Search

Abstract Background To evaluate the utility of glucose chemical exchange saturation transfer (glucoCEST) MRI with non-contrast injection in predicting the histological grade of rectal cancer. Methods This prospective analysis included 60 patients with preoperative rectal cancer who underwent pelvic glucoCEST, amide proton transfer-weighted imaging (APTWI), and diffusion-weighted imaging (DWI). In total, 21 low-grade and 39 high-grade cases were confirmed by postoperative pathology. The MTRasym (1.2 ppm), MTRasym (3.5 ppm), and apparent diffusion coefficient (ADC) values of lesions between the low-grade and high-grade groups were compared. The area under the receiver operating characteristic curve (AUC) was generated to evaluate the diagnostic performance of each technique. Logistic regression (LR) analysis was applied to determine independent predictors and for multi-parameter combined diagnosis. Results Elevated MTRasym (1.2 ppm), MTRasym (3.5 ppm) values and lower ADC values were observed in the high-grade group compared with low-grade cases (all p

Abstract Severe friction on wheel/rail contact interface in the process of a train emergency braking can cause significant thermal and mechanical phenomena. Obvious friction heat and serious material damage will appear on the contact surface. In this article, the variation law of temperature and surface damage during a wheel sliding contact process are investigated. To achieve the research objective, a three-dimensional (3D) thermo-mechanical coupling contact finite element model (FEM) is established, and the temperature-dependent material parameters are used. The FEM is adopted to analyze the temperature distribution law on the contact surface. At the same time, a sliding contact testing machine is used to study the damage of materials in the contact area during the sliding contact. The study results indicate, the highest temperature of wheel and rail material is respectively 1014 ℃ and 461.8 ℃ during sliding contact. High temperatures are located at the subsurface and surface areas of contact region. When the distance to contact surface exceeds 1.4 mm, the temperature changes slightly. The types of damage on wheel surface are grooves and material peeling, while the flaky spalling, corrosive pitting, adhesion and grooves appear on the rail surface. Meanwhile, many cracks can be found on the contact surface, which is a major factor leading to material damage. The research results of this article are of great significance for understanding the thermal and mechanical damage of wheel/rail materials.

Abstract Background A novel positron emission tomography (PET) imaging tracer, [18F] SynVesT-1, targeting synaptic vesicle glycoprotein 2 (SV2A), has been developed to meet clinical demand. Utilizing the Trasis AllinOne-36 (AIO) module, we’ve automated synthesis to Good Manufacturing Practice (GMP) standards, ensuring sterile, pyrogen-free production. The fully GMP-compliant robust synthesis of [18F] SynVesT-1 boosting reliability and introducing a significant degree of simplicity and its comprehensive validation for routine human use. Results [18F] SynVesT-1 was synthesized by small modifications to the original [18F] SynVesT-1 synthesis protocol to better fit AIO module using an in-house designed cassette and sequence. With a relatively small precursor load of 5 mg, [18F] SynVesT-1 was obtained with consistently high radiochemical yields (RCY) of 20.6 ± 1.2% (the decay-corrected RCY, n = 3) at end of synthesis. Each of the final formulated batches demonstrated radiochemical purity (RCP) and enantiomeric purity surpassing 99%. The entire synthesis process was completed within a timeframe of 80 min (75 ± 3.1 min, n = 3), saves 11 min compared to reported GMP automated synthesis procedures. The in-human PET imaging of total body PET/CT and time-of-flight (TOF) PET/MR showed that [18F] SynVesT-1 is an excellent tracer for SV2A. It is advantageous for decentralized promotion and application in multi-center studies. Conclusion The use of AIO synthesizer maintains high production yields and increases reliability, reduces production time and allows rapid training of production staff. Besides, the as-prepared [18F] SynVesT-1 displays excellent in vivo binding properties in humans and holds great potential for the imaging and quantification of synaptic density in vivo.

Abstract Super‐enhancers (SEs) have been recognized as key epigenetic regulators underlying cancer stemness and malignant traits by aberrant transcriptional control and promising therapeutic targets against human cancers. However, the SE landscape and their roles during head and neck squamous cell carcinoma (HNSCC) development especially in cancer stem cells (CSCs) maintenance remain underexplored yet. Here, we identify leukemia inhibitory factor (LIF)‐SE as a representative oncogenic SE to activate LIF transcription in HNSCC. LIF secreted from cancer cells and cancer‐associated fibroblasts promotes cancer stemness by driving SOX2 transcription in an autocrine/paracrine manner, respectively. Mechanistically, enhancer elements E1, 2, 4 within LIF‐SE recruit SOX2/SMAD3/BRD4/EP300 to facilitate LIF transcription; LIF activates downstream LIFR‐STAT3 signaling to drive SOX2 transcription, thus forming a previously unknown regulatory feedback loop (LIF‐SE‐LIF/LIFR‐STAT3‐SOX2) to maintain LIF overexpression and CSCs stemness. Clinically, increased LIF abundance in clinical samples correlate with malignant clinicopathological features and patient prognosis; higher LIF concentrations in presurgical plasma dramatically diminish following cancer eradication. Therapeutically, pharmacological targeting LIF‐SE‐LIF/LIFR‐STAT3 significantly impairs tumor growth and reduces CSC subpopulations in xenograft and PDX models. Our findings reveal a hitherto uncharacterized LIF‐SE‐mediated auto‐regulatory loop in regulating HNSCC stemness and highlight LIF as a novel noninvasive biomarker and potential therapeutic target for HNSCC.

ObjectiveTo establish and validate a new clinical-radiomics nomogram based on the fat-suppressed T2 sequence for differentiating luminal and non-luminal breast cancer.MethodsA total of 593 breast cancer patients who underwent preoperative breast MRI from Jan 2017 to Dec 2020 were enrolled, which were randomly divided into the training (n=474) and test sets (n=119) at the ratio of 8:2. Intratumoral region (ITR) of interest were manually delineated, and peritumoral regions of 3 mm and 5 mm (PTR-3 mm and PTR-5 mm) were automatically obtained by dilating the ITR. Intratumoral and peritumoral radiomics features were extracted from the fat-suppressed T2-weighted images, including first-order statistical features, shape features, texture features, and filtered features. The Mann-Whitney U Test, Z score normalization, K-best method, and least absolute shrinkage and selection operator (LASSO) algorithm were applied to select key features to construct radscores based on ITR, PTR-3 mm, PTR-5 mm, ITR+PTR-3 mm and ITR+ PTR-5 mm. Risk factors were selected by univariate and multivariate logistic regressions and were used to construct a clinical model and a clinical-radiomics model that presented as a nomogram. The performance of models was assessed by sensitivity, specificity, accuracy, the area under the curve (AUC) of receiver operating characteristic (ROC), calibration curves, and decision curve analysis (DCA).ResultsITR+PTR-3 mm radsore and histological grade were selected as risk factors. A clinical-radiomics model was constructed by adding ITR+PTR-3mm radscore to the clinical factor, which was presented as a nomogram. The clinical-radiomics nomogram showed the highest AUC (0.873), sensitivity (72.3%), specificity (78.9%) and accuracy (77.0%) in the training set and the highest AUC (0.851), sensitivity (71.4%), specificity (79.8%) and accuracy (77.3%) in the test set. DCA showed that the clinical-radiomics nomogram had the greatest net clinical benefit compared to the other models.ConclusionThe clinical-radiomics nomogram showed promising clinical application value in differentiating luminal and non-luminal breast cancer.

Abstract Background Evaluate the efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in treating locally advanced cervical cancer (LACC). Methods Retrospective data was collected from LACC patients who were treated at our institution. These patients were categorized into three groups: the single-agent cisplatin (DDP) chemoradiotherapy group, the paclitaxel plus cisplatin (TP) chemoradiotherapy group, and the nanoparticle albumin-bound (nab-) paclitaxel combined with cisplatin (nPP) chemoradiotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) and incidence of adverse events (AEs). Results A total of 124 patients were enrolled (32 in the DDP group, 41 in the TP group, and 51 in the nPP group). There were differences in OS (P = 0.041, HR 0.527, 95% CI 0.314–0.884) and PFS (P = 0.003, HR 0.517, 95% CI 0.343–0.779) between the three groups. Notably, the 2-year OS rate was significantly higher in the nPP group compared to the DDP group (92.2% vs. 85.4%, P = 0.012). The 2-year PFS rates showed a marked increase in the TP group (78.0% vs. 59.4%, P = 0.048) and the nPP group (88.2% vs. 59.4%, P = 0.001) relative to the DPP group, with multiple comparisons indicating that the 2-year PFS rate was significantly superior in the nPP group versus the DDP group (88.2% vs. 59.4%, P = 0.001). Moreover, the ORR was also significantly higher in the nPP group than in the DDP group (P = 0.013); and no statistically significant differences were found in the incidence of AEs among the groups (P > 0.05). Conclusions In LACC treatment, the two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better efficacy than the paclitaxel plus cisplatin regimen. Furthermore, the AEs associated with these regimens were deemed tolerable. These findings could provide a reference for the clinical treatment of LACC. However, further prospective studies are needed to verify it.

BackgroundLarge language models show promise for improving radiology workflows, but their performance on structured radiological tasks such as Reporting and Data Systems (RADS) categorization remains unexplored. ObjectiveThis study aims to evaluate 3 large language model chatbots—Claude-2, GPT-3.5, and GPT-4—on assigning RADS categories to radiology reports and assess the impact of different prompting strategies. MethodsThis cross-sectional study compared 3 chatbots using 30 radiology reports (10 per RADS criteria), using a 3-level prompting strategy: zero-shot, few-shot, and guideline PDF-informed prompts. The cases were grounded in Liver Imaging Reporting & Data System (LI-RADS) version 2018, Lung CT (computed tomography) Screening Reporting & Data System (Lung-RADS) version 2022, and Ovarian-Adnexal Reporting & Data System (O-RADS) magnetic resonance imaging, meticulously prepared by board-certified radiologists. Each report underwent 6 assessments. Two blinded reviewers assessed the chatbots’ response at patient-level RADS categorization and overall ratings. The agreement across repetitions was assessed using Fleiss κ. ResultsClaude-2 achieved the highest accuracy in overall ratings with few-shot prompts and guideline PDFs (prompt-2), attaining 57% (17/30) average accuracy over 6 runs and 50% (15/30) accuracy with k-pass voting. Without prompt engineering, all chatbots performed poorly. The introduction of a structured exemplar prompt (prompt-1) increased the accuracy of overall ratings for all chatbots. Providing prompt-2 further improved Claude-2’s performance, an enhancement not replicated by GPT-4. The interrun agreement was substantial for Claude-2 (k=0.66 for overall rating and k=0.69 for RADS categorization), fair for GPT-4 (k=0.39 for both), and fair for GPT-3.5 (k=0.21 for overall rating and k=0.39 for RADS categorization). All chatbots showed significantly higher accuracy with LI-RADS version 2018 than with Lung-RADS version 2022 and O-RADS (P

Background: Mycoplasma and Ureaplasma spp. especially M. hominis, U. parvum, and U. urealyticum recognized as an important cause of urogenital infections. Sake of the presence of antibiotic resistance and a continuous rise in resistance, the treatment options are limited, and treatment has become more challenging and costlier. Objectives: Therefore, this meta-analysis aimed to estimate worldwide resistance rates of genital Mycoplasmas and Ureaplasma to fluoroquinolones (ciprofloxacin, ofloxacin, moxifloxacin, and levofloxacin) agents. Methods: We searched the relevant published studies in PubMed, Scopus, and Embase from until 3, March 2022. All statistical analyses were carried out using the statistical package R. Results: The 30 studies included in the analysis were performed in 16 countries. In the metadata, the proportions of ciprofloxacin, ofloxacin, moxifloxacin, and levofloxacin resistance in Mycoplasma and Ureaplasma urogenital isolates were reported 59.8% (95% CI 49.6, 69.1), 31.2% (95% CI 23, 40), 7.3% (95% CI 1, 31), and 5.3% (95% CI 1, 2), respectively. According to the meta-regression, the ciprofloxacin, ofloxacin, moxifloxacin, and levofloxacin rate increased over time. There was a statistically significant difference in the fluoroquinolones resistance rates between different continents/countries (P < 0.05). Conclusions: Based on the results obtained in this systematic review and meta-analysis we recommend the use of the newer group of fluoroquinolones especially levofloxacin as the first choice for the treatment of genital mycoplasmosis, as well as ofloxacin for the treatment of genital infections caused by U. parvum.

Abstract Objectives To differentiate benign and malignant solitary pulmonary lesions (SPLs) by amide proton transfer-weighted imaging (APTWI), mono-exponential model DWI (MEM-DWI), stretched exponential model DWI (SEM-DWI), and 18F-FDG PET-derived parameters. Methods A total of 120 SPLs patients underwent chest 18F-FDG PET/MRI were enrolled, including 84 in the training set (28 benign and 56 malignant) and 36 in the test set (13 benign and 23 malignant). MTRasym(3.5 ppm), ADC, DDC, α, SUVmax, MTV, and TLG were compared. The area under receiver-operator characteristic curve (AUC) was used to assess diagnostic efficacy. The Logistic regression analysis was used to identify independent predictors and establish prediction model. Results SUVmax, MTV, TLG, α, and MTRasym(3.5 ppm) values were significantly lower and ADC, DDC values were significantly higher in benign SPLs than malignant SPLs (all P

Abstract Objectives Commercialized total-body PET scanners can provide high-quality images due to its ultra-high sensitivity. We compared the dynamic, regular static, and delayed 18F-fluorodeoxyglucose (FDG) scans to detect lesions in oncologic patients on a total-body PET/CT scanner. Materials & methods In all, 45 patients were scanned continuously for the first 60 min, followed by a delayed acquisition. FDG metabolic rate was calculated from dynamic data using full compartmental modeling, whereas regular static and delayed SUV images were obtained approximately 60- and 145-min post-injection, respectively. The retention index was computed from static and delayed measures for all lesions. Pearson’s correlation and Kruskal–Wallis tests were used to compare parameters. Results The number of lesions was largely identical between the three protocols, except MRFDG and delayed images on total-body PET only detected 4 and 2 more lesions, respectively (85 total). FDG metabolic rate (MRFDG) image-derived contrast-to-noise ratio and target-to-background ratio were significantly higher than those from static standardized uptake value (SUV) images (P 0.05). Dynamic protocol did not significantly differentiate between benign and malignant lesions just like regular SUV, delayed SUV, and retention index. Conclusion The potential quantitative advantages of dynamic imaging may not improve lesion detection and differential diagnosis significantly on a total-body PET/CT scanner. The same conclusion applied to delayed imaging. This suggested the added benefits of complex imaging protocols must be weighed against the complex implementation in the future. Clinical relevance Total-body PET/CT was known to significantly improve the PET image quality due to its ultra-high sensitivity. However, whether the dynamic and delay imaging on total-body scanner could show additional clinical benefits is largely unknown. Head-to-head comparison between two protocols is relevant to oncological management.

Abstract Background Node Reporting and Data System (Node-RADS) was proposed and can be applied to lymph nodes (LNs) across all anatomical sites. This study aimed to investigate the diagnostic performance of Node-RADS in cervical cancer patients. Methods A total of 81 cervical cancer patients treated with radical hysterectomy and LN dissection were retrospectively enrolled. Node-RADS evaluations were performed by two radiologists on preoperative MRI scans for all patients, both at the LN level and patient level. Chi-square and Fisher’s exact tests were employed to evaluate the distribution differences in size and configuration between patients with and without LN metastasis (LNM) in various regions. The receiver operating characteristic (ROC) and the area under the curve (AUC) were used to explore the diagnostic performance of the Node-RADS score for LNM. Results The rates of LNM in the para-aortic, common iliac, internal iliac, external iliac, and inguinal regions were 7.4%, 9.3%, 19.8%, 21.0%, and 2.5%, respectively. At the patient level, as the NODE-RADS score increased, the rate of LNM also increased, with rates of 26.1%, 29.2%, 42.9%, 80.0%, and 90.9% for Node-RADS scores 1, 2, 3, 4, and 5, respectively. At the patient level, the AUCs for Node-RADS scores > 1, >2, > 3, and > 4 were 0.632, 0.752, 0.763, and 0.726, respectively. Both at the patient level and LN level, a Node-RADS score > 3 could be considered the optimal cut-off value with the best AUC and accuracy. Conclusions Node-RADS is effective in predicting LNM for scores 4 to 5. However, the proportions of LNM were more than 25% at the patient level for scores 1 and 2, which does not align with the expected very low and low probability of LNM for these scores.

Purpose: To investigate the potential of radiomics signatures (RSs) from intratumoral and peritumoral regions on multiparametric magnetic resonance imaging (MRI) to noninvasively evaluate HER2 status in breast cancer. Method: In this retrospective study, 992 patients with pathologically confirmed breast cancers who underwent preoperative MRI were enrolled. The breast cancer lesions were segmented manually, and the intratumor region of interest (ROIIntra) was dilated by 2, 4, 6 and 8 mm (ROIPeri2mm, ROIPeri4mm, ROIPeri6mm, and ROIPeri8mm, respectively). Quantitative radiomics features were extracted from dynamic contrast-enhanced T1-weighted imaging (DCE-T1), fat‐saturated T2‐weighted imaging (T2) and diffusion-weighted imaging (DWI). A three-step procedure was performed for feature selection, and RSs were constructed using a support vector machine (SVM) to predict HER2 status. Result: The best single-area RSs for predicting HER2 status were DCE_Peri4mm-RS, T2_Peri4mm-RS, and DWI_Peri4mm-RS, yielding areas under the curve (AUCs) of 0.716 (95% confidence interval (CI), 0.648–0.778), 0.706 (95% CI, 0.637–0.768), and 0.719 (95% CI, 0.651–0.780), respectively, in the test set. The optimal RSs combining intratumoral and peritumoral regions for evaluating HER2 status were DCE-T1_Intra + DCE_Peri4mm-RS, T2_Intra + T2_Peri6mm-RS and DWI_Intra + DWI_Peri4mm-RS, with AUCs of 0.752 (95% CI, 0.686–0.810), 0.754 (95% CI, 0.688–0.812) and 0.725 (95% CI, 0.657–0.786), respectively, in the test set. Combining three sequences in the ROIIntra, ROIPeri2mm, ROIPeri4mm, ROIPeri6mm and ROIPeri8mm areas, the optimal RS was DCE-T1_Peri4mm + T2_Peri4mm + DWI_Peri4mm-RS, achieving an AUC of 0.795 (95% CI, 0.733–0.849) in the test set. Conclusion: This study systematically explored the influence of the intratumoral region, different peritumoral sizes and their combination in radiomics analysis for predicting HER2 status in breast cancer based on multiparametric MRI and found the optimal RS.

Abstract Background Chronic kidney disease (CKD) is a common cause of morbidity and mortality in captive wildlife species. However, CKD has been rarely documented in giant pandas. Case presentation The following report describes a case of an eight-year-old female giant panda showing clinical signs of epistaxis, bloody diarrhea, polyuria, azotemia and anemia. The animal died despite of supportive treatments. Necropsy was performed. Grossly, both kidneys were shrunken and scarred with pallor. Subcutis edema and petechia on the epicardium of the heart were observed. The tissue samples were made into paraffin sections and stained by H.E and special staining including Periodic Acid-Schiff (PAS), von Kossa, Masson’s trichrome, Phosphotungstic acid-hematoxylin (PTAH), and Congo red. Histopathology examination revealed severe chronic tubulointerstitial nephritis with marked interstitial fibrosis, glomerulosclerosis, tubular atrophy and calcification in kidneys, and acute necrotizing hemorrhagic myocarditis with calcification in heart. Other lesions included intestinal hemorrhage, hepatic fatty degeneration and necrosis with hemosiderin, and splenic hemosiderin. Conclusions In summary, chronic kidney disease was finally diagnosed based on the association of clinical, gross, and histopathological findings. Heart failure secondary to CKD is the leading cause of death in this giant panda. The potential cause of CKD in this animal is possibly due to long term and uncontrolled hypertension. Blood pressure monitoring is essential in establishing the diagnosis and management of hypertension in giant panda.

ObjectiveTo investigate the value of predicting axillary lymph node (ALN) metastasis based on intratumoral and peritumoral dynamic contrast-enhanced MRI (DCE-MRI) radiomics and clinico-radiological characteristics in breast cancer.MethodsA total of 473 breast cancer patients who underwent preoperative DCE-MRI from Jan 2017 to Dec 2020 were enrolled. These patients were randomly divided into training (n=378) and testing sets (n=95) at 8:2 ratio. Intratumoral regions (ITRs) of interest were manually delineated, and peritumoral regions of 3 mm (3 mmPTRs) were automatically obtained by morphologically dilating the ITR. Radiomics features were extracted, and ALN metastasis-related radiomics features were selected by the Mann-Whitney U test, Z score normalization, variance thresholding, K-best algorithm and least absolute shrinkage and selection operator (LASSO) algorithm. Clinico-radiological risk factors were selected by logistic regression and were also used to construct predictive models combined with radiomics features. Then, 5 models were constructed, including ITR, 3 mmPTR, ITR+3 mmPTR, clinico-radiological and combined (ITR+3 mmPTR+ clinico-radiological) models. The performance of models was assessed by sensitivity, specificity, accuracy, F1 score and area under the curve (AUC) of receiver operating characteristic (ROC), calibration curves and decision curve analysis (DCA).ResultsA total of 2264 radiomics features were extracted from each region of interest (ROI), 3 and 10 radiomics features were selected for the ITR and 3 mmPTR, respectively. 5 clinico-radiological risk factors were selected, including lesion size, human epidermal growth factor receptor 2 (HER2) expression, vascular cancer thrombus status, MR-reported ALN status, and time-signal intensity curve (TIC) type. In the testing set, the combined model showed the highest AUC (0.839), specificity (74.2%), accuracy (75.8%) and F1 Score (69.3%) among the 5 models. DCA showed that it had the greatest net clinical benefit compared to the other models.ConclusionThe intra- and peritumoral radiomics models based on DCE-MRI could be used to predict ALN metastasis in breast cancer, especially for the combined model with clinico-radiological characteristics showing promising clinical application value.

Phytoplankton face numerous pressures resulting from chemical and physical stressors, primarily induced by human activities. This study focuses on investigating the interactive effects of widely used antifouling agent Irgarol 1051 and UV radiation on the photo-physiology of marine diatoms from diverse latitudes, within the context of global warming. Our findings clearly shown that both Irgarol and UV radiation have a significant inhibitory impact on the photochemical performance of the three diatoms examined, with Irgarol treatment exhibiting more pronounced effects. In the case of the two temperate zone diatoms, we observed a decrease in the inhibition induced by Irgarol 1051 and UVR as the temperature increased up to 25°C. Similarly, for the subarctic species, an increase in temperature resulted in a reduction in the inhibition caused by Irgarol and UVR. These results suggest that elevated temperatures can mitigate the short-term inhibitory effects of both Irgarol and UVR on diatoms. Furthermore, our data indicate that increased temperature could significantly interact with UVR or Irgarol for temperate diatoms, while this was not the case for cold water diatoms, indicating temperate and subarctic diatoms may respond differentially under global warming.

Abstract Chemoimmunotherapy with anti-programmed cell death 1/ligand 1 and cytotoxic chemotherapy is a promising therapeutic modality for women with triple-negative breast cancer, but questions remain regarding optimal chemotherapy backbone and biomarkers for patient selection. We report final outcomes from a phase Ib trial evaluating pembrolizumab (200 mg IV every 3 weeks) with either weekly paclitaxel (80 mg/m2 weekly) or flat-dose capecitabine (2000 mg orally twice daily for 7 days of every 14-day cycle) in the 1st/2nd line setting. The primary endpoint is safety (receipt of 2 cycles without grade III/IV toxicities requiring discontinuation or ≥21-day delays). The secondary endpoint is efficacy (week 12 objective response). Exploratory aims are to characterize immunologic effects of treatment over time, and to evaluate novel biomarkers. The trial demonstrates that both regimens meet the pre-specified safety endpoint (paclitaxel: 87%; capecitabine: 100%). Objective response rate is 29% for pembrolizumab/paclitaxel (n = 4/13, 95% CI: 10–61%) and 43% for pembrolizumab/capecitabine (n = 6/14, 95% CI: 18–71%). Partial responses are observed in two subjects with chemo-refractory metaplastic carcinoma (both in capecitabine arm). Both regimens are associated with significant peripheral leukocyte contraction over time. Response is associated with clinical PD-L1 score, non-receipt of prior chemotherapy, and the H&E stromal tumor-infiltrating lymphocyte score, but also by a novel 27 gene IO score and spatial biomarkers (lymphocyte spatial skewness). In conclusion, pembrolizumab with paclitaxel or capecitabine is safe and clinically active. Both regimens are lymphodepleting, highlighting the competing immunostimulatory versus lymphotoxic effects of cytotoxic chemotherapy. Further exploration of the IO score and spatial TIL biomarkers is warranted. The clinical trial registration is NCT02734290.

Abstract The bacterium Avibacterium paragallinarum, previously known as Haemophilus paragallinarum, is responsible for causing infectious coryza (IC) in chickens and other avian species. In this case report, an outbreak of Avibacterium paragallinarum occurred in the Qinling area of China, resulting in clinical symptoms of facial swelling in several bird species, including Golden pheasant, Temminck's tragopan, and Peafowls, and three Golden pheasants died due to prolonged infection. Specific PCR results confirmed the presence of the pathogen in the infected birds. The report describes the clinical symptoms and pathological changes observed in the affected birds, as well as the isolation and identification of Avibacterium paragallinarum. Whole-genome sequencing and phylogenetic analysis were performed, and this is the first report of inter- and intra-species transmission of infectious coryza among wild birds in China.

This study aimed to investigate the effects of combining anlotinib with camrelizumab on clinical efficacy and short-term prognosis in male patients with advanced gastric cancer. A total of 88 male patients admitted to our hospital between May 2019 and March 2022 with advanced gastric cancer were included and randomly assigned to Group A (treated with anlotinib alone) or Group B (treated with anlotinib combined with camrelizumab) using the envelope method, with 44 patients in each group. Their clinical efficacy, vascular endothelial growth factor (VEGF) and programmeddeath-1 (PD-1) expression on Cluster of differentiation 4+ (CD4+) and cytotoxic Tlymphocyte (CD8+ T) cells in peripheral blood, immune function parameters, tumor markers, incidence of adverse reactions and survival time were compared. The results showed that the patients in Group B had significantly higher objective response rate (ORR) and disease control rate (DCR), superior PD-1 in VEGF, CD4+ T cells and CD8+ T cells, significantly improved immune function indicators and tumor markers (Carbohydrate antigen 50 (CA50), carcinoembryonic antigen (CEA) and cytokeratin 19 fragment (CYFRA21-1)), and significantly longer progression-free survival and overall survival than Group A. In addition, no significant difference in the incidence of adverse reactions between the two groups was observed. Therefore, the combination of anlotinib and camrelizumab could be a clinically beneficial treatment option and recommended for male patients with advanced gastric cancer as it can effectively control tumor progression, improve clinical efficacy and prolong their survival without increasing adverse reactions.

The improvement of corrosion resistance for sintered Nd-Fe-B magnets is usually focused on the modification of grain boundary phase. The main phase is similarly a key point to enhance corrosion resistance. In this work, a novel sintered Nd-Fe-B magnet is designed with the addition of Ni and Cr. This kind of sintered Nd-Ni-Fe-Cr-B magnet maintains a typical 2:14:1 tetragonal phase, and the metallurgical behavior of Ni and Cr is characterized by the distribution of Ni in the grain boundary and Cr in the main phase. Accelerated corrosion and electrochemical corrosion tests were conducted to compare the corrosion resistance of traditional sintered Nd-Fe-B magnet and Nd-Ni-Fe-Cr-B magnet. Results show that sintered Nd-Ni-Fe-Cr-B magnet exhibits superior corrosion resistance. It is found that the corrosion resistance of the grain boundary phase and the main phase is simultaneously increased. Moreover, the reduced potential difference between the grain boundary phase and the main phase further enhances the corrosion resistance of sintered Nd-Ni-Fe-Cr-B magnet. This work could provide an insight into the research aimed at improving the corrosion resistance of uncoated sintered Nd-Fe-B magnets.

Abstract Memristors with nonvolatile storage performance and simulated synaptic functions are regarded as one of the critical devices to overcome the bottleneck in traditional von Neumann computer architecture. 2D van der Waals heterostructures have paved a new way for the development of advanced memristors by integrating the intriguing features of different materials and offering additional controllability over their optoelectronic properties. Herein, planar memristors with both electrical and optical tunability based on ReS2/WS2 van der Waals heterostructure are demonstrated. The devices show unique unipolar nonvolatile behavior with high Roff/Ron ratio of up to 106, desirable endurance, and retention, which are superior to pure ReS2 and WS2 devices. When decreasing the channel length, the set voltage can be notably reduced while the high Roff/Ron ratios are retained. By introducing electrostatic doping through the gate control, the set voltage can be tailored in a wide range from 4.50 to 0.40 V. Furthermore, biological synaptic functions and plasticity, including spike rate‐dependent plasticity and paired‐pulse facilitation, are successfully realized. By employing optical illumination, resistive switching can also be modulated, which is dependent on the illumination energy and power. A mechanism related to the interlayer charge transfer controlled by optical excitation is revealed.

Abstract Precancerous lesions of the oral mucosa, especially those accompanied by moderate to severe dysplasia, contribute to the initiation of oral squamous cell carcinoma (OSCC). However, the cellular compositions and spatial organization of the precancerous stage and how these factors promote human OSCC initiation remain unclear. Here, we built a single-cell transcriptome atlas and a spatial transcriptome map after obtaining data from pairwise human oral mucosal biopsies of 9 individuals consisting of very early-stage OSCC, adjacent precancerous lesions with moderate to severe dysplasia, as well as a matched normal region. An altered epithelial gene-expression profile was identified which favored OSCC initiation. This observation was coupled with distinct fibroblast, monocytic, and regulatory T-cell subclusters involved in reshaping the microenvironment. In particular, a unique immune-inhibitory monocyte subtype and spatial-switching regulation of VEGF signaling were observed surrounding precancerous lesions, concertedly strengthening activities in promoting cancer initiation. Collectively, our work elucidated the cellular landscapes and roles of precancerous lesions underlying OSCC initiation, which is essential for understanding the entire OSCC initiation process and helps inform therapeutic strategies for cancer intervention.

Abstract Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.

Abstract Objective To explore the characteristics of peripheral blood, high resolution computed tomography (HRCT) imaging and the radiomics signature (RadScore) in patients infected with delta variant virus under different coronavirus disease (COVID-19) vaccination status. Methods 123 patients with delta variant virus infection collected from November 1, 2021 to March 1, 2022 were analyzed retrospectively. According to COVID-19 vaccination Status, they were divided into three groups: Unvaccinated group, partially vaccinated group and full vaccination group. The peripheral blood, chest HRCT manifestations and RadScore of each group were analyzed and compared. Results The mean lymphocyte count 1.22 ± 0.49 × 10^9/L, CT score 7.29 ± 3.48, RadScore 0.75 ± 0.63 in the unvaccinated group; The mean lymphocyte count 1.55 ± 0.70 × 10^9/L, CT score 5.27 ± 2.72, RadScore 1.03 ± 0.46 in the partially vaccinated group; The mean lymphocyte count 1.87 ± 0.70 × 10^9/L, CT score 3.59 ± 3.14, RadScore 1.23 ± 0.29 in the fully vaccinated group. There were significant differences in lymphocyte count, CT score and RadScore among the three groups (all p

PurposeThe purpose of this study was to investigate the value of a clinical radiomics model based on Positron emission tomography-computed tomography (PET-CT) radiomics features combined with clinical predictors of Lymphovascular invasion (LVI) in predicting preoperative LVI in patients with colorectal cancer (CRC).MethodsA total of 95 CRC patients who underwent preoperative 18F-fluorodeoxyglucose (FDG) PET-CT examination were retrospectively enrolled. Univariate and multivariate logistic regression analyses were used to analyse clinical factors and PET metabolic data in the LVI-positive and LVI-negative groups to identify independent predictors of LVI. We constructed four prediction models based on radiomics features and clinical data to predict LVI status. The predictive efficacy of different models was evaluated according to the receiver operating characteristic curve. Then, the nomogram of the best model was constructed, and its performance was evaluated using calibration and clinical decision curves.ResultsMean standardized uptake value (SUVmean), maximum tumour diameter and lymph node metastasis were independent predictors of LVI in CRC patients (P 0.05).ConclusionThe clinical radiomics prediction model constructed in this study has high value in the preoperative individualized prediction of LVI in CRC patients.

Abstract Background The total-body positron emission tomography (PET) scanner provides an unprecedented opportunity to scan the whole body simultaneously, thanks to its long axial field of view and ultrahigh temporal resolution. To fully utilize this potential in clinical settings, a dynamic scan would be necessary to obtain the desired kinetic information from scan data. However, in a long dynamic acquisition, patient movement can degrade image quality and quantification accuracy. Methods In this work, we demonstrated a motion correction framework and its importance in dynamic total-body FDG PET imaging. Dynamic FDG scans from 12 subjects acquired on a uEXPLORER PET/CT were included. In these subjects, 7 are healthy subjects and 5 are those with tumors in the thorax and abdomen. All scans were contaminated by motion to some degree, and for each the list-mode data were reconstructed into 1-min frames. The dynamic frames were aligned to a reference position by sequentially registering each frame to its previous neighboring frame. We parametrized the motion fields in-between frames as diffeomorphism, which can map the shape change of the object smoothly and continuously in time and space. Diffeomorphic representations of motion fields were derived by registering neighboring frames using large deformation diffeomorphic metric matching. When all pairwise registrations were completed, the motion field at each frame was obtained by concatenating the successive motion fields and transforming that frame into the reference position. The proposed correction method was labeled SyN-seq. The method that was performed similarly, but aligned each frame to a designated middle frame, was labeled as SyN-mid. Instead of SyN, the method that performed the sequential affine registration was labeled as Aff-seq. The original uncorrected images were labeled as NMC. Qualitative and quantitative analyses were performed to compare the performance of the proposed method with that of other correction methods and uncorrected images. Results The results indicated that visual improvement was achieved after correction of the SUV images for the motion present period, especially in the brain and abdomen. For subjects with tumors, the average improvement in tumor SUVmean was 5.35 ± 4.92% (P = 0.047), with a maximum improvement of 12.89%. An overall quality improvement in quantitative Ki images was also observed after correction; however, such improvement was less obvious in K1 images. Sampled time–activity curves in the cerebral and kidney cortex were less affected by the motion after applying the proposed correction. Mutual information and dice coefficient relative to the reference also demonstrated that SyN-seq improved the alignment between frames over non-corrected images (P = 0.003 and P = 0.011). Moreover, the proposed correction successfully reduced the inter-subject variability in Ki quantifications (11.8% lower in sampled organs). Subjective assessment by experienced radiologists demonstrated consistent results for both SUV images and Ki images. Conclusion To conclude, motion correction is important for image quality in dynamic total-body PET imaging. We demonstrated a correction framework that can effectively reduce the effect of random body movements on dynamic images and their associated quantification. The proposed correction framework can potentially benefit applications that require total-body assessment, such as imaging the brain-gut axis and systemic diseases.

Abstract Purpose Efforts have been made both to avoid invasive blood sampling and to shorten the scan duration for dynamic positron emission tomography (PET) imaging. A total-body scanner, such as the uEXPLORER PET/CT, can relieve these challenges through the following features: First, the whole-body coverage allows for noninvasive input function from the aortic arteries; second, with a dramatic increase in sensitivity, image quality can still be maintained at a high level even with a shorter scan duration than usual. We implemented a dual-time-window (DTW) protocol for a dynamic total-body 18F-FDG PET scan to obtain multiple kinetic parameters. The DTW protocol was then compared to several other simplified quantification methods for total-body FDG imaging that were proposed for conventional setup. Methods The research included 28 patient scans performed on an uEXPLORER PET/CT. By discarding the corresponding data in the middle of the existing full 60-min dynamic scan, the DTW protocol was simulated. Nonlinear fitting was used to estimate the missing data in the interval. The full input function was obtained from 15 subjects using a hybrid approach with a population-based image-derived input function. Quantification was carried out in three areas: the cerebral cortex, muscle, and tumor lesion. Micro- and macro-kinetic parameters for different scan durations were estimated by assuming an irreversible two-tissue compartment model. The visual performance of parametric images and region of interest-based quantification in several parameters were evaluated. Furthermore, simplified quantification methods (DTW, Patlak, fractional uptake ratio [FUR], and standardized uptake value [SUV]) were compared for similarity to the reference net influx rate K i . Results K i and K 1 derived from the DTW protocol showed overall good consistency (P

In order to promote the coordinated and sustainable development of China′s logistics industry and marine industry, the paper comprehensively used neutral cross efficiency model, entropy method, coupling evaluation model and gravity center migration model, selected multi-level evaluation indicators including location entropy, systematically evaluated the logistics efficiency and marine industry agglomeration level of 11 coastal areas in China from 2008 to 2018, analyzed the spatial and temporal pattern characteristics of the coordination relationship between the two and put forward development suggestions. The results showed that from 2008 to 2018, the logistics efficiency and the level of marine industry agglomeration in China′s coastal areas showed an increasing trend, but there was still a large development space and there were large regional differences. The overall coupling coordination degree of logistics efficiency and marine industry agglomeration level had been continuously improved and had developed from primary coordination to intermediate coordination. The coupling coordination level of various coastal areas had varied from near-disorder to good coordination and the center of coupling coordination degree basically showed a NE-SW migration trend. To improve the coordination between logistics efficiency and the level of marine industry agglomeration, the construction of logistics infrastructure should be strengthened and adhered to the two-way linkage between land and sea, and promote the flow of resource elements.

Abstract Achieving high-efficient spin injection in semiconductors is critical for developing spintronic devices. Although a tunnel spin injector is typically used, the construction of a high-quality tunnel barrier remains a significant challenge due to the large lattice mismatch between oxides and semiconductors. In this work, van der Waals h-BN films with the atomically flat interface were engaged as the tunnel barrier to achieve high spin polarization in GaN, and the spin injection and transport in GaN were investigated systematically. Based on the Hanle precession and magnetic resistance measurements, CoFeB was determined as an optimal spin polarizer, bilayer h-BN tunnelling barrier was proven to yield a much higher spin polarization than the case of monolayer, and appropriate carrier concentration as well as higher crystal equality of n-GaN could effectively reduce the defect-induced spin scattering to improve the spin transport. The systematic understanding and the high efficiency of spin injection in this work may pave the way to the development of physical connotations and the applications of semiconductor spintronics.

Abstract Cetuximab is a widely used drug for treating head and neck squamous cell carcinomas (HNSCCs); however, it provides restricted clinical benefits, and its response duration is limited by drug resistance. Here, we conducted randomized “Phase II-like clinical trials” of 49 HNSCC PDX models and reveal multiple informative biomarkers for intrinsic resistance to cetuximab (e.g., amplification of ANKH, up-regulation of PARP3). After validating these intrinsic resistance biomarkers in another HNSCC PDX cohort (61 PDX models), we generated acquired cetuximab resistance PDX models and analyzed them to uncover resistance mechanisms. Whole exome sequencing and transcriptome sequencing revealed diverse patterns of clonal selection in acquired resistant PDXs, including the emergence of subclones with strongly activated RAS/MAPK. Extending these insights, we show that a combination of a RAC1/RAC3 dual-target inhibitor and cetuximab could overcome acquired cetuximab resistance in vitro and in vivo. Beyond revealing intrinsic resistance biomarkers, our PDX-based study shows how clonal architecture changes underlying acquired resistance can be targeted to expand the therapeutic utility of this important drug to more HNSCC patients.

Primary squamous cell carcinoma (PSCC) of the breast, as a rare metaplastic breast cancer, currently has limited clinical data on its biological behavior, treatment and prognosis. At present, the optimal treatment of this tumor is still controversial. We reported a case of a 56-year-old woman with a mass on the right breast. She underwent a modified radical mastectomy and lymph node biopsy, which revealed that the tumor was a metaplastic squamous cell carcinoma with axillary lymph node metastasis, followed by traditional adjuvant chemotherapy and radiotherapy. The patient re-examined by PET/CT after two years in May 2017 and found a recurrence in the right chest wall, so resection of the recurring lesion was resected, then she was given postoperative adjuvant radiotherapy and chemotherapy. In August 2019, the patient re-examined by PET/CT, and there were pulmonary and mediastinal lymph node metastases. After 4 cycles of albumin paclitaxel plus cisplatin chemotherapy combined with nivolumab immunotherapy, the patient achieved complete response (CR), and then switched to nivolumab immune maintenance therapy. So far, no obvious metastasis has been seen. We believe that surgical treatment is necessary for PSCC of the breast;paclitaxel and cisplatin chemotherapy regimens and adjuvant radiotherapy are effective, but it may be resistant to radiotherapy; and immunotherapy may prolong the survival of patients with PSCC of the breast.

Existing high-performance deep learning methods typically rely on large training datasets with high-quality manual annotations, which are difficult to obtain in many clinical applications. Here, the authors introduce an open-source framework to handle imperfect training datasets.

The aberrant activation of STAT3 is associated with the etiology and progression in a variety of malignant epithelial-derived tumors, including head and neck squamous cell carcinoma (HNSCC) and colorectal cancer (CRC). Due to the lack of an enzymatic catalytic site or a ligand-binding pocket, there are no small-molecule inhibitors directly targeting STAT3 that have been approved for clinical translation. Emerging proteolysis targeting chimeric (PROTAC) technology–based approach represents a potential strategy to overcome the limitations of conventional inhibitors and inhibit activation of STAT3 and downstream genes. In this study, the heterobifunctional small-molecule–based PROTACs are successfully prepared from toosendanin (TSN), with 1 portion binding to STAT3 and the other portion binding to an E3 ubiquitin ligase. The optimized lead PROTAC (TSM-1) exhibits superior selectivity, potency, and robust antitumor effects in STAT3-dependent HNSCC and CRC — especially in clinically relevant patient-derived xenografts (PDX) and patient-derived organoids (PDO). The following mechanistic investigation identifies the reduced expression of critical downstream STAT3 effectors, through which TSM-1 promotes cell cycle arrest and apoptosis in tumor cells. These findings provide the first demonstration to our knowledge of a successful PROTAC-targeting strategy in STAT3-dependent epithelial cancer.

BackgroundLung cancer has become one of the deadliest tumors in the world. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for approximately 80%-85% of all lung cancer cases. This study aimed to investigate the value of diffusion kurtosis imaging (DKI), diffusion-weighted imaging (DWI) and 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG PET) in differentiating squamous cell carcinoma (SCC) and adenocarcinoma (AC) and to evaluate the correlation of each parameter with stage and proliferative status Ki-67.MethodsSeventy-seven patients with lung lesions were prospectively scanned by hybrid 3.0-T chest 18F-FDG PET/MR. Mean kurtosis (MK), mean diffusivity (MD), apparent diffusion coefficient (ADC), maximum standard uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured. The independent samples t test or Mann–Whitney U test was used to compare and analyze the differences in each parameter of SCC and AC. The diagnostic efficacy was evaluated by receiver operating characteristic (ROC) curve analysis and compared with the DeLong test. A logistic regression analysis was used for the evaluation of independent predictors. Bootstrapping (1000 samples) was performed to establish a control model, and calibration curves and ROC curves were used to validate its performance. Pearson’s correlation coefficient and Spearman’s correlation coefficient were calculated for correlation analysis.ResultsThe MK and ADC values of the AC group were significantly higher than those of the SCC group (all P< 0.05), and the SUVmax, MTV, and TLG values of the SCC group were significantly higher than those of the AC group (all P

Abstract Two-dimensional Janus materials have great potential for the applications in spintronic devices due to their particular structures and novel characteristics. However, they are usually non-magnetic in nature. Here, different transition metals (TMs: Co, Fe, Mn, Cr, and V) adsorbed WSSe frameworks are constructed, and their structures and magnetic properties are comprehensively investigated by first-principles calculations. The results show that the top of W atom is the most stable absorption site for all the TM atoms, and all the systems exhibit magnetism. Moreover, their magnetic properties significantly depend on the adsorbed elements and the adsorbent chalcogens. A maximal total magnetic moment of 6 μB is obtained in the Cr-adsorbed system. The induced magnetism from S-surface-adsorption is always stronger than that for the Se-surface-adsorption due to its larger electrostatic potential. Interestingly, the easy magnetization axis in the Fe-adsorbed system switches from the in-plane to the out-of-plane when the adsorption surface changes from Se to S surface. The mechanism is analyzed in detail by Fe-3d orbital-decomposed density of states. This work provides a guidance for the modification of magnetism in low-dimensional systems.

A continuous-flow Anaerobic/Anoxic/Oxic (A2/O) system was operated at different organic concentrations to systematically investigate the effect on the nutrient removal, secretion characteristics of extracellular polymer, phosphorus forms transformation and changes in functional flora in this system. The results showed that high organic loading was more conducive to promote the secretion of extracellular polymeric substance (EPS), the increase of polysaccharide content was more obvious compared with protein, the impact of organic loading on the components of loosely bound EPS (LB-EPS) was higher than that of tight-bound EPS (TB-EPS). Phosphorus in sludge floc mainly existed in the form of inorganic phosphorus (IP), and IP mainly existed in the form of apatite inorganic phosphorus (AP). High organic load showed higher phosphorus storage in EPS, and the phosphorus content in EPS was positively correlated with the content of EPS. Non-apatite phosphorus (NAIP) content played an important role in the extracellular dephosphorization. The abundance of Nitrosomonas and Nitrospira responsible for nitrification decreased with the increase in organic loading. The group of denitrifiers was large, and Azospira was the most abundant genus among them. Dechloromonas, Acinetobacter, Povalibacter, Chryseolinea and Pirellula were the functional genera closely associated with phosphorus removal. HIGHLIGHTS High organic loading promoted the secretion of EPS, the impact of organic loading on the components of LB-EPS was higher than that of TB-EPS.; NAIP played an important role in the extracellular phosphorus removal.; Influent organic loading shaped the bacterial community structure.; The core functional genera in N and P removal were identified by correlation analysis.;

Abstract Background The H&E stromal tumor-infiltrating lymphocyte (sTIL) score and programmed death ligand 1 (PD-L1) SP142 immunohistochemistry assay are prognostic and predictive in early-stage breast cancer, but are operator-dependent and may have insufficient precision to characterize dynamic changes in sTILs/PD-L1 in the context of clinical research. We illustrate how multiplex immunofluorescence (mIF) combined with statistical modeling can be used to precisely estimate dynamic changes in sTIL score, PD-L1 expression, and other immune variables from a single paraffin-embedded slide, thus enabling comprehensive characterization of activity of novel immunotherapy agents. Methods Serial tissue was obtained from a recent clinical trial evaluating loco-regional cytokine delivery as a strategy to promote immune cell infiltration and activation in breast tumors. Pre-treatment biopsies and post-treatment tumor resections were analyzed by mIF (PerkinElmer Vectra) using an antibody panel that characterized tumor cells (cytokeratin-positive), immune cells (CD3, CD8, CD163, FoxP3), and PD-L1 expression. mIF estimates of sTIL score and PD-L1 expression were compared to the H&E/SP142 clinical assays. Hierarchical linear modeling was utilized to compare pre- and post-treatment immune cell expression, account for correlation of time-dependent measurement, variation across high-powered magnification views within each subject, and variation between subjects. Simulation methods (Monte Carlo, bootstrapping) were used to evaluate the impact of model and tissue sample size on statistical power. Results mIF estimates of sTIL and PD-L1 expression were strongly correlated with their respective clinical assays (p

Abstract Background Lung cancer (LC) remains the deadliest form of cancer globally. While surgery remains the optimal treatment strategy for individuals with early-stage LC, what the metabolic consequences are of such surgical intervention remains uncertain. Methods Negative enrichment-fluorescence in situ hybridization (NE-FISH) was used in an effort to detect circulating tumor cells (CTCs) in pre- and post-surgery peripheral blood samples from 51 LC patients. In addition, targeted metabolomics analyses, multivariate statistical analyses, and pathway analyses were used to explore surgery-associated metabolic changes. Results LC patients had significantly higher CTC counts relative to healthy controls with 66.67% of LC patients having at least 1 detected CTC before surgery. CTC counts were associated with clinical outcomes following surgery. In a targeted metabolomics analysis, we detected 34 amino acids, 147 lipids, and 24 fatty acids. When comparing LC patients before and after surgery to control patients, metabolic shifts were detected via PLS-DA and pathway analysis. Further surgery-associated metabolic changes were identified when comparing LA (LC patients after surgery) and LB (LC patients before surgery) groups. We identified SM 42:4, Ser, Sar, Gln, and LPC 18:0 for inclusion in a biomarker panel for early-stage LC detection based upon an AUC of 0.965 (95% CI 0.900–1.000). This analysis revealed that SM 42:2, SM 35:1, PC (16:0/14:0), PC (14:0/16:1), Cer (d18:1/24:1), and SM 38:3 may offer diagnostic and prognostic benefits in LC. Conclusions These findings suggest that CTC detection and plasma metabolite profiling may be an effective means of diagnosing early-stage LC and identifying patients at risk for disease recurrence.