Quantification of tire wear particles in road dust based on synthetic/natural rubber ratio using pyrolysis-gas chromatography-mass spectrometry across diverse tire types.

Increase in road traffic leads to increased concentrations of tire-wear particles (TWPs), a prominent source of microplastics from vehicles, in road dust. These particles can re-enter the atmosphere or move into aquatic ecosystems via runoff, impacting the environment. Consequently, accurately assessing and managing TWP levels in road dust is crucial. However, the ISO method (ISO/TS 20593 and 21396) uses a constant ratio of styrene-butadiene rubber (SBR) to natural rubber (NR) for all tires, disregarding the variability in tire composition across different types and brands. Our study found substantial SBR content (15.7 %) in heavyweight truck tires, traditionally believed to be predominantly NR. We evaluated the SBR/NR content in 15 tire types and proposed a method to more accurately evaluate TWP concentrations in road dust from five different locations. Our findings suggest that the conventional ISO method may underestimate the concentrations of TWP due to its reliance on a static ratio of SBR/NR. This study underscores the necessity for a more flexible approach that can adapt to the variability in SBR and NR content across different tire types. By delineating the limitations inherent in current assessment methods, our research contributes to a more adaptable understanding of TWP concentrations in road dust. This advancement prompts the development of a revised methodology that more accurately reflects the diverse compositions of tire rubber in environmental samples.

Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patient with chronic hepatitis B.

BACKGROUND AND AIM: Our study evaluated the outcomes of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB). We assessed viral and biochemical responses as well as changes in the estimated glomerular filtration rate (eGFR) and bone mineral density (BMD). METHODS: This retrospective multicenter study included CHB patients who achieved virologic response (VR) (HBV DNA < 20 IU/mL) while on TDF and were subsequently switched to TAF between April 2018 and October 2021. RESULTS: This study included 309 patients with a median age of 59 years, and 42.1% were male. The mean duration of TDF and TAF administration were 54.0 and 37.5 months, respectively. All patients maintained VR after switching to TAF. Alanine aminotransferase (ALT) normalization rate significantly increased 6 months after switching (74.8%-83.5%; P = 0.008). Adjusted eGFR significantly improved at 6 months (+5.55 ± 10.52 mL/min/1.73 m2; P < 0.001) and 12 months (+6.02 ± 10.70 mL/min/1.73 m2; P < 0.001) after switching. In the subgroup of patients with renal impairment (eGFR < 60 mL/min/1.73 m2), significant improvement in renal function was observed at 6 months (+0.6 ± 10.5 mL/min/1.73 m2; P < 0.001) and 12 months (+1.0 ± 10.7 mL/min/1.73 m2; P < 0.001) after switching to TAF. In patients with osteoporosis (n = 182), switching to TAF resulted in significant improvement in spine and hip BMD at 12 months, with increases of 9.7% (95% CI: 7.0-12.5) and 9.4% (95% CI: 7.0-11.8), respectively. CONCLUSION: In this real-world study, switching to TAF was effective and safe in patients, with notable improvements in ALT levels, renal function, and BMD.

Clinical outcomes of transarterial chemoembolization in Child-Turcotte Pugh class A patients with a single small (≤3 cm) hepatocellular carcinoma.

BACKGROUND AND AIM: Transarterial chemoembolization (TACE) is one of the standard modalities used to treat unresectable hepatocellular carcinoma (HCC), but the effectiveness of TACE for treating patients with a solitary small (≤3 cm) HCC and well-preserved liver function has not been definitively established. This study aimed to determine the therapeutic impact of TACE in patients with these characteristics. METHODS: This multicenter (four university hospitals) retrospective cohort study analyzed the medical records of 250 patients with a solitary small (≤3 cm) HCC and Child-Turcotte-Pugh (CTP) class A liver function diagnosed over 10 years. Posttreatment outcomes, including overall survival (OS), recurrence-free survival (RFS), and adverse events, were assessed following TACE therapy. RESULTS: One hundred and thirty-eight of the 250 patients (55.2%) treated with TACE achieved complete remission (CR). Overall median OS was 77.7 months, and median OS was significantly longer in the CR group than in the non-CR group (89.1 vs. 58.8 months, P = 0.001). Median RFS was 19.1 months in the CR group. Subgroup analysis identified hypertension, an elevated serum albumin level, and achieving CR as significant positive predictors of OS, whereas diabetes, hepatitis c virus infection, and tumor size (>2 cm) were poor prognostic factors of OS. CONCLUSIONS: The study demonstrates the effectiveness of TACE as a viable alternative for treating solitary small (≤3 cm) HCC in CTP class A patients.

Expansion of effector regulatory T cells in steroid responders of severe alcohol-associated hepatitis.

While steroid therapy is the preferred treatment for severe alcohol-associated hepatitis, the role of effector regulatory T (eTreg) cells and their association with steroid response and clinical outcomes in these patients remains to be elucidated. We prospectively enrolled 47 consecutive patients with alcohol-associated hepatitis, consisting of severe alcohol-associated hepatitis treated with steroids (n=18; steroid-treated group) and mild alcohol-associated hepatitis (n=29; nontreated group). After isolating peripheral blood mononuclear cells from the patients at enrollment and again 7 days later, the frequency of eTreg cells was examined using flow cytometry. Single-cell RNA sequencing analysis was conducted using paired peripheral blood mononuclear cells. In vitro experiments were also performed to assess phenotype changes and the suppressive function of Treg cells following steroid treatment. The steroid-treated group exhibited significantly higher Model for End-Stage Liver Disease scores than the nontreated group (p < 0.01). Within the steroid-treated group, the proportion of eTreg cells significantly expanded in the steroid responders (n=13; p = 0.01). Furthermore, a significant positive correlation was observed between the decrease in the Model for End-Stage Liver Disease score and the increase in eTreg cells (p < 0.05). Single-cell RNA sequencing using paired peripheral blood mononuclear cells (pre-steroid and post-steroid therapy) from a steroid responder revealed gene expression changes in T cells and monocytes, suggesting enhancement of Treg cell function. In vitro results showed an elevation in the proportion of eTreg cells after steroid therapy. In conclusion, our findings suggest that the efficacy of steroid therapy in patients with severe alcohol-associated hepatitis is mediated by an increase in the number of eTreg cells.

Assessment of biodegradation and toxicity of alternative plasticizer di(2-ethylhexyl) terephthalate: Impacts on microbial biofilms, metabolism, and reactive oxygen species-mediated stress response.

Although di(2-ethylhexyl) terephthalate (DOTP) is being widely adopted as a non-phthalate plasticizer, existing research primarily focuses on human and rat toxicity. This leaves a significant gap in our understanding of their impact on microbial communities. This study assessed the biodegradation and toxicity of DOTP on microbes, focusing on its impact on biofilms and microbial metabolism using Rhodococcus ruber as a representative bacterial strain. DOTP is commonly found in mass fractions between 0.6 and 20% v/v in various soft plastic products. This study used polyvinyl chloride films (PVC) with varying DOTP concentrations (range 1-10% v/v) as a surface for analysis of biofilm growth. Cell viability and bacterial stress responses were tested using LIVE/DEAD™ BacLight™ Bacterial Viability Kit and by the detection of reactive oxygen species using CellROX™ Green Reagent, respectively. An increase in the volume of dead cells (in the plastisphere biofilm) was observed with increasing DOTP concentrations in experiments using PVC films, indicating the potential negative impact of DOTP on microbial communities. Even at a relatively low concentration of DOTP (1%), signs of stress in the microbes were noticed, while concentrations above 5% compromised their ability to survive. This research provides a new understanding of the environmental impacts of alternative plasticizers, prompting the need for additional research into their wider effects on both the environment and human health.

Increase of the indoor concentration of volatile organic compounds after the use of incense and scented candle in studio apartments determined using passive sampling.

Burning incenses and scented candles may provide harmful chemicals. Although many studies have evaluated volatile organic chemicals emitted by their use and related health risks, extension of our understanding for guiding appropriate use under various use conditions is necessary. In this study, emission characteristics of commercial incenses and scented candles were evaluated in a laboratory chamber using real-time measurement and the time-weighted average exposure concentrations of monoaromatic compounds and monoterpenes were assessed using passive samplers while volunteers living in a studio apartment use them. After burning incense, the average levels of benzene increased from 1.4 to 100 µg m-3. The presence of a wood core in commercial incense products was the main cause of high benzene emission by burning them although the increase in benzene was also influenced by factors such as the brand of the products, the number of incense sticks burned, the duration of each burning session, and ventilation period. Electrical warming of scented candles increased the levels of monoterpenes by factors of 16-30 on average. Considering the emission characteristics found in this study, exposure to benzene and monoterpenes could be mitigated by cautious use of those products in residential areas.

Analysis of Response and Progression Patterns of Tyrosine Kinase Inhibitors in Recurrent or Metastatic Adenoid Cystic Carcinoma: A Post Hoc Analysis of Two KCSG Phase II Trials.

Purpose: In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). Materials and Methods: We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed. Results: In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and 3 patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6, 12.4, and 18.1 months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor. Conclusion: Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.

A Machine Learning Algorithm Facilitates Prognosis Prediction and Treatment Selection for Barcelona Clinic Liver Cancer Stage C Hepatocellular Carcinoma.

BACKGROUND: Given its heterogeneity and diverse clinical outcomes, precise subclassification of BCLC-C hepatocellular carcinoma (HCC) is required for appropriately determining patient prognosis and selecting treatment. METHODS: We recruited 2,626 patients with BCLC-C stage HCC from multiple centers, comprising training/test (n=1,693) and validation cohorts (n=933). The XGBoost was chosen for maximum performance among the machine learning (ML) models. Patients were categorized into low-/intermediate-/high-/very high-risk subgroups which were based on the estimated prognosis, and this subclassification was named the CLAssification via Machine learning of BCLC-C (CLAM-C). RESULTS: The areas under the receiver operating characteristic curve of the CLAM-C for predicting the 6-/12-/24-month survival of patients with BCLC-C were 0.800/0.831/0.715, respectively-significantly higher than those of the conventional models, which was consistent in the validation cohort. The four subgroups had significantly different median overall survivals, and this difference was maintained among various patient subgroups and treatment modalities. Immune-checkpoint inhibitors and transarterial therapies were associated with significantly better survival than tyrosine kinase inhibitors (TKIs) in the low- and intermediate-risk subgroups. In cases with first-line systemic therapy, the CLAM-C identified atezolizumab-bevacizumab as the best therapy particularly in the high-risk group. In cases with later-line systemic therapy, nivolumab had better survival than TKIs in the low-to-intermediate-risk subgroup, whereas TKIs had better survival in the high-to-very high-risk subgroup. CONCLUSIONS: ML modeling effectively subclassified patients with BCLC-C HCC, potentially aiding treatment allocation. Our study underscores the potential utilization of ML modeling in terms of prognostication and treatment allocation in patients with BCLC-C HCC.

The release, degradation, and distribution of PVC microplastic-originated phthalate and non-phthalate plasticizers in sediments.

This study investigated the leaching of phthalate and non-phthalate plasticizers from polyvinyl chloride microplastics (MPs) into sediment and their degradation over a 30-d period via abiotic and biotic processes. The results showed that 3579% of plasticizers were released into the sediment from the MPs and > 99.9% degradation was achieved. Although a significantly higher degradation was found in plasticizer-added microcosms under biotic processes (overall, 94%), there was a noticeable abiotic loss (72%), suggesting that abiotic processes also play a role in plasticizer degradation. Interestingly, when compared with the initial sediment-water partitioning for plasticizers, the partition constants for low-molecular-weight compounds decreased in both microcosms, whereas those for high-molecular-weight compounds increased after abiotic degradation. Furthermore, changes in the bacterial community, abundance of plasticizer-degrading bacterial populations, and functional gene profiles were assessed. In all the microcosms, a decrease in bacterial community diversity and a notable shift in bacterial composition were observed. The enriched potential plasticizer-degrading bacteria were Arthrobacter, Bacillus, Desulfovibrio, Desulfuromonas, Devosia, Gordonia, Mycobacterium, and Sphingomonas, among which Bacillus was recognized as the key plasticizer degrader. Overall, these findings shed light on the factors affecting plasticizer degradation, the microbial communities potentially involved in biodegradation, and the fate of plasticizers in the environment.

Uncovering the health implications of abandoned mines through protein profiling of local residents.

Residents in areas with abandoned mines risk significant exposure to abundant heavy metals in the environment. However, current clinical indicators cannot fully reflect the health changes associated with abandoned mine exposure. The aim of this study was to identify biological changes in the residents of abandoned mine areas via proteomic analysis of their blood. Blood samples were collected from abandoned mine and control areas, and mass spectrometry was used for protein profiling. A total of 138 unique or common proteins that were differentially expressed in low-exposure abandoned mine area (LoAMA) or high-exposure abandoned mine area (HiAMA) compared to non-exposure control area (NEA) were analyzed, and identified 4 clusters based on functional similarity. Among the 10 proteins that showed specific change in LoAMA, 4 proteins(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) were cluded in cluster 1(plasma lipoprotein remodeling), and linked to proteins that showed specific change in protein expression in HiAMA. Therefore, it is suggested that 4 proteins are changed at low exposure to an abandoned mine (or initial exposure), and then at high exposure, changes in various proteins involved in linked plasma lipoprotein remodeling are induced, which might triggered by the 4 proteins. Interestingly, in addition to plasma lipoprotein remodeling, proteins involved in other functional networks were changed in the high exposure group. These were all directly or indirectly linked to the 4 biomarkers(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) that changed during low exposure. This suggests their potential utility in identifying areas impacted by abandoned mines. Especially, proteins involved in lipid metabolism and renal function-related diseases in individuals exposed to heavy metals in abandoned mine areas were correlated. Chronic kidney disease is predominantly instigated by cardiovascular disease and is commonly accompanied by dyslipidemia.

Assessment of Bone Marrow Involvement in B-Cell non-Hodgkin Lymphoma Using Immunoglobulin Gene Rearrangement Analysis with Next-Generation Sequencing.

BACKGROUND: Assessment of bone marrow involvement (BMI) in non-Hodgkin lymphoma (NHL) is crucial for determining patient prognosis and treatment strategy. We assessed the prognostic value of next-generation sequencing (NGS)-based immunoglobulin (Ig) gene clonality analysis as an ancillary test for BMI evaluation in NHL. METHODS: A retrospective cohort of 124 patients newly diagnosed with B-cell NHL between 2019 and 2022 was included. NGS-based Ig clonality analysis was conducted using LymphoTrak IGH FR1 Assay and IGK Assay (Invivoscribe Technologies, San Diego, CA, USA) on BM aspirate samples, and the results were compared with those of histopathological BMI (hBMI). RESULTS: Among the 124 patients, hBMI was detected in 16.9% (n = 21). The overall agreement of BMI between Ig clonality analyses and histopathological analysis for IGH, IGK, and either IGH or IGK was 86.3%, 92.7%, and 90.3%. The highest positive percent agreement was observed with clonal rearrangements of either IGH or IGK gene (90.5%), while the highest negative percent agreement was observed with clonal rearrangement of IGK gene (96.1%). For the prediction of hBMI, positive prediction value ranged between 59.1% and 80.0% and the negative prediction value ranged between 91.3% and 97.9%. CONCLUSION: NGS-based clonality analysis is an analytic platform with a substantial overall agreement with histopathological analysis. Assessment of both IGH and IGK genes for the clonal rearrangement analysis could be considered for the optimal diagnostic performance of BMI detection in B-cell NHL.

What do we know about dermal bioaccessibility of metals coated on antibacterial films?

Antibacterial films have gained attention since the outbreak of the COVID-19 pandemic; however, the impact of metals contained in antibacterial films on human safety have not been sufficiently investigated. This study reports on the important features that must be considered when assessing the bioaccessibility of Ag, Cu, and Zn in antibacterial films. Specifically, the effects of the artificial sweat component (i.e., amino acid and pH), surface weathering of antibacterial films, wipe sampling, and sebum were carefully examined. Our findings suggest that amino acids greatly affect bioaccessibility as amino acids act as ligands to facilitate metal ion leaching. In addition, constant exposure to ultraviolet C causes the film surface to oxidize, which significantly increases metal bioaccessibility due to the electrostatic repulsion between metal oxides and organic substrates. The presence of sebum in artificial sweat and physical damage to the film surface had no significant effects. Furthermore, the wipe sampling used to mimic the realistic dermal contact suggests the feasibility of applying this method for the assessment of bioaccessibility of metals in antibacterial films. The method offers significant advantages for evaluating the human safety aspects of skin contact with consumer products in future research.

Genomic epidemiology of highly pathogenic avian influenza A (H5N1) virus in wild birds in South Korea during 2021-2022: Changes in viral epidemic patterns.

Clade 2.3.4.4b highly pathogenic avian influenza A (HPAI) viruses have been detected in wild birds worldwide, causing recurrent outbreaks since 2016. During the winter of 2021-2022, we detected one H5N8 and forty-three H5N1 clade 2.3.4.4b HPAI viruses from wild birds in South Korea. Phylogenetic analysis revealed that HA gene of H5N1 viruses was divided into two genetically distinct groups (N1.G1 and N1.G2). Bayesian phylodynamic analysis demonstrated that wild birds play a vital role in viral transmission and long-term maintenance. We identified five genotypes (N1.G1.1, N1.G2, N1.G2.1, N1.G2.2, and N1.G2.2.1) having distinct gene segment constellations most probably produced by reassortments with low-pathogenic avian influenza viruses. Our results suggest that clade 2.3.4.4b persists in wild birds for a long time, causing continuous outbreaks, compared with previous clades of H5 HPAI viruses. Our study emphasizes the need for enhancing control measures in response to the changing viral epidemiology.

Long-Term HBsAg Titer Kinetics with Entecavir/Tenofovir: Implications for Predicting Functional Cure and Low Levels.

The long-term kinetics of quantitative HBsAg levels in HBV-infected patients treated with entecavir or tenofovir, as well as the role of quantitative HBsAg in predicting functional cure (HBsAg loss) and low HBsAg levels (<2 log IU/mL) remain unclear. Of some 1661 consecutively enrolled patients newly treated with entecavir or tenofovir, we analyzed 852 patients who underwent serial HBsAg level checks every 6-12 months. The primary outcomes included long-term kinetics in HBsAg levels and the rate of functional cure and achieving low HBsAg levels. Over a mean 6.3-year follow-up, the functional cure rate was 2.28% (n = 19), and 12.9% (n = 108) achieved low HBsAg levels. A significant HBsAg level reduction was seen in the first treatment year (p < 0.05), with another stepwise decrease between year 6-7. These trends were pronounced in patients with chronic hepatitis and HBeAg-positivity compared to those with cirrhosis and HBeAg-negativity, respectively. Baseline HBsAg of ≤3 log IU/mL and the first-year HBsAg reduction were key predictors for both functional cure and low HBsAg levels (p < 0.05). In conclusion, our findings elucidate the stepwise reduction in quantitative HBsAg dynamics during high-potency NA therapy (entecavir or tenofovir) along with variations based on different conditions. We also underscore the significance of quantitative HBsAg titer in predicting functional cure and low-HBsAg levels.

Differential liver function at cessation of atezolizumab-bevacizumab versus lenvatinib in HCC: a multicenter, propensity-score matched comparative study.

Background: Atezolizumab+bevacizumab (AB) and lenvatinib have been proposed as first-line treatment options for patients with advanced hepatocellular carcinoma (HCC), but comparative efficacy and associated factors are controversial. Materials and methods: This real-world multicenter study analysed patients with HCC who received AB (n=169) or lenvatinib (n=177). Results: First, 1:1 propensity score matching (PSM) was performed, resulting in 141 patients in both the AB and lenvatinib groups. After PSM, overall survival (OS) was better in the AB group than in the lenvatinib group [hazard ratio (HR)=0.642, P=0.009], but progression-free survival (PFS) did not vary between the two groups (HR=0.817, P=0.132). Objective response rate (ORR) was also similar between AB and lenvatinib (34.8% vs. 30.8%, P=0.581). In a subgroup of patients with objective responses (OR, n=78), OS (HR=0.364, P=0.012) and PFS (HR=0.536, P=0.019) were better in the AB group (n=41) than in the lenvatinib group (n=37). Time-to-progression from time of OR was also better in the AB group (HR=0.465, P=0.012). Importantly, residual liver function was a significant factor related to OS in both treatments. Child-Pugh score following cessation of the respective treatments was better in the AB group (n=105) than in the lenvatinib group (n=126) (median 6 versus 7, P=0.008), and proportion of salvage treatment was also higher in the AB group (52.4% versus 38.9%, P=0.047). When we adjusted for residual liver function or salvage treatment, there was no difference in OS between the two treatments. Conclusion: Our study suggests that residual liver function and subsequent salvage treatments are major determinants of clinical outcomes in patients treated with AB and lenvatinib; these factors should be considered in future comparative studies.

Impact of PIK3CA and cell cycle pathway genetic alterations on durvalumab efficacy in patients with head and neck squamous cell carcinoma: Post hoc analysis of TRIUMPH study.

OBJECTIVES: This study aimed to investigate whether genetic alterations in PI3KCA and the cell cycle pathways influence the efficacy of durvalumab, an immune checkpoint inhibitor, in patients with head and neck squamous cell carcinoma (HNSCC) who had previously failed platinum-based treatment. MATERIALS AND METHODS: We obtained data from a phase II umbrella trial of patients with HNSCC who failed platinum-based treatment (TRIUMPH, NCT03292250). Patients receiving durvalumab treatment comprised those with PIK3CA alterations (Group A), those with cell cycle pathway alterations such as CDKN2A (Group B), and those with no druggable genetic alterations (Group C). We analyzed the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in each group and evaluated the potential predictive factors for durvalumab. RESULTS: We analyzed the data of 87 patients: 18, 12, and 57 in groups A, B, and C, respectively. The ORRs were 27.8 %, 8.3 %, and 15.8 % in Groups A, B, and C, respectively (P = 0.329), and the median PFS for each group was 2.3, 1.6, and 1.7 months, respectively, with no significant differences between the groups (P = 0.24). Notably, patients with lower neutrophil-lymphocyte ratio (NLR) (≤5.8) had longer PFS (median, 2.8 vs 1.6 months, P < 0.001), while those with lower platelet-lymphocyte ratio (PLR) (≤491.2) exhibited longer PFS (median, 1.8 vs 1.2 months, P < 0.001). CONCLUSION: Durvalumab's efficacy was similar, irrespective of the presence of PIK3CA or cell cycle pathway genetic alterations in patients with platinum-resistant HNSCC. The NLR and PLR may be promising predictive biomarkers.

Cystic Features in Renal Epithelial Neoplasms and Their Increasing Clinical and Pathologic Significance.

Most cystic renal tumors after resection (Boniak IIF to IV cysts) have an indolent course despite the significantly higher proportion of malignant [ie, renal cell carcinoma (RCC)] diagnosis. Most cystic renal tumors have clear cell histology that include cystic clear cell RCC and multilocular cystic renal neoplasm of low malignant potential (MCNLMP). There is growing evidence to suggest that MCNLMP, cystic clear cell RCC, and noncystic clear cell RCC form a cystic-to-solid biological spectrum with MCNLMP representing the most indolent form and with cystic clear cell RCC behaving better than noncystic (solid) clear cell RCC. Extensively (>75%) cystic clear cell RCC also has an excellent outcome similar to MCNLMP stressing the need to reevaluate the histologic criteria that separate these 2 cystic clear cell tumors. Other tumors with clear cells that can be extensively cystic such as the recently reclassified noncancerous clear cell papillary renal tumor and the newly described MED15::TFE3 RCC also have indolent course and may mimic MCNLMP. Cystic features occur also in renal tumors with nonclear cell histology including tumors capable of metastasis such as acquired cystic disease-associated, tubulocystic, fumarate hydratase-deficient, and eosinophilic solid and cystic RCCs. Cystic imaging presentation of some renal tumors such as papillary RCC can be attributed in part to pseudocystic necrosis and hemorrhage. It is important to know that tubulocystic RCC may have a lower Bosniak class presentation that overlaps with benign renal cysts (Bosniak I to IIF) that are managed conservatively. This review highlights the cystic renal tumors with clear cell and nonclear cell morphologies including some novel RCC subtypes that may have cystic features. The presence of cystic features and their extent may aid in the classification and prognostication of renal neoplasms underscoring its increasing importance in the pathologic diagnosis and reporting of renal neoplasia.

Cysteine-binding adjuvant enhances survival and promotes immune function in a murine model of acute myeloid leukemia.

ABSTRACT: Therapeutic vaccination has long been a promising avenue for cancer immunotherapy but is often limited by tumor heterogeneity. The genetic and molecular diversity between patients often results in variation in the antigens present on cancer cell surfaces. As a result, recent research has focused on personalized cancer vaccines. Although promising, this strategy suffers from time-consuming production, high cost, inaccessibility, and targeting of a limited number of tumor antigens. Instead, we explore an antigen-agnostic polymeric in situ cancer vaccination platform for treating blood malignancies, in our model here with acute myeloid leukemia (AML). Rather than immunizing against specific antigens or targeting adjuvant to specific cell-surface markers, this platform leverages a characteristic metabolic and enzymatic dysregulation in cancer cells that produces an excess of free cysteine thiols on their surfaces. These thiols increase in abundance after treatment with cytotoxic agents such as cytarabine, the current standard of care in AML. The resulting free thiols can undergo efficient disulfide exchange with pyridyl disulfide (PDS) moieties on our construct and allow for in situ covalent attachment to cancer cell surfaces and debris. PDS-functionalized monomers are incorporated into a statistical copolymer with pendant mannose groups and TLR7 agonists to target covalently linked antigen and adjuvant to antigen-presenting cells in the liver and spleen after IV administration. There, the compound initiates an anticancer immune response, including T-cell activation and antibody generation, ultimately prolonging survival in cancer-bearing mice.

Detection of multiple recombinations of avian coronavirus in South Korea by whole-genome analysis.

Infectious bronchitis virus (IBV), an avian coronavirus, has caused considerable damage to the poultry industry. In Korea, indigenous KM91-like and newly introduced QX-like lineages belonging to the GI-19 lineage have been prevalent despite constant vaccination. In this study, complete genome sequences of 23 IBV isolates in Korea from 2010 to 2020 were obtained using next-generation sequencing, and their phylogenetic relationship and recombination events were analyzed. Phylogenetic analysis based on the S1 gene showed that all isolates belonged to the GI-19 lineage and were divided into five subgroups (KM91-like, K40/09-like, and QX-like II to IV). Among the 23 isolates, 14 recombinants were found, including frequent recombination between KM91-like and QX-like strains. In addition, it was observed that other lineages, such as GI-1, GI-13, and GI-16, were involved in recombination. Most recombination breakpoints were detected in the ORF1ab gene, particularly nsp3. However, when considering the size of each genome, recombination occurred more frequently in the 3a, E and 5a genes. Taken together, genetic recombination frequently occurred throughout the entire genome between various IBV strains in Korea, including live attenuated vaccine strain. Our study suggests the necessity of further research on the contribution of recombination of genomes outside the spike region to the biological characteristics of IBV.