MRI versus Dual-Energy CT in Local-Regional Staging of Gastric Cancer.

Background Preoperative local-regional tumor staging of gastric cancer (GC) is critical for appropriate treatment planning. The comparative accuracy of multiparametric MRI (mpMRI) versus dual-energy CT (DECT) for staging of GC is not known. Purpose To compare the diagnostic accuracy of personalized mpMRI with that of DECT for local-regional T and N staging in patients with GC receiving curative surgical intervention. Materials and Methods Patients with GC who underwent gastric mpMRI and DECT before gastrectomy with lymphadenectomy were eligible for this single-center prospective noninferiority study between November 2021 and September 2022. mpMRI comprised T2-weighted imaging, multiorientational zoomed diffusion-weighted imaging, and extradimensional volumetric interpolated breath-hold examination dynamic contrast-enhanced imaging. Dual-phase DECT images were reconstructed at 40 keV and standard 120 kVp-like images. Using gastrectomy specimens as the reference standard, the diagnostic accuracy of mpMRI and DECT for T and N staging was compared by six radiologists in a pairwise blinded manner. Interreader agreement was assessed using the weighted κ and Kendall W statistics. The McNemar test was used for head-to-head accuracy comparisons between DECT and mpMRI. Results This study included 202 participants (mean age, 62 years ± 11 [SD]; 145 male). The interreader agreement of the six readers for T and N staging of GC was excellent for both mpMRI (κ = 0.89 and 0.85, respectively) and DECT (κ = 0.86 and 0.84, respectively). Regardless of reader experience, higher accuracy was achieved with mpMRI than with DECT for both T (61%-77% vs 50%-64%; all P < .05) and N (54%-68% vs 51%-58%; P = .497-.005) staging, specifically T1 (83% vs 65%) and T4a (78% vs 68%) tumors and N1 (41% vs 24%) and N3 (64% vs 45%) nodules (all P < .05). Conclusion Personalized mpMRI was superior in T staging and noninferior or superior in N staging compared with DECT for patients with GC. Clinical trial registration no. NCT05508126 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Méndez and Martín-Garre in this issue.

High Hydrophilic and Antibacterial Efficient UV-Curable Silicone-Containing Choline Chloride Quaternary Ammonium Salts Functionalized Materials.

Antibacterial materials with high hydrophobicity have drawbacks such as protein adsorption, bacterial contamination, and biofilm formation, which are responsible for some serious adverse health events. Therefore, antibacterial materials with high hydrophilicity are highly desired. In this paper, UV-curable antibacterial materials are prepared from silicone-containing Choline chloride (ChCl) functionalized hyperbranched quaternary ammonium salts (QAS) and tri-hydroxylethyl acrylate phosphate (TAEP). The materials show high hydrophilic performance because their water contact angle is as low as 19.3°. The materials also exhibit quite high antibacterial efficiency against S. aureus over 95.6%, fairly high transmittance over 90%, and good mechanical performance with tensile strength as high as 6.5 MPa. It reveals that it is a feasible strategy to develop antibacterial materials with low hydrophobicity from silicone-modified ChCl-functionalized hyperbranched QAS.

Combining CD38 antibody with CD47 blockade is a promising strategy for treating hematologic malignancies expressing CD38.

Background: CD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs). Methods: Five suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 "mAb-trap" platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems. Results: Using hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38+ tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a "mAb-trap" platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605-26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605-12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605-12C10 efficiently eradicated all established tumors in all mice. Conclusion: A panel of BsAbs targeting CD38 and CD47 developed based on the "mAb-tarp" platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile.

Research situation, hot spots, and global trends of melasma therapy: Bibliometric insights and visual analysis from 2000 to 2023.

BACKGROUND: Melasma is a prevalent pigmented disease, yet its pathogenesis remains unclear, posing challenges for effective treatment. Bibliometric analysis, a novel approach to literature research, offers the opportunity to evaluate research trends through qualitative and quantitative methods. This study utilizes bibliometric methods to analyze the existing literature on melasma treatment, examining influential publications, institutions, countries, and authors through statistical analysis. METHODS: In order to retrieve manuscripts related to the topic of melasma treatment, we conducted a search using the search formula: (TS = (melasma or Chloasma or "mask of pregnancy")) AND TS = (treatment or therapy). We searched through the Web of Science Core Collection database, covering publications from 2000 to 2023. VOSviewer, CiteSpace and the Bibliometric online site (https://bibliometric.com/app) were used to conduct this bibliometric analysis. Our analysis focused on various factors including publications, authors co-authorship, institutions, countries, citation analysis, keywords co-occurrence, references co-citation and journal co-citation. RESULTS: A total of 943 articles and 200 reviews were published between 2000 and 2023, accumulating a total of 8628 citations. The average number of citations per item was 18.85, and the average number of citations per year was 292.69. The most prolific author, Sungeun Chang, contributed a total of 9 articles. Cario University emerged as the top research institution. The United States led in terms of article publications with a count of 276. In the past 5 years, the research trends in this field have primarily focused on tranexamic acid and epidermal melasma, as indicated by the burst analysis of publications and keywords. CONCLUSIONS: The United States continues to lead in terms of institutions and research output. The current emphasis is on the meticulous implementation of tranexamic acid and laser therapy. It is crucial to foster enhanced collaboration among countries, institutions, and authors to facilitate improved research.

Development and application of a cycleave dual-probe fluorescence quantitative PCR method for simultaneous detection of Mycoplasma gallisepticum ts-11 vaccine strain and non-ts-11 strains.

An attenuated vaccine against the Mycoplasma gallisepticum ts-11 strain has become an effective prevention and control method against MG infection. However, the ts-11 strain is usually difficult to distinguish from the non-ts-11 strain (including field isolates and other vaccine strains (F and 6/85)). Therefore, it is critical to establish a rapid and effective method to distinguish ts-11 strains from non-ts-11 strains. The gene sequences of the ts-11 strain (CP044225.1) and the non-ts-11 strain (including the wild-type (CP006916.3), 6/85 (CP044224.1), and F strains (NC_017503.1) were used to construct a conserved region containing a single point mutation in the potC gene in the ts-11 strain, after which a primer-probe combination method was designed. The primer-probe method was able to accurately and efficiently identify the ts-11 and non-ts-11 strains with minimum detection limits of 2.43 copies/µL and 1.65 copies/µL, respectively. Moreover, it could simultaneously distinguish the ts-11 strain from a non-ts-11 strain, and amplifications of avian influenza virus, infectious bronchitis virus, Newcastle disease virus, fowl adenovirus, infectious laryngotracheitis virus, infectious bursal disease virus, chicken anemia virus, Marek's disease virus, Mycoplasma synoviae, and Ornithobacter rhinotracheale were negative. The detection of clinical samples revealed that the established dual-probe fluorescence quantitative PCR method could be used to screen for mixed and single infections of the ts-11 strain and non-ts-11 strains effectively, with lower variation coefficients for intra- and interbatch repetition. The established cycleave dual-probe fluorescence quantitative PCR method showed good specificity, sensitivity, and repeatability and provides powerful technical support for the rapid and efficient differential diagnosis of the MG ts-11 strain from non-ts-11 strains.

Deep learning-accelerated T2WI: image quality, efficiency, and staging performance against BLADE T2WI for gastric cancer.

PURPOSE: The purpose of our study is to investigate image quality, efficiency, and diagnostic performance of a deep learning-accelerated single-shot breath-hold (DLSB) against BLADE for T2-weighted MR imaging (T2WI) for gastric cancer (GC). METHODS: 112 patients with GCs undergoing gastric MRI were prospectively enrolled between Aug 2022 and Dec 2022. Axial DLSB-T2WI and BLADE-T2WI of stomach were scanned with same spatial resolution. Three radiologists independently evaluated the image qualities using a 5-scale Likert scales (IQS) in terms of lesion delineation, gastric wall boundary conspicuity, and overall image quality. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated in measurable lesions. T staging was conducted based on the results of both sequences for GC patients with gastrectomy. Pairwise comparisons between DLSB-T2WI and BLADE-T2WI were performed using the Wilcoxon signed-rank test, paired t-test, and chi-squared test. Kendall's W, Fleiss' Kappa, and intraclass correlation coefficient values were used to determine inter-reader reliability. RESULTS: Against BLADE, DLSB reduced total acquisition time of T2WI from 495 min (mean 4:42 per patient) to 33.6 min (18 s per patient), with better overall image quality that produced 9.43-fold, 8.00-fold, and 18.31-fold IQS upgrading against BALDE, respectively, in three readers. In 69 measurable lesions, DLSB-T2WI had higher mean SNR and higher CNR than BLADE-T2WI. Among 71 patients with gastrectomy, DLSB-T2WI resulted in comparable accuracy to BLADE-T2WI in staging GCs (P > 0.05). CONCLUSIONS: DLSB-T2WI demonstrated shorter acquisition time, better image quality, and comparable staging accuracy, which could be an alternative to BLADE-T2WI for gastric cancer imaging.

A high-throughput differential scanning fluorimetry method for rapid detection of thermal stability and iron saturation in lactoferrin.

Thermal stability and iron saturation of lactoferrin (LF) are of great significance not only for the evaluation of the biological activities of LF but also for the optimization of the isolation and drying process parameters. Differential scanning calorimetry (DSC) is a well-established and efficient method for thermal stability and iron saturation detection in LF. However, multiple DSC measurements are typically performed sequentially, thus time-consuming and low throughput. Herein, we introduced the differential scanning fluorimetry (DSF) approach to overcome such limitations. The DSF can monitor LF thermal unfolding with a commonly available real-time PCR instrument and a fluorescent dye (SYPRO orange or Glomelt), and the measured melting temperature of LF is consistent with that determined by DSC. On the basis of that, a new quantification method was established for determination of iron saturation levels using the linear correlation of the degree of ion saturation of LF with DSF measurements. Such DSF method is simple, inexpensive, rapid (<15 min), and high throughput (>96 samples per experiment), and provides a valuable alternative tool for thermal stability detection of LF and other whey proteins.

Using a New Fe3O4@CPAM Magnetic Flocculant and Microwave to Demulsify Heavy Oil-in-Water Emulsions.

In this study, cationic polyacrylamide (CPAM)-coated magnetic nanoparticles (MNPs) Fe3O4@CPAM were synthesized for treating heavy O/W emulsions. This Fe3O4@CPAM was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and vibrating sample magnetometry (VSM) techniques, and its synergistic performances with microwaves were evaluated in detail with respect to the microwave radiation power, radiation time, and magnetic nanoparticle concentration. On this basis, the distribution of oil droplets and the wettability and chargeability of magnetic nanoparticles were measured without or with microwave radiation using biomicroscopy, contact angle measurement instrument, and a ζ-potential analyzer, thus revealing the synergistic demulsification mechanism between microwave and magnetic nanoparticles. The results showed that excessively high or low microwave radiation parameters had an inhibitory effect on the magnetic nanoparticle demulsification, and microwave promoted the magnetic nanoparticle demulsification only when the radiation parameters were in the optimal range. In addition, the water separation rate showed an increasing and then decreasing trend with the increase of magnetic nanoparticles concentration, with or without microwave action. As an example, the water separation rate of the emulsion for 1 h was 21.34% when the Fe3O4 concentration was 175 mg/L without microwave action, while it increased to 55.56% with microwave action. In contrast, when the concentration of Fe3O4@CPAM was 175 mg/L, the water separation rate was 42.86% without microwave radiation, while it was further increased to 77.38% under microwave radiation. These results indicate that magnetic nanoparticles and their complexes significantly affect the water separation process under different conditions. There is a more obvious coupling synergistic effect between Fe3O4@CPAM and microwave. This was due to the lower absolute potential of Fe3O4@CPAM and its higher hydrophobicity.

Study on the Effect of Polymer-Modified Magnetic Nanoparticles on Viscosity Reduction of Heavy Oil Emulsion.

To overcome the problems of large dosage, fast sedimentation, and the unsatisfactory emulsification effect of traditional magnetic nanoparticles, polymer-modified magnetic nanoparticle Co3O4@HPAM was synthesized as an emulsifier for heavy oil O/W emulsion by modifying the surface of Co3O4. The composition of Co3O4@HPAM was characterized by Fourier transform infrared spectroscopy, X-ray diffraction analysis, thermogravimetric analysis, and scanning electron microscopy. Then, the effects of the mass fraction of magnetic nanoparticles before and after modification on the stability and rheology of the emulsion were compared and analyzed. The experiments show that the degree of reduction of the water-separation rate under the action of Co3O4@HPAM was 13 times higher than that under the action of Co3O4 at the same mass fraction. By using Co3O4@HPAM, the water separation of the emulsion was only 6.74% at 4 h, while the viscosity reduction was greater than 97% at a mass fraction of 0.04%. Finally, combined with the test results of zeta potential, interfacial tension, contact angle, and oil droplet distribution, the effect mechanism of Co3O4@HPAM on the viscosity reduction of heavy oil emulsification was investigated. It is found that the polymer-modified magnetic nanoparticles have stronger negative electricity, a larger contact angle, and smaller interfacial tension, while the oil droplets under their action have a smaller radius and a more homogeneous distribution. The research in this paper provides a theoretical basis for the application of magnetic nanoparticles in heavy oil emulsification and viscosity reduction technology.

Genotoxicity evaluation of food additive titanium dioxide using a battery of standard in vivo tests.

The increasing use of titanium dioxide (TiO2) nanoparticles (NPs) has raised concern about the safety of food additive TiO2. TiO2 has been considered no longer safe by EFSA due to concerns over genotoxicity, however, there are conflicting opinions upon the safety of TiO2 as a food additive, and the number of in vivo genotoxicity studies conducted on food additive TiO2 was limited. In order to investigate the potential genotoxicity of food additive TiO2, we evaluated the genotoxicity of a commercial food additive TiO2 (average size of 135.54 ± 41.01 nm, range from 60.83 to 230.16 nm, NPs account for 30% by number) using a battery of standard in vivo tests, including mammalian erythrocyte micronucleus test, mammalian bone marrow chromosomal aberration test and in vivo mammalian alkaline comet test. After 15 days of consecutive intragastric administration at doses of 250, 500, and 1000 mg/kgBW, food additive TiO2 neither increased the frequencies of bone marrow micronuclei or chromosomal aberration in mice, nor induced DNA strand breakage in rat liver cells. These results indicate that under the condition of this study, food additive TiO2 does not have genotoxic potential although it contains a fraction of NPs.

Microwave-Assisted Rapid Synthesis of MOF-Based Single-Atom Ni Catalyst for CO2 Electroreduction at Ampere-Level Current.

Carbon-based single-atom catalysts (SACs) have attracted tremendous interest in heterogeneous catalysis. However, the common electric heating techniques to produce carbon-based SACs usually suffer from prolonged heating time and tedious operations. Herein, a general and facile microwave-assisted rapid pyrolysis method is developed to afford carbon-based SACs within 3 min without inert gas protection. The obtained carbon-based SACs present high porosity and comparable carbonization degree to those obtained by electric heating techniques. Specifically, the single-atom Ni implanted N-doped carbon (Ni1 -N-C) derived from a Ni-doped metal-organic framework (Ni-ZIF-8) exhibits remarkable CO Faradaic efficiency (96 %) with a substantial CO partial current density (jCO ) up to 1.06 A/cm2 in CO2 electroreduction, far superior to the counterpart obtained by traditional pyrolysis with electric heating. Mechanism investigations reveal that the resulting Ni1 -N-C presents abundant defective sites and mesoporous structure, greatly facilitating CO2 adsorption and mass transfer. This work establishes a versatile approach to rapid and large-scale synthesis of SACs as well as other carbon-based materials for efficient catalysis.

Genotoxicity assessment of titanium dioxide nanoparticles using a standard battery of in vivo assays.

As one representative of nanometal oxides, titanium dioxide nanoparticles (TiO2-NPs) have been widely used, particularly in the food industry. The genotoxicity of TiO2-NPs has attracted great attention over the years. This study was undertaken to investigate the chromosome and DNA damage effects of TiO2-NPs (0, 50, 150, and 500 mg/kg BW) using rodent models. After a comprehensive characterization, we conducted a standard battery of in vivo genotoxicity tests, including the chromosomal aberration test (CA), micronucleus (MN) test, and the comet test. The results of all these tests were negative. There were no structural or numerical chromosomal abnormalities in mice bone marrow cells, no increase in the frequency of micronucleated polychromatic erythrocytes in mice bone marrow cells, and no elevation in % tail DNA in rat hepatocytes. This indicated that TiO2-NPs did not cause chromosomal damage or have a direct impact on DNA. These findings suggested that TiO2-NPs did not exhibit genotoxicity and provided valuable data for risk assessment purposes.

The novel high-affinity humanized antibody IMM40H targets CD70, eliminates tumors via Fc-mediated effector functions, and interrupts CD70/CD27 signaling.

Background: A significant level of CD70 can be detected in various types of tumor tissues and CD27 is expressed on Treg cells, but CD70 expression is low in normal tissues. The interaction between CD70 and CD27 can stimulate the proliferation and survival of cancer cells and increase the level of soluble CD27, which is associated with poor prognosis in patients with lymphoma and certain solid tumors. Thus, it is a promising therapeutic target for the treatment of many major CD70+ cancer indications, including CD70+ lymphoma, RCC, NSCLC, HNSCC and OC. Methods: IMM40H was obtained through hybridoma screening and antibody humanization techniques. IMM40H was evaluated for its binding, blocking, Fc-dependent effector functions and antitumor activity characteristics in various in vitro and in vivo systems. The safety and tolerability profile of IMM40H were evaluated through single and repeated administration in cynomolgus monkeys. Results: In vitro cell-based assays demonstrated that IMM40H had considerably stronger CD70-binding affinity than competitor anti-CD70 antibodies, including cusatuzumab, which enabled it to block the interaction of between CD70 and CD27 more effectively. IMM40H also exhibited potent Fc-dependent effector functions (ADCC/CDC/ADCP), and could make a strong immune attack on tumor cells and enhance therapeutic efficacy. Preclinical findings showed that IMM40H had potent antitumor activity in multiple myeloma U266B1 xenograft model, and could eradicate subcutaneously established tumors at a low dose of 0.3 mg/kg. IMM40H (0.3 mg/kg) showed therapeutic effects faster than cusatuzumab (1 mg/kg). A strong synergistic effect between IMM01 (SIRPα-Fc fusion protein) and IMM40H was recorded in Burkitt's lymphoma Raji and renal carcinoma cell A498 tumor models. In cynomolgus monkeys, the highest non-severely toxic dose (HNSTD) for repeat-dose toxicity was up to 30 mg/kg, while the maximum tolerated dose (MTD) for single-dose toxicity was up to 100 mg/kg, confirming that IMM40H had a good safety and tolerability profile. Conclusion: IMM40H is a high-affinity humanized IgG1 specifically targeting the CD70 monoclonal antibody with enhanced Fc-dependent activities. IMM40H has a dual mechanism of action: inducing cytotoxicity against CD70+ tumor cells via various effector functions (ADCC, ADCP and CDC) and obstructs the proliferation and activation of Tregs by inhibiting CD70/CD27 signaling.

Monitoring Prevalence and Persistence of Environmental Contamination by SARS-CoV-2 RNA in a Makeshift Hospital for Asymptomatic and Very Mild COVID-19 Patients.

Objective: To investigate the details of environmental contamination status by SARS-CoV-2 in a makeshift COVID-19 hospital. Methods: Environmental samples were collected from a makeshift hospital. The extent of contamination was assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) for SARS-CoV-2 RNA from various samples. Results: There was a wide range of total collected samples contaminated with SARS-CoV-2 RNA, ranging from 8.47% to 100%. Results revealed that 70.00% of sewage from the bathroom and 48.19% of air samples were positive. The highest rate of contamination was found from the no-touch surfaces (73.07%) and the lowest from frequently touched surfaces (33.40%). The most contaminated objects were the top surfaces of patient cubic partitions (100%). The median Ct values among strongly positive samples were 33.38 (IQR, 31.69-35.07) and 33.24 (IQR, 31.33-34.34) for ORF1ab and N genes, respectively. SARS-CoV-2 relic RNA can be detected on indoor surfaces for up to 20 days. Conclusion: The findings show a higher prevalence and persistence in detecting the presence of SARS-CoV-2 in the makeshift COVID-19 hospital setting. The contamination mode of droplet deposition may be more common than contaminated touches.

Contamination dynamics of personal protective equipment (PPE) by SARS-CoV-2 RNA in a makeshift hospital with COVID-19 positive occupants.

Background: Personal protective equipment (PPE) helps protect healthcare workers (HCWs) from infection and prevents cross-contamination. Knowledge of the contamination dynamics of PPE during the management of COVID-19 patients in a makeshift hospital is limited. Aim: To describe the rate of SARS-CoV-2 contamination in PPE and to assess the change of contamination at different time points. Methods: HCWs were followed up for up to 4 hours with hourly collection of swab samples from PPE surfaces in a makeshift COVID-19 hospital setting. Swabs were tested using quantitative reverse transcription polymerase chain reaction (RT-qPCR) for SARS-CoV-2 RNA. Results: SARS-CoV-2 was detected on 50.9% of the 1620 swabbed samples from 9 different sites of full-body PPE worn by HCWs. The proportion of sites contaminated with SARS-CoV-2 RNA varied from 10.6% to 95.6%. Viral RNA was most frequently detected from the sole of the outer foot cover (95.6%) and least frequently on the face shield (10.6%). The median Ct values among positive samples were 34.20 (IQR, 32.61-35.22) and 34.05 (IQR, 32.20-35.39) for ORF1ab and N genes, respectively. The highest rate of contamination with SARS-CoV-2 RNA for the PPE swab samples was found after 3 hours of use. The positive rate of outer surface of HEPA filters from air supply device was 82.1% during the full capacity period of the makeshift hospital. Conclusion: A higher rate of contamination was identified at 3 hours after the entrance to the COVID-19 patient care area. Virus-containing aerosols were trapped in the HEPA filter of air supply equipment, representing a potential protective factor against infection to HCWs.

Neoadjuvant sintilimab and chemotherapy in patients with potentially resectable esophageal squamous cell carcinoma (KEEP-G 03): an open-label, single-arm, phase 2 trial.

BACKGROUND: The standard neoadjuvant treatments in patients with esophageal squamous cell carcinoma (ESCC) still have either poor safety or efficacy. Better therapies are needed in China. METHODS: This was an open-label, single-arm, phase 2 trial. Patients with potentially resectable ESCC (cT1b-3, Nany, M0 or T4a, N0-1, or M0) received preoperative intravenous sintilimab plus triplet chemotherapy (liposomal paclitaxel, cisplatin, and S-1) every 3 weeks for two cycles. The primary endpoints were safety and surgical feasibility; the secondary endpoint was major pathological response (MPR) rate. Genomic biomarkers (genetic mutations, tumor mutational burden (TMB), circulating tumor DNA status and immune microenvironment) in baseline tumor samples were investigated. RESULTS: All 30 patients completed two cycles of neoadjuvant treatment and underwent surgical resection. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 36.7% (11/30) of patients. The most frequent TRAEs were decreased white cell count (76.7%), anemia (76.7%), and decreased neutrophil count (73.3%). All TRAEs were hematological toxicities; none caused ≥30 days surgical delay. The MPR and pathological complete response (pCR) rates were 50.0% (15/30; 95% CI 33.2 to 66.9) and 20.0% (6/30; 95% CI 9.5 to 37.3), respectively. Patients with higher TMB and more clonal mutations were more likely to respond. ERBB2 alterations and ctDNA high-releaser status have a negative correlation with neoadjuvant ICI response. No significant difference was observed between therapeutic response and tumor immune microenvironment. CONCLUSIONS: Neoadjuvant sintilimab plus platinum-based triplet chemotherapy appeared safe and feasible, did not delay surgery and induced a pCR rate of 20.0% in patients with potentially resectable ESCC. TRIAL REGISTRATION NUMBER: NCT03946969.

Modulation of similarity on the distraction resistance of visual working memory representation.

Controversy exists regarding the distraction resistance of priority items in visual working memory (VWM). The protection account proposes that high-priority items resist distraction more than low-priority items, while the vulnerability account proposes that distractors impair high-priority items more. We proposed another available resource threshold account: distraction will not impair items if available resources exceed their threshold needed for sufficient processing. Using a change-detection paradigm, we manipulated item priority by color similarity and inserted distractors during VWM retention. We investigated the effect of similarity on distraction resistance of relevant (color) and irrelevant (shape) feature representations (Experiments 1-2), and the neural mechanism of this effect using event-related potentials (ERPs; Experiment 3). Behavioral results showed distractors impaired the accuracy of dissimilar items when relevant features were memorized and of similar items when irrelevant features were memorized under simultaneous presentation of similar and dissimilar items. Moreover, distractors impaired the accuracy of dissimilar items when relevant features were memorized and of both similar and dissimilar items when irrelevant features were memorized under separate presentation of items. ERP results showed a smaller negative slow wave and P2 but larger N2 under the similar condition. Similarity protected relevant features of similar items against distraction by reducing memory load, decreasing attentional resources allocated to distractors, and strengthening inhibition of distractors. However, similarity did not protect irrelevant features of similar items. Our results support the available resource threshold account, suggesting that VWM is a flexible and intelligent system despite its limited capacity.

Nomogram for preoperative estimation of histologic grade in gastrointestinal neuroendocrine tumors.

Background: The treatment strategies and prognosis for gastroenteropancreatic neuroendocrine tumors were associated with tumor grade. Preoperative predictive grading could be of great benefit in the selection of treatment options for patients. However, there is still a lack of effective non-invasive strategies to detect gastrointestinal neuroendocrine tumors (GI-NETs) grading preoperatively. Methods: The data on 147 consecutive GI-NETs patients was retrospectively collected from January 1, 2012, to December 31, 2019. Logistic regression was used to construct a predictive model of gastrointestinal neuroendocrine tumor grading using preoperative laboratory and imaging parameters.The validity of the model was assessed by area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results: The factors associated with GI-NETs grading were age, tumor size, lymph nodes, neuron-specific enolase (NSE), hemoglobin (HGB) and sex, and two models were constructed by logistic regression for prediction. Combining these 6 factors, the nomogram was constructed for model 1 to distinguish between G3 and G1/2, achieving a good AUC of 0.921 (95% CI: 0.884-0.965), and the sensitivity, specificity, accuracy were 0.9167, 0.8256, 0.8630, respectively. The model 2 was to distinguish between G1 and G2/3, and the variables were age, tumor size, lymph nodes, NSE, with an AUC of 0.847 (95% CI: 0.799-0.915), and the sensitivity, specificity, accuracy were 0.7882, 0.8710, 0.8231, respectively. Two online web servers were established on the basis of the proposed nomogram to facilitate clinical use. Both models showed an excellent calibration curve through 1000 times bootstrapped dataset and the clinical usefulness were confirmed using decision curve analysis. Conclusion: The model served as a valuable non-invasive tool for differentiating between different grades of GI-NETs, personalizing the calculation which can lead to a rational treatment choice.

Experimental Study on Synergistic Demulsification of Microwave-Magnetic Nanoparticles.

Owing to the difficulty in the demulsification of heavy oil-in-water (O/W) emulsions, the demulsification rules of magnetic nanoparticles, microwave radiation, and magnetic-nanoparticle-assisted microwaves were investigated in this study. The surface potential and droplet size of the emulsion under different demulsification conditions were investigated by using a ζ potentiometer and polarizing microscopy to reveal the mechanism of demulsification. The results showed that γ-Fe2O3 exhibited the best demulsification performance among the six magnetic nanoparticles used for demulsification. With an increase in the concentration of γ-Fe2O3, the water separation of the heavy O/W emulsion first increased and then decreased, and with a decrease in pH, the demulsification performance gradually increased. The experimental results showed that microwave demulsification had an optimal power. The demulsification efficiency was significantly improved at the synergistic action between magnetic nanoparticles and the microwave, proving that magnetic nanoparticles had a promoting effect on microwave demulsification. In addition, the recycling experiment results showed that the magnetic nanoparticles exhibited good recyclability and reusability. Finally, a temperature field model of the emulsion under the synergistic effect of microwaves and magnetic nanoparticles was established and evaluated. Both before and after the addition of the magnetic nanoparticles, the theoretical temperature of the heavy O/W emulsion was consistent with the experimental temperature at different microwave powers and radiation times.