The predictive value of inflammatory biomarkers for major pathological response in non-small cell lung cancer patients receiving neoadjuvant chemoimmunotherapy and its association with the immune-related tumor microenvironment: a multi-center study.

BACKGROUND: Inflammatory biomarkers in the peripheral blood have been established as predictors for immunotherapeutic efficacy in advanced non-small cell lung cancer (NSCLC). Whether they can also predict major pathological response (MPR) in neoadjuvant setting remains unclear. METHODS: In this multi-center retrospective study, 122 and 92 stage I-IIIB NSCLC patients from six hospitals who received neoadjuvant chemoimmunotherapy followed by surgery were included in the discovery and external validation cohort, respectively. Baseline and on-treatment neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII) were calculated and associated with MPR. Furthermore, resected tumor samples from 37 patients were collected for RNA-sequencing to investigate the immune-related tumor microenvironment. RESULTS: In both the discovery and validation cohorts, the on-treatment NLR, dNLR, PLR, and SII levels were significantly lower in the patients with MPR versus non-MPR. On-treatment SII remained an independent predictor of MPR in multivariate logistic regression analysis. The area under the curve (AUC) of on-treatment SII for predicting MPR was 0.75 (95%CI, 0.67-0.84) in the discovery cohort. Moreover, the predictive value was further improved by combining the on-treatment SII and radiological tumor regression data, demonstrating an AUC of 0.82 (95%CI, 0.74-0.90). The predictive accuracy was validated in the external cohort. Compared with the SII-high group, patients with SII-Low were associated with the activated B cell receptor signaling pathway and a higher intratumoral immune cell infiltration level. CONCLUSIONS: On-treatment SII was independently associated with MPR in NSCLC patients receiving neoadjuvant chemoimmunotherapy. Further prospective studies are warranted.

Major pathological response exhibited distinct prognostic significance for lung adenocarcinoma post different modalities of neoadjuvant therapy.

AIMS: For non-small-cell lung cancer (NSCLC) patients receiving neoadjuvant therapy, the major pathological response (MPR) is defined as the percentage of residual viable tumour cells (%RVT) in the tumour bed of no more than 10%. It has been proposed as a predictor of survival in neoadjuvant therapy-treated cohorts. Nonetheless, the significance of %RVT in the pathological assessment of lung adenocarcinoma cohorts remains undetermined. METHODS AND RESULTS: Overall, 152 lung adenocarcinoma patients were included in this retrospective study, among whom 67 received neoadjuvant targeted therapy and 85 received neoadjuvant chemotherapy. Clinicopathological characteristics, neoadjuvant treatment response and survival status were investigated. The routinely adopted standard for MPR (%RVT ≤ 10%) failed to differentiate prognosis in the lung adenocarcinoma population. For the neoadjuvant chemotherapy cohort, the optimal %RVT cut-off value of RFS was 60%. However, this cut-off value was clinically insignificant in the neoadjuvant targeted-therapy cohort. Hence, for these patients, we built a nomogram model including high-grade patterns and ypN stage to predict disease recurrence, demonstrating high efficacy (a bootstrap-corrected C-index of 0.731). CONCLUSIONS: %RVT served as a strong indicator of the prognosis of lung adenocarcinoma in patients receiving neoadjuvant chemotherapy but not neoadjuvant targeted therapy. Residual high-grade pathological patterns might substitute MPR in prognostic evaluation of lung adenocarcinoma post-targeted therapy.

Management of massive cerebral infarction as a complication of post-tonsillectomy and analysis of the risk factors: a case report.

BACKGROUND: The majority of postoperative complications of tonsillectomy are bleeding. However, massive cerebral infarction following haemostasis is a very rare and serious complication and has rarely been reported clinically. CASE PRESENTATION: We performed a left tonsillectomy on a patient with chronic tonsillitis. After that, active bleeding was found under the tonsillar fossa, so an exploratory hypopharyngeal haemostasis was performed. However, the bleeding worsened intraoperatively, so the patient was converted to a cervical angiographic embolization. The interventional procedure was completed successfully without an ectopic embolic event. After the procedure, the patient was transferred to the intensive care unit (ICU) and was diagnosed with acute massive cerebral infarction in the left cerebral hemisphere after awakening symptoms combined with cranial computed tomography angiography (CTA) results. Symptomatic treatment such as sedation and analgesia, dehydration to lower intracranial pressure, and maintenance of respiratory and circulatory stability was then administered. After treatment, the patient's condition stabilized and he was transferred to the rehabilitation physiotherapy unit for rehabilitation. CONCLUSION: Post-tonsillectomy haemorrhage can be augmented with a carotid arteriogram to clarify whether the tonsillar fossa is at a safe distance from the posterior internal carotid artery. Furthermore, interventional haemostasis can also be performed as early as possible to reduce the incidence of complications in cases of persistent post-tonsillectomy bleeding.

Theoretical estimation of attenuation coefficient of resonant ultrasound contrast agents.

Acoustic characterization of ultrasound contrast agents (UCAs, coated microbubbles) relies on the attenuation theory that assumes the UCAs oscillate linearly at sufficiently low excitation pressures. Effective shell parameters of the UCAs can be estimated by fitting a theoretical attenuation curve to experimentally measured attenuation data. Depending on the excitation frequency and properties of the shell, however, an UCA may oscillate nonlinearly even at sufficiently low excitation pressures, violating the assumption in the linear attenuation theory. Notably, the concern over the estimation of the attenuation coefficient of a microbubble at resonance using linearized approximation has long been addressed. This article investigated the attenuation phenomenon through analyzing the energy dissipation of a single UCA and propagating waves in an UCA suspension, both of which employed a nonlinear Rayleigh-Plesset equation. Analytical formulas capable of estimating the attenuation coefficient due to the weakly nonlinear oscillations of the UCA were obtained with a relatively rigorous mathematical analysis. The computed results that were verified by numerical simulations showed the attenuation coefficient of the UCA at resonance was pressure-dependent and could be significantly smaller than that predicted by the linear attenuation theory. Polydispersity of the UCA population enlarged the difference in the estimation of attenuation between the linear and present second-order nonlinear theories.

Analysis of acoustic nonlinearity parameter B/A in liquids containing ultrasound contrast agents.

The acoustic nonlinearity parameter B/A plays a significant role in the characterization of acoustic properties of various biomaterials and biological tissues. It has the potential to be a favorable imaging modality in contrast ultrasound imaging with coated microbubbles. However, the development of effective means for evaluating the nonlinearity parameter of suspensions of ultrasound contrast agents (UCAs, also known as bubbly liquids) remains open. The present paper formulates a new equation based on the thermodynamic method that correlates both attenuation and phase velocity of linear ultrasound. The simplicity of the present method makes the B/A estimation possible with a relatively rigorous mathematical derivation. The calculated nonlinearity parameter contains the contribution of dynamic effects of bubbles, and its low-frequency limit agrees with B/A estimated by the method of mixture law when the volume fraction is below 10-4. Furthermore, the maximum B/A in bubbly liquids can reach up to105, while the minimum can be as low as -105. The negative nonlinearity parameter indicates significantly different thermodynamic properties of bubbly liquids.

Tissue-Penetrating, Hypoxia-Responsive Echogenic Polymersomes For Drug Delivery To Solid Tumors.

Hypoxia in solid tumors facilitates the progression of the disease, develops resistance to chemo and radiotherapy, and contributes to relapse. Due to the lack of tumor penetration, most of the reported drug carriers are unable to reach the hypoxic niches of the solid tumors. We have developed tissue-penetrating, hypoxia-responsive echogenic polymersomes to deliver anticancer drugs to solid tumors. The polymersomes are composed of a hypoxia-responsive azobenzene conjugated and a tissue penetrating peptide functionalized polylactic acid-polyethylene glycol polymer. The drug-encapsulated, hypoxia-responsive polymersomes substantially decreased the viability of pancreatic cancer cells in spheroidal cultures. Under normoxic conditions, polymersomes were echogenic at diagnostic ultrasound frequencies but lose the echogenicity under hypoxia. In-vivo imaging studies with xenograft mouse model further confirmed the ability of the polymersomes to target, penetrate, and deliver the encapsulated contents in hypoxic pancreatic tumor tissues.

Nucleus-Targeted, Echogenic Polymersomes for Delivering a Cancer Stemness Inhibitor to Pancreatic Cancer Cells.

Chemotherapeutic agents for treating cancers show considerable side effects, toxicity, and drug resistance. To mitigate the problems, we designed nucleus-targeted, echogenic, stimuli-responsive polymeric vesicles (polymersomes) to transport and subsequently release the encapsulated anticancer drugs within the nuclei of pancreatic cancer cells. We synthesized an alkyne-dexamethasone derivative and conjugated it to N3-polyethylene glycol (PEG)-polylactic acid (PLA) copolymer employing the Cu2+ catalyzed "Click" reaction. We prepared polymersomes from the dexamethasone-PEG-PLA conjugate along with a synthesized stimuli-responsive polymer PEG-S-S-PLA. The dexamethasone group dilates the nuclear pore complexes and transports the vesicles to the nuclei. We designed the polymersomes to release the encapsulated drugs in the presence of a high concentration of reducing agents in the nuclei of pancreatic cancer cells. We observed that the nucleus-targeted, stimuli-responsive polymersomes released 70% of encapsulated contents in the nucleus-mimicking environment in 80 min. We encapsulated the cancer stemness inhibitor BBI608 in the vesicles and observed that the BBI608 encapsulated polymersomes reduced the viability of the BxPC3 cells to 43% in three-dimensional spheroid cultures. The polymersomes were prepared following a special protocol so that they scatter ultrasound, allowing imaging by a medical ultrasound scanner. Therefore, these echogenic, targeted, stimuli-responsive, and drug-encapsulated polymersomes have the potential for trackable, targeted carrier of chemotherapeutic drugs to cancer cell nuclei.

4D printing of polymeric materials for tissue and organ regeneration.

Four dimensional (4D) printing is an emerging technology with great capacity for fabricating complex, stimuli-responsive 3D structures, providing great potential for tissue and organ engineering applications. Although the 4D concept was first highlighted in 2013, extensive research has rapidly developed, along with more-in-depth understanding and assertions regarding the definition of 4D. In this review, we begin by establishing the criteria of 4D printing, followed by an extensive summary of state-of-the-art technological advances in the field. Both transformation-preprogrammed 4D printing and 4D printing of shape memory polymers are intensively surveyed. Afterwards we will explore and discuss the applications of 4D printing in tissue and organ regeneration, such as developing synthetic tissues and implantable scaffolds, as well as future perspectives and conclusions.

Interpreting attenuation at different excitation amplitudes to estimate strain-dependent interfacial rheological properties of lipid-coated monodisperse microbubbles.

Broadband attenuation of ultrasound measured at different excitation pressures being different raises a serious theoretical concern, because the underlying assumption of linear and independent propagation of different frequency components nominally requires attenuation to be independent of excitation. Here, this issue is investigated by examining ultrasound attenuation through a monodisperse lipid-coated microbubble suspension measured at four different acoustic excitation amplitudes. The attenuation data are used to determine interfacial rheological properties (surface tension, surface dilatational elasticity, and surface dilatational viscosity) of the encapsulation according to three different models. Although different models result in similar rheological properties, attenuation measured at different excitation levels (4-110 kPa) leads to different values for them; the dilatation elasticity (0.56 to 0.18 N/m) and viscosity (2.4 × 10(-8) to 1.52 × 10(-8) Ns/m) both decrease with increasing pressure. Numerically simulating the scattered response, nonlinear energy transfer between frequencies are shown to be negligible, thereby demonstrating the linearity in propagation and validating the attenuation analysis. There is a second concern to the characterization arising from shell properties being dependent on excitation amplitude, which is not a proper constitutive variable. It is resolved by arriving at a strain-dependent rheology for the encapsulation. The limitations of the underlying analysis are discussed.

An algorithm for retrieving land surface temperatures using VIIRS data in combination with multi-sensors.

A practical algorithm was proposed to retrieve land surface temperature (LST) from Visible Infrared Imager Radiometer Suite (VIIRS) data in mid-latitude regions. The key parameter transmittance is generally computed from water vapor content, while water vapor channel is absent in VIIRS data. In order to overcome this shortcoming, the water vapor content was obtained from Moderate Resolution Imaging Spectroradiometer (MODIS) data in this study. The analyses on the estimation errors of vapor content and emissivity indicate that when the water vapor errors are within the range of ±0.5 , the mean retrieval error of the present algorithm is 0.634 K; while the land surface emissivity errors range from -0.005 to +0.005, the mean retrieval error is less than 1.0 K. Validation with the standard atmospheric simulation shows the average LST retrieval error for the twenty-three land types is 0.734 K, with a standard deviation value of 0.575 K. The comparison between the ground station LST data indicates the retrieval mean accuracy is -0.395 K, and the standard deviation value is 1.490 K in the regions with vegetation and water cover. Besides, the retrieval results of the test data have also been compared with the results measured by the National Oceanic and Atmospheric Administration (NOAA) VIIRS LST products, and the results indicate that 82.63% of the difference values are within the range of -1 to 1 K, and 17.37% of the difference values are within the range of ±2 to ±1 K. In a conclusion, with the advantages of multi-sensors taken fully exploited, more accurate results can be achieved in the retrieval of land surface temperature.

Monitoring the leaf damage by the rice leafroller with deep learning and ultra-light UAV.

BACKGROUND: Rice leafroller is a serious threat to the production of rice. Monitoring the damage caused by rice leafroller is essential for effective pest management. Owing to limitations in collecting decent quality images and high-performing identification methods to recognize the damage, studies recommending fast and accurate identification of rice leafroller damage are rare. In this study, we employed an ultra-lightweight unmanned aerial vehicle (UAV) to eliminate the influence of the downwash flow field and obtain very high-resolution images of the damaged areas of the rice leafroller. We used deep learning technology and the segmentation model, Attention U-Net, to recognize the damaged area by the rice leafroller. Further, a method is presented to count the damaged patches from the segmented area. RESULTS: The result shows that Attention U-Net achieves high performance, with an F1 score of 0.908. Further analysis indicates that the deep learning model performs better than the traditional image classification method, Random Forest (RF). The traditional method of RF causes a lot of false alarms around the edge of leaves, and is sensitive to the changes in brightness. Validation based on the ground survey indicates that the UAV and deep learning-based method achieve a reasonable accuracy in identifying damage patches, with a coefficient of determination of 0.879. The spatial distribution of the damage is uneven, and the UAV-based image collecting method provides a dense and accurate method to recognize the damaged area. CONCLUSION: Overall, this study presents a vision to monitor the damage caused by the rice leafroller with ultra-light UAV efficiently. It would also contribute to effectively controlling and managing the hazardous rice leafroller. © 2024 Society of Chemical Industry.

Perioperative outcomes comparison of robotic and video-assisted thoracoscopic thymectomy for thymic epithelial tumor: a single-center experience.

BACKGROUND: The advent of robot-assisted thoracoscopic surgery (RATS) has completely revolutionized the modality of thymectomy, which could reportedly achieve equivalent efficacy compared with a minimally invasive approach. This study was conducted to further compare the perioperative outcomes between these two modalities. METHODS: A retrospective single-center study that included patients receiving either a robotic or video-assisted thoracoscopic (VAT) thymectomy between February 2021 and January 2023 was conducted. All the patients were pathologically confirmed with thymic epithelial tumors. Clinical and pathological characteristics and perioperative outcomes were collected and compared between these two cohorts. RESULTS: A total of 190 patients were included in this study, with 61 (32.1%) and 129 (67.9%) receiving robotic and video-assisted thymectomy, respectively. The clinicopathological characteristics were not significantly different between these 2 groups. The size of the resected specimens in the RATS cohort was larger than the VATS cohort [median (IQR), 13.0 (8.0-16.0) vs. 9.0 (6.7-12.0) cm, p < 0.001], while the procedural duration was longer for the RATS group than its counterpart [median (IQR), 105 (85-143) vs. 85 (69-115) min, p = 0.001]. Moreover, no other significant difference was observed between these two groups. Since more than half of the robotic thymectomy was performed using a subxiphoid approach, a subgroup analysis was further conducted. Similarly, the robotic group through a subxiphoid approach harbored a longer procedural duration, and the size of the specimens obtained was larger than the VATS group [median (IQR), 14.0 (11.0-16.5) vs. 12.5 (8.5-15.0) cm, p = 0.061]. CONCLUSIONS: The early clinical efficacy of robotic thymectomy was proven comparable to the established VATS approach, and such a modality might have strength when obtaining larger specimens, which could contribute to improving long-term efficacy. Despite the longer procedural duration recorded in the early stage of conducting robotic thymectomy, further accumulation would help decrease the time.

The IASLC grading system for invasive pulmonary adenocarcinoma: a potential prognosticator for patients receiving neoadjuvant therapy.

Background: Grading system for resected invasive pulmonary adenocarcinoma proposed by the International Association for the Study of Lung Cancer (IASLC) was validated as a strong prognostic indicator. Nonetheless, the efficacy of utilizing such grading system in prognostic assessment of patients receiving neoadjuvant therapy still needs elucidating. Methods: A retrospective study was conducted including patients with resected adenocarcinoma following neoadjuvant chemotherapy or targeted therapy from August 2012 to December 2020 in Shanghai Pulmonary Hospital. All the surgical specimens were re-evaluated and graded. The prognostic value of the grading system was further validated. Results: Ultimately, a total of 198 patients were enrolled in this study, and subdivided into three cohorts according to the grading system. There were 13 (6.6%), 37 (18.7%), and 148 (74.7%) patients belonging to Grades 1, 2, and 3, respectively. IASLC grading system demonstrated significant power in prognosis differentiation of the entire cohort [recurrence-free survival (RFS), p < 0.001; overall survival (OS), p < 0.001] and the neoadjuvant chemotherapy and targeted therapy cohorts separately, and was further verified as a significant prognostic indicator for RFS and OS in multivariable Cox analysis. Since the majority of the patients (84.8%) did not achieve major pathologic response (MPR), representing a wide spectrum of survival, the prognostic value of grading system in non-MPR cohort was further evaluated. Similar results were also obtained that IASLC grading system was assessed significant in univariable analysis of RFS (p < 0.001) and univariable analysis of OS (p = 0.001). Conclusions: The prognostic efficacy of pathological evaluation of the residual proportion of pulmonary adenocarcinoma post-neoadjuvant therapy using IASLC grading system was preliminarily verified. Such grading system might assist prognostic evaluation of neoadjuvant cohort other than traditional pathological parameters.

Stereolithographic 4D Bioprinting of Multiresponsive Architectures for Neural Engineering.

4D printing represents one of the most advanced fabrication techniques for prospective applications in tissue engineering, biomedical devices, and soft robotics, among others. In this study, a novel multiresponsive architecture is developed through stereolithography-based 4D printing, where a universal concept of stress-induced shape transformation is applied to achieve the 4D reprogramming. The light-induced graded internal stress followed by a subsequent solvent-induced relaxation, driving an autonomous and reversible change of the programmed configuration after printing, is employed and investigated in depth and details. Moreover, the fabricated construct possesses shape memory property, offering a characteristic of multiple shape change. Using this novel multiple responsive 4D technique, a proof-of-concept smart nerve guidance conduit is demonstrated on a graphene hybrid 4D construct providing outstanding multifunctional characteristics for nerve regeneration including physical guidance, chemical cues, dynamic self-entubulation, and seamless integration. By employing this fabrication technique, creating multiresponsive smart architectures, as well as demonstrating application potential, this work paves the way for truly initiation of 4D printing in various high-value research fields.

Acoustic Characterization of Echogenic Polymersomes Prepared From Amphiphilic Block Copolymers.

Polymersomes are a class of artificial vesicles prepared from amphiphilic polymers. Like lipid vesicles (liposomes), they too can encapsulate hydrophilic and hydrophobic drug molecules in the aqueous core and the hydrophobic bilayer respectively, but are more stable than liposomes. Although echogenic liposomes have been widely investigated for simultaneous ultrasound imaging and controlled drug delivery, the potential of the polymersomes remains unexplored. We prepared two different echogenic polymersomes from the amphiphilic copolymers polyethylene glycol-poly-DL-lactic acid (PEG-PLA) and polyethylene glycol-poly-L-lactic acid (PEG-PLLA), incorporating multiple freeze-dry cycles in the synthesis protocol to ensure their echogenicity. We investigated acoustic behavior with potential applications in biomedical imaging. We characterized the polymeric vesicles acoustically with three different excitation frequencies of 2.25, 5 and 10 MHz at 500 kPa. The polymersomes exhibited strong echogenicity at all three excitation frequencies (about 50- and 25-dB enhancements in fundamental and subharmonic, respectively, at 5-MHz excitation from 20 µg/mL polymers in solution). Unlike echogenic liposomes, they emitted strong subharmonic responses. The scattering results indicated their potential as contrast agents, which was also confirmed by clinical ultrasound imaging.

[Space-Time Estimations and Mapping of PM2.5 Fine Particulates Based on Multi-source Data].

PM2.5 pollution in China has become an extreme environmental and social problem and has generated widespread public concern. We estimate ground-level PM2.5 from satellite-derived aerosol optical depth (AOD), topography data, meteorological data, and pollutant emissions using a new technique, Bayesian maximum entropy (BME) combined with geographically weighted regression (GWR), to evaluate the spatial and temporal characteristics of PM2.5 exposure in an eastern region of China in winter. The overall 10-fold cross-validation R2 is 0.92, and the root mean squared prediction error (RMSE) is 8.32 µg·m-3. The mean prediction error (MPE) of the predicted monthly PM2.5 is -0.042 µg·m-3, the mean absolute prediction error (MAE) is 4.60 µg·m-3. Compared with the results of the Geographically Weighted Regression model-GWR (R2=0.71, RMSE=15.68 µg·m-3, MPE=-0.095 µg·m-3, MAE=11.14 µg·m-3), the prediction by the BME were greatly improved. In this location, the high PM2.5concentration area is mainly concentrated in North China, the Yangtze River Delta, and Sichuan Basin. The low concentration area is mainly concentrated in the south of China, including the Pearl River Delta and southwest of Yunnan. Temporally, there is migration trend from the coastal areas inland, and PM2.5 pollution is most serious in December 2015 and January 2016. It is relatively low in November 2015 and February 2016.