An artificial intelligence system for comprehensive pathologic outcome prediction in early gastric cancer through endoscopic image analysis (with video).

BACKGROUND: Accurate prediction of pathologic results for early gastric cancer (EGC) based on endoscopic findings is essential in deciding between endoscopic and surgical resection. This study aimed to develop an artificial intelligence (AI) model to assess comprehensive pathologic characteristics of EGC using white-light endoscopic images and videos. METHODS: To train the model, we retrospectively collected 4,336 images and prospectively included 153 videos from patients with EGC who underwent endoscopic or surgical resection. The performance of the model was tested and compared to that of 16 endoscopists (nine experts and seven novices) using a mutually exclusive set of 260 images and 10 videos. Finally, we conducted external validation using 436 images and 89 videos from another institution. RESULTS: After training, the model achieved predictive accuracies of 89.7% for undifferentiated histology, 88.0% for submucosal invasion, 87.9% for lymphovascular invasion (LVI), and 92.7% for lymph node metastasis (LNM), using endoscopic videos. The area under the curve values of the model were 0.992 for undifferentiated histology, 0.902 for submucosal invasion, 0.706 for LVI, and 0.680 for LNM in the test. In addition, the model showed significantly higher accuracy than the experts in predicting undifferentiated histology (92.7% vs. 71.6%), submucosal invasion (87.3% vs. 72.6%), and LNM (87.7% vs. 72.3%). The external validation showed accuracies of 75.6% and 71.9% for undifferentiated histology and submucosal invasion, respectively. CONCLUSIONS: AI may assist endoscopists with high predictive performance for differentiation status and invasion depth of EGC. Further research is needed to improve the detection of LVI and LNM.

Blood Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Promising Screening Biomarkers for Brain Metastases in Patients with Lung Cancer.

The diagnosis of brain metastases (BMs) in patients with lung cancer (LC) predominantly relies on magnetic resonance imaging (MRI), a method that is constrained by high costs and limited accessibility. This study explores the potential of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) as screening biomarkers for BMs in LC patients. We conducted a retrospective analysis of 700 LC cases at the National Cancer Center, Korea, from July 2020 to June 2022, measuring sNfL and sGFAP levels at initial LC diagnosis. The likelihood of BM was evaluated using multivariate analysis and a predictive nomogram. Additionally, we prospectively monitored 177 samples from 46 LC patients initially without BM. Patients with BMs (n= 135) had significantly higher median sNfL (52.5 pg/mL) and sGFAP (239.2 pg/mL) levels compared to those without BMs (n = 565), with medians of 17.8 pg/mL and 141.1 pg/mL, respectively (p < 0.001 for both). The nomogram, incorporating age, sNfL, and sGFAP, predicted BM with an area under the curve (AUC) of 0.877 (95% CI 0.84-0.914), showing 74.8% sensitivity and 83.5% specificity. Over nine months, 93% of samples from patients without BM remained below the cutoff, while all patients developing BMs showed increased levels at detection. A nomogram incorporating age, sNfL, and sGFAP provides a valuable tool for identifying LC patients at high risk for BM, thereby enabling targeted MRI screenings and enhancing diagnostic efficiency.

Metabolomic Comparison of Guava (Psidium guajava L.) Leaf Extracts Fermented by Limosilactobacillus fermentum and Lactiplantibacillus plantarum and Their Antioxidant and Antiglycation Activities.

Probiotic fermentation of plant-based materials can lead to the generation of various bioactive substances via bacterial metabolites and the biotransformation of phenolic compounds. We compared the metabolic differences between fermentation by Limosilactobacillus fermentum KCTC15072BP (LFG) and fermentation by Lactiplantibacillus plantarum KGMB00831 (LPG) in guava leaf extract (0%, 0.5%, and 2% (w/v))-supplemented medium via non-targeted metabolite profiling. By performing multivariate statistical analysis and comparing the different guava leaf extract groups, 21 guava-derived and 30 bacterial metabolites were identified. The contents of guava-derived glucogallin, gallic acid, and sugar alcohols were significantly higher in LFG than they were in LPG. Similarly, significantly higher contents of guava-derived pyrogallol, vanillic acid, naringenin, phloretin, and aromatic amino acid catabolites were obtained with LPG than with LFG. LFG led to significantly higher antioxidant activities than LPG, while LPG led to significantly higher antiglycation activity than LFG. Interestingly, the fermentation-induced increase in the guava-leaf-extract-supplemented group was significantly higher than that in the control group. Thus, the increased bioactivity induced by guava fermentation with the Lactobacillaceae strain may be influenced by the synergistic effects between microbial metabolites and plant-derived compounds. Overall, examining the metabolic changes in plant-based food fermentation by differentiating the origin of metabolites provides a better understanding of food fermentation.

Disseminating Necrotizing Leukoencephalopathy Associated With Intra-CSF Methotrexate Chemotherapy: A Retrospective Observational Study.

BACKGROUND AND OBJECTIVES: Leptomeningeal metastases (LMs) are neoplasms that proliferate to membranes lining the brain and spinal cord. Intra-CSF methotrexate (MTX) chemotherapy is a prevalent treatment option. However, resultant long-term neurotoxicity can lead to irreversible disseminated necrotizing leukoencephalopathy (DNL). This study aims to determine the incidence, characteristics, risk factors, and outcomes of DNL following intra-CSF MTX chemotherapy for LM. METHODS: We retrospectively reviewed patients with LM who received intra-CSF MTX between 2001 and 2021 at the National Cancer Center of Korea. Patients with a follow-up duration of <3 months and those without follow-up MRI after MTX administration were excluded. The primary outcome was the development of DNL, evaluated based on the clinical and radiologic definitions of DNL. Logistic and Cox proportional regression models were used to assess the risk of DNL in patients with LM receiving intra-CSF MTX chemotherapy. RESULTS: Of the 577 patients included in the DNL investigation, 13 (2.3%) were identified to have irreversible DNL. The MRI features of DNL typically include necrotic changes in the bilateral anterior temporal region, extensive white matter, and/or brainstem lesions. All patients with DNL experienced fatal clinical course despite MTX cessation. Logistic regression analysis revealed that a cumulative dose of MTX significantly affected DNL occurrence. Multivariable analysis showed that the factor of ≥10 MTX rounds was significant for DNL development after adjusting for route of MTX administration and prior brain radiotherapy (odds ratio 7.32, 95% CI 1.42-37.77 at MTX rounds ≥10 vs < 10). In the Cox proportional hazards model considering time to occurrence of DNL, ≥10 rounds of MTX were identified as an independent predictor of DNL (hazard ratio 12.57, 95% CI 1.62-97.28, p = 0.015), even after adjusting for the synergistic effect of brain radiotherapy. DISCUSSION: DNL is a rare but fatal complication of intra-CSF MTX chemotherapy, and its progression cannot be prevented despite early recognition. The cumulative dose of intra-CSF MTX was an independent risk factor for DNL occurrence. Thus, intra-CSF MTX treatment for patients with LM should be administered with caution considering the possibility of the cumulative irreversible neurotoxicity.

Latent tuberculosis infection in Korean patients with multiple sclerosis and neuromyelitis optica spectrum disorder.

BACKGROUND: Latent tuberculosis infection (LTBI) is defined as an immune response to Mycobacterium tuberculosis infection that does not manifest clinically as active tuberculosis (TB). Since some immunotherapies can alter cellular immunity, LTBI screening has been recommended for patients with multiple sclerosis (pwMS) before initiation of long-term immunotherapies. In this study, we investigated the frequency of LTBI in Korean pwMS and patients with neuromyelitis optica spectrum disorder (pwNMOSD) and reported the long-term observation of untreated LTBI under various immunotherapies. METHODS: We enrolled pwMS or pwNMOSD who visited the Neurology department of the National Cancer Center between 2017 and 2021. LTBI was determined based on positive results of interferon-gamma release assay (IGRA) using QuantiFERON Gold Plus test and no evidence of active TB. Annual chest X-ray and careful monitoring for TB symptoms were performed until April 2023 or the time of follow-up loss. RESULTS: Among 531 patients who underwent the IGRA test, 25 pwMS (10.5%) and 42 pwNMOSD (14.3%) were diagnosed with LTBI. Of the 67 patients with LTBI, 59 patients (24 pwMS and 35 pwNMOSD) declined to receive preventive anti-TB drugs. None of the 59 with untreated LTBI demonstrated TB reactivation during 74.8 person-years in pwMS and 166.1 person-years in pwNMOSD. In addition, eight patients who completed the treatment for LTBI experienced no TB reactivation for a median of 5.5 years. CONCLUSION: The LTBI prevalence in Korean pw MS and pwNMOSD was 10.5% and 14.3%, respectively, which was much higher than that in pwMS from Western countries. Notably, none of the 59 patients with untreated LTBI showed TB reactivation over 240 person-years even under long-term immunotherapies, indicating the need for additional research to stratify the risk of LTBI-reactivation.

Neuronal IGF-1 overexpression restores hippocampal newborn cell survival and recent CFC memory consolidation in Cav1.3 knock-out mice.

Insulin-like growth factor-1 (IGF-1) exogenously supplied in the brain was shown to enhance the survival of hippocampal dentate gyrus (DG) newborn cells and some cognitive functions of mice. This study aims to test whether IGF-1 requires Cav1.3 activity critically while enhancing newborn cell survival and cognitive functions. We used Cav1.3 KO mice, where both DG newborn cell survival and the recent (1 day) single-trial contextual fear conditioning (CFC) memory consolidation were impaired. To supply IGF-1, we overexpressed (OX) IGF-1 in DG mature neurons by injecting an adeno-associated virus (AAV-IGF-1-mCherry) into the hippocampal areas of Cav1.3 KO mice. Our results, first, confirmed the enhanced expression of IGF-1 in the DG granule cell layer by immunohistochemistry. Next, we found this IGF-1 OX resulted in fully restoring both the survival rate of DCX (+) newborn cells and the recent single-trial CFC memory formation in Cav1.3 KO mice. Our results show that IGF-1 can enhance the survival of DG immature newborn cells and the recent CFC memory formation in a Cav1.3 channel-independent manner in vivo, suggesting activation of complementary pathways including the Cav1.2 channel. The result will help the application of adult newborn cell-based therapy improve the cognitive functions of neurological disorders.

De Novo ANCA-Negative Pauci-Immune Crescentic Glomerulonephritis After COVID-19 mRNA Vaccination: A Case Report.

To prevent the spread of the coronavirus disease 2019 (COVID-19) pandemic, vaccines have been authorized for emergency use and implemented worldwide. We present a case of de novo glomerulonephritis (GN) after use of the COVID-19 mRNA vaccine BNT162b2. A 48-year-old man with no relevant medical history was referred for sudden and persistent worsening of renal insufficiency 1.5 months after the second vaccine dose. He had arthralgia and skin rash a week after vaccination. Abdominal pain and diarrhea started 2 weeks later, and he was admitted to the hospital for enteritis treatment. Colonoscopy showed multiple ulcerations and petechiae suggestive of vasculitis in the terminal ileum. After prednisolone therapy, his gastrointestinal symptoms improved, but his renal function continued to deteriorate. Based on kidney biopsy findings and nephrotic-range proteinuria (5,306 mg/24 hours), he was diagnosed with anti-neutrophil cytoplasmic autoantibody (ANCA)-negative pauci-immune crescentic GN (CrGN). He received high-dose steroid pulse therapy and oral cyclophosphamide, and then, gradually underwent steroid tapering, with improvement in proteinuria and renal function over several weeks. Several cases of GN suspected to be related to COVID-19 vaccines have been reported. To our knowledge, this is the first case report of ANCA-negative pauci-immune crescentic CrGN with extrarenal involvement after COVID-19 mRNA vaccination. Our finding expands the spectrum of COVID-19 vaccine-associated GN.

Efficacy of White Spot Syndrome Virus Protein VP28-Expressing Chlorella vulgaris as an Oral Vaccine for Shrimp.

The white spot syndrome virus (WSSV) is the causative agent of white spot disease, which kills shrimp within a few days of infection. Although WSSV has a mortality rate of almost 100% and poses a serious threat to the shrimp farming industry, strategies for its prevention and treatment are extremely limited. In this study, we examined the efficacy of VP28, a recombinant WSSV protein expressed in Chlorella vulgaris (C. vulgaris), as an oral shrimp vaccine. When compared with the control group, in which WSSV had a cumulative mortality of 100%, shrimp treated with 5% VP28-expressing C. vulgaris in their feed only had a 20% cumulative mortality rate 12 days after the WSSV challenge. When compared with the nonvaccinated group, the transcription of anti-lipopolysaccharide factor, C-type lectin, and prophenoloxidase genes, which are involved in shrimp defense against WSSV infection, was upregulated 29.6 fold, 15.4 fold, and 11.5 fold, respectively. These findings highlight C. vulgaris as a potential host for industrial shrimp vaccine production.

Aquaporin-4-IgG positive neuromyelitis optica spectrum disorder in a paraneoplastic context.

OBJECTIVE: The association between aquaporin-4-immunoglobulin-G-positive neuromyelitis optica spectrum disorder (AQP4-IgG-NMOSD) and cancer via a plausible immunological response has been reported. Here, we investigated the frequency of cancer in a large cohort of patients with AQP4-IgG-NMOSD. METHODS: Between May 2005 and January 2023, patients with AQP4-IgG-NMOSD and a history of cancer were included by searching for diagnostic codes of both NMOSD and cancer in the electronic medical records and/or reviewing the database of the National Cancer Center registry of inflammatory diseases of the central nervous system. Probable paraneoplastic AQP4-IgG-NMOSD was defined according to the 2021 Criteria for Paraneoplastic Neurological Syndrome. RESULTS: Of 371 patients with AQP4-IgG-NMOSD, 23 (6.2%) had a history of cancer and four (1.1%) experienced NMOSD in a paraneoplastic context. Among the four patients with probable paraneoplastic AQP4-IgG-NMOSD, the types of cancer were lung (1 adenocarcinoma, 1 squamous cell carcinoma) and colorectal (2 adenocarcinomas). In three patients, the first NMOSD symptoms developed after a cancer diagnosis (median, 8 months [range, 4-23]), and one patient's symptoms preceded the cancer diagnosis (6 months). Compared to the 367 non-paraneoplastic patients, those in the paraneoplastic context had an older age at onset (median: 59.5 vs. 37 years, p = 0.012) and a higher proportion of longitudinally extensive transverse myelitis (LETM) as an initial manifestation (4/4[100%] vs. 130/367[35.4%], p = 0.017). CONCLUSIONS: In a large cohort of patients with AQP4-IgG-NMOSD, the frequency of cancer was low. Older age, LETM features at onset, and adenocarcinoma as the histological type were usually observed in patients with AQP4-IgG-NMOSD in a paraneoplastic context.

Low Serum Creatinine as Well as High Serum Creatinine Is Associated with Prognosis of Patients with Cancer in End-of-Life.

Background: The prognosis of end-of-life patients is challenging, and clinicians have attempted to predict survival more accurately. High serum creatinine (sCr) levels are associated with lower survival rates in patients with various cancers; however, low sCr levels are commonly expected in patients with terminal cancer because of muscle wasting and malnutrition. Therefore, we investigated the prevalence of low and high sCr levels and their association with survival duration in patients with terminal cancer in a palliative care unit. Methods: We analyzed the medical records of 280 patients admitted to a palliative care unit. Patients were divided into low (<0.5 mg/dL), normal (0.5-1.2 mg/dL), and high (>1.2 mg/dL) sCr groups. Kaplan-Meier survival curves using sCr levels were plotted and compared using the log-rank test. Using stepwise selection, a multivariable Cox proportional hazards model was used to identify the significant prognostic factors. Results: The median survival durations in the high-, low-, and normal-sCr groups were 9.57 days, 22.26 days, and 27.51 days, respectively. Multivariable Cox proportional hazard model identified that males (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.16-2.85), poor performance status (HR, 3.43; 95% CI, 1.12-10.54), total parenteral nutrition use (HR, 1.84; 95% CI, 1.09-3.1), high sCr (HR, 2.74; 95% CI, 1.52-4.94), and low sCr (HR, 1.22; 95% CI, 1.07-1.43) were significantly associated with a shorter survival time. Conclusion: Low and high serum creatinine levels were significantly associated with poor survival in patients with cancer at the end-of-life stage. Therefore, readily available and simple biomarkers may help plan advanced care in palliative care settings.

Serum neurofilament and glial fibrillary acidic protein in idiopathic and seropositive transverse myelitis.

BACKGROUND: Serum levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) reflect the disease activity and disability in central nervous system (CNS) demyelinating diseases. However, the clinical significance of NfL and GFAP in idiopathic transverse myelitis (iTM), an inflammatory spinal cord disease with unknown underlying causes, remains unclear. This study aimed to investigate NfL and GFAP levels in iTM and their association with the clinical parameters compared with those in TM with disease-specific antibodies such as anti-aquaporin 4 or myelin oligodendrocyte glycoprotein antibodies (sTM). METHODS: We collected serum and clinical data of 365 patients with CNS inflammatory diseases from 12 hospitals. The serum NfL and GFAP levels were measured in patients with iTM (n = 37) and sTM (n = 39) using ultrasensitive single-molecule array assays. Regression analysis was performed to investigate the associations between serum levels of NfL and GFAP and the clinical parameters such as higher EDSS scores (EDSS ≥ 4.0). RESULTS: Mean NfL levels were not significantly different between iTM (50.29 pg/ml) and sTM (63.18 pg/ml) (p = 0.824). GFAP levels were significantly lower in iTM (112.34 pg/ml) than in sTM (3814.20 pg/ml) (p = 0.006). NfL levels correlated with expanded disability status scale (EDSS) scores in sTM (p = 0.001) but not in iTM (p = 0.824). Disease duration also correlated with higher EDSS scores in sTM (p = 0.017). CONCLUSION: NfL levels and disease duration correlated with EDSS scores in sTM, and GFAP levels could be a promising biomarker to differentiate iTM from sTM.

Corrigendum: Blood neurofilament light chain as a biomarker for monitoring and predicting paclitaxel-induced peripheral neuropathy in patients with gynecological cancers.

[This corrects the article DOI: 10.3389/fonc.2022.942960.].

A questionnaire survey on the diagnosis and treatment of Fabry nephropathy in clinical practice.

BACKGROUND: Fabry nephropathy is characterized by a deficiency of lysosomal alpha-galactosidase A, which results in proteinuria and kidney disease. The ineffectiveness of enzyme replacement therapy (ERT) for severe kidney failure highlights the need for early detection and meaningful markers. However, because the diagnosis and treatment of Fabry disease can vary according to the expertise of physicians, we evaluated the opinions of Korean specialists. METHODS: A questionnaire regarding the management of Fabry nephropathy was emailed to healthcare providers with the experience or ability to treat individuals with Fabry nephropathy. RESULTS: Of the 70 experts who responded to the survey, 43 were nephrologists, and 64.3% of the respondents reported having treated patients with Fabry disease. Pediatricians are treating primarily patients with classic types of the disease, while nephrologists and cardiologists are treating more patients with variant types. Only 40.7% of non-nephrologists agreed that a kidney biopsy was required at the time of diagnosis, compared with 81.4% of nephrologists. Thirty-eight of 70 respondents (54.3%) reported measuring globotriaosylsphingosine (lyso-Gb3) as a biomarker. The most common period to measure lyso-Gb3 was at the time of diagnosis, followed by after ERT, before ERT, and at screening. For the stage at which ERT should begin, microalbuminuria and proteinuria were chosen by 51.8% and 28.6% of respondents, respectively. CONCLUSION: Nephrologists are more likely to treat variant Fabry disease rather than classic cases, and they agree that ERT should be initiated early in Fabry nephropathy, using lyso-Gb3 as a biomarker.

Applying a Radiation Therapy Volume Analysis Pipeline to Determine the Utility of Spectroscopic MRI-Guided Adaptive Radiation Therapy for Glioblastoma.

Accurate radiation therapy (RT) targeting is crucial for glioblastoma treatment but may be challenging using clinical imaging alone due to the infiltrative nature of glioblastomas. Precise targeting by whole-brain spectroscopic MRI, which maps tumor metabolites including choline (Cho) and N-acetylaspartate (NAA), can quantify early treatment-induced molecular changes that other traditional modalities cannot measure. We developed a pipeline to determine how spectroscopic MRI changes during early RT are associated with patient outcomes to provide insight into the utility of adaptive RT planning. Data were obtained from a study (NCT03137888) where glioblastoma patients received high-dose RT guided by the pre-RT Cho/NAA twice normal (Cho/NAA ≥ 2x) volume, and received spectroscopic MRI scans pre- and mid-RT. Overlap statistics between pre- and mid-RT scans were used to quantify metabolic activity changes after two weeks of RT. Log-rank tests were used to quantify the relationship between imaging metrics and patient overall and progression-free survival (OS/PFS). Patients with lower Jaccard/Dice coefficients had longer PFS (p = 0.045 for both), and patients with lower Jaccard/Dice coefficients had higher OS trending towards significance (p = 0.060 for both). Cho/NAA ≥ 2x volumes changed significantly during early RT, putting healthy tissue at risk of irradiation, and warranting further study into using adaptive RT planning.

Sub-10 fJ/bit radiation-hard nanoelectromechanical non-volatile memory.

With the exponential growth of the semiconductor industry, radiation-hardness has become an indispensable property of memory devices. However, implementation of radiation-hardened semiconductor memory devices inevitably requires various radiation-hardening technologies from the layout level to the system level, and such technologies incur a significant energy overhead. Thus, there is a growing demand for emerging memory devices that are energy-efficient and intrinsically radiation-hard. Here, we report a nanoelectromechanical non-volatile memory (NEM-NVM) with an ultra-low energy consumption and radiation-hardness. To achieve an ultra-low operating energy of less than 10 [Formula: see text], we introduce an out-of-plane electrode configuration and electrothermal erase operation. These approaches enable the NEM-NVM to be programmed with an ultra-low energy of 2.83 [Formula: see text]. Furthermore, due to its mechanically operating mechanisms and radiation-robust structural material, the NEM-NVM retains its superb characteristics without radiation-induced degradation such as increased leakage current, threshold voltage shift, and unintended bit-flip even after 1 Mrad irradiation.

Severe neuromuscular immune-related adverse events of immune checkpoint inhibitors at national cancer center in Korea.

PURPOSE: Neuromuscular immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs) have been increasingly recognized as a consequence of expanding use of ICIs in advanced cancers. We aimed to evaluate the frequency, phenotypes, rescue treatment, and clinical outcomes of severe neuromuscular irAEs of ICIs at National Cancer Center (NCC), Korea. MATERIALS AND METHODS: Consecutive patients with newly developed severe neuromuscular irAEs (common terminology criteria for adverse events grade 3 or greater) after ICI treatment at NCC in Korea between December 2018 and April 2022 were included by searching neuromuscular diagnostic codes in electronic medical records and/or reviewing neurological consultation documentations. RESULTS: Of the 1,503 ICI-treated patients, nine (0.6%) experienced severe neuromuscular irAEs; five with pembrolizumab and four with atezolizumab. The patients included five women and four men; their median age at onset was 59 years. The irAEs included Guillain-Barre syndrome (n = 5) and myasthenia gravis (MG) crisis with myositis (n = 4), and developed after a median of one (range 1-5) ICI cycle. The median modified Rankin score (mRS) was 4 (range 3-5) at the nadir. ICIs were discontinued in all patients, and rescue immunotherapy included corticosteroids (n = 9), intravenous immunoglobulin (n = 7), and plasmapheresis (n = 2). Eight patients showed improvements, with a median mRS of 3 (range 1-4); however, one patient (who had MG crisis with myocarditis) died. CONCLUSIONS: In this real-world monocentric study, ICI-induced neuromuscular irAEs were rare but potentially devastating; thus, physicians should remain vigilant to enable prompt recognition and management of irAEs.

Acceleration of Polybutylene Succinate Biodegradation by Terribacillus sp. JY49 Isolated from a Marine Environment.

Polybutylene succinate (PBS) is a bioplastic substitute for synthetic plastics that are made from petroleum-based products such as polyethylene and polypropylene. However, the biodegradation rate of PBS is still low and similar to that of polylactic acid (PLA). Moreover, our knowledge about degrader species is limited to a few fungi and mixed consortia. Here, to identify a bacterial degrader to accelerate PBS degradation, we screened and isolated Terribacillus sp. JY49, which showed significant degradability. In order to optimize solid and liquid culture conditions, the effect of factors such as temperature, additional carbon sources, and salt concentrations on degradation was confirmed. We observed a degradation yield of 22.3% after 7 days when adding 1% of glucose. Additionally, NaCl was added to liquid media, and degradation yield was decreased but PBS films were broken into pieces. Comparing the degree of PBS degradation during 10 days, the degradation yield was 31.4% after 10 days at 30 °C. Alteration of physical properties of films was analyzed by using scanning electron microscopy (SEM), gel permeation chromatography (GPC), and Fourier transform infrared (FT-IR). In addition, Terribacillus sp. JY49 showed clear zones on poly(butylene adipate-co-terephthalate) (PBAT), polycaprolactone (PCL), and copolymers such as P(3HB-co-3HV) and P(3HV-co-4HB), exhibiting a broad spectrum of degradation activities on bioplastics. However, there was no significant difference in absorbance when esterase activity was examined for different types of bioplastics. Overall, Terribacillus sp. JY49 is a potential bacterial strain that can degrade PBS and other bioplastics, and this is the first report of Terribacillus sp. as a bioplastic degrader.

Cerebrospinal fluid neurofilament light chain as a potential prognostic biomarker for leptomeningeal metastasis.

The present study aimed to evaluate whether the cerebrospinal fluid (CSF) neurofilament light chain (NfL) is a potential prognostic marker for patients with leptomeningeal metastasis (LM). NfL levels were measured in CSF using a single-molecule array assay. A total of 42 patients with LM who were treated with ventriculo-lumbar perfusion (VLP) chemotherapy and had available stored CSF samples from the lumbar subarachnoid space before VLP chemotherapy were included in the present study, in order to investigate the prognostic value of CSF NfL. The median CSF NfL level in patients with LM was 8.15 ng/ml; 30% of patients who had died at the time of analysis had CSF NfL levels higher than the calculated overall prognostic cut-off value (11 ng/ml). The median overall survival after initiation of VLP chemotherapy was significantly longer in patients with LM and low CSF NfL levels compared with in patients with LM and high CSF NfL levels (P<0.001). The statistical significance remained after adjusting for other known prognostic factors and in a subgroup analysis according to age. In conclusion, CSF NfL could be considered a putative prognostic marker in patients with LM treated with VLP chemotherapy.

Enhanced tolerance of Cupriavidus necator NCIMB 11599 to lignocellulosic derived inhibitors by inserting NAD salvage pathway genes.

Polyhydroxybutyrate (PHB) is a bio-based, biodegradable and biocompatible plastic that has the potential to replace petroleum-based plastics. Lignocellulosic biomass is a promising feedstock for industrial fermentation to produce bioproducts such as polyhydroxybutyrate (PHB). However, the pretreatment processes of lignocellulosic biomass lead to the generation of toxic byproducts, such as furfural, 5-HMF, vanillin, and acetate, which affect microbial growth and productivity. In this study, to reduce furfural toxicity during PHB production from lignocellulosic hydrolysates, we genetically engineered Cupriavidus necator NCIMB 11599, by inserting the nicotine amide salvage pathway genes pncB and nadE to increase the NAD(P)H pool. We found that the expression of pncB was the most effective in improving tolerance to inhibitors, cell growth, PHB production and sugar consumption rate. In addition, the engineered strain harboring pncB showed higher PHB production using lignocellulosic hydrolysates than the wild-type strain. Therefore, the application of NAD salvage pathway genes improves the tolerance of Cupriavidus necator to lignocellulosic-derived inhibitors and should be used to optimize PHB production.