Nesfatin-1 ameliorates pathological abnormalities in Drosophila hTau model of Alzheimer's disease.

In human Alzheimer's disease (AD), the aggregation of tau protein is considered a significant hallmark, along with amyloid-beta. The formation of neurofibrillary tangles due to aberrant phosphorylation of tau disrupts microtubule stability, leading to neuronal toxicity, dysfunction, and subsequent cell death. Nesfatin-1 is a neuropeptide primarily known for regulating appetite and energy homeostasis. However, the function of Nesfatin-1 in a neuroprotective role has not been investigated. In this study, we aimed to elucidate the effect of Nesfatin-1 on tau pathology using the Drosophila model system. Our findings demonstrate that Nesfatin-1 effectively mitigates the pathological phenotypes observed in Drosophila human Tau overexpression models. Nesfatin-1 overexpression rescued the neurodegenerative phenotypes in the adult fly's eye and bristle. Additionally, Nesfatin-1 improved locomotive behavior, neuromuscular junction formation, and lifespan in the hTau AD model. Moreover, Nesfatin-1 controls tauopathy by reducing the protein level of hTau. Overall, this research highlights the potential therapeutic applications of Nesfatin-1 in ameliorating the pathological features associated with Alzheimer's disease.

Prognostic effect of microscopically negative but close resection margin in gastric cancer.

INTRODUCTION: Microscopically positive resection margin (RM) following curative surgery has been linked to disease recurrence in gastric cancer (GC), but the impact of microscopically negative but close RM (CRM) remains unclear. This study aimed to evaluate the prognostic implications of a CRM of ≤0.5 cm in GC patients. METHODS: A retrospective review of the institutional GC database identified 1958 patients who underwent curative gastrectomy for pathologically proven GC between January 2011 and December 2015. The patients were categorized into CRM (RM ≤0.5 cm) and sufficient RM (SRM, RM >0.5 cm) groups. The impact of CRM on recurrence-free survival (RFS) and overall survival (OS) was analyzed compared to the SRM group. RESULTS: The cohort comprised 1264 patients with early GC (EGC, 64.6%) and 694 with advanced GC (AGC, 35.4%). Forty-four patients (2.2%) had RM of ≤0.5 cm. CRM was associated with worse RFS in AGC (5-year RFS in the CRM vs. SRM groups; 41.6% vs. 68.7%, p = 0.011); however, the effect on OS was not significant (p = 0.159). Multivariate analysis revealed that CRM was an independent prognostic factor for RFS (hazard ratio [HR] 2.035, 95% confidence interval [CI] 1.097-3.776). In AGC, the locoregional recurrence rate was significantly higher in the CRM group than in the SRM group (15.4% vs. 4.9%, p = 0.044). CONCLUSION: CRM of ≤0.5 cm was a significant prognostic factor for RFS in GC patients and was associated with a significant increase in locoregional recurrence in AGC.

A study on the formative usability testing for modular powered wheelchair.

The increasing prevalence of mobility impairments underscores the urgent need for accessible and affordable mobility aids. To overcome the mobility limitations of people with disabilities, there is an increasing need for the development of lightweight and portable powered wheelchairs that can be easily loaded. This study aimed to perform an early health technology assessment and a formative usability evaluation on a modular (detachable) powered wheelchair. It aimed to gauge device satisfaction among users, pinpoint areas for improvement, and detect any unforeseen errors to inform future development. Engaging 16 participants, including powered wheelchair users, healthcare professionals, and caregivers, the research evaluated the wheelchair's functionality in various scenarios, emphasizing safety, effectiveness, and convenience. Statistical analyses of task performance and satisfaction surveys highlighted that, while powered wheelchair users successfully completed tasks focusing on driving and power control, healthcare professionals and caregivers encountered difficulties with the wheelchair's assembly and disassembly. Despite general positivity, the surveys indicated mixed satisfaction levels regarding safety, validity, and convenience, with specific issues related to frame durability, seat comfort, and control mechanisms. These findings suggest that refining the wheelchair's design and addressing user concerns could significantly enhance satisfaction and mobility services. Future efforts will include a thorough review of an advanced prototype and further satisfaction assessments.

We believe that our study makes a significant contribution to the literature by addressing a critical gap in the understanding of user-centric design and usability testing for powered wheelchairs.By emphasizing the importance of early assessments and incorporating user feedback into the development process, our research offers practical insights for creating more accessible and user-friendly mobility solutions.This contribution is particularly relevant in the context of advancing assistive technology and improving the quality of life for individuals with disabilities.

The overexpression of DSP1 in neurons induces neuronal dysfunction and neurodegeneration phenotypes in Drosophila.

Dorsal switch protein 1(DSP1), a mammalian homolog of HMGB1, is firstly identified as a dorsal co-repressor in 1994. DSP1 contains HMG-box domain and functions as a transcriptional regulator in Drosophila melanogaster. It plays a crucial role in embryonic development, particularly in dorsal-ventral patterning during early embryogenesis, through the regulation of gene expression. Moreover, DSP1 is implicated in various cellular processes, including cell fate determination and tissue differentiation, which are essential for embryonic development. While the function of DSP1 in embryonic development has been relatively well-studied, its role in the adult Drosophila brain remains less understood. In this study, we investigated the role of DSP1 in the brain by using neuronal-specific DSP1 overexpression flies. We observed that climbing ability and life span are decreased in DSP1-overexpressed flies. Furthermore, these flies demonstrated neuromuscular junction (NMJ) defect, reduced eye size and a decrease in tyrosine hydroxylase (TH)-positive neurons, indicating neuronal toxicity induced by DSP1 overexpression. Our data suggest that DSP1 overexpression leads to neuronal dysfunction and toxicity, positioning DSP1 as a potential therapeutic target for neurodegenerative diseases.

Cardiovascular disease risk and associated physical activity factors in gastrointestinal cancer survivors.

INTRODUCTION: Although the risk of CVD is increased in cancer survivors, few studies have investigated the CVD risk in survivors of gastrointestinal (GI) cancer. Therefore, we evaluated the CVD risk using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score for GI cancer survivors and associated physical activity factors. METHODS: Using the 2014-2019 Korean National Health and Nutrition Examination Surveys, data were collected for 262 GI cancer survivors and 1,310 cancer-free controls matched at a 1:5 ratio based on age and sex. The International Physical Activity Questionnaire Short-Form was used to assess physical activity, and the Euro QoL Questionnaire 5-Dimensional Classification (EQ-5D) was used to assess the health-related quality of life. RESULTS: A multiple logistic regression analysis demonstrated a lower risk of ASCVD in GI cancer survivors than in controls (adjusted odds ratio [aOR] = 0.73, 95% confidence interval [CI] = 0.55-0.97). Moreover, the risk of having a high ASCVD score was significantly lower in individuals who performed sufficient aerobic physical activity (aOR = 0.59, 95% CI = 0.47-0.75) and those with an EQ-5D score 1 or 2 (aOR = 0.36, 95% CI = 0.20-0.65 and aOR = 0.31, 95% CI = 0.16-0.58, respectively). CONCLUSIONS: This population-based study demonstrated that engaging in sufficient physical activity can reduce the ASCVD risk among GI cancer survivors.

Detection of Cervical Foraminal Stenosis from Oblique Radiograph Using Convolutional Neural Network Algorithm.

PURPOSE: This study was conducted to develop a convolutional neural network (CNN) algorithm that can diagnose cervical foraminal stenosis using oblique radiographs and evaluate its accuracy. MATERIALS AND METHODS: A total of 997 patients who underwent cervical MRI and cervical oblique radiographs within a 3-month interval were included. Oblique radiographs were labeled as "foraminal stenosis" or "no foraminal stenosis" according to whether foraminal stenosis was present in the C2-T1 levels based on MRI evaluation as ground truth. The CNN model involved data augmentation, image preprocessing, and transfer learning using DenseNet161. Visualization of the location of the CNN model was performed using gradient-weight class activation mapping (Grad-CAM). RESULTS: The area under the curve (AUC) of the receiver operating characteristic curve based on DenseNet161 was 0.889 (95% confidence interval, 0.851-0.927). The F1 score, accuracy, precision, and recall were 88.5%, 84.6%, 88.1%, and 88.5%, respectively. The accuracy of the proposed CNN model was significantly higher than that of two orthopedic surgeons (64.0%, p<0.001; 58.0%, p<0.001). Grad-CAM analysis demonstrated that the CNN model most frequently focused on the foramen location for the determination of foraminal stenosis, although disc space was also frequently taken into consideration. CONCLUSION: A CNN algorithm that can detect neural foraminal stenosis in cervical oblique radiographs was developed. The AUC, F1 score, and accuracy were 0.889, 88.5%, and 84.6%, respectively. With the current CNN model, cervical oblique radiography could be a more effective screening tool for neural foraminal stenosis.

Enhanced Crystallization of Sustainable Polylactic Acid Composites Incorporating Recycled Industrial Cement.

Globally, the demand for single-use plastics has increased due to the rising demand for food delivery and household goods. This has led to environmental challenges caused by indiscriminate dumping and disposal. To address this issue, non-degradable plastics are being replaced with biodegradable alternatives. Polylactic acid (PLA) is a type of biodegradable plastic that has excellent mechanical properties. However, its applications are limited due to its low crystallinity and brittleness. Studies have been conducted to combat these limitations using carbon or inorganic nucleating agents. In this study, waste cement and PLA were mixed to investigate the effect of the hybrid inorganic nucleating agent on the crystallinity and mechanical properties of PLA. Waste cement accelerated the lamellar growth of PLA and improved its crystallinity. The results indicate that the flexural and impact strengths increased by approximately 3.63% and 76.18%, respectively.

Assessing the Reproducibility of the Structured Abstracts Generated by ChatGPT and Bard Compared to Human-Written Abstracts in the Field of Spine Surgery: Comparative Analysis.

BACKGROUND: Due to recent advances in artificial intelligence (AI), language model applications can generate logical text output that is difficult to distinguish from human writing. ChatGPT (OpenAI) and Bard (subsequently rebranded as "Gemini"; Google AI) were developed using distinct approaches, but little has been studied about the difference in their capability to generate the abstract. The use of AI to write scientific abstracts in the field of spine surgery is the center of much debate and controversy. OBJECTIVE: The objective of this study is to assess the reproducibility of the structured abstracts generated by ChatGPT and Bard compared to human-written abstracts in the field of spine surgery. METHODS: In total, 60 abstracts dealing with spine sections were randomly selected from 7 reputable journals and used as ChatGPT and Bard input statements to generate abstracts based on supplied paper titles. A total of 174 abstracts, divided into human-written abstracts, ChatGPT-generated abstracts, and Bard-generated abstracts, were evaluated for compliance with the structured format of journal guidelines and consistency of content. The likelihood of plagiarism and AI output was assessed using the iThenticate and ZeroGPT programs, respectively. A total of 8 reviewers in the spinal field evaluated 30 randomly extracted abstracts to determine whether they were produced by AI or human authors. RESULTS: The proportion of abstracts that met journal formatting guidelines was greater among ChatGPT abstracts (34/60, 56.6%) compared with those generated by Bard (6/54, 11.1%; P<.001). However, a higher proportion of Bard abstracts (49/54, 90.7%) had word counts that met journal guidelines compared with ChatGPT abstracts (30/60, 50%; P<.001). The similarity index was significantly lower among ChatGPT-generated abstracts (20.7%) compared with Bard-generated abstracts (32.1%; P<.001). The AI-detection program predicted that 21.7% (13/60) of the human group, 63.3% (38/60) of the ChatGPT group, and 87% (47/54) of the Bard group were possibly generated by AI, with an area under the curve value of 0.863 (P<.001). The mean detection rate by human reviewers was 53.8% (SD 11.2%), achieving a sensitivity of 56.3% and a specificity of 48.4%. A total of 56.3% (63/112) of the actual human-written abstracts and 55.9% (62/128) of AI-generated abstracts were recognized as human-written and AI-generated by human reviewers, respectively. CONCLUSIONS: Both ChatGPT and Bard can be used to help write abstracts, but most AI-generated abstracts are currently considered unethical due to high plagiarism and AI-detection rates. ChatGPT-generated abstracts appear to be superior to Bard-generated abstracts in meeting journal formatting guidelines. Because humans are unable to accurately distinguish abstracts written by humans from those produced by AI programs, it is crucial to exercise special caution and examine the ethical boundaries of using AI programs, including ChatGPT and Bard.

Comparison of depression and suicide between dialysis and kidney transplant recipients in Korea: a nationwide population study.

Background: Kidney transplantation (KT) improves physical and psychological prognoses for patients with end-stage kidney disease (ESKD). However, few comparative studies have examined depression and suicide rates among patients with ESKD treated with dialysis versus KT. Methods: Data on 21,809 patients with ESKD were extracted from the Korean National Health Insurance Service database, extending from January 2002 to December 2018. These patients exhibited no history of depression or insomnia before starting renal replacement therapy. Outcomes were compared between dialysis and KT recipients using 1:2 propensity score matching (PSM). Results: Of the patients, 17,649 received dialysis (hemodialysis, 15,537; peritoneal dialysis, 2,112), while 4,160 underwent KT. Of those on dialysis, 45.04% (7,949) experienced insomnia, compared to 25.72% (1,070) of KT recipients (P<0.001). Depression was more frequent among dialysis recipients (22.77%, 4,019) than KT recipients (8.61%, 358; P<0.001). Additionally, those on dialysis had a higher incidence of suicide (0.19%, 33) than recipients of KT (0.12%, 5; P=0.047). After PSM, the hazard ratio (HR) for depression in patients on dialysis compared to KT recipients was 1.76 (95% confidence interval [CI], 1.56-1.99). In subgroup analysis, the relative likelihood of depression among dialysis recipients was particularly high for residents of urban areas (HR, 2.10; 95% CI, 1.80-2.44) and patients under 65 years old (HR, 1.82; 95% CI, 1.62-2.09). Conclusions: KT recipients exhibit a lower suicide rate than patients on dialysis. Furthermore, KT is associated with a lower prevalence of depression among Korean patients with ESKD, particularly urban residents and individuals under 65 years old.

First report of leaf spot caused by Colletotrichum camelliae in mung beans (Vigna radiata (L.) R. Wilczek) in South Korea.

Mung bean (Vigna radiata (L.) R. Wilczek) is a legume with high nutritional and economic value that is cultivated widely across Asia (Kang et al. 2014). In March 2022, a leaf spot disease in mung bean was observed at the Gangneung-Wonju National University Experimental farm (Gangneung, South Korea, 37.77°N, 128.86°E). The affected plants had irregular brown-gray leaf spots, and the bottom of the leaves showed concentric brown-gray rings that eventually progressed to necrotic lesions. Regardless of the cultivar, approximately 30% of the plants in the field were infected. To isolate the pathogen, the affected leaves were surface-sterilized by washing with 70% ethanol for 1 min, followed by washing with 2% NaClO for 2 min, then rinsing with sterile distilled water. We placed 3-mm sized diseased lesions on potato-dextrose agar (PDA), then incubated them at 27 ± 1 °C in the dark for 7 days and we obtained 1 isolate (CC1). The fungus on PDA had white aerial mycelia that became gray toward the center. Single spore cultures were obtained from fungal isolate. Isolated conidia were single celled, hyaline, cylindrical, and measured between 20.75 to 22.07 µm × 5.85 to 6.92 µm (n = 20), similar to other reports of C. camelliae(Wang et al. 2016). Mycelium from the single spore isolate was used for DNA extraction using Exgene™ Plant SV / (GeneAll®, Cat.No. 117-152), and we amplified the ITS region with primers ITS1 + ITS2 and ITS3 + ITS4, a portion of the actin gene with primers ACT-512F + 738R, and a portion of the beta-tubulin gene with primers BT2aF + BT2bR (Carbone et al. 1999; Glass et al. 1995; White et al. 1990). The amplified regions were sequenced by by Macrogen® (Seoul, South Korea). Sequences were deposited under GenBank accession numbers OR523262 (ITS), OR582483 (Actin), and OR566953 (beta-tubulin). MegaBLAST analysis of the ITS1, ITS2, ACT, and TUB regions showed 99% (216/217 bp) similarity with C. camelliae strain HNCS-26 (MK041440.1), 99% (303/305 bp) similarity with C. camelliae strain G3 (ON025203.1), 99% (242/244 bp) similarity with C. camelliae strain FWT41 (MN525820.1), and 99% (456/460 bp) with C. camelliae strain LF152 (KJ955239.1), respectively. To fulfill Koch's postulates, we conducted a pathogenicity teston the mung bean cultivar VC1973A (Seonhwanokdu) grown for four weeks at 25 °C with a 16-h day/8-h night cycle, simulating the field conditions when the symptoms were observed. We tested the pathogenicity on six plants , three control and three infected plants. Using three leaf replicates per plant resulting in total of nine leaves per group. Leaves were first injured using a sterile needle then either sterile 5 mm PDA plugs or plugs with C. camelliae were placed on the leaf for control and infected conditions, respectively. Irregular gray leaf spots were observed on the abaxial and adaxial of the infected leaf after 2 weeks, like the symptoms observed in the field. This was observed only on infected leaves and nowhere else on the plant and the control plants had no infection. We re-isolated the pathogen from diseased leaves and identified it as C. camelliae using the same molecular markers described previously, completing Koch's postulate. To the best of our knowledge, this is the first report of leaf spot caused by C. camelliae in mung bean plants in Korea, previously the fungi was reported to infect tea plants in Korea (Hassan et al. 2023). More studies are required to investigate potentially resistant mung bean varieties to minimize future damage caused by this fungus.

Comparison of disposable digital single-operator cholangioscopy versus direct peroral cholangioscopy for the diagnosis of intraductal superficial lesions of the bile duct.

BACKGROUND: Disposable digital single-operator cholangioscopy (D-SOC) and direct peroral cholangioscopy (D-POC) using an ultraslim endoscope are established POC modalities for the diagnosis and treatment of various biliary diseases. We compared the usefulness of D-SOC and D-POC for the diagnosis of intraductal superficial lesions of the bile duct (ISL-Bs). METHODS: 38 consecutive patients with suspected biliary diseases who underwent both D-SOC and D-POC were enrolled. The primary outcome was ISL-B detection rate, and the secondary outcomes were technical success of POC and POC-guided forceps biopsy sampling (POC-FB), procedure time, visualization quality, and tissue adequacy. RESULTS: D-SOC had a higher technical success rate than D-POC but the difference was not statistically significant (100% vs. 92.1%, P = 0.25). D-POC had a marginally higher ISL-B detection rate (34.2% vs. 28.9%, P = 0.68) and significantly higher visualization quality (P = 0.03). The mean (SD) procedure time was significantly shorter with D-SOC (11.00 [1.33] vs. 19.03 [2.95] minutes, P<0.001). The technical success rate of POC-FB and tissue adequacy did not differ between the two techniques (D-SOC vs. D-POC: 81.8% vs. 84.6%, P = 0.69 and 77.8% vs. 90.9%, P = 0.57, respectively). CONCLUSIONS: Both POC systems were safe and useful for the detection, characterization, and diagnosis of minute ISL-Bs. While D-SOC displayed a shorter procedure time and a tendency for higher technical success rate, D-POC provided superior visualization quality, allowing detailed observation of the surface structure and microvascular patterns.

Impact of obesity on renal function in elderly Korean adults: a national population-based cohort study.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13-1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84-1.11), 1.10 (0.96-1.27), 1.24 (1.06-1.45), 1.37 (1.12-1.66), and 1.99 (1.42-2.79), respectively (p for trend < 0.001). Conclusion: In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

Comparative Analysis of Monoaxial and Polyaxial Pedicle Screws in the Surgical Correction of Adolescent Idiopathic Scoliosis.

Background: Although several biomechanical studies have been reported, few clinical studies have compared the efficacy of monoaxial and polyaxial pedicle screws in the surgical treatment of adolescent idiopathic scoliosis (AIS). This study aims to compare the radiological and clinical outcomes of mono- and polyaxial pedicle screws in the surgical treatment of AIS. Methods: A total of 46 AIS patients who underwent surgery to treat scoliosis using pedicle screw instrumentation (PSI) and rod derotation (RD) were divided into two groups according to the use of pedicle screws: the monoaxial group (n = 23) and polyaxial group (n = 23). Results: The correction rate of the main Cobb's angle was higher in the monoaxial group (70.2%) than in the polyaxial group (65.3%) (p = 0.040). No differences in the rotational correction of the apical vertebra were evident between the two groups. SRS-22 scores showed no significant differences according to the type of pedicle screws used. Conclusions: The use of polyaxial pedicle screws resulted in coronal, sagittal, and rotational correction outcomes comparable to those associated with the use of monoaxial pedicle screws for surgical treatment using PSI and RD to treat moderate cases of AIS.

Quintic refractive index profile-based funnel-shaped silicon antireflective structures for enhanced photodetector performance.

Antireflection, vital in optoelectronics devices such as solar cells and photodetectors, reduces light reflection and increases absorption. Antireflective structures (ARS), a primary method by which to realize this effect, control the refractive index (RI) profile based on their shape. The antireflection efficiency depends on the refractive index profile, with the quintic RI profile being recognized as ideal for superior antireflection. However, fabricating nano-sized structures with a desired shape, particularly in silicon with a quintic RI profile, has been a challenge. In this study, we introduce a funnel-shaped silicon (Si) ARS with a quintic RI profile. Its antireflective properties are demonstrated through reflectance measurements and by an application to a photodetector surface. Compared to the film Si and cone-shaped ARS types, which are common structures to achieve antireflection, the funnel-shaped ARS showed reflectance of 4.24% at 760 nm, whereas those of the film Si and cone-shaped ARS were 32.8% and 10.6%, respectively. Photodetectors with the funnel-shaped ARS showed responsivity of 0.077 A/W at 950 nm, which is 19.54 times higher than that with the film Si and 2.45 times higher than that with the cone-shaped ARS.

Impact of temperature-controlled endobiliary radiofrequency ablation for inoperable hilar cholangiocarcinoma: A propensity score-matched analysis.

Background and study aims Endobiliary radiofrequency ablation (RFA) can be an effective palliative treatment, but few studies have evaluated its outcomes for malignant obstruction in the hilar bile duct, which has a thin wall and complex duct-vascular contacts. We evaluated the efficacy and safety of temperature-controlled endobiliary RFA, which can reduce the risk of unintentional thermal injury by maintaining the temperature of the ablation segment, in the treatment of inoperable hilar cholangiocarcinoma (CCA). Patients and methods After propensity score matching, 64 patients with inoperable hilar CCA were categorized to the RFA + stent group (endobiliary RFA with stenting; n=32) or stent-only group (stenting only; n=32). The evaluated outcomes were the median time to recurrent biliary obstruction (RBO), overall survival (OS), and adverse events (AEs). Results Technical success was achieved in all patients. The clinical success rate was 93.8% in the RFA + stent group and 87.5% in the stent-only group ( P =0.672). The median time to RBO was 242 days in the RFA + stent group and 168 days in the stent-only group ( P =0.031). The median OS showed a non-significant tendency to be higher in the RFA + stent group (337 versus 296 days; P =0.260). Overall AE rates were comparable between the two groups (12.5% vs 9.4%, P =1.000). Conclusions Temperature-controlled endobiliary RFA resulted in favorable stent patency without increasing the rate of AEs but it did not significantly increase OS in patients with inoperable hilar CCA (Clinical trial registration number: KCT0008576).

The Nevus Lipomatosus Superficialis of Face: A Case Report and Literature Review.

Nevus lipomatosus superficialis (NLS) is a hamartoma of adipose tissue, rarely reported in the past 100 years. We treated one case, and we conducted a systematic review of the literature. A 41-year-old man presented with a cutaneous multinodular lesion in the posterior region near the right auricle. The lesion was excised and examined histopathologically. To review the literature, we searched PubMed with the keyword "NLS." The search was limited to articles written in English and whose full text was available. We analyzed the following data: year of report, nation of corresponding author, sex of patient, age at onset, duration of disease, location of lesion, type of lesion, associated symptoms, pathological findings, and treatment. Of 158 relevant articles in PubMed, 112 fulfilled our inclusion criteria; these referred to a total of 149 cases (cases with insufficient clinical information were excluded). In rare cases, the diagnosis of NLS was confirmed when the lesion coexisted with sebaceous trichofolliculoma and Demodex infestation. Clinical awareness for NLS has increased recently. NLS is an indolent and asymptomatic benign neoplasm that may exhibit malignant behavior in terms of huge lesion size and specific anatomical location. Early detection and curative treatment should be promoted.

BRD2-specific inhibitor, BBC0403, inhibits the progression of osteoarthritis pathogenesis in osteoarthritis-induced C57BL/6 male mice.

BACKGROUND AND PURPOSE: The discovery of new bromo- and extra-terminal inhibitors presents new drugs to treat osteoarthritis (OA). EXPERIMENTAL APPROACH: The new drug, BBC0403, was identified in the DNA-encoded library screening system by searching for compounds that target BRD (bromodomain-containing) proteins. The binding force with BRD proteins was evaluated using time-resolved fluorescence energy transfer (TR-FRET) and binding kinetics assays. Subsequently, in vitro and ex vivo analyses demonstrated the effects of the BRD2 inhibitor, BBC0403, on OA. For animal experiments, medial meniscus destabilization was performed to create a 12-week-old male C57BL/6 mouse model, and intra-articular (i.a.) injections were administered. Histological and immunohistochemical analyses were then performed. The underlying mechanism was confirmed by gene set enrichment analysis (GSEA) using RNA-seq. KEY RESULTS: TR-FRET and binding kinetics assays revealed that BBC0403 exhibited higher binding specificity for BRD2 compared to BRD3 and BRD4. The anti-OA effects of BBC0403 were tested at concentrations of 5, 10 and 20 µM (no cell toxicity in the range tested). The expression of catabolic factors, prostaglandin E2 (PGE2) production and extracellular matrix (ECM) degradation was reduced. Additionally, the i.a. injection of BBC0403 prevented OA cartilage degradation in mice. Finally, BBC0403 was demonstrated to suppress NF-κB and MAPK signalling pathways. CONCLUSION AND IMPLICATIONS: This study demonstrated that BBC0403 is a novel BRD2-specific inhibitor and a potential i.a.-injectable therapeutic agent to treat OA.

Comparison of Survival Outcomes between Radical Antegrade Modular Pancreatosplenectomy and Conventional Distal Pancreatosplenectomy for Pancreatic Body and Tail Cancer: Korean Multicenter Propensity Score Match Analysis.

(1) Background: The aim of this study was to compare the survival benefit of radical antegrade modular pancreatosplenectomy (RAMPS) with conventional distal pancreatosplenectomy (cDPS) in left-sided pancreatic cancer. (2) Methods: A retrospective propensity score matching (PSM) analysis was conducted on 333 patients who underwent RAMPS or cDPS for left-sided pancreatic cancer at four tertiary cancer centers. The study assessed prognostic factors and compared survival and operative outcomes. (3) Results: After PSM, 99 patients were matched in each group. RAMPS resulted in a higher retrieved lymph node count than cDPS (15.0 vs. 10.0, p < 0.001). No significant differences were observed between the two groups in terms of R0 resection rate, blood loss, hospital stay, or morbidity. The 5-year overall survival rate was similar in both groups (cDPS vs. RAMPS, 44.4% vs. 45.2%, p = 0.853), and disease-free survival was also comparable. Multivariate analysis revealed that ASA score, preoperative CA19-9, histologic differentiation, R1 resection, adjuvant treatment, and lymphovascular invasion were significant prognostic factors for overall survival. Preoperative CA19-9, histologic differentiation, T-stage, adjuvant treatment, and lymphovascular invasion were independent significant prognostic factors for disease-free survival. (4) Conclusions: Although RAMPS resulted in a higher retrieved lymph node count, survival outcomes were not different between the two groups. RAMPS was a surgical option to achieve R0 resection rather than a standard procedure.

A triple cysteine motif as major determinant of the modulation of neuronal KV7 channels by the paracetamol metabolite N-acetyl-p-benzo quinone imine.

BACKGROUND AND PURPOSE: The analgesic action of paracetamol involves KV7 channels, and its metabolite N-acetyl-p-benzo quinone imine (NAPQI), a cysteine modifying reagent, was shown to increase currents through such channels in nociceptors. Modification of cysteine residues by N-ethylmaleimide, H2O2, or nitric oxide has been found to modulate currents through KV7 channels. The study aims to identify whether, and if so which, cysteine residues in neuronal KV7 channels might be responsible for the effects of NAPQI. EXPERIMENTAL APPROACH: To address this question, we used a combination of perforated patch-clamp recordings, site-directed mutagenesis, and mass spectrometry applied to recombinant KV7.1 to KV7.5 channels. KEY RESULTS: Currents through the cardiac subtype KV7.1 were reduced by NAPQI. Currents through all other subtypes were increased, either by an isolated shift of the channel voltage dependence to more negative values (KV7.3) or by such a shift combined with increased maximal current levels (KV7.2, KV7.4, KV7.5). A stretch of three cysteine residues in the S2-S3 linker region of KV7.2 was necessary and sufficient to mediate these effects. CONCLUSION AND IMPLICATION: The paracetamol metabolite N-acetyl-p-benzo quinone imine (NAPQI) modifies cysteine residues of KV7 subunits and reinforces channel gating in homomeric and heteromeric KV7.2 to KV7.5, but not in KV7.1 channels. In KV7.2, a triple cysteine motif located within the S2-S3 linker region mediates this reinforcement that can be expected to reduce the excitability of nociceptors and to mediate antinociceptive actions of paracetamol.