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Yong-Pyo Lee,1,* Sang Eun Yoon,2,* Junhun Cho,3 Young Hyeh Ko,3 Dongryul Oh,4 Yong Chan Ahn,4 Won Seog Kim,2,5 Seok Jin Kim2,5 1Division of Hematology-Oncology, Department of Internal Medicine, Chungbuk National University Hospital, Cheongju, Korea; 2Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 3Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 4Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 5Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea*These authors contributed equally to this workCorrespondence: Seok Jin Kim, Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro Gangnam-gu, Seoul, 06351, Korea, Tel +82-2-3410-1766, Fax +82-2-3410-1754, Email kstwoh@skku.eduBackground: Primary testicular lymphoma is a rare type of non-Hodgkin lymphoma, mostly of the diffuse large B cell lymphoma (DLBCL). Although a consensus on standard treatment has been established, unresolved issues remain, such as recurrence in the central nervous system (CNS).Methods: We retrospectively analyzed the clinical characteristics and survival outcomes of 65 testicular DLBCL patients according to clinical settings and treatment modalities.Results: The median age of the patients in our study was 65 years, and two-thirds of them had disease limited to one testis. There was no right or left lateralization of testicular involvement. Over a median follow-up of 53.9 months (95% confidence interval 34.0– 73.7 months), patients with stage I disease and a low international prognostic index score showed better survival outcomes than those in other categories. Orchiectomy, six cycles of chemotherapy, and radiation therapy (RT) to the contralateral testis demonstrated survival benefits, whereas CNS prophylaxis therapy did not reduce CNS recurrence. During the follow-up period, the survival curves showed continuous decline, mostly due to disease progression. CNS recurrence was observed in 15% of patients, and parenchymal involvement was dominant. However, no factors were associated with CNS recurrence in our analyses. Although our molecular analyses were performed in a small number of patients, MYD88, CD79B, and PIM1 mutations were frequent.Conclusion: In our study, treatment with orchiectomy, six cycles of immunochemotherapy, and contralateral RT was effective. However, because CNS prophylaxis is an essential part of testicular DLBCL management, better treatment strategies than intrathecal therapy are required.Keywords: testis, diffuse large B cell lymphoma, central nervous system, survival outcome

Arthur G Mikaelian,1 Eric Traboulay,1 Xiaofei Michael Zhang,1 Emma Yeritsyan,2 Peter L Pedersen,3 Young Hee Ko,3 Khalid Z Matalka4 1Medolife Corporation, Beverly Hills, CA, USA; 2Yerevan State Medical University, Yerevan, Armenia; 3Johns Hopkins University, School of Medicine Laboratory, Baltimore, MD, USA; 4OncoTherapeutica, Inc., Cambridge, MA, USACorrespondence: Arthur G Mikaelian 433 North Camden Drive, Beverly Hills, CA 90210, USAEmail artur@medolife.comAbstract: To date, the success of conventional chemotherapy, radiotherapy, and targeted biological therapies in cancer treatment is not satisfactory. The main reasons for such outcomes rely on low target selectivity, primarily in chemo- and radiotherapy, ineffectiveness to metastatic disease, drug resistance, and severe side effects. Although immune checkpoint inhibitors may offer better clinical promise, success is still limited. Since cancer is a complex systemic disease, the need for new therapeutic modalities that can target or block several steps of cancer cell characteristics, modulate or repolarize immune cells, and are less toxic to healthy tissues is essential. Of these promising therapeutic modalities are pleiotropic natural products in which scorpion venom (SV) is an excellent example. SV consists of complex bioactive peptides that are disulfide-rich of different peptides’ length, potent, stable, and exerts various multi-pharmacological actions. SV peptides also contain ion channel inhibitors. These ion channels are dysregulated and overexpressed in cancer cells, and play essential roles in cancer development and invasion, as well as depolarizing immune cells. Furthermore, SV has been found to induce cancer cell apoptosis, and inhibit cancer cells proliferation, invasion, metastasis, and angiogenesis. In the current review, we are presenting data that show the pleiotropic effect of SV against different types of human cancer as well as revealing one potential anticancer agent, Rhopalurus princeps venom. Furthermore, we are addressing what is needed to be done to translate these potential cancer therapeutics to the clinic.Keywords: angiogenesis, apoptosis, cell arrest, cytotoxicity, immunomodulation, ion channels, metastasis, polarization

Objective: To investigate the clinical usefulness of intraoral sonography-assisted resection for securing adequate deep resection margins in T1-2 tongue cancers. Study Design: Prospective clinical trial. Materials and Methods: Twenty consecutive patients with clinical T1-2 tongue cancers were enrolled and their lesions were removed by intraoral sonography-assisted resection. We then retrospectively collected data from 20 T stage-matched patients without intraoral sonography-assisted resection as the control group. All resections were performed with a goal of 15 mm margin. The mucosal and deep safety margins were compared between the two groups. Results: Intraoral sonography could predict the paraffin-embedded tumor thickness with an error of 3.16 +/- 2.24 mm. The deep safety margins were more adequate for intraoral sonography-assisted resection (9.8 +/- 5.2 mm) than for conventional resection (4.0 +/- 2.03 mm) (P < 0.001), while the mucosal safety margins were not different. Conclusion: Intraoral sonography-assisted resection provides a more adequate deep resection margin for early T-stage tongue cancers. [ABSTRACT FROM AUTHOR]

The sarcomatoid variant is a rare subtype of salivary duct carcinoma that comprises epithelial and sarcomatoid components. The authors present the first reported case of sarcomatoid salivary duct carcinoma occurring in the larynx, which was successfully treated by partial laryngectomy with ipsilateral neck dissection, with no evidence of recurrence after five years. Microscopic analysis revealed a composite epithelial and sarcomatoid tumour. The epithelial component was characterized by papillary proliferation of glandular and ductal structures lined with multilayered epithelial tumour cells. The sarcomatoid component was characterized by pleomorphic spindle cells with cytologic atypia, accompanied by small lymphoid cells, extensive proliferation of blood vessels and focal myxoid changes. To the best of our knowledge, only one case of sarcomatoid salivary duct carcinoma outside a major salivary gland has been reported previously in the literature, and this is the first report of sarcomatoid salivary duct carcinoma arising from the larynx. [ABSTRACT FROM AUTHOR]

Background: In patients with metastatic renal cell carcinoma (mRCC), sites of metastatic involvement have been reported to be associated with a difference in survival. However, the frequency and survival according to different sites of metastases in Korean patients with mRCC remain unclear. Therefore, this study aimed to assess the frequency of metastatic site involvement and the association between sites of metastatic involvement and survival in Korean patients with mRCC., Methods: This retrospective study used the multicenter cohort of the Korean Renal Cancer Study Group mRCC database to identify patients who started targeted therapy between December 2005 and March 2018. Data on the frequency of metastatic organ involvement at the time of mRCC diagnosis and oncologic outcomes according to different sites of metastasis were analyzed., Results: A total of 1,761 patients were eligible for analysis. Of the 1,761 patients, 1,564 (88.8%) had clear cell RCC, and 1,040 (59.1%) had synchronous metastasis. The median number of metastasis sites was 2 (interquartile range [IQR], 1-6). The median age at the initiation of systemic therapy was 60 years (IQR, 29-88), 1,380 (78.4%) were men, and 1,341 (76.1%) underwent nephrectomy. Based on the International Metastatic Renal Cell Carcinoma Database Consortium model, patients were stratified into favorable-, intermediate-, and poor-risk groups with 359 (20.4%), 1,092 (62.0%), and 310 (17.6%) patients, respectively. The lung (70.9%), lymph nodes (37.9%), bone (30.7%), liver (12.7%), adrenal gland (9.8%), and brain (8.2%) were the most common sites of metastasis, followed by the pancreas, pleura, peritoneum, spleen, thyroid, and bowel. Among the most common sites of metastasis (> 5%), the median cancer-specific survival (CSS) ranged from 13.9 (liver) to 29.1 months (lung). An association was observed between liver, bone, and pleural metastases and the shortest median CSS (< 19 months)., Conclusion: In Korean patients with mRCC, metastases to the lung, lymph nodes, bone, liver, adrenal gland, and brain were more frequent than those to other organs. Metastases to the liver, bone, and pleura were associated with poor CSS. The findings of this study may be valuable for patient counseling and guiding future study designs., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Antimicrobial peptides (AMPs) are a current solution to combat antibiotic resistance, but they have limitations, including their expensive production process and the induction of cytotoxic effects. We have developed novel AMP candidate (peptide 3.1) based on indolicidin, among the shortest naturally occurring AMP. The antimicrobial activity of this peptide is demonstrated by the minimum inhibitory concentration, while the hemolysis tests and MTT assay indicate its low cytotoxicity. In optical diffraction tomography, red blood cells treated with peptide 3.1 showed no discernible effects, in contrast to indolicidin. However, peptide 3.1 did induce cell lysis in E. coli, leading to a reduced potential for the development of antibiotic resistance. To investigate the mechanism underlying membrane selectivity, the structure of peptide 3.1 was analyzed using nuclear magnetic resonance spectroscopy and molecular dynamics simulations. Peptide 3.1 is structured with an increased distinction between hydrophobic and charged residues and remained in close proximity to the eukaryotic membrane. On the other hand, peptide 3.1 exhibited a disordered conformation when approaching the prokaryotic membrane, similar to indolicidin, leading to its penetration into the membrane. Consequently, it appears that the amphipathicity and structural rigidity of peptide 3.1 contribute to its membrane selectivity. In conclusion, this study may lead to the development of Peptide 3.1, a promising commercial candidate based on its low cost to produce and low cytotoxicity. We have also shed light on the mechanism of action of AMP, which exhibits selective toxicity to bacteria while not damaging eukaryotic cells., (© 2024 International Union of Biochemistry and Molecular Biology.)

Cytoplasmic aggregation of the TAR-DNA binding protein of 43 kDa (TDP-43) is the hallmark of sporadic amyotrophic lateral sclerosis (ALS). Most ALS patients with TDP-43 aggregates in neurons and glia do not have mutations in the TDP-43 gene but contain aberrantly post-translationally modified TDP-43. Here, we found that a single acetylation-mimetic mutation (K82Q) near the TDP-43 minor Nuclear Localization Signal (NLS) box, which mimics a post-translational modification identified in an ALS patient, can lead to TDP-43 mislocalization to the cytoplasm and irreversible aggregation. We demonstrate that the acetylation mimetic disrupts binding to importins, halting nuclear import and preventing importin α1/β anti-aggregation activity. We propose that perturbations near the NLS are an additional mechanism by which a cellular insult other than a genetically inherited mutation leads to TDP-43 aggregation and loss of function. Our findings are relevant to deciphering the molecular etiology of sporadic ALS., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

While covalent organic frameworks (COFs) have been extensively investigated in the field of organic electrolyte materials, there is potential for further enhancement of their room-temperature ionic conductivity. This study introduces a novel methodology to induce self-exfoliation in the parent COF during synthesis through a postmodification technique. This process yields covalent organic nanosheets that feature pyridinium sulfobetaine groups, referred to as PS-CON. Due to the strategic arrangement of pyridinium cations and sulfobetaine anions, the charge distribution in PS-CON varies substantially, leading to a significant enhancement in lithium-ion dissociation. The methodically organized one-dimensional pore channels, along with the linear structure of the pyridinium sulfobetaine groups, facilitate the lithium-ion transport. PS-CON demonstrated a remarkable ionic conductivity of 2.19 × 10 -4 S cm -1 and a low activation energy (0.26 eV) coupled with a broad electrochemical stabilization window (4.05 V). Furthermore, the symmetrical cell (Li|Li@PS-CON|Li) demonstrates stable Li plating/stripping for more than 1200 h, which highlights the vast potential of pyridinium-sulfobetaine based zwitterionic nanosheets as high-performance organic electrolytes.

Importin β-superfamily nuclear import receptors (NIRs) mitigate mislocalization and aggregation of RNA-binding proteins (RBPs), like FUS and TDP-43, which are implicated in neurodegenerative diseases. NIRs potently disaggregate RBPs by recognizing their nuclear localization signal (NLS). However, disease-causing mutations in NLS compromise NIR binding and activity. Here, we define features that characterize the anti-aggregation activity of NIR and NLS. We find that high binding affinity between NIR and NLS, and optimal NLS location relative to the aggregating domain plays a role in determining NIR disaggregation activity. A designed FUS chimera (FUS IBB ), carrying the importin β binding (IBB) domain, is solubilized by importin β in vitro, translocated to the nucleus in cultured cells, and downregulates the expression of endogenous FUS. In this study, we posit that guiding the mutual recognition of NLSs and NIRs will aid the development of therapeutics, illustrated by the highly soluble FUS IBB replacing the aggregation-prone endogenous FUS., (© 2024. The Author(s).)

Purpose: To investigate the form and level of daily caffeine intake recommended above 400 mg in medical students expected to consume caffeinated beverages to enhance their performance., Methods: From May to June 2023, freshman through senior medical students at a medical school in Korea were administered a seven-item questionnaire designed to measure the amount of caffeine-containing foods consumed, the weekly interval between consumption, the reason for consumption, and the level of caffeine-induced symptoms experienced., Results: Out of 443 students, 361 responded (81.5%). The most commonly consumed caffeine beverages were coffee (79.2%), followed by soda (33.2%), tea (27.4%), chocolate (25.2%), and energy drinks (20.5%). The estimated (average±standard deviation) daily intake was estimated to 274.6±276.5 mg, and they consumed caffeine on an average of 4.25±2.26 days per week. Students who consumed 400 mg or more of caffeine daily consumed 19.9%. The primary motivation for caffeine intake was "to improve academic performance" (60.9%) and "preferred food" (51.8%). Among the responders, 98% of them replied they had symptoms that could be caused by caffeine, in order of palpitations (47.4%), frequent urination (42.9%), anxiety (27.1%), indigestion (17.5%), and excitement (17.5%). A total of 45.7% reported two symptoms, and 24.7% reported three or more., Conclusion: Caffeinated beverage consumption was routine among current medical students, with 20% consuming more than the recommended daily amount. Most students experienced at least one caffeine-induced symptom, with two symptoms in half, suggesting the need for policy measures and warnings about caffeine-containing foods.

Background and Purpose: Cytoplasmic fragile X messenger ribonucleoprotein 1 (FMR1)-interacting protein 2 (CYFIP2), as a component of the Wiskott-Aldrich syndrome protein family verprolin-homologous protein (WAVE) regulatory complex, is involved in actin polymerization, contributing to neuronal development and structural plasticity. Mutating serine-968 to phenylalanine (S968F) in CYFIP2 causes an altered cocaine response in mice. The neuronal mechanisms underlying this response remain unknown., Experimental Approach: We performed cocaine reward-related behavioural tests and examined changes in synaptic protein phenotypes and neuronal morphology in the nucleus accumbens (NAc), using CYFIP2 S968F knock-in mice to investigate the role of CYFIP2 in regulating cocaine reward., Key Results: CYFIP2 S968F mutation attenuated cocaine-induced behavioural sensitization and conditioned place preference. Cocaine-induced c-Fos was not observed in the NAc of CYFIP2 S968F knock-in mice. However, c-Fos induction was still evident in the medial prefrontal cortex (mPFC). CYFIP2 S968F mutation altered cocaine-associated CYFIP2 signalling, glutamatergic protein expression and synaptic density in the NAc following cocaine exposure. To further determine the role of CYFIP2 in NAc neuronal activity and the mPFC projecting to the NAc activity-mediating reward response, we used optogenetic tools to stimulate the NAc or mPFC-NAc pathway and observed that optogenetic activation of the NAc or mPFC-NAc pathway induced reward-related behaviours. This effect was not observed in the S968F mutation in CYFIP2., Conclusion and Implications: These results suggest that CYFIP2 plays a role in controlling cocaine-mediated neuronal function and structural plasticity in the NAc, and that CYFIP2 could serve as a target for regulating cocaine reward., (© 2024 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Backgruound: Dipeptidyl peptidase-4 (DPP4) inhibitors are frequently prescribed for patients with type 2 diabetes; however, their cost can pose a significant barrier for those with impaired kidney function. This study aimed to estimate the economic benefits of substituting non-renal dose-adjusted (NRDA) DPP4 inhibitors with renal dose-adjusted (RDA) DPP4 inhibitors in patients with both impaired kidney function and type 2 diabetes., Methods: This retrospective cohort study was conducted from January 1, 2012 to December 31, 2018, using data obtained from common data models of five medical centers in Korea. Model 1 applied the prescription pattern of participants with preserved kidney function to those with impaired kidney function. In contrast, model 2 replaced all NRDA DPP4 inhibitors with RDA DPP4 inhibitors, adjusting the doses of RDA DPP4 inhibitors based on individual kidney function. The primary outcome was the cost difference between the two models., Results: In total, 67,964,996 prescription records were analyzed. NRDA DPP4 inhibitors were more frequently prescribed to patients with impaired kidney function than in those with preserved kidney function (25.7%, 51.3%, 64.3%, and 71.6% in patients with estimated glomerular filtration rates [eGFRs] of ≥60, <60, <45, and <30 mL/min/1.73 m2, respectively). When model 1 was applied, the cost savings per year were 7.6% for eGFR <60 mL/min/1.73 m2 and 30.4% for eGFR <30 mL/min/1.73 m2. According to model 2, 15.4% to 51.2% per year could be saved depending on kidney impairment severity., Conclusion: Adjusting the doses of RDA DPP4 inhibitors based on individual kidney function could alleviate the economic burden associated with medical expenses.

Objectives: South Korea has the highest suicide rate among Organisation for Economic Co-operation and Development countries; there is an increasing trend in suicide attempts among middle and high school students. Various factors contribute to the risk of suicide among adolescents, and the perception of suicide prevention has emerged as a significant factor. This study aimed to investigate the association between emotional and behavioral difficulties among middle and high school students and their perceptions of suicide prevention and to explore differences in suicide perception according to age., Methods: A survey was conducted among community middle and high school students, including 530 participants, between 2020 and 2021. Emotional and behavioral difficulties were assessed using the Strengths and Difficulties Questionnaire-Korean version, and participants were asked to complete a questionnaire on the importance and possibility of suicide prevention. A correlation test and analysis of variance were used to examine the relationships between the variables, and suicide awareness was compared according to age., Results: The participants who displayed higher strength or lower difficulty were more likely to respond positively to suicide prevention measures. They also exhibited high strength and low difficulty levels, thus agreeing with the importance of suicide prevention. Regarding age-related perceptions of suicide, adults aged 20-29 years reported the lowest probability of suicide prevention., Conclusion: Suicide perceptions influence the incidence of suicide. Therefore, active societal engagement through suicide prevention campaigns and related education is essential to improve such perceptions. Continuous attention and support are required to address this issue., Competing Interests: Conflicts of Interest The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Korean Academy of Child and Adolescent Psychiatry.)

We aim to investigate the peri-operative outcomes after extraperitoneal single-port based robot-assisted radical prostatectomy (eSP-RARP) utilizing the da Vinci SP system compared to conventional transperitoneal multi-port counterparts (tMP-RARP), in an era when pelvic lymph node dissection (PNLD) was omitted for the node-negative case. With exclusion criteria of volume  + 50 g, suspicious rectal invasion, and node-positive disease given relatively weak grasping power and limited range of motion from the current SP system, 50 consecutive patients (Since December 2021) with localized prostate cancer underwent eSP-RARP by a single urologist maintaining identical surgical technique for 100 consecutive tMP-RARP cases (Since December 2020). Given initial selection criteria, each group was matched to a 1:1 ratio based on the risk-stratification parameters and the prostate volume. The operative time, which was maintained in each group during the study period, was significantly faster in eSP-RARP groups than in tMP-RARP (149.2 vs. 163.2 min, p = 0.025), while the weight of the removed specimen (27.1 vs. 29.0 g, p = 0.420) and margin positivity (14.7% vs. 11.7% in pT2, p = 0.812) were similar. The gas-out (1.5 vs. 1.88 days, p = 0.003) and solid diet dates (2.26 vs. 3.22 days, p < 0.001) were faster in the eSP-RARP group. The single-pad continence dates (30.5 vs. 51.9 days, p = 0.145) and zero-pad continence dates (105.5 vs. 146.2 days, p = 0.210) were identical. 90-day single-pad continence rate was 92% vs. 82% (p = 0.142, 52% vs. 56% in zero-pad continence). Based on these, daVinci SP-based RARP restored bowel function faster with shorter operative time through an extraperitoneal approach than the conventional transperitoneal multi-port counterpart while maintaining similar incontinence outcomes in cases without a routine PNLD., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Competing Interests: The authors have nothing to disclose.

Purpose: This study investigated the efficacy of intravesical gemcitabine as an alternative to bacillus Calmette-Guérin (BCG) therapy., Materials and Methods: Data were retrospectively collected across seven institutions from February 1999 to May 2023. Inclusion criteria included patients with intermediate- or high-risk non-muscle invasive bladder cancer (NMIBC) who underwent transurethral resection of bladder tumors (TURBT) and received at least four sessions of intravesical gemcitabine or BCG induction therapy. Patient characteristics, complete remission (CR), occurrence, and progression rates were compared., Results: In total, 149 patients were included in this study (gemcitabine, 63; BCG, 86). No differences were apparent between the two groups in baseline characteristics, except for the follow-up period (gemcitabine, 9.2±5.9 months vs. BCG, 43.9±41.4 months, p<0.001). There were no consistent significant differences observed between the two groups in the 3-month (gemcitabine, 98.4% vs. BCG, 95.3%; p=0.848), 6-month (94.9% vs. 90.0%, respectively; p=0.793) and 1-year CR rates (84.2% vs. 83.3%, respectively; p=0.950). Also, there was no significant statistical difference in progression-free survival between the two groups (p=0.953). The occurrence rates of adverse events were similar between the groups (22.2% vs. 22.1%; p=0.989); however, the rate of Clavien-Dindo grade 2 or higher was significantly higher in the BCG group (1.6% vs. 16.3%, respectively; p<0.001)., Conclusions: Intravesical gemcitabine demonstrated efficacy comparable to BCG therapy for the first year in patients with intermediate- and high-risk NMIBC. However, long-term follow-up studies are warranted., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association.)

The Arctic is severely affected by climate change and various forms of environmental pollution. Enriched with nutrients and light-absorbing compounds, the wildfire plume has the potential to affect biological carbon fixation and sequestration within the Arctic Ocean. In this study, we utilized satellite-derived oceanic data (phytoplankton and sea ice) and atmospheric reanalysis products (black carbon, BC, indicative of wildfire impact) to evaluate the effect of the pronounced increase in wildfires from 2019 to 2021 on the East Siberian Sea. During these years, chlorophyll-a levels rose by ∼213 % compared to the previous decadal average, which had notably lower wildfire activities. This increase in chlorophyll-a is attributable to the deposition of nitrogen from the wildfire plume. Concurrently, the period required for sea ice concentration to decrease by 25 % was on average ∼ 10 days shorter than usual. This suggests that BC-induced acceleration of sea ice melting might extend the growing season for phytoplankton., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

When we make a decision, we also estimate the probability that our choice is correct or accurate. This probability estimate is termed our degree of decision confidence. Recent work has reported event-related potential (ERP) correlates of confidence both during decision formation (the centro-parietal positivity component; CPP) and after a decision has been made (the error positivity component; Pe). However, there are several measurement confounds that complicate the interpretation of these findings. More recent studies that overcome these issues have so far produced conflicting results. To better characterise the ERP correlates of confidence we presented participants with a comparative brightness judgment task while recording electroencephalography. Participants judged which of two flickering squares (varying in luminance over time) was brighter on average. Participants then gave confidence ratings ranging from "surely incorrect" to "surely correct". To elicit a range of confidence ratings we manipulated both the mean luminance difference between the brighter and darker squares (relative evidence) and the overall luminance of both squares (absolute evidence). We found larger CPP amplitudes in trials with higher confidence ratings. This association was not simply a by-product of differences in relative evidence (which covaries with confidence) across trials. We did not identify postdecisional ERP correlates of confidence, except when they were artificially produced by pre-response ERP baselines. These results provide further evidence for neural correlates of processes that inform confidence judgments during decision formation., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

This study investigated the carbonate system and air-sea CO 2 exchange in the inshore waters along South Korea's western coastline in 2020. Overlooking these waters might introduce significant errors in estimating air-sea CO 2 fluxes of the southeastern Yellow Sea, given their interaction with land, offshore regions, and sediments. During periods other than summer, seasonal variations in seawater CO 2 partial pressure (pCO 2 ) could be generally explained by thermal effects. Tidal mixing and shallow depths resulted in weaker stratification-induced carbon export compared to offshore regions. However, during summer, inshore waters exhibited high spatial variability in pCO 2 , ranging from approximately 185 to 1000 μatm. In contrast to offshore waters that modestly absorbed CO 2 , inshore waters shallower than 20 m emitted ∼100 Gg C yr -1 to the atmosphere. However, considering the high heterogeneity of the study area, additional observations with high spatial and temporal resolution are required to refine estimates of air-sea CO 2 exchange., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: To investigate the long-term effects of taking 5-alpha reductase inhibitors (5ARIs) on the development of bladder cancer (BC) and the implementation of radical cystectomy (RC), a standard procedure for advanced BC., Materials and Methods: From the National Health Insurance Sharing Service database, males aged over 40 years who underwent serum prostate-specific antigen testing from 2006 through 2017 were identified, which is required for the prescription of 5ARIs. The association between the administration duration of 5ARIs and the practice for BC was analyzed., Results: Of the 3,843,968 subjects, 1,514,713 (39.4%) took 5ARIs for an average of 1.53 years, remaining 2,329,255 (60.6%) as non-5ARI counterparts. The incidence of BC was higher in the non-5ARI than in the 5ARI group (1.25% vs. 0.87%, p<0.001), as was the implementation rate of RC (11.1% vs. 10.4%, p=0.037). In a multivariate analysis, the non-5ARI group had a significant risk of BC (hazard ratio [HR]=2.289, 95% confidence interval [CI]=2.241-2.338) and RC (HR=2.199, 95% CI=2.061-2.348) than the 5ARI group. Among the 5ARIs group, though the incidence of BC was maintained (slope=-0.002 per year, p=0.79) after an initial increase for two years, the rate of RC decreased (slope=-1.1, p<0.001) consistently for ten years during the administration., Conclusions: Compared to the untreated group, 5ARIs use was associated with lower rates of BC and RC. In contrast to the increase in BC seen with short-term use of less than two years, long-term use of 5ARIs decreased the rate of RC in a duration-dependent manner for ten years, suggesting a strategy to prevent disease progression., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Novel psychoactive substances (NPSs) are new psychotropic drugs designed to evade substance regulatory policies. 25E-NBOMe (2-(4-ethyl-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine) has recently been identified as an NPS, and its recreational misuse has been reported to be rapidly increasing. However, the psychopharmacological effects and mechanisms of 25E-NBOMe have not been studied. We examined the abuse potential of 25E-NBOMe using the conditioned place preference in male mice and self-administration paradigms in male rats. Additionally, immunoblot assay, enzyme-linked immunosorbent assay, and microdialysis were used to determine the molecular effects of 25E-NBOMe in the nucleus accumbens (NAc). Our data demonstrated that 25E-NBOMe induces conditioned place preference, and the dopaminergic signaling in the NAc mediates these. Following 25E-NBOMe administration, expression of dopamine transporter and dopamine D1 receptor (D1DR) were enhanced in the NAc of male mice, and NAc dopamine levels were reduced in both male mice and rats. Induction of intracellular dopaminergic pathways, DARPP32, and phosphorylation of CREB in the NAc of male mice was also observed. Significantly, pharmacological blockade of D1DR or chemogenetic inhibition of D1DR-expressing medium spiny neurons in the NAc attenuated 25E-NBOMe-induced conditioned place preference in male mice. We also examined the hallucinogenic properties of 25E-NBOMe using the head twitch response test in male mice and found that this behavior was mediated by serotonin 2A receptor activity. Our findings demonstrate that D1DR signaling may govern the addictive potential of 25E-NBOMe. Moreover, our study provides new insights into the potential mechanisms of substance use disorder and the improvement of controlled substance management., (© 2024. The Pharmaceutical Society of Korea.)

We demonstrate an understanding of different physicochemical properties of copolymers induced by systematic changes in their structural parameters, i.e., the chemical structure of the comonomer unit, composition, molecular weight, and dispersity. The terpolymers were designed to be implemented in a chemically amplified resist (CAR) to form negative-tone patterns. With two basic repeating units of 4-hydroxystyrene and 2-ethyl-2-methacryloxyadamantane as monomers for conventional CARs, the pendant group of the third methacrylate comonomer was varied from aromatic, aliphatic lactone to lactone rings to modulate the interaction capability of the copolymer chains with n -butyl acetate, which is a negative-tone developer. Along with these structures, the monomer composition, molecular weight, and dispersity were also controlled. Physicochemical properties of the synthesized copolymers having controlled structures, i.e., dissolution behaviors and quantified Hansen solubility parameters, surface wetting characteristics, and surface roughness, which can be important properties affecting patterning capability in high-resolution lithography, were explored. Furthermore, the feasibility to use experimentally determined Hansen solubility parameters of the copolymers for the prediction of pattern formation using a coarse-grained model was assessed. Our comprehensive studies on the correlation of the structural parameters of the copolymers with final properties offer fundamental avenues to attain effective designs of the complex CAR system toward the lithographic process to achieve a sub-10 nm dimension, which is close to a single-chain dimension.

Altered glycolytic metabolism has been associated with chemoresistance in acute myeloid leukemia (AML). However, there are still aspects that need clarification, as well as how to explore these metabolic alterations in therapy. In the present study, we aimed to elucidate the role of glucose metabolism in the acquired resistance of AML cells to cytarabine (Ara-C) and to explore it as a therapeutic target. Resistance was induced by stepwise exposure of AML cells to increasing concentrations of Ara-C. Ara-C-resistant cells were characterized for their growth capacity, genetic alterations, metabolic profile, and sensitivity to different metabolic inhibitors. Ara-C-resistant AML cell lines, KG-1 Ara-R, and MOLM13 Ara-R presented different metabolic profiles. KG-1 Ara-R cells exhibited a more pronounced glycolytic phenotype than parental cells, with a weaker acute response to 3-bromopyruvate (3-BP) but higher sensitivity after 48 h. KG-1 Ara-R cells also display increased respiration rates and are more sensitive to phenformin than parental cells. On the other hand, MOLM13 Ara-R cells display a glucose metabolism profile similar to parental cells, as well as sensitivity to glycolytic inhibitors. These results indicate that acquired resistance to Ara-C in AML may involve metabolic adaptations, which can be explored therapeutically in the AML patient setting who developed resistance to therapy.

Pancreatic cancer has a five-year survival rate of only 10%, mostly due to late diagnosis and limited treatment options. In patients with unresectable disease, either FOLFIRINOX, a combination of 5-fluorouracil (5-FU), oxaliplatin and irinotecan, or gemcitabine plus nab-paclitaxel combined with radiation are frontline standard regimens. However, chemo-radiation therapy has shown limited success because patients develop resistance to chemotherapy and/or radiation. In this study, we evaluated the role of pancreatic cancer stem cells (CSC) using OCT4 and SOX2, CSC markers in mouse pancreatic tumor organoids. We treated pancreatic tumor organoids with 4 or 8 Gy of radiation, 10 μM of 5-FU (5-Fluorouracil), and 100 μM 3-Bromopyruvate (3BP), a promising anti-cancer drug, as a single treatment modalities, and in combination with RT. Our results showed significant upregulation of, OCT4, and SOX2 expression in pancreatic tumor organoids treated with 4 and 8 Gy of radiation, and downregulation following 5-FU treatment. The expression of CSC markers with increasing treatment dose exhibited elevated upregulation levels to radiation and downregulation to 5-FU chemotherapy drug. Conversely, when tumor organoids were treated with a combination of 5-FU and radiation, there was a significant inhibition in SOX2 and OCT4 expression, indicating CSC self-renewal inhibition. Noticeably, we also observed that human pancreatic tumor tissues exhibited heterogeneous and aberrant OCT4 and SOX2 expression as compared to normal pancreas, indicating their potential role in pancreatic cancer growth and therapy resistance. In addition, the combination of 5-FU and radiation treatment exhibited significant inhibition of the β-catenin pathway in pancreatic tumor organoids, resulting in sensitization to treatment and organoid death. In conclusion, our study emphasizes the crucial role of CSCs in therapeutic resistance in PC treatment. We recommend using tumor organoids as a model system to explore the impact of CSCs in PC and identify new therapeutic targets., (© 2024. The Author(s).)