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Abstract Background Neoadjuvant chemotherapy may be considered for patients with ovarian cancer (OC) whose tumors are deemed unlikely to be completely cytoreduced to no gross residual disease (R0) or who are poor surgical candidates. This Ib/II study was designed to assess the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus carboplatin as neoadjuvant chemotherapy for stages III–IV, unresectable OC. Methods Eligible patients with stage III–IV, unresectable OC were enrolled in this phase Ib/II study. All patients received neoadjuvant nab-paclitaxel (260 mg/m2, day 1, every 3 weeks) plus carboplatin (AUC 5, day 1, every 3 weeks) for 3 cycles before surgery, followed by 3–6 cycles of adjuvant chemotherapy. The phase Ib primary endpoint was safety; the phase II primary endpoint was the R0 resection rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety (for all populations). Results Sixty-two patients were enrolled and were given neoadjuvant therapy treated between October 2019 and December 2020, of whom 9 were in the phase Ib portion and 53 in the phase II portion. A total of 53 patients underwent surgery with an R0 resection rate of 73.6% (95% CI, 59.7–84.7%). With a median follow-up of 17.5 (range 0.7–36.7) months, for all patients, the best ORR was 83.9% (95% CI, 71.7–92.4%) with 47 partial responses, the median PFS was 18.6 (95% CI, 13.8–23.3%) months, and median OS was not reached. During the neoadjuvant chemotherapy, treatment-related adverse events (TRAEs) of any grade occurred in 91.9% (57/62) of all patients. The most common hematologic TRAEs were neutropenia (55/62, 88.7%), and non-hematologic toxicity was alopecia (36/62, 58.1%). Forty-nine patients (79.0%) experienced at least one grade 3–4 TRAEs, with the most common was neutropenia (44/62, 71.0%). Besides, delays in neoadjuvant chemotherapy and surgery due to AEs were observed in 9 (1 in phase Ib; 8 in phase II) and 7 (phase II) patients, respectively. Conclusions The study demonstrated an encouraging efficacy and manageable safety profile of neoadjuvant chemotherapy nab-paclitaxel plus carboplatin in stage III-IV, unresectable OC. In addition, AEs resulting in chemotherapy and surgery delays should be cautiously considered in this clinical setting. Trial registration ClinicalTrials.gov, ChiCTR1900026893. Registered at 25 October 2019.

Abstract Background This study aimed to establish a consensus on the delineation of target volumes for neoadjuvant radiation therapy (nRT) in esophageal squamous cell carcinoma (ESCC) within China. Methods From February 2020 to June 2021, nine ESCC patients who received nRT were retrospectively selected from Sun Yat-sen University Cancer Center and Shandong Cancer Hospital. A panel from eight cancer radiotherapy centers performed two rounds of nRT target volume delineation for these patients: the first round for cases 1–6 and the second for cases 7–9. Online meetings were held after each delineation round to discuss findings. The consistency of delineations across centers was compared using mean undirected Hausdorff distances (Hmean), dice similarity coefficients (DSC), and total volumes, analyzed with the Mann-Whitney U test. Results The second round of delineations showed improved consistency across centers (total clinical target volume (CTVtotal): mean DSC = 0.76–0.81; mean Hmean = 2.11–3.14 cm) compared to the first round (CTVtotal: mean DSC = 0.63–0.64; mean Hmean = 5.66–7.34 cm; DSC and Hmean: P

The GRACE and GRACE Follow-On (GFO) missions, led by American and German teams, along with the European mission Swarm, have revolutionized the study of Earth's dynamic gravity field through precise measurements. Our objective is to fill the data GRACE gaps and the gap between GRACE and GFO missions using Swarm data, focusing on Africa. We utilized data from GRACE processing centers (CSR, GFZ, and JPL), Swarm data from the Czech Academy of Sciences (ASU) and the International Combination Service for Time-variable Gravity (COST-G), QF, as well as IGG data. Both frequency and space domains were examined, evaluating Potential Degree Variances (PDV), harmonic coefficients, Terrestrial Water Storage (TWS), gravity anomaly, and potential/geoid using GRACE, GFO, and Swarm. Results indicated agreement among processing centers for potential degree variances, gravity anomaly, and geoid undulation. However, discrepancies were observed in harmonic coefficients and TWS. To address this, we employed parametric least square adjustment to estimate new Swarm-modified coefficients, selecting Swarm ASU and GRACE/GFO CSR data. Comparison of Singular Spectrum Analysis method (SSA), IGG, and Swarm-modified SHCs during the data gap period exhibited correlation coefficients exceeding 0.86. Overall, the new coefficients significantly improved agreement between original GRACE coefficients and modified coefficients in all aspects.

Abstract Background Radiotherapy (RT) has been identified as a vital treatment for esophageal squamous cell carcinoma (ESCC), while the development of radioresistance remains a major obstacle in ESCC management. The aim of this study was to investigate the effect of NIMA-related kinase 2 (NEK2) on radioresistance in ESCC cells and to reveal potential molecular mechanisms. Methods Human esophageal epithelial cells (HEEC) and human ESCC cell lines were obtained from the Research Center of the Fourth Hospital of Hebei Medical University (Shijiazhuang, China). Cell Counting Kit-8 (CCK-8) and flow cytometry assays were applied to assess the proliferation ability, cell cycle, apoptosis rates, and ROS production of ESCC cells. The colony-forming assay was used to estimate the effect of NEK2 on radiosensitivity. Autophagy was investigated by western blotting analysis, GFP-mRFP-LC3 fluorescence assay, and transmission electron microscopy (TEM). Results In the present study, our results showed that NEK2 was associated with radioresistance, cell cycle arrest, apoptosis, ROS production, and survival of ESCC. NEK2 knockdown could significantly inhibit growth while enhancing radiosensitivity and ROS production in ESCC cells. Interestingly, NEK2 knockdown inhibited ESCC cell autophagy and reduced autophagic flux, ultimately reversing NEK2-induced radioresistance. Mechanistically, NEK2 bound to and regulated the stability of tripartite motif-containing protein 21 (TRIM21). The accumulation of NEK2-induced light chain 3 beta 2 (LC3B II) can be reversed by the knockdown of TRIM21. Conclusion These results demonstrated that NEK2 activated autophagy through TRIM21, which may provide a promising therapeutic strategy for elucidating NEK2-mediated radioresistance in ESCC.

Abstract The presence of a static tilt between the inner core and mantle is an ongoing discussion encompassing the geodynamic state of the inner core. Here, we confirm an approximate 8.5 yr signal in polar motion is the inner core wobble (ICW), and find that the ICW is also contained in the length-of-day variations of the Earth’s rotation. Based on the determined amplitudes of the ICW and its good phase consistency in both polar motion and the length-of-day variations, we infer that there must be a static tilt angle θ between the inner core and the mantle of about 0.17 ± 0.03°, most likely towards ~90°W relative to the mantle, which is two orders of magnitude lower than the 10° assumed in certain geodynamic research. This tilt is consistent with the assumption that the average density in the northwestern hemisphere of the inner core should be greater than that in the other regions. Further, the observed ICW period (8.5 ± 0.2 yr) suggests a 0.52 ± 0.05 g/cm3 density jump at the inner core boundary.

ObjectiveSubthreshold depression (StD)/subsyndromal depression refers to a threatening precursor to depression. Aerobic exercise is a promising self-supportive adjunctive intervention and an effective measure for StD. Our study utilizes regional homogeneity (ReHo) to investigate the impact of aerobic exercise on resting-state brain function.MethodsA total of 78 subjects, aged between 18 and 48 years, (StD group, n = 44; healthy control (HC) group, n = 34) engaged in moderate-intensity aerobic exercise 3–4 times per week for 8 weeks. Resting-state brain function and structural images were acquired before and after the exercise intervention. The ReHo method was employed to analyze abnormal changes in regional brain function, and a correlation analysis was performed using the Patient Health Questionnaire-9 (PHQ-9) and Self-Rating Anxiety Scale (SAS) scores.ResultsThe principal observation reveals synchronous abnormalities in the right anterior cingulate gyrus of the brain in StD subjects compared to HCs at baseline, with these differences dissipating after the implementation of aerobic exercise. After completing the aerobic exercise program, the StD group exhibited a difference in the right middle cingulate gyrus, while the left supplementary motor area (SMA) was altered in the HC group.ConclusionDisparities in neural synchronization are evident between HCs and StD subjects, and the implementation of aerobic exercise intervention can effectively mitigate these distinctions, leading to a significant reduction in depressive symptoms among StD subjects. The primary mechanism of StD symptoms may involve the inhibition of the anterior cingulate gyrus, while the effects of aerobic exercise may be related to the modulation of neural synchronization of emotional reflexes. The discovery of these fMRI evidence findings may offer novel strategies for early detection and intervention in cases of StD.

Summary: Background: Concurrent chemoradiotherapy is the standard nonoperative treatment for locally advanced esophageal squamous cell carcinoma. However, local recurrence is still the main failure pattern, accounting for more than half of all treatment failures, indicating that the sensitivity of radiotherapy still needs to be improved. This trial aimed at demonstrating whether PD-1 inhibitors followed by chemoradiotherapy could promote esophageal tumor vascular normalization, alleviate hypoxia, and thus enhance radiosensitivity and improve local control. Methods: We did a multicenter, single-arm, phase 2 trial in China. Patients with locally advanced esophageal cancer were enrolled in this study. In induction phase, patients received two cycles of sintilimab, paclitaxel and carboplatin once per 21 days. In concurrent phase, patients were treated with five cycles of carboplatin and paclitaxel once per week concurrent with radiotherapy of 50.4Gy delivered in 28 fractions. The primary endpoint was 2-year local control rate. Hypoxia and vessel normalization was assessed before and after induction phase using immunofluorescence and perfusion CT. This trial is registered with ClinicalTrials.gov (NCT03985046). Findings: Seventy-five patients with esophageal cancer were enrolled in this study between October 2019 and April 2021. The median follow-up of surviving patients was 33.6 months (IQR 29.3–35.7). The 2-year local control rate was 81.7% (95% confidence interval, 72.7%–90.7%), which was much higher than that in concurrent chemoradiation only (71.3%) in previous studies. Vascular normalization and hypoxia alleviation were observed in both biopsy specimens and perfusion CT. Interpretation: The addition of induction immunotherapy to standard concurrent chemoradiotherapy could improve radiosensitivity for locally advanced esophageal cancer as non-surgical treatment. New treatment combination led to higher local control rate through promoting vascular normalization and alleviating hypoxia. Our findings suggest that induction immunotherapy followed by concurrent chemoradiotherapy could be a potential option in future treatment. Funding: National Natural Science Foundation of China and Shanghai Rising-Star Program.

Abstract Background Intestinal lymphangiectasia (IL) is a rare protein-losing enteropathy caused by disorders of the intestinal lymphatics. There are only a few case reports and case series concerning the VCE (video capsule endoscopy) findings of IL. This work aimed to evaluate the VCE characteristics of small intestinal mucosal abnormalities in patients with IL, and to investigate the relationship between clinical and VCE characteristics. Methods Consecutive patients with IL who underwent VCE were enrolled in this retrospective study. The cases were classified into the white villi group and non-white villi group according to mucosal abnormalities detected by VCE. Clinical and endoscopic characteristics were investigated and analyzed. Results A total of 98 patients with IL with a median onset age of 26.3 ± 19.2 years were included. VCE revealed the following small intestinal lesions: (i) white villi type (57/98, 58.2%), i.e.: white-tipped or granular villi, white nodular villi or plaques; (ii) non-white villi type (41/98, 41.8%), i.e.: diffused low and round villi; (iii) complications (46/98, 46.9%), i.e.: bleeding, ulcers, protruding or vesicular-shaped lesions, stenosis and lymphatic leakage. A total of 58.2% (57) and 41.8% (41) of the cases were classified into the white villi and non-white villi groups respectively. The percentage of chylothorax in the white villi group was significantly lower than that in the non-white villi group (12/57 vs. 19/41, p = 0.008). In VCE, there were no significant differences in the involved segments and total detected rate of complications between the white villi and non-white villi groups (p > 0.05), while the detected rate of lymphatic leakage in the white villi group was significantly higher than that in the non-white villi group (31.6% vs. 12.2%, p = 0.026). Conclusions Our study evaluated the entire small intestinal mucosal abnormalities of IL by VCE, especially endoscopic complications. IL has specific VCE abnormalities in addition to classical endoscopic findings.

Abstract Background stewart-treves syndrome (STS) is an angiosarcoma associated with chronic lymphedema. Objectives This article analyses the characteristics of twenty-two patients and proposes active intervention in lymphedema and the early diagnosis of STS. Methods Twenty-two patients with STS were diagnosed at the centre over an 11-year period. Clinical manifestations, a series of conventional analyses, and histopathology were used to study these cases retrospectively. Results The age range of 22 patients with STS was 15 to 78 years. The main clinical manifestations included multiple skin and subcutaneous nodules and scattered red or purplish-red rashes in the lymphoedematous limbs. These patients often showed clinical symptoms such as lymphedema, weakness, emaciation, pain, mass, lymphadenopathy and so on. The positive rates of ultrasonography, MRI and radionuclide imaging were 66.7% (6/9), 92.3% (12/13) and 18.2% (2/11), respectively. The main points regarding active intervention in lymphedema and early diagnosis of STS were summarized. Study limitations Since this was a retrospective study, the main points summarized by the author need to be further quantified in clinical work to guide the diagnosis of this kind of disease more conveniently. In addition, further clinical trials are needed to evaluate the role of lymphedema in the occurrence and development of malignant tumors. Conclusions STS can appear in lymphoedematous tissue many years after lymphedema onset. To avoid delays in the diagnosis and therapy of STS, physicians should actively look for signs or symptoms of malignant lymphedema during the follow-up period and promptly manage patients developing problems.

IntroductionFor locally advanced, inoperable esophageal cancer, concurrent chemoradiotherapy (CCRT) becomes the norm. Combining immunotherapy with radiotherapy has been shown to improve efficacy. Circulating tumor DNA (ctDNA) is a strong predictor of effectiveness and tumor recurrence and is indicative of minimal residual disease (MRD). Patients with inoperable stage II-III esophageal squamous cell carcinoma (ESCC) are enrolled in the ECMRD-001 trial to evaluate changes in MRD status before and after CCRT combined with immunotherapy and adjuvant immunotherapy following neoadjuvant immunochemotherapy.Methods and analysisThe ECMRD-001 trial is a prospective cohort study. Eligible patients will receive radical concurrent chemoradiotherapy combined with immunotherapy after neoadjuvant immunochemotherapy, followed by adjuvant immunotherapy for at least one year. Follow-up will be up to three years. MRD-related blood and tissue samples and T-cell immunohistobank related blood and tissue samples collected before, during and after treatment and follow-up will be grouped into sample collection time points. The relationship between MRD status at different time points and treatment efficacy is the primary outcome. Correlation between MRD status and immune microenvironment, radiotherapy dose, and tumor recurrence are the secondary outcomes. Examination of ctDNA mutations is the exploratory outcome.DiscussionctDNA-based MRD may be a potential predictive marker for the efficacy and tumor recurrence of inoperable ESCC patients. Elevated ctDNA-MRD may predict tumor recurrence earlier than imaging. ctDNA-based MRD analysis and ctDNA-based MRD guided diagnosis and treatment should be implemented into clinical practice to improve efficacy and reduce tumor recurrence of inoperable stage II-III ESCC.Trial registrationThe ECMRD-001 study has been registered at ClinicalTrials.gov as NCT05952661 (July 19, 2023), https://classic.clinicaltrials.gov/ct2/show/NCT05952661.

[This corrects the article DOI: 10.1371/journal.pone.0255479.].

Abstract Objectives The NEK2 (never in mitosis gene A-related kinase 2), a serine/threonine kinase involved in chromosome instability and tumorigenesis. Hence, this study aimed to explore the molecular function of NEK2 in esophageal squamous cell carcinoma (ESCC). Methods By available transcriptome datasets (GSE53625 cohort, GSE38129 cohort, and GSE21293 cohort), we analyzed the differentially expressed genes in invading and non-invading ESCC. Subsequently, we evaluated the association between NEK2 expression level and clinical outcomes through Kaplan–Meier analysis method. The quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting (WB) analyses were performed to determine the expression levels of NEK2 mRNA and protein, respectively. We knocked down the NEK2 expression in ESCC cells (ECA109 and TE1), and evaluated the NEK2 biology function associated with ESCC cell proliferation, migration, invasion, and colony formation abilities. Finally, the downstream pathway of NEK2 was analyzed through Gene Set Enrichment Analysis (GSEA) and validated the regulatory mechanism of NEK2 on the potential pathway through WB. Results We found that NEK2 was highly expressed in ESCC cells compared with human esophageal epithelial cells (HEEC) (P

This study addresses the imperative to comprehend gravity shifts resulting from groundwater storage (GWS) variations in the Arabian Peninsula. Despite the critical importance of water resource sustainability and its relationship with gravity, limited research emphasizes the need for expanded exploration. The investigation explores the impact of GWS extraction on the gravity field, utilizing Gravity Recovery and Climate Experiment (GRACE) and Global Land Data Assimilation System (GLDAS) data in addition to validation using the WaterGAP Global Hydrology Model (WGHM). Spanning April 2002 to June 2023, this study predicts GWS trends over the next decade using the Seasonal Autoregressive Integrated Moving Average (SARIMA) model. The comprehensive time-series analysis reveals a significant GRACE-derived groundwater storage (GWS) trend of approximately −4.90 ± 0.32 mm/year during the study period. This trend has a notable impact on the gravity anomaly (GA) values, as observed through the decomposition analysis. The projected GWS indicates a depletion rate of 14.51 km3/year over the next decade. The correlation between GWS and GA is substantial at 0.80, while the GA and rainfall correlation is negligible due to low precipitation rates. Employing multiple linear regression explains 80.61% of the variance in gravity anomaly due to GWS, precipitation, and evapotranspiration. This study investigates climate change factors—precipitation, temperature, and evapotranspiration—providing a holistic understanding of the forces shaping GWS variations. Precipitation and evapotranspiration exhibit nearly equal values, limiting GWS replenishment opportunities. This research holds significance in studying extensive GWS withdrawal in the Arabian Peninsula, particularly concerning crust mass stability.

Over the past two decades, the Gravity Recovery and Climate Experiment (GRACE) satellite mission and its successor, GRACE-follow on (GRACE-FO), have played a vital role in climate research. However, the absence of certain observations during and between these missions has presented a persistent challenge. Despite numerous studies attempting to address this issue with mathematical and statistical methods, no definitive optimal approach has been established. This study introduces a practical solution using Linear Regression Analysis (LRA) to overcome data gaps in both GRACE data types—mascon and spherical harmonic coefficients (SHCs). The proposed methodology is tailored to monsoon patterns and demonstrates efficacy in filling data gaps. To validate the approach, a global analysis was conducted across eight basins, monitoring changes in total water storage (TWS) using the technique. The results were compared with various geodetic products, including data from the Swarm mission, Institute of Geodesy and Geoinformation (IGG), Quantum Frontiers (QF), and Singular Spectrum Analysis (SSA) coefficients. Artificial data gaps were introduced within GRACE observations for further validation. This research highlights the effectiveness of the monsoon method in comparison to other gap-filling approaches, showing a strong similarity between gap-filling results and GRACE’s SHCs, with an absolute relative error approaching zero. In the mascon approach, the coefficient of determination (R2) exceeded 91% for all months. This study offers a readily usable gap-filling product—SHCs and smoothed gridded observations—with accurate error estimates. These resources are now accessible for a wide range of applications, providing a valuable tool for the scientific community.

Abstract Background This study aimed to investigate the potential prognostic value of DNA damage repair genes (DDRGs) in esophageal squamous cell carcinoma (ESCC) and their relationship with immune-related characteristics. Methods We analyzed DDRGs of the Gene Expression Omnibus database (GSE53625). Subsequently, the GSE53625 cohort was used to construct a prognostic model based on least absolute shrinkage and selection operator regression, and Cox regression analysis was used to construct a nomogram. The immunological analysis algorithms explored the differences between the potential mechanism, tumor immune activity, and immunosuppressive genes in the high- and low-risk groups. Of the prognosis model-related DDRGs, we selected PPP2R2A for further investigation. Functional experiments were conducted to evaluate the effect on ESCC cells in vitro. Results A 5-DDRG (ERCC5, POLK, PPP2R2A, TNP1 and ZNF350) prediction signature was established for ESCC, stratifying patients into two risk groups. Multivariate Cox regression analysis showed that the 5-DDRG signature was an independent predictor of overall survival. Immune cells such as CD4 T cells and monocytes displayed lower infiltration levels in the high-risk group. Additionally, the immune, ESTIMATE, and stromal scores in the high-risk group were all considerably higher than those in the low-risk group. Functionally, knockdown of PPP2R2A significantly suppressed cell proliferation, migration and invasion in two ESCC cell lines (ECA109 and TE1). Conclusion The clustered subtypes and prognostic model of DDRGs could effectively predict the prognosis and immune activity of ESCC patients.

Abstract Background Radioresistance is a major cause of treatment failure in esophageal squamous cell carcinoma (ESCC) radiotherapy, and the underlying mechanisms of radioresistance are still unclear. Irradiation (IR) stimulates changes in tumor-derived exosome contents, which can be taken up by recipient cells, playing an important role in the proliferation, cell cycle and apoptosis of recipient cells. This study investigated the effect of IR-induced exosomal high mobility group box 1 (HMGB1) on radioresistance in ESCC cells. Methods Plasma exosomes were isolated from 21 ESCC patients and 24 healthy volunteers, and the expression of HMGB1 was examined. Then, the therapeutic effect of radiotherapy was analyzed according to the different expression levels of plasma exosomal HMGB1 in ESCC patients. The uptake of exosomes by recipient cells was verified by immunofluorescence staining, and the localization of exosomes and HMGB1 in cells before and after IR was evaluated. The effects of IR-induced exosomes on cell proliferation, invasion, apoptosis, cell cycle distribution and radioresistance after HMGB1 knockdown were verified. Moreover, western blotting was used to measure changes in the expression of cyclin B1, CDK1, Bax, Bcl2, phosphorylated histone H2AX and the PI3K/AKT/FOXO3A pathway in the HMGB1-knockdown exosome group and the negative control group. Results The expression of HMGB1 in ESCC plasma exosomes was significantly increased compared with that in healthy volunteers, and high expression of HMGB1 in plasma exosomes was associated with radioresistance (P = 0.016). IR-induced the release of exosomal HMGB1 and promoted proliferation and radioresistance in recipient cells, with a sensitization enhancement ratio (SER) of 0.906 and 0.919, respectively. In addition, IR-induced exosomal HMGB1 promotes G2/M phase arrest by regulating the proteins cyclin B1 and CDK1, cooperating with the proteins Bax and Bcl2 to reduce the apoptosis rate through the PI3K/AKT/FOXO3A signaling pathway, and participated in IR-induced DNA damage repair through γH2AX. Conclusion These findings indicate that high expression of plasma exosomal HMGB1 is associated with an adverse radiotherapy response. IR-induced exosomal HMGB1 enhances the radioresistance of ESCC cells.

Objective: To explore the clinical and imaging characteristics and application value CT lymphangiography (CTL) in patients with different types of primary intestinal lymphangiectasia (PIL). Methods: Patients diagnosed as PIL in our center were recruited in this retrospective study from January 2016 to December 2019, All CTL data were blindly reviewed by two radiologists separately, and the evaluation indicators included: sex, onset age, symptoms and signs, serum albumin, wall thickening, serous cavity effusion, abnormal distribution of lymphatics, lymph reflux, lymph nodes, fistula and abnormal lymphatics around neck area. Based on the abnormal lymphatics in intestinal wall and/or mesentery, PIL was classified into type Ⅰ (positive type) and type Ⅱ (negative type). The clinical and imaging features were compared between the two groups. Results: 34 PIL patients were recruited in this study, including 15 cases of Ⅰ and 19 cases of Ⅱ. Type I showed older age of first onset (15.3±9.4 vs. 8.3±3.8), higher rate of diarrhea, and lower rate of limb and/or facial edema than type Ⅱ, with no statistical difference in sex and serum albumin. For imaging features comparisons, type Ⅰ demonstrated higher rate of abnormal dilated lymphatics and fistula, lower rate of increased attenuation of mesentery and lymph nodes, while no statistical difference was found between wall thickening, serous cavity effusion, lymph reflux and abnormal dilated lymphatics around neck area. Conclusion: CTL demonstrated capability of evaluation in detection of location, distribution and range of abnormal lymphatics in PIL. Based on CTL, the imaging classification of PIL was proposed. Different types of PIL showed different clinical and imaging features, which was useful for therapeutic adoptions.

ObjectiveThis systematic review and meta-analysis aimed to investigate the role of neoadjuvant immunochemotherapy with or without radiotherapy [NIC(R)T] compared to traditional neoadjuvant therapies, without immunotherapy [NC(R)T].Summary background dataNCRT followed by surgical resection is recommended for patients with early-stage esophageal cancer. However, it is uncertain whether adding immunotherapy to preoperative neoadjuvant therapy would improve patient outcomes when radical surgery is performed following neoadjuvant therapy.MethodsWe searched PubMed, Web of Science, Embase, and Cochrane Central databases, as well as international conference abstracts. Outcomes included R0, pathological complete response (pCR), major pathological response (mPR), overall survival (OS) and disease-free survival (DFS) rates.ResultsWe included data from 5,034 patients from 86 studies published between 2019 and 2022. We found no significant differences between NICRT and NCRT in pCR or mPR rates. Both were better than NICT, with NCT showing the lowest response rate. Neoadjuvant immunotherapy has a significant advantage over traditional neoadjuvant therapy in terms of 1-year OS and DFS, with NICT having better outcomes than any of the other three treatments. There were no significant differences among the four neoadjuvant treatments in terms of R0 rates.ConclusionsAmong the four neoadjuvant treatment modalities, NICRT and NCRT had the highest pCR and mPR rates. There were no significant differences in the R0 rates among the four treatments. Adding immunotherapy to neoadjuvant therapy improved 1-year OS and DFS, with NICT having the highest rates compared to the other three modalities.Systematic Review Registrationhttps://inplasy.com/inplasy-2022-12-0060/, identifier INPLASY2022120060.

Cross-modal correspondence has been consistently evidenced between shapes and other sensory attributes. Especially, the curvature of shapes may arouse the affective account, which may contribute to understanding the mechanism of cross-modal integration. Hence, the current study used the functional magnetic resonance imaging (fMRI) technique to examine brain activity’s specificity when people view circular and angular shapes. The circular shapes consisted of a circle and an ellipse, while the angular shapes consisted of a triangle and a star. Results show that the brain areas activated by circular shapes mainly involved the sub-occipital lobe, fusiform gyrus, sub and middle occipital gyrus, and cerebellar VI. The brain areas activated by angular shapes mainly involve the cuneus, middle occipital gyrus, lingual gyrus, and calcarine gyrus. The brain activation patterns of circular shapes did not differ significantly from those of angular shapes. Such a null finding was unexpected when previous cross-modal correspondence of shape curvature was considered. The different brain regions detected by circular and angular shapes and the potential explanations were discussed in the paper.

ObjectiveIn this work, we studied the clinical effect of liposuction followed by lymphovenous anastomosis (LVAs) for the treatment of breast cancer-related lymphedema (BCRL).MethodsWe analyzed 158 patients with unilateral upper limb BCRL who underwent liposuction followed by LVAs 2–4 months later. Arm circumferences before and 7 days after the combined treatments were prospectively recorded. Circumferences of different upper extremities were measured before the procedure, 7 days after LVAs, and during the follow-ups. Volumes were calculated with the frustum method. During the follow-ups, the conditions of patients’ treated arms, i.e., the frequency of erysipelas episodes and dependence on compression garments, were recorded.ResultsThe mean circumference difference between two upper limbs decreased significantly from M (P25, P75) of 5.3 (4.1, 6.9) preoperatively to 0.5 (−0.8, 1.0) (P

Objective: To explore the application value of CT bilateral lower extremity volume measurement in the grading of secondary lower extremity lymphedema. Materials and methods: Patients with secondary lower extremity lymphedema who were admitted to our hospital and underwent CT of both lower extremities were collected from June 2019 to January 2020. The clinician completed the multiple-circumference measurement of lower extremity within one week of CT scanning, and recorded the volumes of both lower extremities, thighs and calfs obtained by CT bilateral lower extremity volume measurement and clinical multiple-circumference method, respectively. Based on the percentage enlargement in the volume of the affected side compared with the healthy side, the grading of the whole lower extremity, thigh and calf was obtained by CT and clinical measurement results,respectively. Kappa analysis was used to compare the consistency between CT and clinical in the grading of whole lower extremity. Results: Thirty-eight patients were finally enrolled. The volumes of lower extremities measured respectively by CT bilateral lower extremity volume measurement and clinical multiple-circumference method were (cm3): the affected side (9984±2217 and 11308±2373), the healthy side (7154±1417 and 8265±1704). The CT grading of whole lower extremity was 1 case in preclinical stage, 6 cases of mild, 14 cases of moderate, and 17 cases of severe. The clinical grading of whole lower extremity was 1 case in preclinical stage, 8 cases of mild, 11 cases of moderate, and 18 cases of severe. The consistency between CT and clinical in grading of whole lower extremity is excellent (Kappa=0.878). Conclusion: CT bilateral lower extremity volume measurement can be used as an imaging tool in the grading of secondary lower extremity lymphedema.

The Gravity Recovery and Climate Experiment (GRACE) provided valuable insights into variations in Groundwater Storage (GWS). However, the sensitivity of utilizing Global Positioning System (GPS) time series displacement data for detecting changes in GWS remains a subject of ongoing discussion. In order to estimate the spatiotemporal GWS, we selected a vertical displacement from 65 GPS stations located in the Main Karoo Aquifer (MKA). We performed total water storage (TWS) inversion on GPS vertical displacement components; after that, we deducted surface water components based on the Global Land Data Assimilation System (GLDAS) from January 2013 to December 2021. Additionally, for validation, we compared our GWS estimates with the GRACE-derived GWS and observed GWS values derived from the WaterGAP Global Hydrology Model (WGHM) compartments. We discovered that the TWS and GWS trends derived from GPS and GRACE exhibited similar behaviors with trend values overestimated by GRACE and WGHM. Our findings demonstrate relatively typical behavior between GPS and GRACE in the first and second principal component behaviors (PCs) and empirical orthogonal function (EOF) loadings (or spatial patterns). With a contribution of 71.83% to GPS-derived GWS variability and 68.92% to GRACE-derived GWS variability, EOF-1 is a relatively potent factor. For Principal Components PC1 and PC2, the GRACE and GPS PCs have correlation coefficients of 0.75 and 0.84, respectively. Finally, with higher temporal resolution, GPS can perform the same task as GRACE in hydrological applications. In addition, GPS can add important and valuable information to assess regional GWS change.

Abstract Background Lymphedema is a progressive, noncurable condition consisting of increases in subcutaneous fat and interstitial fluid in the limbs and fibrosis during later stages. The disease most commonly affects the limbs following injury to or removal of the lymph nodes. The aim of this study was to investigate the therapeutic outcomes of liposuction for cancer-related lower extremity lymphedema. Methods Sixty-two patients with cancer-related lymphedema in the unilateral lower extremity were recruited for this study, and all patients underwent liposuction. The volume of hemorrhage and lipids, the operation time, and the volume changes of the affected extremity were compared by applying the t tests, and the subjective feelings of patients were compared with the chi-square tests. Results The total lipid volume was 2539 ± 1253.5 ml, and the hemorrhage volume was 828 ± 311.8 ml. For the comparison of objective indices, (1) the percent volume differences (PVDs) before surgery, intraoperatively, and at the 3-month follow-up were 5.5 ± 12.2 vs. 11.6 ± 18.4 vs. 43.2 ± 23.7, P < 0.05, respectively; (2) greater lipid volumes and higher liposuction rates were observed for female patients, as was a smaller volume of hemorrhage; (3) greater hemorrhage volumes were observed in patients with a history of recurrent erysipelas; and (4) greater lipid volumes and liposuction rates (LRs) and smaller hemorrhage volumes were observed for stage II than for stage III patients. Conclusions Liposuction is an effective therapy for cancer-related lower extremity lymphedema. Sex, stage, and recurrent erysipelas history influence the course and effect of liposuction.

Abstract Lymphatic system is identified the second vascular system after the blood circulation in mammalian species, however the research on lymphatic system has long been hampered by the lack of comprehensive imaging modality. Nanomaterials have shown the potential to enhance the quality of lymphatic imaging due to the unparalleled advantages such as the specific passive targeting and efficient co-delivery of cocktail to peripheral lymphatic system, ease molecular engineering for precise active targeting and prolonged retention in the lymphatic system of interest. Multimodal lymphatic imaging based on nanotechnology provides a complementary means to understand the kinetics of lymphoid tissues and quantify its function. In this review, we introduce the established approaches of lymphatic imaging used in clinic and summarize their strengths and weaknesses, and list the critical influence factors on lymphatic imaging. Meanwhile, the recent developments in the field of pre-clinical lymphatic imaging are discussed to shed new lights on the design of new imaging agents, the improvement of delivery methods and imaging-guided surgery strategies. Graphical Abstract

The development of remote frequency transfer techniques, especially the appearance of optical clocks with unprecedented stability, has prompted geoscientists to study their applications in geodesy. Using remote frequency transfer technique, by frequency comparison of two optical clocks at two points P and Q connected by optical fibers, one can measure the signal's frequency shift between them, and the geopotential difference between them can be determined based on the gravity frequency shift equation. Given the orthometric height of P, the orthometric height of Q can be determined. Since the present stability of the optical clock has achieved 1 × 10−18 or better and comparing the frequency transfer via optical fiber provides stability at 10−19 level, the optical clock network enables determining the orthometric height at centimeter-level. This study provides a formulation to determine the height difference at one-centimeter level between two points on the ground based on the optical fiber frequency transfer technique.

ObjectiveThis study aimed to analyze whether involved field irradiation (IFI) is associated with improving survival outcomes and reducing adverse events compared with elective nodal irradiation (ENI) in patients of esophageal cancer who underwent definitive radiotherapy or chemoradiotherapy.Summary background dataRadiotherapy plays an important role for not surgery patients. However, the role of radiation target size is still uncertain.MethodsWe searched Web of Science, Embase, PubMed, and Cochrane Central for English and non-English publications comparing esophageal cancer patients who received radiotherapy with IFI with those with ENI. Primary outcomes included overall survival (OS) and adverse events related to radiotherapy. The risk of bias was assessed using the Cochrane Risk of Bias tool for randomized studies and the Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality Standard for non-randomized studies. We evaluated the certainty of evidence by Grading of Recommendations, Assessment, Development, and Evaluation.ResultsTotally, 23 studies with 4120 patients were included. IFI group demonstrated significant improvement in the OS rates at 5 years, but not at 1, 2, and 3 years, compared with the ENI group (pooled Risk Ratio [RR], 0.78; 95% confidence interval [CI], 0.68–0.90; P = 0.0004; high certainty). In addition, IFI demonstrated a significant decrease in the incidence of grade ≥2 acute esophagitis (AE) (pooled RR, 0.79; 95% CI, 0.69–0.90; P = 0.0005; high certainty) and grade ≥3 AE (pooled RR, 0.51; 95% CI, 0.38–0.69; P < 0.00001; high certainty) compared with ENI, but not in the incidence of grades ≥3 acute pneumonia, late esophagitis, and late pneumonia.ConclusionsCompared to ENI, IFI demonstrated significant improvement in OS at 5 years. The addition of intensity-modulated radiotherapy (IMRT) to IFI increased the 5-year OS; however, similar results were not observed with the addition of three-dimensional conformal radiotherapy to IFI and ENI. Furthermore, IFI demonstrated a significant decrease in grade ≥2 and grade ≥3 AE, while IMRT demonstrated no difference in the incidence of grade ≥3 AE. IFI and ENI do not differ in the incidence of grades ≥3 acute pneumonia, late esophagitis, and late pneumonia.

Entrepreneurship has been called “high quality employment” in China. Therefore, universities have paid more attention to entrepreneurship education, which is a crucial element for entrepreneurial success. Based on the theory of “informed intentions” planned behavior and dual cognitive processing theory, this manuscript studies the relationship among entrepreneurial cognition, entrepreneurial intention, recognition perception of university entrepreneurship education, and entrepreneurial behavior from the perspective of mass innovation and mass entrepreneurship in China. The hypotheses are tested using a hierarchical linear regression model based on data from 786 valid questionnaires from more than 400 universities across China. This study finds that student’s entrepreneurial cognition positively affects their entrepreneurial behavior, and entrepreneurial intention plays a mediating role by positively strengthening the relationship between these two, and that the recognition perception of university entrepreneurship education strengthens the positive relationship between entrepreneurial intention and entrepreneurial behavior. These findings provide a new perspective and framework for studying the entrepreneurial cognitive education of university students, and they have certain practical implications for the reform of entrepreneurship education in China.

PurposeThe prognostic effect of postoperative radiotherapy (PORT) on pathological T3N0M0 (pT3N0M0) esophageal squamous cell carcinoma (ESCC) remains inconclusive. This study aimed to retrospectively investigate patterns of failure and whether PORT after R0 resection improves survival in patients with pT3N0M0 ESCC, compared with surgery alone.Patients and methodsThe clinical data of 256 patients with pT3N0M0 ESCC from January 2007 to December 2010 were retrospectively reviewed. The included patients were classified into two groups: the surgery-plus-postoperative radiotherapy group (S + R) and the surgery-alone group (S). Propensity score matching (PSM) was used to create comparable groups that were balanced across several covariates (n = 71 in each group). Statistical analyses were performed using the Kaplan–Meier method and Chi-squared test.ResultsIn the study cohort, the 5- and 10-year overall survival (OS) rates in the S + R group were 53.4% and 38.4%, and those in the S group were 50.3%, 40.9% (p = 0.810), respectively. The 5- and 10-year disease-free survival (DFS) rates in the S + R group were 47.9% and 32.9%, and those in the S group were 43.2%, 24.0% (p = 0.056), respectively. The results were coincident in the matched samples (p = 0.883, 0.081) after PSM. Subgroup analysis showed that patients with upper thoracic lesions in the S + R group had significantly higher OS than patients in the S group (p = 0.013), in addition, patients with upper and middle thoracic lesions in the S + R group had significantly higher DFS than patients in the S group (p = 0.018, 0.049). The results were also confirmed in the matched samples after PSM. The locoregional recurrence between the two groups were significantly different before and after PSM (p = 0.009, 0.002). The locoregional control rate (LCR) in the S + R group was significantly higher than that in the S group before and after PSM (p = 0.015, 0.008).ConclusionPostoperative radiotherapy may be associated with a survival benefit for patients with pT3N0M0 upper thoracic ESCC. A multicenter, randomized phase III clinical trial is required to confirm the results of this study.

We introduce an approach for the direct measurement of the gravitational potential (GP) along the trajectory of a satellite, with a specific focus on Low-Earth Orbit (LEO) satellites. A LEO satellite communicates with several Geosynchronous Equatorial Orbit (GEO) satellites via frequency signal links. The GP difference can be measured in real-time using the gravitational frequency shift approach by equipping both LEO and GEO satellites with precise atomic clocks. Since the GP at the high orbits of the GEO satellites can be precisely determined by the present gravitational field model EGM2008, the GP along the LEO satellite’s trajectory can be determined. In this study, simulation experiments were conducted, featuring a GRACE-type satellite as the LEO satellite in communication with three equidistant GEO satellites. The results indicated that the accuracy of the GP measurements along the LEO satellite’s trajectory primarily depends on the precision of the onboard atomic clocks. Supposing optical atomic clocks attain an instability level of 1×10−17τ−1/2 (τ in seconds), we determined the GP distribution covered by the LEO satellite’s trajectories with 30-day observations. Then, we determined a gravitational field at the centimeter level based on the GP distribution. The GP data derived from the trajectory of a LEO satellite can be utilized to establish temporal gravitational fields, which have broad applications in different disciplines.

The International Association of Geodesy (IAG) aims to establish the International Height Reference System (IHRS) as one of its primary scientific objectives. Central to the realization of the IHRS is global vertical datum unification, which requires the connection of existing local vertical height reference systems (VHS) robustly and consistently. However, conventional methods are not suitable for estimating the offsets between two distant local height systems. In this paper, we propose a framework for connecting two local VHSs using ultraprecise clock frequency signal links between satellites and ground stations, referred to as the satellite frequency signal transmission (SFST) approach. The SFST approach allows for the direct determination of the geopotential and height differences between two ground datum stations without any location restrictions between the two VHSs. The simulation results show that the VHSs of China and the US can be unified with an accuracy of several centimeters, provided that the stability of atomic clocks used on-board the satellite and at on-ground datum locations reaches 4.8×10−17τ−1/2 for an averaging time τ (in seconds). We conclude that the SFST approach shows promise for achieving centimeter-level accuracy in unifying the global vertical height datum and represents a new paradigm for the realization of the IHRS.

Shallow layer method (SLM) based on the definition of the geoid can determine the gravity field inside the shallow layer. In this study, the orthometric height of Mount Everest (HME) is calculated based on SLM, in which the key is to construct the shallow layer model. The top and bottom boundaries of the shallow layer model are the natural surface of the Earth and the surface at a certain depth below the reference geoid, respectively. The model-combined strategies to determine the geoid undulation (N) based on SLM are applied to calculate the HME by two approaches: (1) direct calculation by combining N and geodetic height (h); (2) calculation by the segment summation approach (SSA) using the gravity field inside the shallow layer. On December 8, 2020, the Chinese and Nepalese governments announced an authoritative value of 8848.86 m, which is referred to a geoid determined by the International Height Reference System (IHRS) (i.e., the geopotential is 62636853.4 m2s-2). Here, our results (combined strategies (1) EGM2008 and CRUST1.0, (2) EGM2008 and CRUST2.0, (3) EIGEN-6C4 and CRUST1.0, and (4) EIGEN-6C4 and CRUST2.0) are referred to the geoid defined by WGS84 (i.e., the geopotential is 62636851.7 m2s-2). The differences between our results and the authoritative value (8848.86 m) are 0.448 m, −0.009 m, −0.295 m, and −0.741 m by the first approach, and 0.539 m, 0.083 m, −0.214 m, and −0.647 m by the second approach. When the reference surface WGS84 geoid is converted to the IHRS geoid, the differences are 0.620 m, 0.163 m, −0.123 m, and −0.569 m by the first approach, and 0.711 m, 0.225 m, −0.042 m, and −0.475 m by the second approach.

In constructing modern Earth model, Earth's interior layered structure is mainly determined according to seismic data; while the density and elastic parameters of the interior Earth, especially the large-scale structure of the density distribution below the mantle, are mainly determined according to the Earth's free oscillation observations. This paper summarizes the theories and methods of solving the eigenvalues of normal modes of Earth's free oscillation, introduces the expressions of the displacement fields in spheroidal and toroidal modes, and discusses attenuation, splitting and coupling effects of the free oscillation modes. In addition, this paper summarizes the methods of detecting the splitting spectral lines of multiplets and estimating the corresponding splitting parameters, and reviews the main progress and existing problems in researching the constraints and inversion of the seismic moment tensor, three-dimensional (3D) heterogeneous structure of the Earth and inner core's super rotation by using elastic normal modes. Finally, we discuss the future development trend in studying normal modes of Earth's free oscillation.

ObjectiveTo analyze and compare the efficacy and safety of simultaneous integrated boost intensity-modulation radiation therapy (SIB-IMRT) combined with systematic and standardized management for esophageal cancer.MethodsFrom January 2012 to January 2019, 200 patients with esophageal cancer who received radical chemoradiotherapy in our hospital were treated with lymphatic drainage area radiation prevention combined with systematic and standardized management. According to difference in radiotherapy methods, the patients were divided into local lesion 92 patients treated with simultaneous integrated boost intensity-modulation radiation therapy (SIB-IMRT) combined with systematic standardized management (SIB-IMRT group), and late course boost intensity-modulation radiation therapy (LCB-IMRT) combined with systematic standardized management 108 patients (LCB-IMRT group). The short-term eficacy of the two groups were compared. The dose volume parameters of the organ in danger are evaluated based on the dose volume histogram. The related adverse reactions during chemoradiotherapy were compared between two groups. The local control rate and survival rate were compared between the two groups.ResultsThe recent total effective rates of rats in the SIB-IMRT group and LCB-IMRT group were 95.65% and 90.74%, respectively, and there was no significant difference between the two groups (p > 0.05). The mean doses to left and right lung, heart and spinal cord in the SIB-IMRT group were significantly lower than that in the LCB-IMRT group (p 0.05). The one-year and three-year overall survival rates in the SIB-IMRT group and LCB-IMRT groups were 82.61%, 42.39% and 77.78%, 34.26%, respectively, and the median survival times were 38 and 29 months, respectively. The local control rates in the SIB-IMRT group and LCB-IMRT group in one and three years were 84.78%, 56.52% and 75.93%, 41.67%, respectively. The 3-year local control rate in the SIB-IMRT group was higher than that in the LCB-IMRT group (p 0.05).ConclusionSIB-IMRT combined with systematic and standardized management in the treatment of esophageal cancer can reduce the amount of some organs at risk and improve the local control rate of the lesion.

Background and ObjectiveLiposuction is an effective treatment for fat disposition in lymphedema. Blood transfusion has been seldom investigated in lymphedema liposuction surgery. The purpose of the study was to analyze clinical factors associated with blood transfusion in liposuction surgery of lymphedema patients and compare the autologous and allogeneic transfusion patterns.MethodsA total of 1,187 cases of liposuction due to lymphedema were recruited. Demographic, laboratory tests and operation information were collected. Patients were divided into a transfusion and a non-transfusion group. Different transfusion patterns were compared and analyzed.ResultsBetween the two groups, there is a significant difference in postoperative hemoglobin levels, and as well as gender, age, surgery duration, body weight change, intraoperative transfusion volume and blood loss, hospital length of stay, and surgical site distribution. There is a significant difference in the comparison of hospital stay length, autologous transfusion volume, combined allogeneic volume, operative blood loss, intraoperative transfusion volume, and change in hemoglobin levels between predonation and acute normovolemic hemodilution (ANH) transfusion. In comparison with the allogeneic transfusion-only patients, the mean allogeneic transfusion volume in either ANH group, predonated transfusion group, or mixed group is statistically lower. Allogeneic transfusion volume in the predonated-only group is significantly lower than that of either the ANH-only group or the mixing ANH with predonation group. Ordinary least squares regression analysis suggests that autologous transfusion in the ANH-only mode is statistically associated with allogeneic transfusion.ConclusionsThis study described the blood transfusion in lymphedema liposuction surgery and compared autologous and allogeneic transfusion patterns in these patients. Autologous transfusion can reduce the transfusion volume of allogeneic blood and might be a beneficial mode of transfusion in these patients.

Until now, the calculation of the principal inertia moment of the triaxial three-layered Earth mainly adopts the scaling method. This method assumes that the corresponding principal inertia axes of the layers coincide each other, but this is not the case. In this paper, a rigorous tensor transformation rule is adopted to calculate the principal inertia moments (PIMs) of different layers. Appling the new estimated PIMs to the triaxial three-layered Earth rotation theory with considering various couplings, the numerical calculations show that the periods of the Chandler Wobble (CW), Free Core Nutation (FCN), Free Inner Core Nutation (FICN) and Inner Core Wobble (ICW) are respectively 433.0, 430.8, 943.9 and 2735.9 mean solar days, which are well comparable with the corresponding values accepted at present in geoscience community. Better estimates of the PIMs of different layers may provide better constrains on relevant physical parameters of the Earth's interior.

General relativity theory (GRT) concludes that a precise clock ticks at different running rates if it is under the influence of different geopotentials. Therefore, by comparing the running rates of clocks at arbitrary two stations, the geopotential difference between them can be determined. In this study, with the help of two hydrogen atomic clocks (noted as H-masers), using the two-way satellite time and frequency transfer (TWSTFT) technique, we carried out experiments of the geopotential difference determination at the China Aerospace Science & Industry Corporation (CASIC), Beijing. Here the ensemble empirical mode decomposition (EEMD) method is adopted to remove periodic signals included in the original observations. Finally, the clock-comparison-determined geopotential difference in the experiments is determined. Results show that the difference between the geopotential difference determined by GRT and that determined by measuring tape is about 1316.1 ± 931.0 m2s-2, which is equivalent to 134.3 ± 95.0 m in height, and in consistence with the stability of the H-masers applied in the experiments (at the level of 10−15/day). With the rapid improvement of atomic clocks' accuracy, the geopotential determination by accurate clocks is prospective, and it is promising to realize the unification of the world vertical height system (WVHS).

The Earth is an elastic body, and the surface mass loading changes will lead to elastic loading deformation on the surface of the Earth. In this study, we investigated the surface seasonal mass changes and vertical crustal deformation in North China using the data obtained by the techniques of the Global Positioning System (GPS), Gravity Recovery and Climate Experiment (GRACE) and Surface Loading Models (SLMs). The seasonal annual signal and semi-annual signal obtained by the three techniques show strong correlations. The average value of the weighted root-mean-square (WRMS) of the all 30 sites is 58% after deducting the GRACE-obtained vertical deformation from the GPS-derived vertical deformation. However, the consistency of results between GPS and SLMs is not so good, with a 31% mean WRMS reduction, due to the fact that the global SLMs perform not well in North China. The GRACE-measured long-term trend is deducted from the GPS-obtained vertical rates to reveal the crustal displacement caused by the underground factors such as tectonic movement and groundwater in North China. The results show that the rates of stations HECX and TJBH are very large, more than 10 mm/yr, which suggests that the surface subsidence is caused by excessive exploitation of groundwater. Keywords: Continuous GPS measurement, GRACE measurement, Surface Loading Models, Seasonal mass changes, Vertical crustal displacement

The lymphatic system plays a crucial role in the immune system’s recognition and response to disease. Therefore, the imaging of the lymphatic system, especially lymphatic vessels, has emerged as a valuable tool for the diagnosis of metastasis. FDA-approved small-molecule dyes, namely, indocyanine green (ICG), have been widely applied to lymphatic vessels imaging. However, due to the small physical size, such molecule-based agents show no selectivity, and rapid clearance from lymph nodes. Herein, a biodegradable lymphatic targeting imaging agent based on the ICG-mesoporous silicon system (ICG@HMONs-HA) was obtained, which not only could target lymph vessels but also had a long residence time. The reported work provides a practical way for lymph vessel fluorescence imaging and paves the way for clinical translation of nanomaterial-based tracers.

Applications of optical clocks in physical geodesy for determining geopotential are of increasing interest to scientists as the accuracy of optical clocks improves and the clock size becomes more and more compact. In this study, we propose a data processing method using the ensemble empirical mode decomposition technique to determine the geopotential difference between two sites in Wuhan based on the frequency comparison of two optical clocks. We use the frequency comparison record data of two Ca+ optical clocks based on the optical fiber frequency transfer method, provided by the Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (Wuhan, China). By optical clock comparisons we obtained a geopotential difference of 42.50 ± 1.03 m2∙s−2 (equivalent to height difference of 4.33 ± 0.11 m) between the two sites, which is excellent compared to the geopotential difference of 42.56 ± 0.29 m2∙s−2 (equivalent to height difference of 4.34 ± 0.03 m) measured by a spirit leveling. The results show that the optical fiber frequency transfer method is promising in determining the geopotential and potential for unifying the world height system.

Different modification methods and software programs were developed to obtain accurate local geoid models in the past two decades. The quantitative effect of the main factors on the accuracy of local geoid modeling is still ambiguous and has not been clearly diagnosed yet. This study presents efforts to find the most influential factors on the accuracy of the local geoid model, as well as the amount of each factor's effect quantitatively. The methodology covers extracting the quantitative characteristics of 16 articles regarding local geoid models of different countries. The Statistical Package of Social Sciences (SPSS) software formulated a strong multiple regression model of correlation coefficient r = 0.999 with a high significance coefficient of determination R2 = 0.997 and adjusted R2 = 0.98 for the required effective factors. Then, factor analysis is utilized to extract the dominant factors which include: accuracy of gravity data (40%), the density of gravity data (25%) (total gravity factors is 65%), the Digital Elevation Model (DEM) resolution (16%), the accuracy of GPS/leveling points (10%) and the area of the terrain of the country/state under the study (9%). These results of this study will assist in developing more accurate local geoid models. Keywords: Accuracy of local geoid model, Multiple regression model, Influence factors

The Earth's rotational normal modes depend on Earth model used, including the layer structures, principal inertia moments of different layers and the compliances. This study focuses on providing numerical solution of the rotational normal modes of a triaxial two-layered anelastic Earth model without external forces but with considering the complex forms of compliances and the electromagnetic coupling between the core and mantle. Based on the present knowledge of the Chandler wobble (CW) and Free Core Nutation (FCN), we provide a set of complete compliances which could be used for reference in further investigations. There are eight rotational normal mode solutions, four of which might exist in nature. However, in reality only two of these four solutions correspond to the present motion status of the prograde CW and the retrograde FCN. On one hand, our numerical calculations show that the periods and quality factors (Qs) of CW and FCN are respectively 434.90 and 429.86 mean solar days (d) and 76.56 and 23988.47 under frequency-dependent assumption, and the triaxiality prolongs CW about 0.01 d and has hardly effect on FCN. On the other hand, we analyze the sensibility of compliances and electromagnetic coupling parameter on the periods and Qs of CW and FCN and find the sensitive parameters with respect to them. Keywords: Earth rotation, Triaxial two-layered anelastic Earth model, Compliances, Rotational normal modes, Numerical solution

The global oceanic/atmospheric tides exert decelerating/accelerating secular torques on the Earth rotation. We developed new formulations to accurately calculate amounts of two kinds of secular tidal torques. After Melchior, we found that an additional factor 1+k-l = 1.216, which has been formerly neglected, must be multiplied unto the tidal torque integral. By using our refined formulations and the recent oceanic/atmospheric global tide models, we found that: (i) semidiurnal oceanic lunar/solar tides exert decelerating torques of about −4.462×1016/−0.676×1016Nm respectively and (ii) atmospheric S2 tide exerts accelerating torque of 1.55×1015Nm. Former estimates of the atmospheric S2 tidal torque were twice as large as our estimate due to improper consideration of loading effect. We took the load Love number for atmospheric loading effect from Guo et al. (2004). For atmospheric loading of spherical harmonic degree two, the value of k'=−0.6031 is different from that for ocean loading as k'=−0.3052, while the latter is currently used for both cases – ocean/atmospheric loading – without distinction. We discuss (i) the amount of solid Earth tidal dissipation (which has been left most uncertain) and (ii) secular changes of the dynamical state of the Earth-Moon-Sun system. Our estimate of the solid Earth tidal torque is −4.94×1015Nm. Keywords: Earth rotation, Oceanic and atmospheric tides, Tidal torque, Secular deceleration and acceleration

Filtering for GRACE temporal gravity fields is a necessary step before calculating surface mass anomalies. In this study, we propose a new denoising and decorrelation kernel (DDK) filtering scheme called adaptive DDK filter. The involved error covariance matrix (ECM) adopts nothing but the monthly time-variable released by several data centers. The signal covariance matrix (SCM) involved is monthly time-variable also. Specifically, it is parameterized into two parameters, namely the regularization coefficient and the power index of signal covariances, which are adaptively determined from the data themselves according to the generalized cross validation (GCV) criterion. The regularization coefficient controls the global constraint on the signal variances of all degrees, while the power index adjusts the attenuation of the signal variances from low to high degrees, namely local constraint. By tuning these two parameters for the monthly SCM, the adaptability to the data and the optimality of filtering strength can be expected. In addition, we also devise a half-weight polygon area (HWPA) of the filter kernel to measure the filtering strength of the anisotropic filter more reasonably. The proposed adaptive DDK filter and filtering strength metric are tested based on CSR GRACE temporal gravity solutions with their ECMs from January 2004 to December 2010. Results show that the selected optimal power indices range from 3.5 to 6.9, with the corresponding regularization parameters range from 1 × 1014 to 5 × 1019. The adaptive DDK filter can retain comparable/more signal amplitude and suppress more high-degree noise than the conventional DDK filters. Compared with the equivalent smoothing radius (ESR) of filtering strength, the HWPA has stronger a distinguishing ability, especially when the filtering strength is similar.

Esophageal cancer is a common tumor of the digestive system with poor prognosis. This study was to gain a better understanding of the mechanisms involved in esophageal cancer and to identify new prognostic markers. We downloaded the esophageal cancer miRNA expression profile microarray data (GSE113740, GSE112264, GSE122497, GSE113486, and GSE106817) from the GEO database, extracted the esophageal cancer miRNA sequencing data from The Cancer Genome Atlas (TCGA) database, and then used a bioinformatics approach to select common differentially expressed miRNAs (DEMs). Differentially expressed genes (DEGs) were selected by predicting DEM target genes using the miRWalk database and intersecting with differential genes obtained from TCGA database for esophageal cancer. The STRING database was used to obtain protein-protein interaction (PPI) relationships to construct the DEM-DEG network. Furthermore, we selected core genes and core miRNAs associated with esophageal cancer prognosis by performing survival and univariate/multivariate COX analysis on DEMs and DEGs in the network and performed GSEA analysis on core genes alone, and finally the expression of the markers was verified by qPCR in esophageal cancer cell lines Eca109, SKGT-4 and normal esophageal epithelial cells HEEC. Nine DEMs were obtained, of which three were upregulated and six were downregulated, and 326 DEGs were obtained, of which 105 were upregulated and 221 were downregulated. Survival univariate/multivariate COX analysis revealed that five genes, ZBTB16, AQP4, ADCYAP1R1, PDGFD, and VIPR2, and two microRNAs, miR-99a-5p, and miR-508-5p, were related to esophageal cancer prognosis. GSEA analysis showed that the following genes may be involved in esophageal cancer prognosis: ZBTB16 may through the MTOR signaling pathway, AQP4 through the GNRH signaling pathway, ADCYAP1R1 through the PPAR signaling pathway, VIPR2 through the P53 signaling pathway and PDGFD through the PENTOSE-PHOSPHATE signaling pathway.

Exercise is believed to have significant cognitive benefits. Although an array of experimental paradigms have been employed to test the cognitive effects on exercising individuals, the mechanism as to how exercise induces cognitive benefits in the brain remains unclear. This study explores the effect of dynamic neural network processing with the classic Go/NoGo task with regular exercisers. We used functional magnetic resonance imaging to analyze the brain activation of areas involved in executive function, especially inhibitory control. Nineteen regular joggers and twenty-one subjects as a control group performed the task, and their brain imaging data were analyzed. The results showed that at the attentive visual period, the frontal and parietal areas, including the prefrontal cortex, putamen, thalamus, lingual, fusiform, and caudate, were significantly enhanced in positive activities than the control group. On the other hand, in the following inhibitory control processing period, almost the same areas of the brains of the exercise group have shown stronger negative activation in comparison to the control group. Such dynamic temporal response patterns indicate that sports augment cognitive benefits; i.e., regular jogging increases the brain’s visual attention and inhibitory control capacities.

The continuing impact between the Eurasia Plate and India results in the thickening and shortening of the N-S Tibetan Plateau. There has been strong tectonic movement along the boundary of the zones of deformation of the NE corner of the Tibetan plateau (NET) since the new tectonic period, with its dynamic mechanisms remaining controversial. Here, we use observations of 39 Continuous Global Positioning System (CGPS) gauges and 451 Crustal Movement Observation Network of China (CMONOC) campaign-mode stations to detect the three-dimensional deformation of the crust in the NET. Improved processing procedures are implemented to strengthen the patterns of strain throughout the NET. The principal component analysis (PCA) technique is introduced to decompose the time series into spatial eigenvectors and principal components (PCs), and the first three PCs are used to estimate and rectify common mode errors (CMEs). In addition, GRACE observations are used to detect deformation changes that account for non-tidal oceanic mass loading, hydrological loading, and surface pressure. The rectified deformation of the crust indicates the anisotropic nature of both the subsidence and uplift, and that the highest uplift rate of the Longmen Shan fault uplift reaches 7.13 ± 0.53 mm/yr. Finally, the horizontal velocity is further used to enumerate the strain rates throughout the NET. The results show that the shear band retained property in line with the strike-slip fault along the Altyn Tagh fault, the Qilian Shan faults, the Haiyuan fault, the West Qinling fault, the East Kunlun fault, and the Longmen Shan fault. In addition, the results further indicate that the whole NET shows a strong relationship with the mean principal rates of horizontal shortening strain. Extension and compression of the crust reasonably describe its sinking and uplifting.

Aim: To evaluate long-term outcome and prognostic factors of stage III esophageal cancer after definitive radiotherapy using three dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) techniques.Methods: Patients with T3N1M0/T4N0-1M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy from 2002 to 2016 in 10 Chinese medical centers were retrospectively analyzed. Overall survival (OS) and progression-free survival (PFS) rates were calculated. Prognostic factors were analyzed by Log-rank test and multivariable Cox model.Results: Survival data of 1,450 patients were retrospectively collected. With a median follow-up time of 65.9 months, 1-, 3-, and 5-year OS rates were 69.3, 36.7, and 27.7%, respectively, and PFS rates were 58.6, 32.7, and 27.4%, respectively. Univariable analyses showed that gender, age, lesion location, lesion length, largest tumor diameter, lymph node metastasis, gross tumor volume, EQD2, short-term response, and concurrent chemotherapy were prognostic factors for OS. Multivariable analyses showed that lesion location, T-classification, GTV size, EQD2, and short-term response to RT were independent prognostic factors for OS, and tumor diameter, GTV size, and short-term response were independent prognostic factors for PFS.Conclusions: This study demonstrated that definitive radiotherapy using 3DCRT and IMRT provides promising outcomes for locally advanced ESCC.

Porous organic polymers have an open architecture, excellent stability, and tunable structural components, revealing great application potential in the field of fluorescence imaging, but this part of the research is still in its infancy. In this study, we aimed to tailor the physical and chemical characteristics of indocyanine green using sulfonic acid groups and conjugated fragments, and prepared amino-grafted porous polymers. The resulting material had excellent solvent and thermal stability, and possessed a relatively large pore structure with a size of 3.4 nm. Based on the synergistic effect of electrostatic bonding and π–π interactions, the fluorescent chromogenic agent, indocyanine green, was tightly incorporated into the pore cavity of POP solids through a one-step immersion method. Accordingly, the fluorescent chromogenic POP demonstrated excellent imaging capabilities in biological experiments. This preparation of fluorescent chromogenic porous organic polymer illustrates a promising application of POP-based solids in both fluorescence imaging and biomedicine applications.

According to general relativity theory (GRT), the clock at a position with lower geopotential ticks slower than an identical one at a position with higher geopotential. Here, we provide a geopotential comparison using a non-transportable hydrogen clock and a transportable hydrogen clock for altitude transmission based on the two-way satellite time and frequency transfer (TWSTFT) technique. First, we set one hydrogen clock on the fifth floor and another hydrogen clock on the ground floor, with their height difference of 22.8 m measured by tape, and compared the time difference between these two clocks by TWSTFT for 13 days. Then, we set both clocks on the ground floor and compared the time difference between the two clocks for seven days for zero-baseline calibration (synchronization). Based on the measured time difference between the two clocks at different floors, we obtained the height difference 28.0 ± 5.4 m, which coincides well with the tape-measured result. This experiment provides a method of height propagation using precise clocks based on the TWSTFT technique.