Covalent-Frameworked 2D Crown Ether with Chemical Multifunctionality.

Here, we present the synthesis and characterization of a novel 2D crystalline framework, named C2O, which mainly consists of carbon and oxygen in a 2:1 molar ratio and features crown ether holes in its skeletal structure. The covalent-frameworked 2D crown ether can be synthesized on a gram-scale and exhibits fine chemical stability in various environments, including acid, base, and different organic solvents. The C2O efficiently activates KI through the strong coordination of K+ with crown ether holes in a rigid framework, which enhances the nucleophilicity of I- and significantly improves its catalytic activity for CO2 fixation with epoxides. The presence of C2O with KI results in remarkable increases in CO2 conversion from 5.7% to 99.9% and from 2.9% to 74.2% for epichlorohydrin and allyl glycidyl ether, respectively. Moreover, C2O possesses both electrophilic and nucleophilic sites at the edge of its framework, allowing for the customization of physicochemical properties by a diverse range of chemical modifications. Specifically, incorporating allyl glycidyl ether (AGE) as an electrophile or ethoxyethylamine (EEA) as a nucleophile into C2O enables the synthesis of C2O-AGE or C2O-EEA, respectively. These modified frameworks exhibit improved conversions of 97.2% and 99.9% for CO2 fixation with allyl glycidyl ether, outperforming unmodified C2O showing a conversion of 74.2%. This newly developed scalable, durable, and customizable covalent framework holds tremendous potential for the design and preparation of outstanding materials with versatile functionalities, rendering them highly attractive for a wide range of applications.

Virucidal activity of Cu-doped TiO2 nanoparticles under visible light illumination: Effect of Cu oxidation state.

Copper (Cu) is an effective antimicrobial material; however, its activity is inhibited by oxidation. Titanium dioxide (TiO2) photocatalysis prevents Cu oxidation and improves its antimicrobial activity and stability. In this study, the virucidal efficacy of Cu-doped TiO2 nanoparticles (Cu-TiO2) with three different oxidation states of the Cu dopant (i.e., zero-valent Cu (Cu0), cuprous (CuI), and cupric (CuII) oxides) was evaluated for the phiX174 bacteriophage under visible light illumination (Vis/Cu-TiO2). CuI-TiO2 exhibited superior virucidal activity (5 log inactivation in 30 min) and reusability (only 11 % loss of activity in the fifth cycle) compared to Cu0-TiO2 and CuII-TiO2. Photoluminescence spectroscopy and photocurrent measurements showed that CuI-TiO2 exhibited the highest charge separation efficiency and photocurrent density (approximately 0.24 µA/cm2) among the three materials, resulting in the most active redox reactions of Cu. Viral inactivation tests under different additives and viral particle integrity analyses (i.e., protein oxidation and DNA damage analyses) revealed that different virucidal species played key roles in the three Vis/Cu-TiO2 systems; Cu(III) was responsible for the viral inactivation by Vis/CuI-TiO2. The Vis/CuI-TiO2 system exhibited substantial virucidal performance for different viral species and in different water matrices, demonstrating its potential practical applications. The findings of this study offer valuable insights into the design of effective and sustainable antiviral photocatalysts for disinfection.

Confined growth of Ag nanogap shells emitting stable Raman label signals for SERS liquid biopsy of pancreatic cancer.

To develop a reliable surface-enhanced Raman scattering (SERS) immunoassay as a new liquid biopsy modality, SERS nanoprobes emitting strong and stable signals are necessary. However, Ag nanoparticles used as SERS nanoprobes are prone to rapid fading of SERS signals by oxidation. This has driven the development of a new strategy for Ag-based SERS nanoprobes emitting stable and strong SERS signals over time. Herein, Ag nanogap shells entrapping Raman labels are created in the confined pores of mesoporous silica nanoparticles (AgNSM) through a rapid single-step reaction for SERS liquid biopsy. Each AgNSM nanoprobe possesses multiple nanogaps of 1.58 nm to entrap Raman labels, allowing superior long-term SERS signal stability and large enhancement of 1.5 × 106. AgNSM nanoprobes conjugated with an antibody specific for carbohydrate antigen (CA)19-9 are employed in the SERS sandwich immunoassay including antibody-conjugated magnetic nanoparticles for CA19-9 detection, showing a two orders of magnitude lower limit of detection (0.025 U mL-1) than an enzyme-linked immunosorbent assay (0.3 U mL-1). The AgNSM nanoprobe immunoassay accurately quantifies CA19-9 levels from clinical serum samples of early and advanced pancreatic cancer. AgNSM nanoprobes with stable SERS signals provide a new route to SERS liquid biopsy for effective detection of blood biomarkers.

Analysis of Recent Improvement of Survival Outcomes in Patients with Pancreatic Cancer Who Underwent Upfront Surgery.

Background/Aims: : Recently, patients with pancreatic cancer (PC) who underwent resection have exhibited improved survival outcomes, but comprehensive analysis is limited. We analyzed the trends of contributing factors. Methods: : Data of patients with resected PC were retrospectively collected from the Korean Health Insurance Review and Assessment Service (HIRA) database and separately at our institution. Cox regression analysis was conducted with the data from our institution a survival prediction score was calculated using the ß coefficients. Results: : Comparison between the periods 2013-2015 (n=3,255) and 2016-2018 (n=3,698) revealed a difference in the median overall survival (25.9 months vs not reached, p<0.001) when analyzed with the HIRA database which was similar to our single-center data (2013-2015 [n=119] vs 2016-2018 [n=148], 20.9 months vs 32.2 months, p=0.003). Multivariable analyses revealed six factors significantly associated with better OS, and the scores were as follows: age >70 years, 1; elevated carbohydrate antigen 19-9 at diagnosis, 1; R1 resection, 1; stage N1 and N2, 1 and 3, respectively; no adjuvant treatment, 2; FOLFIRINOX or gemcitabine plus nab-paclitaxel after recurrence, 4; and other chemotherapy or supportive care only after recurrence, 5. The rate of R0 resection (69.7% vs 80.4%), use of adjuvant treatment (63.0% vs 74.3%), and utilization of FOLFIRINOX or gemcitabine plus nab-paclitaxel (25.2% vs 47.3%) as palliative chemotherapeutic regimen, all increased between the two time periods, resulting in decreased total survival prediction score (mean: 7.32 vs 6.18, p=0.004). Conclusions: : Strict selection of surgical candidates, more use of adjuvant treatment, and adoption of the latest combination regimens for palliative chemotherapy after recurrence were identified as factors of recent improvement.

Outcomes of Palliative Chemotherapy for Ampulla of Vater Adenocarcinoma: A Multicenter Cohort Study.

Background/Aims: : Palliative chemotherapy (PC) is not standardized for patients with advanced ampulla of Vater adenocarcinoma (AA). This multicenter, retrospective study evaluated first-line PC outcomes in patients with AA. Methods: : Patients diagnosed with AA between January 2010 and December 2020 who underwent PC were enrolled from 10 institutions. Overall survival (OS) and progression-free survival (PFS) according to the chemotherapy regimen were analyzed. Results: : Of 255 patients (mean age, 64.0±10.0 years; male, 57.6%), 14 (5.5%) had locally advanced AA and 241 (94.5%) had metastatic AA. Gemcitabine plus cisplatin (GP) was administered as first-line chemotherapy to 192 patients (75.3%), whereas capecitabine plus oxaliplatin (CAPOX) was administered to 39 patients (15.3%). The median OS of all patients was 19.8 months (95% confidence interval [CI], 17.3 to 22.3), and that of patients who received GP and CAPOX was 20.4 months (95% CI, 17.2 to 23.6) and 16.0 months (95% CI, 11.2 to 20.7), respectively. The median PFS of GP and CAPOX patients were 8.4 months (95% CI, 7.1 to 9.7) and 5.1 months (95% CI, 2.5 to 7.8), respectively. PC for AA demonstrated improved median outcomes in both OS and PFS compared to conventional bile duct cancers that included AA. Conclusions: : While previous studies have shown mixed prognostic outcomes when AA was analyzed together with other biliary tract cancers, our study unveils a distinct clinical prognosis specific to AA on a large scale with systemic anticancer therapy. These findings suggest that AA is a distinct type of tumor, different from other biliary tract cancers, and AA itself could be expected to have a favorable response to PC.

Simultaneously enhancing the resolution and signal-to-background ratio in STED optical nanoscopy via differential depletion.

STED (stimulated emission depletion) far-field optical nanoscopy achieves resolution beyond the diffraction limit by depleting fluorescence at the periphery of excitation with a donut-shaped depletion laser. What is traded off with the superior resolution of STED nanoscopy is the unwanted elevation of structured background noise which hampers the quality of STED images. Here, we alleviate the background noise problem by adopting the differential stimulated emission depletion (diffSTED) approach. In diffSTED nanoscopy, signals obtained with different depletion strengths are compared and properly subtracted to remove two major background noise sources in STED nanoscopy. We show via simulations that by using diffSTED nanoscopy, background noise is significantly decreased, and the image contrast is improved. In addition, we show by simulation and analytical calculation that diffSTED improves resolution simultaneously. We assess the effect of different parameters, such as the STED beam intensity, depletion intensity ratio of two STED beams, and the subtraction factor, on the signal-to-background ratio (SBR) and the resolution of diffSTED nanoscopy. We introduce a logical algorithm to determine the optimal subtraction factor and the depletion intensity ratio. DiffSTED nanoscopy is a versatile technique that can be readily applied to any STED system without requiring any hardware modifications. We predict the wide applicability of diffSTED for its enhanced resolution, improved SBR, and easiness of implementation.

Interweaving Elastic and Hydrogen Bond-Forming Polymers into Highly Tough and Stress-Relaxable Binders for High-Performance Silicon Anode in Lithium-Ion Batteries.

A central challenge in practically using high-capacity silicon (Si) as anode materials for lithium-ion batteries is alleviating significant volume change of Si during cycling. One key to resolving the failure issues of Si is exploiting carefully designed polymer binders exhibiting mechanical robustness to retain the structural integrity of Si electrodes, while concurrently displaying elasticity and toughness to effectively dissipate external stresses exerted by the volume changes of Si. Herein, a highly elastic and tough polymer binder is proposed by interweaving polyacrylic acid (PAA) with poly(urea-urethane) (PUU) elastomer for Si anodes. By systematically tuning molecular parameters, including molecular weights of hard/soft segments and structures of hard segment components, it is demonstrated that the mechanical properties of polymer binders, such as elasticity, toughness, and stress relaxation ability, strongly affect the cycling performance of Si electrodes. This study provides new insight into the rational design of polymer binders capable of accommodating the volume changes of Si, primarily by judicious modulation of the mechanical properties of polymer binders.

Analysis of Phase Heterogeneity in Lipid Membranes Using Single-Molecule Tracking in Live Cells.

In live cells, the plasma membrane is composed of lipid domains separated by hundreds of nanometers in dynamic equilibrium. Lipid phase separation regulates the trafficking and spatiotemporal organization of membrane molecules that promote signal transduction. However, visualizing domains with adequate spatiotemporal accuracy remains challenging because of their subdiffraction limit size and highly dynamic properties. Here, we present a single lipid-molecular motion analysis pipeline (lipid-MAP) for analyzing the phase heterogeneity of lipid membranes by detecting the instantaneous velocity change of a single lipid molecule using the excellent optical properties of nanoparticles, high spatial localization accuracy of single-molecule localization microscopy, and separation capability of the diffusion state of the hidden Markov model algorithm. Using lipid-MAP, individual lipid molecules were found to be in dynamic equilibrium between two statistically distinguishable phases, leading to the formation of small (∼170 nm), viscous (2.5× more viscous than surrounding areas), and transient domains in live cells. Moreover, our findings provide an understanding of how membrane compositional changes, i.e., cholesterol and phospholipids, affect domain formation. This imaging method can contribute to an improved understanding of spatiotemporal-controlled membrane dynamics at the molecular level.

A Multifunctional Interlocked Binder with Synergistic In Situ Covalent and Hydrogen Bonding for High-Performance Si Anode in Li-ion Batteries.

Silicon has garnered significant attention as a promising anode material for high-energy density Li-ion batteries. However, Si can be easily pulverized during cycling, which results in the loss of electrical contact and ultimately shortens battery lifetime. Therefore, the Si anode binder is developed to dissipate the enormous mechanical stress of the Si anode with enhanced mechanical properties. However, the interfacial stability between the Si anode binder and Cu current collector should also be improved. Here, a multifunctional thiourea polymer network (TUPN) is proposed as the Si anode binder. The TUPN binder provides the structural integrity of the Si anode with excellent tensile strength and resilience due to the epoxy-amine and silanol-epoxy covalent cross-linking, while exhibiting high extensibility from the random coil chains with the hydrogen bonds of thiourea, oligoether, and isocyanurate moieties. Furthermore, the robust TUPN binder enhances the interfacial stability between the Si anode and current collector by forming a physical interaction. Finally, the facilitated Li-ion transport and improved electrolyte wettability are realized due to the polar oligoether, thiourea, and isocyanurate moieties, respectively. The concept of this work is to highlight providing directions for the design of polymer binders for next-generation batteries.

Removal of the red tide dinoflagellate Cochlodinium polykrikoides using chemical disinfectants.

For decades, red tide control has been recognized as necessary for mitigating financial damage to fish farms. Chemical disinfectants, frequently used for water disinfection, can reduce the risk of red tides on inland fish farms. This study systematically evaluated four different chemical disinfectants (ozone (O3), permanganate (MnO4-), sodium hypochlorite (NaOCl), and hydrogen peroxide (H2O2)) for their potential use in inland fish farms to control red tides by investigating their (i) inactivation efficacy regarding C. polykrikoides, (ii) total residual oxidant and byproduct formation, and (iii) toxicity to fish. The inactivation efficacy of C. polykrikoides cells by chemical disinfectants from highest to lowest followed the order of O3 > MnO4- > NaOCl > H2O2 for different cell density conditions and disinfectant doses. The O3 and NaOCl treatments generated bromate as an oxidation byproduct by reacting with bromide ions in seawater. The acute toxicity tests of the disinfectants for juvenile red sea bream (Pagrus major) showed that 72-h LC50 values were 1.35 (estimated), 0.39, 1.32, and 102.61 mg/L for O3, MnO4-, NaOCl, and H2O2, respectively. Considering the inactivation efficacy, exposure time of residual oxidants, byproduct formation, and toxicity toward fish, H2O2 is suggested as the most practical disinfectant for controlling red tides in inland fish farms.

Real-world dose reduction of standard and modified FOLFIRINOX in metastatic pancreatic cancer: a systematic review, evidence-mapping, and meta-analysis.

Background: FOLFIRINOX, used in metastatic pancreatic cancer (MPC), is highly efficacious but also toxic. Various dose modifications for FOLFIRINOX have been introduced to reduce toxicity. However, these studies lack a unified pattern for 'planned' dose modification, and the 'actually administered' dose varied more. Objective: To map a 10-year trend for 'planned' and 'actual' doses of FOLFIRINOX and investigate the clinical outcomes according to dose modification. Data sources and methods: A comprehensive systematic literature search was conducted from January 2011 to September 2021. All studies for FOLFIRINOX as first-line treatment in MPC were considered. Selected studies were firstly classified according to prospective versus retrospective research, secondly standard versus modified FOLFIRINOX, and thirdly 'planned' versus 'actual' dose. For evidence-mapping for the trend of dose modification, we developed a web-based interactive bubble-plot program (www.RDI-map.com). Objective response rate (ORR) and hematologic toxicity were set as endpoints for the comparison of clinical outcomes according to dose modification. Results: A total of 37 studies were identified for evidence-mapping (11 prospective and 26 retrospective studies). There were 12 different types of 'planned' dose modification in FOLFIRINOX ranging 75-100% oxaliplatin, 75-100% irinotecan, 0-100% 5-fluorouracil (5-FU) bolus, and 75-133% 5-FU continuous injection. The 'actual' dose further decreased to 54-96%, 61-88%, 0-92%, and 63-98%, respectively. For the standard versus modified FOLFIRINOX, the ORR was 28.2% (95% CI: 22.5-33.9%) and 33.8% (95% CI: 30.3-37.3%), respectively (p = 0.100), and the incidence of febrile neutropenia was 11.6% (95% CI: 0-16.0%) and 5.5% (95% CI: 0-8.9%), respectively (p = 0.030). Conclusions: RDI-map.com enables multifactorial evidence-mapping for practical FOLFIRINOX dose reduction. The pattern of dose modification was not consistent across studies, and there was a significant gap between the 'planned' and 'actual' doses. Modified FOLFIRINOX showed similar efficacy to the standard regimen with reduced incidence of febrile neutropenia.

Adjuvant Chemotherapy and Effect on Long-Term Survival in Ampullary Adenocarcinoma: A Multicenter Cohort Study.

BACKGROUND: The role of adjuvant chemotherapy (AC) in patients with ampullary adenocarcinoma (AA) remains controversial. This study aimed to determine if AC could improve the prognosis of patients with resected AA. STUDY DESIGN: This study enrolled patients diagnosed with AA at 9 tertiary teaching hospitals. Patients who did and did not receive AC were matched 1:1 using propensity score. The overall survival (OS) and recurrence-free survival (RFS) were compared between the 2 groups. RESULTS: Of the 1,057 patients with AA, 883 underwent curative-intent pancreaticoduodenectomy, and 255 received AC. Because patients with advanced-stage AA received AC more frequently, the no AC group unexpectedly had a longer OS (not reached vs 78.6 months; p < 0.001) and RFS (not reached vs 18.7 months; p < 0.001) than did the AC group in the unmatched cohort. In the propensity score-matched cohort (n = 296), no difference between the 2 groups in terms of OS (95.9 vs 89.8 months, p = 0.303) and RFS (not reached vs 25.5 months; p = 0.069) was found. By subgroup analysis, patients with advanced stage (pT4 or pN1-2) showed longer OS in the AC group than in the no AC group (not reached vs 15.7 months, p = 0.007: 89.8 vs 24.2 months, p = 0.006, respectively). There was no difference in RFS according to AC in the propensity score-matched cohort. CONCLUSIONS: Given its favorable long-term outcomes, AC can be recommended for patients with resected AA, especially those in the advanced stage (pT4 or pN1-2).

Efficacy improvement in searching MEDLINE database using a novel PubMed visual analytic system: EEEvis.

PubMed is the most extensively used database and search engine in the biomedical and healthcare fields. However, users could experience several difficulties in acquiring their target papers facing massive numbers of search results, especially in their unfamiliar fields. Therefore, we developed a novel user interface for PubMed and conducted three steps of study: step A, a preliminary user survey with 76 medical experts regarding the current usability for the biomedical literature search task at PubMed; step B is implementing EEEvis, a novel interactive visual analytic system for the search task; step C, a randomized user study comparing PubMed and EEEvis. First, we conducted a Google survey of 76 medical experts regarding the unmet needs of PubMed and the user requirements for a novel search interface. According to the data of preliminary Google survey, we implemented a novel interactive visual analytic system for biomedical literature search. This EEEvis provides enhanced literature data analysis functions including (1) an overview of the bibliographic features including publication date, citation count, and impact factors, (2) an overview of the co-authorship network, and (3) interactive sorting, filtering, and highlighting. In the randomized user study of 24 medical experts, the search speed of EEEvis was not inferior to PubMed in the time to reach the first article (median difference 3 sec, 95% CI -2.1 to 8.5, P = 0.535) nor in the search completion time (median difference 8 sec, 95% CI -4.7 to 19.1, P = 0.771). However, 22 participants (91.7%) responded that they are willing to use EEEvis as their first choice for a biomedical literature search task, and 21 participants (87.5%) answered the bibliographic sorting and filtering functionalities of EEEvis as a major advantage. EEEvis could be a supplementary interface for PubMed that can enhance the user experience in the search for biomedical literature.

Long-term outcomes of endoscopic papillectomy for ampullary adenoma with high-grade dysplasia or adenocarcinoma: a propensity score-matched analysis.

BACKGROUND: Evidence of endoscopic papillectomy (EP) for ampullar adenoma with high-grade dysplasia (HGD) or adenocarcinoma is insufficient. Here we investigated the long-term outcomes of the advanced ampullary tumors treated by EP with careful surveillance comparing to subsequent surgery after EP. METHODS: Patients treated with EP for ampullary adenoma with HGD or adenocarcinoma from the multi-center retrospective Korean cohort of ampulla of Vater tumor were categorized into EP alone versus EP with subsequent surgery groups. The overall survival (OS) and recurrence-free survival (RFS) were analyzed for unmatched and matched cohorts using propensity score with nearest neighbor method. RESULTS: During a median 43.3 months of follow-up, 5-year OS was not significantly different between the EP alone and EP surgery groups (91.9% vs. 82.3%, P = 0.443 for unmatched cohort; 89.2% vs. 82.3%, P = 0.861 for matched cohort, respectively). Furthermore, 5-year RFS was not significantly different between the two groups (82.1% vs. 86.7%, P = 0.520 for unmatched cohort; 66.1% vs. 86.7%, P = 0.052 for matched cohort, respectively). However, the patients with positive both (lateral and deep) margins showed significantly poorer survival outcomes than those with negative margins within the EP alone group (P = 0.007). CONCLUSION: EP alone with careful surveillance showed comparable survival outcomes to those of EP with subsequent surgery for ampullar HGD or adenocarcinoma. Resection margin status could be a parameter to determine whether to perform subsequent radical surgery after EP.

Impact of histopathological type on the prognosis of ampullary carcinoma: A systematic review and meta-analysis.

Histologically, ampullary carcinomas (ACs) can be classified into intestinal (INT-AC) and pancreatobiliary (PB-AC) subtypes. However, the prognostic implications of these subtypes remain unclear. This study aimed to evaluate the impact of the histopathologic phenotype of ACs on survival following pancreaticoduodenectomy. We searched PubMed, Embase, and Medline for studies published in English from 1994 to 2021. A meta-analysis was performed using Review Manager 5.3. The primary endpoint was overall survival (OS). We identified 3,890 articles; of these, 37 articles involving 3,455 participants (1,659 INT-ACs and 1,796 PB-ACs) were included. Patients in the PB-ACs group had significantly shorter OS than those in the INT-ACs group (hazard ratio [HR]: 1.79, 95% confidence interval [95% CI]: 1.51-2.13, p < 0.001, I2 = 61%). A similar tendency was observed in the immunohistochemistry staining group (HR: 1.76, 95% CI: 1.33-2.33, p < 0.001, I2 = 67%), which included 24 studies and 1,638 patients, and the non-immunohistochemistry group (HR: 1.84, 95% CI: 1.53-2.22, p = 0.04, I2 = 46%), which included 13 studies and 1,817 patients. Subgroup analysis revealed that patients with PB-AC had higher frequencies of advanced (III, IV) and pT3-4 stage AC, lymph node metastasis, poorly differentiated tumor, positive surgical margins, lymphovascular invasion, and perineural invasion, than those with INT-AC. Patients with PB-AC had a significantly shorter OS than those with INT-AC due to a higher aggressiveness. Because the histopathologic subtype is a major prognostic factor in patients with resected AC, routine histopathologic classification should be considered even in clinical settings without immunohistochemistry.

Continued adjuvant FOLFIRINOX for BRPC or LAPC after neoadjuvant FOLFIRINOX.

PURPOSE: We aimed to assess the role of adjuvant FOLFIRINOX, in comparison with other adjuvant therapy, in patients who received neoadjuvant FOLFIRINOX and surgery for borderline resectable or locally advanced pancreatic cancer (BRPC or LAPC). METHODS: Our target population was patients with BRPC or LAPC, who received adjuvant therapy following neoadjuvant FOLFIRINOX and surgery between June 2013 and October 2020. Multivariable Cox proportional-hazard model was used to identify factors associated with overall survival (OS) and recurrence free survival (RFS). RESULTS: Among 244 patients with BRPC or LAPC who received neoadjuvant FOLFIRINOX, 79 patients underwent subsequent surgery. Among them, 58 who received adjuvant therapy [median age, 63 years; 33 females (56.9%)] were included. Thirty patients received adjuvant modified FOLFIRINOX (mFOLFIRINOX), while 28 received adjuvant therapy other than FOLFIRINOX. In multivariable analysis, mFOLFIRINOX and post-treatment carbohydrate antigen 19-9 (CA 19-9) were significantly associated with OS and RFS. According to mFOLFIRINOX vs. other adjuvant therapy, median OS was not reached at 37.5 months of follow-up vs. 29.7 months (P = .012); and median RFS was 30.5 vs. 11.0 months (P = .028). According to post-treatment CA 19-9 (< 37 vs. ≥ 37 U/mL), median OS was 46.0 vs. 25.5 months (P = .022); and median RFS was 25.9 vs. 7.6 months (P = .012). CONCLUSION: Continued adjuvant mFOLFIRINOX and post-treatment CA 19-9 level were associated with survival in patients with BRPC or LAPC who received neoadjuvant FOLFIRINOX and surgery. Continued adjuvant mFOLFIRINOX after neoadjuvant FOLFIRINOX could be considered for patients with good performance.

Increased incidence of indeterminate pancreatic cysts and changes of management pattern: Evidence from nationwide data.

BACKGROUND: Pancreatic cysts are common. However, most studies are based on data collected from individual centers. The present study aimed to evaluate the changes of management patterns for pancreatic cystic lesions (PCLs) by analyzing large epidemiologic data. METHODS: Between January 2007 and December 2018, information regarding pancreatic cystic lesions was acquired from the nationwide Health Insurance Review and Assessment Service database in Korea. RESULTS: The final number of patients with pancreatic cysts was 165 277 among the total claims for reimbursement of 855 983 associated with PCLs over 12 years. The total number of claims were increased from 19 453 in 2007 to 155 842 in 2018 and the prevalence increased from 0.04% to 0.23%. For 12 years, 2874 (1.7%) had pancreatic cancer and 8212 (5.0%) underwent surgery, and 36 had surgery for twice (total 8248 pancreatectomy). After ruling out claims from the first 3 years of washout period, the incidence increased from 9891 to 24 651 and the crude incidence rate of PCLs expanded from 19.96 per 100 000 to 47.77 per 100 000. Compared to specific neoplasm codes (D136 or D377), the use of pancreatic cyst code (K862) has been remarkably increased and the most common since 2010. The annual number of pancreatectomies increased from 518 to 861 between 2007 and 2012, and decreased to 596 until 2018. The percentage of pancreatic cancer in patients who received pancreatectomy increased from 5.6% in 2007 to 11.7% in 2018. CONCLUSIONS: The incidence of PCLs is rapidly increasing. Among PCLs, indeterminate cyst is increasing outstandingly. A trend of decreasing in the number of resections and increasing cancer rates among resected cysts may be attributed to the updated international guidelines.

Pushing the Resolution Limit of Stimulated Emission Depletion Optical Nanoscopy.

Optical nanoscopy, also known as super-resolution optical microscopy, has provided scientists with the means to surpass the diffraction limit of light microscopy and attain new insights into nanoscopic structures and processes that were previously inaccessible. In recent decades, numerous studies have endeavored to enhance super-resolution microscopy in terms of its spatial (lateral) resolution, axial resolution, and temporal resolution. In this review, we discuss recent efforts to push the resolution limit of stimulated emission depletion (STED) optical nanoscopy across multiple dimensions, including lateral resolution, axial resolution, temporal resolution, and labeling precision. We introduce promising techniques and methodologies building on the STED concept that have emerged in the field, such as MINSTED, isotropic STED, and event-triggered STED, and evaluate their respective strengths and limitations. Moreover, we discuss trade-off relationships that exist in far-field optical microscopy and how they come about in STED optical nanoscopy. By examining the latest developments addressing these aspects, we aim to provide an updated overview of the current state of STED nanoscopy and its potential for future research.

NGS-based targeted gene mutational profiles in Korean patients with pancreatic cancer.

According to molecular profiling studies, a considerable number of patients with pancreatic cancer harbor potentially actionable mutations. However, there are limited relevant data from the Korean population. We assessed the molecular profiles of patients with pancreatic cancer in Korea. This study collected molecular profiling data from patients with pancreatic cancer who visited Seoul National University Bundang Hospital between March 2018 and August 2020. Formalin-fixed, paraffin-embedded tumor specimens were sequenced using a targeted next-generation sequencing (NGS) platform. Cancer-associated mutations were analyzed, and potentially actionable mutations were identified. Potentially actionable mutations were classified into "highly actionable" and "modifies options" based on the Know Your Tumor registry study. In total, 87 patients with NGS tumor panel data were identified. Sixty-one patients (70.1%) had metastatic disease at the time of tissue acquisition. Tissues were obtained from the primary tumors and metastatic sites in 41 (47.1%) and 46 (52.9%) patients, respectively. At least one pathogenic mutation was reported in 86 patients (98.9%). The frequencies of four common mutations in our cohort were similar to those in The Cancer Genome Atlas data. Potentially actionable mutations were identified in 27 patients (31.0%). Of these, mutations categorized as highly actionable and modifies options were identified in 12 (13.8%) and 18 patients (20.7%), respectively. The most frequent highly actionable mutations were located in DNA damage response genes, such as BRCA1, BRCA2, or ATM (n = 6, 6.9%). Two patients with germline BRCA1 mutations received maintenance poly(adenosine diphosphate-ribose) polymerase inhibitor therapy. One patient has been receiving maintenance treatment for 18 months while remaining in radiologically complete remission. Mutational profiles using targeted NGS in Korean patients with pancreatic cancer were similar to those in Western patients. The present study supports the clinical potential and possible expanded clinical use of genetic profiling.

Association between progression-free survival and metal stent patency in patients with advanced pancreatic cancer.

Background: Chemotherapy reportedly affects the patency of self-expandable metal stents (SEMSs) in patients with cancer. However, knowledge regarding the association between SEMS patency and progression-free survival (PFS) remains limited. This study aimed to assess PFS and SEMS patency in patients with advanced pancreatic cancer. Methods: Between January 2012 and June 2021, 74 patients with locally advanced or metastatic pancreatic cancer (MPC) were enrolled in the study. Patients received gemcitabine plus nab-paclitaxel (GnP) or fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) as initial chemotherapy and SEMS within 1 month before or after the initial chemotherapy. Longer PFS was defined as PFS ≥7 months. Results: This study enrolled 38 male patients (51.4%); the mean age was 66.2 [95% confidence interval (CI), 63.7-68.6] years. Of the patients, 46 (62.2%) had MPC and 58 (78.4%) received FOLFIRINOX as the initial chemotherapy. Of the patients, 61 (82.4%) underwent endoscopic SEMS insertion. The median stent patency and PFS were 6.9 [interquartile range (IQR), 4.5-12.9] and 6.4 (IQR, 4.2-12.5) months, respectively; the median overall survival (OS) was 10.5 (IQR, 6.7-16.5) months. Of the clinical parameters assessed using multivariate analysis, shorter PFS [PFS <7 months; hazard ratio (HR), 2.117; 95% CI, 1.020-4.393; P=0.044] and metastatic cancer (HR, 2.414; 95% CI, 1.159-5.018; P=0.019) were found to be associated with shorter SEMS patency. The median SEMS patency in patients with longer PFS and those with shorter PFS was 14.3 and 7.0 months (P=0.012), respectively, and that in patients with locally advanced cancer and those with metastatic cancer was 16.7 and 7.0 months (P=0.006), respectively. The coefficient of determination between stent patency and PFS was 0.624. Conclusions: SEMS patency may be associated with PFS in patients with advanced pancreatic cancer who receive GnP or FOLFIRINOX.