted proteins’ native states, we provide the first numerical evidence of a double-loop folding mechanism in trefoil proteins.

Presents several studies related to sexual functions. Effects of sex steroid hormones on nitric oxide synthase and arginase activity in the vagina; Unidentified neurotransmitter in the vaginal wall; Development of a model of female genital sexual response elicited by stimulation of the clitoris.

Mast cells are a significant source of cytokines and chemokines that play a role in pathological processes. Gangliosides, which are complex lipids with a sugar chain, are present in all eukaryotic cell membranes and comprise lipid rafts. Ganglioside GM3, the first ganglioside in the synthetic pathway, is a common precursor of the specifying derivatives and is well known for its various functions in biosystems. Mast cells contain high levels of gangliosides; however, the involvement of GM3 in mast cell sensitivity is unclear. Therefore, in this study, we elucidated the role of ganglioside GM3 in mast cells and skin inflammation. GM3 synthase (GM3S)-deficient mast cells showed cytosolic granule topological changes and hyperactivation upon IgE-DNP stimulation without affecting proliferation and differentiation. Additionally, inflammatory cytokine levels increased in GM3S-deficient bone marrow-derived mast cells (BMMC). Furthermore, GM3S-KO mice and GM3S-KO BMMC transplantation showed increased skin allergic reactions. Besides mast cell hypersensitivity caused by GM3S deficiency, membrane integrity decreased and GM3 supplementation rescued this loss of membrane integrity. Additionally, GM3S deficiency increased the phosphorylation of p38 mitogen-activated protein kinase. These results suggest that GM3 increases membrane integrity, leading to the suppression of the p38 signalling pathway in BMMC and contributing to skin allergic reaction., (© 2023 Federation of European Biochemical Societies.)

Neural population dynamics provide a key computational framework for understanding information processing in the sensory, cognitive, and motor functions of the brain. They systematically depict complex neural population activity, dominated by strong temporal dynamics as trajectory geometry in a low-dimensional neural space. However, neural population dynamics are poorly related to the conventional analytical framework of single-neuron activity, the rate-coding regime that analyzes firing rate modulations using task parameters. To link the rate-coding and dynamic models, we developed a variant of state-space analysis in the regression subspace, which describes the temporal structures of neural modulations using continuous and categorical task parameters. In macaque monkeys, using two neural population datasets containing either of two standard task parameters, continuous and categorical, we revealed that neural modulation structures are reliably captured by these task parameters in the regression subspace as trajectory geometry in a lower dimension. Furthermore, we combined the classical optimal-stimulus response analysis (usually used in rate-coding analysis) with the dynamic model and found that the most prominent modulation dynamics in the lower dimension were derived from these optimal responses. Using those analyses, we successfully extracted geometries for both task parameters that formed a straight geometry, suggesting that their functional relevance is characterized as a unidimensional feature in their neural modulation dynamics. Collectively, our approach bridges neural modulation in the rate-coding model and the dynamic system, and provides researchers with a significant advantage in exploring the temporal structure of neural modulations for pre-existing datasets., Competing Interests: The authors declare no competing financial interests., (Copyright © 2023 Chen et al.)

The standard consolidation theory suggests that the hippocampus (HPC) is critically involved in acquiring new memory, while storage and recall gradually become independent of it. Converging studies have shown separate involvements of the perirhinal cortex (PRC) and parahippocampal cortex (PHC) in item and spatial processes, whereas HPC relates the item to a spatial context. These 2 strands of literature raise the following question; which brain region is involved in the recall process of item-location associative memory? To solve this question, this study applied an item-location associative (ILA) paradigm in a single-unit study of nonhuman primates. We trained 2 macaques to associate 4 visual item pairs with 4 locations on a background map in an allocentric manner before the recording sessions. In each trial, 1 visual item and the map image at a tilt (-90° to 90°) were sequentially presented as the item-cue and the context-cue, respectively. The macaques chose the item-cue location relative to the context-cue by positioning their gaze. Neurons in the PRC, PHC, and HPC, but not area TE, exhibited item-cue responses which signaled retrieval of item-location associative memory. This retrieval signal first appeared in the PRC, followed by the HPC and PHC. We examined whether neural representations of the retrieved locations were related to the external space that the macaques viewed. A positive representation similarity was found in the HPC and PHC, but not in the PRC, thus suggesting a contribution of the HPC to relate the retrieved location from the PRC with a first-person perspective of the subjects and provide the self-referenced retrieved location to the PHC. These results imply distinct but complementary contributions of the PRC and HPC to recall of item-location associative memory that can be used across multiple spatial contexts., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yang, Naya. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: An accurate understanding of the mechanical response of ligaments is important for preventing their damage and rupture. To date, ligament mechanical responses are being primarily evaluated using simulations. However, many mathematical simulations construct models of uniform fibre bundles or sheets using merely collagen fibres and ignore the mechanical properties of other components such as elastin and crosslinkers. Here, we evaluated the effect of elastin-specific mechanical properties and content on the mechanical response of ligaments to stress using a simple mathematical model., Methods: Based on multiphoton microscopic images of porcine knee collateral ligaments, we constructed a simple mathematical simulation model that individually includes the mechanical properties of collagen fibres and elastin (fibre model) and compared with another model that considers the ligament as a single sheet (sheet model). We also evaluated the mechanical response of the fibre model as a function of the elastin content, from 0 to 33.5%. Both ends of the ligament were fixed to a bone, and tensile, shear, and rotational stresses were applied to one of the bones to evaluate the magnitude and distribution of the stress applied to the collagen and elastin at each load., Results: Uniform stress was applied to the entire ligament in the sheet model, whereas in the fibre model, strong stress was applied at the junction between collagen fibres and elastin. Even in the same fibre model, as the elastin content increased from 0 to 14.4%, the maximum stress and displacement applied to the collagen fibres during shear stress decreased by 65% and 89%, respectively. The slope of the stress-strain relationship at 14.4% elastin was 6.5 times greater under shear stress than that of the model with 0% elastin. A positive correlation was found between the stress required to rotate the bones at both ends of the ligament at the same angle and elastin content., Conclusions: The fibre model, which includes the mechanical properties of elastin, can provide a more precise evaluation of the stress distribution and mechanical response. Elastin is responsible for ligament rigidity during shear and rotational stress., (© 2023. The Author(s).)

Objective: Loneliness is an important health problem in rural areas of Japan because of its ageing and declining population. Therefore, we investigated the association between loneliness and health. Materials and Methods: Self-administered questionnaires were distributed to rural adult residents. The Japanese 3-item versions of the UCLA Loneliness Scale, self-rated health (SRH), and objective health status (whether the respondents had a physical and/or mental illness) were used. We defined a UCLA score of four points or more as loneliness, an SRH of four points or more as a subjective healthy state, and no physical or mental illness as an objective healthy state. The association was adjusted for sociodemographic data, lifestyle habits, and isolation risk using logistic regression analysis. Results: The five-year population decline rate in the target areas was 10.2 to 12.3%. Of the 2,700 participants, there were 1,211 male and 1,489 female respondents, with an average age of 65.4 years. Moreover, 358 (13.6%) were living alone, and 829 (31.5%) were living in couple-only households. Among the participants, 1,395 (53.2%) experienced loneliness, 1,751 (65.7%) had good self-rated health, and 1,587 (60.8%) had objective health status. Loneliness was negatively associated with good SRH (OR=0.56, CI=0.45-0.70) and objective health status (OR=0.57, CI=0.46-0.71) after adjusting for sociodemographic data, lifestyle habits, and the risk of isolation. Statistically significant confounding factors for subjective and/or objective health status were employment, not smoking, obesity, exercise, having a family doctor, having an above-average number of teeth, and the ability to leave home. Conclusion: In an ageing and declining population, loneliness is an independent factor affecting the health status of rural residents and is not limited to older adults. Therefore, measures to reduce it are needed., (©2023 The Japanese Association of Rural Medicine.)

To the Editor, Benign prostatic hyperplasia (BPH) is a common cause of lower urinary tract symptoms (LUTS) in elderly males. The current guidelines recommend the use of a 5-alpha reductase inhibitor (5ARI) to treat males with moderate-to-severe LUTS and an enlarged prostate. Combination therapy with an alpha blocker and a 5ARI has proven effective at ameliorating LUTS and reducing the total prostate volume (TPV) and the risk of the disease progression.

Objective: The reasons why anticholinergic drugs or β3 adrenergic agonists are selected as treatments for overactive bladder (OAB) are unclear. The aim of this study was to investigate the background data of female OAB patients that were prescribed anticholinergic drugs or β3 adrenergic agonists in a real-world setting., Materials and Methods: Between January 2013 and December 2014, 75 patients who had been diagnosed with OAB were included in this study. Administered medications, age, the persistence on treatment rate at one-year, medical history, pretreatment total Overactive Bladder Symptom Score (OABSS), pretreatment score for each OABSS factor, body mass index (BMI), and various comorbidities were evaluated retrospectively. Since there were many types of anticholinergic drugs and few patients, we grouped the patients into those that were prescribed anticholinergic drugs (group A) and those that were prescribed β3 adrenergic agonists (group B)., Results: 75 patients (29 in group A and 46 in group B) were included in this study. There were no significant differences in age, BMI, obesity, medical history, pretreatment total OABSS, or pretreatment score for each OABSS factor. There was a significant difference in the post-voiding residual urine volume (PVR) between the groups (group A: 22 ml, group B: 9 ml; p = 0.0252). The 1-year persistence on treatment rate was 28% in both groups., Conclusions: There were no significant differences in clinical characteristics of patients who were prescribed anticholinergics and β3 adrenergic agonists for OAB treatment, but a marginal difference of PVR value before treatment. The 1-year persistence rates of anticholinergic drugs and β3 adrenergic agonists were considered to be almost equivalent.

Prostate cancer is the most common genitourinary cancer in men. Population-based serum prostate-specific antigen (PSA) testing is used to screen men for the early detection of asymptomatic prostate cancer. The present study compared the features of patients with prostate cancer in Kusatsu City, the only municipality in Shiga Prefecture of Japan to implement organized PSA screening, with those in other municipalities. The target population for organized PSA screening by mail invitation was men ≥50 years. Patients were pathologically diagnosed via prostate biopsy because of elevated serum PSA. This multicenter observational study was subsequently conducted in 14 hospitals. The following information was extracted from patient records: age, reason for PSA testing, initial PSA level, Gleason score, clinical stage, and place of residence. Risk classification was defined as low, intermediate, high, and advanced. Each patient was stratified according to their city/town. A total of 984 patients diagnosed with prostate cancer in Shiga in 2012 and 2017 were analyzed, of which 955 (97%) were opportunistically tested, with the remaining 29 (3%) assessed by organized screening. In Kusatsu, 93 patients were diagnosed, of whom 26 (28%) were detected by organized screening. By contrast, only three of 891 patients (0.3%) were detected by organized screening in other municipalities. Of patients in Kusatsu, cases identified by opportunistic testing had a higher initial PSA value (P=0.010) than those identified by organized screening. However, patients detected through opportunistic testing in Kusatsu City were younger (P=0.034), had a lower PSA value (P=0.001), and improved risk classification (P<0.001) than those in other municipalities. It was concluded that more patients were diagnosed with early-stage cancer by organized PSA screening. Furthermore, population-based PSA screening in Kusatsu City may have indirectly affected early detection, even by opportunistic testing., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Kageyama et al.)

L-type amino acid transporter 1 (LAT1) is upregulated in various malignant tumors in humans. LAT1 expression correlates with the grade of cancer and prognosis. LAT1 is responsible for the supply of many essential amino acids to cancer cells. Inhibition of LAT1 reduces the amino acids that enter the cell and inhibits cancer cell growth. Therefore, novel anticancer drugs targeting LAT1 have attracted much attention in recent years. In this study, to explore the applicability of using LAT1 expression in intracranial tumors as a prognostic factor and therapeutic target, we investigated the expression of LAT1 in surgically resected primary and secondary intracranial tumor tissues from dogs and cats. Immunohistochemical analysis of LAT1 was performed on intracranial tumor tissue from 14 dogs and 3 cats. Primary intracranial tumors were seen in 10 dogs and included meningiomas, histiocytic sarcomas, pituitary tumors, and gliomas, and 9 out of 10 cases were positive for LAT1. Primary intracranial tumors were seen in 2 cats and included meningioma and lymphoma; both cases were positive for LAT1. Secondary intracranial tumors were positive for LAT1 in 3 out of 4 cases in dogs and 1 out of 1 in cats. Since the majority of intracranial tumors in dogs and cats were positive for LAT1, immunostaining for LAT1 is expected to be a prognostic indicator and therapeutic target in the future.

A dataset consisting of whole-brain fMRI (functional magnetic resonance imaging)/MEG (magnetoencephalography) images, eye tracking files, and behavioral records from healthy adult human participants when they performed a spatial-memory paradigm in a virtual environment was collected to investigate the neural representation of the cognitive map defined by unique spatial relationship of three objects, as well as the neural dynamics of the cognitive map following the task demand from localizing self-location to remembering the target location relative to the self-body. The dataset, including both fMRI and MEG, was also used to investigate the neural networks involved in representing a target within and outside the visual field. The dataset included 19 and 12 university students at Peking University for fMRI and MEG experiments, respectively (fMRI: 12 women, 7 men; MEG: 4 women, 8 men). The average ages of those participants were 24.9 years (MRI: 18-30 years) and 22.5 years (MEG: 19-25 years), respectively. fMRI BOLD and T1-weighted images were acquired using a 3T Siemens Prisma scanner (Siemens, Erlangen, Germany) equipped with a 20-channel receiver head coil. MEG neuromagnetic data were acquired using a 275-channel MEG system (CTF MEG, Canada). The dataset could be further used to investigate a range of neural mechanisms involved in human spatial cognition or to develop a bioinspired deep neural network to enhance machines' abilities in spatial processing., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

A cell line (PL38PB) was established from blood samples of a 6-month-old pig that was diagnosed with lymphoma with CD5 expression. Histopathological examination revealed neoplastic lesions in the spleen, liver and lymph nodes. Tumor cells were immunohistochemically positive for CD20 and immunoglobulin heavy chains (μ, γ and α). Membranous CD5 and cytoplasmic Immunoglobulin M (IgM), ​Immunoglobulin G (IgG) and ​Immunoglobulin A (IgA) were detected in PL38PB cells by flow cytometry. In addition, the cytoplasm of PL38PB cells were positive for IgM, IgG and IgA by immunofluorescent. However, no Ig secretion was detected in culture supernatant by Ouchterlony gel diffusion method. Results suggest that PL38PB cells express three Ig isotypes that are produced but not secreted.

Our mental representation of egocentric space is influenced by the disproportionate sensory perception of the body. Previous studies have focused on the neural architecture for egocentric representations within the visual field. However, the space representation underlying the body is still unclear. To address this problem, we applied both functional Magnitude Resonance Imaging (fMRI) and Magnetoencephalography (MEG) to a spatial-memory paradigm by using a virtual environment in which human participants remembered a target location left, right, or back relative to their own body. Both experiments showed larger involvement of the frontoparietal network in representing a retrieved target on the left/right side than on the back. Conversely, the medial temporal lobe (MTL)-parietal network was more involved in retrieving a target behind the participants. The MEG data showed an earlier activation of the MTL-parietal network than that of the frontoparietal network during retrieval of a target location. These findings suggest that the parietal cortex may represent the entire space around the self-body by coordinating two distinct brain networks., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Recent work has shown that the medial temporal lobe (MTL), including the hippocampus (HPC) and its surrounding limbic cortices, plays a role in scene perception in addition to episodic memory. The two basic factors of scene perception are the object ("what") and location ("where"). In this review, we first summarize the anatomical knowledge related to visual inputs to the MTL and physiological studies examining object-related information processed along the ventral pathway briefly. Thereafter, we discuss the space-related information, the processing of which was unclear, presumably because of its multiple aspects and a lack of appropriate task paradigm in contrast to object-related information. Based on recent electrophysiological studies using non-human primates and the existing literature, we proposed the "reunification theory," which explains brain mechanisms which construct object-location signals at each gaze. In this reunification theory, the ventral pathway signals a large-scale background image of the retina at each gaze position. This view-center background signal reflects the first person's perspective and specifies the allocentric location in the environment by similarity matching between images. The spatially invariant object signal and view-center background signal, both of which are derived from the same retinal image, are integrated again (i.e., reunification) along the ventral pathway-MTL stream, particularly in the perirhinal cortex. The conjunctive signal, which represents a particular object at a particular location, may play a role in scene perception in the HPC as a key constituent element of an entire scene., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen and Naya.)

Background/aim: We investigated the changes in and characteristics of renal function in Japanese patients with high-risk prostate cancer (PCa) who underwent radiotherapy and long-term androgen deprivation therapy (ADT), including those seen after the ADT was discontinued., Patients and Methods: Among 60 patients who were pathologically diagnosed with PCa and received ADT for 24 months and radiotherapy, 36 patients who underwent treatment for stage B or C PCa were eligible. We assessed renal function using the estimated glomerular filtration rate (eGFR) and investigated the rate of change in the eGFR (ΔeGFR) during and after ADT. Univariate and multivariate logistic analyses were carried out to identify clinical factors that were significantly associated with renal dysfunction at 36 months., Results: The incidence of renal dysfunction at 36 months was 75% (27/36). Multivariate analysis showed that the presence/absence of HF was an independent predictor of renal dysfunction at 36 months., Conclusion: Renal function tended to recover after ADT was received for 24 months and subsequently discontinued. The presence/absence of HF represents new and meaningful information for patients receiving ADT, and high-risk PCa patients prior to ADT., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Androgen deprivation therapy (ADT) is one of the most effective treatments for advanced prostate cancer (PCa). However, it has been reported that the use of ADT is significantly associated with an increased risk of acute kidney injury (AKI) among patients with newly diagnosed non-metastatic PCa. We investigated changes in renal function that occurred in Japanese patients with PCa after ADT was discontinued., Patients and Methods: Among 121 patients who underwent prostate biopsies, were pathologically diagnosed with PCa, and received ADT for ≥6 months at our Institution between 2009 and 2014, 60 patients who underwent radiotherapy for stage B or C PCa were eligible for inclusion in this retrospective study. Renal function was assessed using the estimated glomerular filtration rate (eGFR) before treatment and at 1, 3, 6, 9, and 12 months after the initiation of ADT and the rate of change in the eGFR (ΔeGFR) during ADT and after the discontinuation of ADT was investigated. We divided patients into two groups: Group 1 received ADT for 6 months, and group 2 received ADT for 12 months. Age; ΔeGFR; prostate-specific antigen, testosterone and hemoglobin levels; clinical stage; Gleason score; comorbidities; body mass index; heart rate; and the cardiothoracic ratio were analyzed., Results: A total of 60 patients (group 1: n=23, group 2: n=37) were analyzed. The Gleason score of group 2 was higher than that of group 1 (p=0.0011). Regarding clinical stage, group 1 had more patients with stage B disease, and group 2 had more with stage C (p<0.0001). The eGFR decreased with the duration of ADT treatment. At 12 months, renal function had started to recover in group 1, while it had continued to decrease in group 2., Conclusion: Discontinuation of ADT tended to result in improvements in renal function. Furthermore, this study indicated that renal dysfunction caused by 6 months of ADT is transient. Normalization of the serum testosterone level seen after the discontinuation of ADT may be associated with improvements in renal function. Thus, intermittent ADT may be a useful treatment for PCa, as it would help to preserve renal function., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The linearity of BOLD responses is a fundamental presumption in most analysis procedures for BOLD fMRI studies. Previous studies have examined the linearity of BOLD signal increments, but less is known about the linearity of BOLD signal decrements. The present study assessed the linearity of both BOLD signal increments and decrements in the human primary visual cortex using a contrast adaptation paradigm. Results showed that both BOLD signal increments and decrements kept linearity to long stimuli (e.g., 3 s, 6 s), yet, deviated from linearity to transient stimuli (e.g., 1 s). Furthermore, a voxel-wise analysis showed that the deviation patterns were different for BOLD signal increments and decrements: while the BOLD signal increments demonstrated a consistent overestimation pattern, the patterns for BOLD signal decrements varied from overestimation to underestimation. Our results suggested that corrections to deviations from linearity of transient responses should consider the different effects of BOLD signal increments and decrements., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lin, Zhou, Naya, Gardner and Sun.)

Background/aim: Recently, it was reported that the use of androgen deprivation therapy (ADT) is significantly associated with an increased risk of acute kidney injury (AKI) in patients with newly diagnosed non-metastatic prostate cancer. This study aimed to investigate the incidence of early renal dysfunction in Japanese prostate cancer patients receiving ADT and the factors associated with it., Patients and Methods: A total of 135 patients who had been pathologically diagnosed with prostate cancer and had received ADT for at least 6 months were eligible for study inclusion. The estimated glomerular filtration rate (eGFR) before treatment, and at 1, 3, and 6 months of ADT were evaluated retrospectively. We assessed renal function using eGFR and investigated the rate of change in the eGFR (ΔeGFR) during ADT. Univariate and multivariate logistic analyses were carried out to identify clinical factors that were significantly associated with renal dysfunction after 6 months ADT., Results: A total of 110 cases were evaluated in this study. The incidence of renal dysfunction after 6 months ADT was 63% (69/110). The mean ΔeGFR after 1, 3, and 6 months of ADT were -0.6%, -3.1% and -1.7%, respectively (p<0.001). Multivariate analysis showed that renal dysfunction after 3 months of ADT and hypertension were independent risk factors for renal dysfunction after 6 months ADT., Conclusion: Renal dysfunction occurs from 1 month of ADT and hypertensive prostate cancer patients receiving ADT are at high risk of developing renal dysfunction, and that such patients should be treated very carefully. Therefore, patients that are started on ADT should undergo periodic prostate-specific antigen, renal function, and urinary salt intake examinations., Competing Interests: The Authors declare that they have no conflicts of interest related to this study., (Copyright 2021, International Institute of Anticancer Research.)

Background/aim: This study aimed to access the effectiveness of serum neutrophil-to-lymphocyte ratio (NLR) in patients undergoing prostate needle biopsy with a prostate specific antigen (PSA) between 4.0 and 10.0 ng/ml., Patients and Methods: A total of 633 cases were eligible. We evaluated several factors including age, PSA, PSA-density (PSAD), platelet-to-lymphocyte ratio (PLR) and NLR in the presence or absence of prostate cancer (PCa), retrospectively. We evaluated statistically the associations between each factor and pathological findings or Gleason score., Results: A total of 201 were evaluated in this study. Regarding the presence or absence of prostate cancer, there were statistically significant differences in age, PSA levels, PSAD, the PLR and NLR. The mean NLR value of the patients with PCa was significantly lower compared to the entire cohort. Multivariate analysis showed that age, PSAD, and NLR were independent risk factors predicting PCa., Conclusion: For patients having a PSA between 4.0 and 10.0 ng/ml, NLR was a predicting factor of PCa prior to prostate needle biopsy and an effective biomarker and useful tool for avoiding unnecessary biopsies., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: To determine whether an alkaline phosphatase (ALP) flare after androgen deprivation therapy (ADT) is associated with the treatment response in castration-resistant prostate cancer (CRPC) and predicts the prognosis of metastatic prostate cancer (PCa) patients., Methods: One hundred and nineteen patients diagnosed with metastatic PCa between 2008 and 2017 were retrospectively studied. The ALP flare ratio was calculated as the ratio of ALP levels 1 month after beginning ADT to ALP levels at diagnosis. The association of the ALP flare ratio with the prostate-specific antigen (PSA) response to CRPC treatment (second-generation androgen receptor targeted therapy (ART) or docetaxel), time to CRPC, and overall survival (OS) were investigated., Results: The time to CRPC and OS was significantly longer in patients with an ALP flare ratio less than 1.33 compared to a ratio more than 1.33. No difference in PSA response was seen regarding the ALP flare ratio in both ART and docetaxel treatment. Second-generation ART-treated patients with a low ALP flare ratio showed longer OS than those with a higher ALP flare ratio ( p =0.0367). However, no difference was seen between a high and low ALP flare ratio ( p =0.8054) in docetaxel-treated patients. The ALP flare ratio was the most significant prognostic factor for OS ( p < 0.0001)., Conclusions: A higher ALP flare ratio after first-line ADT was a significant prognostic factor in metastatic PCa, especially in patients treated with second-generation ART for CRPC. Chemotherapy for patients with a higher ALP flare ratio 1 month after induction of ADT may be a clinically relevant decision., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Satoko Kojima et al.)

The ability to use stored information in a highly flexible manner is a defining feature of the declarative memory system. However, the neuronal mechanisms underlying this flexibility are poorly understood. To address this question, we recorded single-unit activity from the hippocampus of 2 nonhuman primates performing a newly devised task requiring the monkeys to retrieve long-term item-location association memory and then use it flexibly in different circumstances. We found that hippocampal neurons signaled both mnemonic information representing the retrieved location and perceptual information representing the external circumstance. The 2 signals were combined at a single-neuron level to construct goal-directed information by 3 sequentially occurring neuronal operations (e.g., convergence, transference, and targeting) in the hippocampus. Thus, flexible use of knowledge may be supported by the hippocampal constructive process linking memory and perception, which may fit the mnemonic information into the current situation to present manageable information for a subsequent action., Competing Interests: The authors have declared that no competing interests exist.