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Funding Information: This work was supported by a research grant from the German Federal Ministry of Education and Research ( BMBF ) (GCBS grant 01EE1501 ). TP Mutanen has been funded by the Academy of Finland, Finland (Grant No. 321631 ). Publisher Copyright: © 2023 The Authors Neurophysiological effects of transcranial direct current stimulation (tDCS) have been extensively studied over the primary motor cortex (M1). Much less is however known about its effects over non-motor areas, such as the prefrontal cortex (PFC), which is the neuronal foundation for many high-level cognitive functions and involved in neuropsychiatric disorders. In this study, we, therefore, explored the transferability of cathodal tDCS effects over M1 to the PFC. Eighteen healthy human participants (11 males and 8 females) were involved in eight randomized sessions per participant, in which four cathodal tDCS dosages, low, medium, and high, as well as sham stimulation, were applied over the left M1 and left PFC. After-effects of tDCS were evaluated via transcranial magnetic stimulation (TMS)-electroencephalography (EEG), and TMS-elicited motor evoked potentials (MEP), for the outcome parameters TMS-evoked potentials (TEP), TMS-evoked oscillations, and MEP amplitude alterations. TEPs were studied both at the regional and global scalp levels. The results indicate a regional dosage-dependent nonlinear neurophysiological effect of M1 tDCS, which is not one-to-one transferable to PFC tDCS. Low and high dosages of M1 tDCS reduced early positive TEP peaks (P30, P60), and MEP amplitudes, while an enhancement was observed for medium dosage M1 tDCS (P30). In contrast, prefrontal low, medium and high dosage tDCS uniformly reduced the early positive TEP peak amplitudes. Furthermore, for both cortical areas, regional tDCS-induced modulatory effects were not observed for late TEP peaks, nor TMS-evoked oscillations. However, at the global scalp level, widespread effects of tDCS were observed for both, TMS-evoked potentials and oscillations. This study provides the first direct physiological comparison of tDCS effects applied over different brain areas and therefore delivers crucial information for future tDCS applications.

Metabolic profiling using nonsputum samples has demonstrated excellent performance in diagnosing infectious diseases. But little is known about the lipid metabolism alternation in children with tuberculosis (TB). Therefore, the study was performed to explore lipid metabolic changes caused by Mycobacterium tuberculosis infection and identify specific lipids as diagnostic biomarkers in children with TB using UHPLC-MS/MS. Plasma samples obtained from 70 active TB children, 21 non-TB infectious disease children, and 21 healthy controls were analyzed by a partial least-squares discriminant analysis model in the training set, and 12 metabolites were identified that can separate children with TB from non-TB controls. In the independent testing cohort with 49 subjects, three of the markers, PC (15:0/17:1), PC (17:1/18:2), and PE (18:1/20:3), presented with high diagnostic values. The areas under the curve of the three metabolites were 0.904, 0.833, and 0.895, respectively. The levels of the altered lipid metabolites were found to be associated with the severity of the TB disease. Taken together, plasma lipid metabolites are potentially useful for diagnosis of active TB in children and would provide insights into the pathogenesis of the disease.

The difference in equilibrium cations of the two compounds results in a big distinction in the dense hydrogen grid. This distinction further leads to the disparity in the proton conductivity of both compounds.

Preparation of HFH-COF and its application for HPLC-MS/MS of MCs.

A graphene-base hot electron transistor integrated with a 2D material heterojunction is demonstrated as a frequency modulator. Our device can operate as a doubler or tripler with AC signals from 100 kHz to 10 MHz in single tunneling transistor.

Knowledge graphs have been introduced into recommender systems due to the rich connectivity information. Many knowledge-aware recommendation methods use graph neural networks (GNNs) to capture the high-order structural and semantic information of knowledge graphs. However, previous GNN-based methods have the following limitations: (1) they fail to make full use of the neighborhood information of entities and (2) they ignore the importance of user interaction sequences on reflecting user preferences. As such, these models are insufficient for generating accurate representations of users and items. In this study, we propose a Knowledge-aware Hierarchical Attention Network (KHAN) to provide better recommendation. Specifically, the proposed model mainly consists of an item encoder and a user encoder. The item encoder is equipped with a hierarchical attention network, which is used to generate entity (item) representations by carefully aggregating neighborhood information of entities. The user encoder is also designed to learn more informative user representations from user interaction sequences using multi-head self-attention. The learned user representations are then combined with user representations introduced in the item encoder through a gating mechanism to generate the final user representations. Extensive experiments on two real-world datasets about movie and restaurant recommendation demonstrate the effectiveness of our model.

Diffuse large B cell lymphoma, not otherwise specified (DLBCL, NOS) is the most common type of non-Hodgkin lymphoma (NHL). The 2016 World Health Organization (WHO) classification defined DLBCL, NOS and its subtypes based on clinical findings, morphology, immunophenotype, and genetics. However, even within the WHO subtypes, it is clear that additional clinical and genetic heterogeneity exists. Significant efforts have been focused on utilizing advanced genomic technologies to further subclassify DLBCL, NOS into clinically relevant subtypes. These efforts have led to the implementation of novel algorithms to support optimal risk-oriented therapy and improvement in the overall survival of DLBCL patients. We gathered an international group of experts to review the current literature on DLBCL, NOS, with respect to genomic aberrations and the role they may play in the diagnosis, prognosis and therapeutic decisions. We comprehensively surveyed clinical laboratory directors/professionals about their genetic testing practices for DLBCL, NOS. The survey results indicated that a variety of diagnostic approaches were being utilized and that there was an overwhelming interest in further standardization of routine genetic testing along with the incorporation of new genetic testing modalities to help guide a precision medicine approach. Additionally, we present a comprehensive literature summary on the most clinically relevant genomic aberrations in DLBCL, NOS. Based upon the survey results and literature review, we propose a standardized, tiered testing approach which will help laboratories optimize genomic testing in order to provide the maximum information to guide patient care.

Polycyclic aromatic hydrocarbons (PAHs) are among the most harmful persistent organic pollutants that possess high carcinogenicity and teratogenicity; hence, establishing a highly sensitive analytical method for monitoring PAHs in environmental samples is an urgent need. However, due to the low PAHs content in environmental samples and the complex matrix of the samples, it is difficult to directly determine the amount of PAHs using the existing analytical instruments. Therefore, an essential pretreatment of environmental samples should be carried out before instrumental analysis. In most pretreatment techniques, the extraction efficiency depends on the characteristics of the extraction materials. Currently, metal-organic framework materials (MOFs), which are porous materials self-assembled by metal ions and organic ligands, are used as solid-phase microextraction (SPME) coating materials for the extraction of PAHs. However, the following problems limit the application of MOFs in the SPME field: (1) MOF coating materials often require a long equilibration time for extraction because the it is difficult for the target to reach the deep adsorption sites; (2) In addition, most MOFs are formed by the coordination of single metal ions with organic monomers. The single type of open metal active sites is not conducive for realizing high extraction performance. In this study, a hollow bimetal-organic framework (H-BiMOF) was synthesized by the solvothermal method and characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), nitrogen adsorption-desorption analysis, thermogravimetric analysis, etc. The TEM images and XRD patterns demonstrated the successful synthesis of H-BiMOF with a hollow structure, which was formed through the competitive coordination between benzoic acid and water. The H-BiMOF material showed type-Ⅳ isotherms with a surface area of 1437 m

The line widths of broad line regions (BLRs) of AGNs are key parameters for understanding the central super massive black holes (SMBHs). However, due to obscuration from dusty torus, optical recombination lines from BLRs in type II AGNs can not be directly detected. Radio recombination lines (RRLs), with low extinction, can be ideal tracers to probe emission from BLRs in type II AGNs. We performed RRL observations for H35$\alpha$ and H36$\alpha$ toward the center of Circinus galaxy with ALMA. Narrow components of H35$\alpha$ and H36$\alpha$, which are thought to be mainly from star forming regions around the nuclear region, are detected. However, only upper limits are obtained for broad H35$\alpha$ and H36$\alpha$. Since Circinus galaxy is one of the nearest AGN, non-detection of broad RRLs in Circinus galaxy at this band tells us that it is hopeless to detect broad RRL emission in local AGNs with current facilities. Submillimetre RRLs, with flux densities that are dozens of times higher than those at the millimetre level, could be the tools to directly detect BLRs in type II AGNs with ALMA, once its backend frequency coverage has been upgraded to several times better than its current capabilities., Comment: 5 pages, 2 Figures, published in MNRAS Letters

Background The aim of the study was to explore the treatment outcomes and prognostic factors for patients with previously irradiated but unresectable recurrent head and neck squamous cell carcinoma (rHNSCC) treated by stereotactic body radiotherapy (SBRT) plus cetuximab at a single institute in Taiwan. Methods From February 2016 to March 2019, 74 patients with previously irradiated but unresectable rHNSCC were treated with SBRT plus cetuximab. All patients received irradiation to the gross tumor and/or nodal area with 40-50 Gy in five fractions, with each fraction interval ≥ 2 days over a 2-week period by using the CyberKnife M6 machine. An18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) scan was performed before treatment for treatment target delineation (n = 74) and 2 months later for response evaluation (n = 60). The median follow-up time was 9 months (range 1-36 months). Results The treatment response rate was complete response: 25.0%, partial response: 41.7%, stable disease: 11.7%, and progressive disease: 21.7% based on the criteria of the Response Evaluation Criteria in Solid Tumors (n = 72) and complete metabolic response: 21.7%, partial metabolic response: 51.7%, stable metabolic disease: 13.3%, and progressive metabolic disease: 13.3% based on PET-CT (n = 60), respectively. The 1-/2-year overall survival (OS) and progression-free survival (PFS) rates were 42.8%/22.0% and 40.5%/19.0%, respectively. In the logistic regression model, a re-irradiation interval > 12 months was observed to be the only significant prognostic factor for a favorable treatment response. In the Cox proportional hazards model, a re-irradiation interval > 12 months and gross tumor volume (GTV) ≦ 50 ml were favorable prognostic factors of OS and PFS. Conclusion SBRT plus cetuximab provides a promising salvage strategy for those patients with previously irradiated but unresectable rHNSCC, especially those with a re-irradiation interval > 12 months or GTV ≦ 50 ml.

A systematic review of randomized controlled trials (RCTs) was conducted to assess the potential effect of therapeutic massage/Tuina on functional dyspepsia (FD) patients.Twelve databases and three clinical trial registries were searched until December 2021, for RCTs that compared Tuina combined with or without conventional therapy versus conventional therapy in FD. We assessed the methodological quality of included trials by the Cochrane Risk of Bias tool, and graded the quality of the evidence. The data were presented as risk ratio (RR) or mean difference (MD) respectively with their 95% confidence interval (CI).In total, 14 RCTs with 1128 FD participants were included. Compared with conventional therapy, Tuina showed significant beneficial effects on improving overall symptom (RR = 1.12, 95% CI 1.06 to 1.19, low certainty evidence), and early satiation (MD -0.44 scores, 95% CI -0.72 to -0.16, very low certainty evidence). Compared with conventional therapy, Tuina plus conventional therapy also significantly improved overall symptom (RR = 1.14, 95% CI 1.06-1.23, low certainty evidence), quality of life (MD 10.44 scores, 95% CI 7.65-13.23, low certainty evidence), and epigastric pain (MD -0.76 scores, 95% CI -1.11 to -0.41, low certainty evidence). No adverse events related to Tuina and cost-effectiveness were reported.Low certainty evidence showed that Tuina significantly improved overall symptom of FD participants compared with conventional therapy. Low certainty evidence showed that Tuina plus conventional therapy obviously improved overall symptom and quality of life of FD participants compared with conventional therapy.

Measurable residual disease (MRD) before hematopoietic cell transplantation (HCT) is an independent established prognostic factor in patients with acute myeloid leukemia (AML). Several methods exist to evaluate the presence of residual leukemia cells, but how these are used best in combination is unclear. In order to examine how residual cytogenetic abnormalities and MRD testing by multiparameter flow cytometry (MFC) may refine risk assessment before HCT, we analyzed 506 adults with cytogenetically abnormal AML who underwent both routine karyotyping and MFC MRD testing before receiving a first allograft while in morphologic remission. Testing for residual cytogenetic abnormalities and MFC MRD identified four groups of patients with differential relapse-free survival (RFS) (hazard ratio [HR]=1.63 for Cytoabnormal/MFCnegative [P=0.01, n=63], HR=3.24 for Cytonormal/MFCpositive [P

(1) Background: Breast cancer is the second leading cause of cancer death among women. The accurate prediction of survival intervals will help physicians make informed decisions on treatment strategies or the use of palliative care for patients; (2) Methods: The gene expression is predictive and correlates to patient prognosis. To establish a reliable prediction tool, we collected the RNA-seq data of breast cancer patients, a total of 1187 RNA-seq data (median age 58 years), in FPKM format from the TCGA database. Among them, 144 RNA-seq data with date of death information was selected to establish the SaBrcada-AD dataset. We first normalized the SaBrcada-AD dataset to transcripts per million (TPM) to build survival prediction model SaBrcada. After normalization and dimension raising, the differential gene expression data were used for testing eight different deep learning architectures. Among them, GoogLeNet performed the best. Considering the effect of age on prognosis, we examined all ages between the lower and upper quartiles of patient age for a stratified random sampling test; (3) Results: Stratifying by age based on a cut-off of 61 years of age improved the accuracy of SaBrcada compared to previous findings, resulting in an accuracy of 0.798. We also built a free website tool to provide 5 kinds of predicted survival period information for clinician reference; (4) Conclusions: We established a breast cancer survival analysis prediction model, SaBrcada, and a website tool with the same name. Through this highly reliable survival analysis model and website tool, information on survival intervals will be provided for clinicians as part of precision medicine.

Purpose The immunotherapy combined chemotherapy has been the standard treatment strategy for extensive-stage small lung cancer (ES-SCLC). The CREST trial reported consolidative thoracic radiotherapy (cTRT) improved overall survival (OS) for ES-SCLC with intrathoracic residual after chemotherapy. This study was aimed to evaluate the efficacy and safety of TRT for ES-SCLC after first line chemoimmunotherapy.Methods ES-SCLC patients who received immunotherapy in Zhejiang Cancer Hospital has been retrospectively analyzed between January 2020 and November 2021. Patients were assigned to receive either TRT or no TRT. Oligo-metastatic disease was defined as 3 or less discrete distant metastases with no more than 2 organs. Propensity score matching (PSM) was performed in two groups. The main outcome measures were progression-free survival (PFS), local recurrence-free survival (LRFS) and OS.Results 111 patients with ES-SCLC were enrolled in this study, the median OS was 14 months. 39 patients received TRT after chemoimmunotherapy (TRT group) and 72 patients did not receive TRT (no TRT group). TRT group improved OS (HR 0.58, 95% CI 0.34–0.99, p = 0.0445), PFS (HR 0.59, 95% CI 0.38–0.90, p = 0.0149) and LRFS (HR 0.3, 95% CI 0.16–0.56, p = 0.0001). Further sub-cohort analysis, TRT significantly improved LRFS in patients with oligo-metastasis and without liver metastasis. This trend persisted after PSM. However, OS in oligo-metastasis and non-liver metastasis subgroup was without significant difference.Conclusion TRT improved LRFS, PFS and OS for ES-SCLC with thoracic residual after chemoimmunotherapy with well tolerated toxicity.

Purpose: Donor-derived infection (DDI) has become an important factor affecting the prognosis of lung transplantation patients. The risks versus benefits of using donor organs infected with multidrug-resistant organisms (MDRO), especially carbapenem-resistant Enterobacterales (CRE), are frequently debated. Traditional microbial culture and antimicrobial susceptibility testing at present fail to meet the needs of quick CRE determination for donor lung before acquisition. In this study, we explored a novel accurate screening method by using Xpert® Carba-R assay for CRE in donor lungs in a real-time manner to reduce CRE-associated DDI mortality. Methods: This study was registered on chictr.org.cn (ChiCTR2100053687) on November, 2021. In the Xpert Carba-R screening group, donor lungs were screened for CRE infection by Xpert Carba-R test on bronchoalveolar lavage fluid (BALF) before acquisition. If the result was negative, donor lung acquisition and subsequent lung transplantation were performed. In the control group, the recipients underwent lung transplants without Xpert Carba-R screening. The incidence and mortality of CRE-associated DDI were collected and contrasted between the two groups. Results: Multivariate analysis showed that CRE-related death due to DDI within 60 days was significantly lower in the Xpert Carba-R screening group than that in the control group (OR = 0.049, 95% CI = 0.003-0.736, p = 0.029). Conclusion: Real-time CRE screening of donor lungs before transplantation at the point of care by the Xpert Carba-R helps clinicians formulate lung transplantation strategies quickly and reduces the risk of subsequent CRE infection improving the prognosis of lung transplantation.

Background A high incidence of severe acute radiation dermatitis (ARD) has been reported for cancer patients treated by proton beam therapy (PBT). This prospective study investigated the prognostic factors and treatment outcomes of ARD among patients with nasopharyngeal carcinoma (NPC) treated with PBT. Methods Fifty-seven patients with newly diagnosed NPC and treated with PBT were enrolled. ARD was recorded weekly based on the criteria of Common Terminology Criteria for Adverse Events version 4.0 in a prospective fashion at treatment visits (1st to 7th weeks) and 1 week (8th week) and 1 month (11th week) after the completion of PBT. Topical corticosteroid was used when grade 1 ARD appeared, and silver sulfadiazine was added if ARD progressed to grade 2 or more. Results The maximum ARD grade was 1, 2, and 3 in 26 (45.6%), 24 (42.1%), and 7 (12.3%) of the patients, respectively. The peak incidence of grade 2 and 3 ARD was observed during the period of the 6th to 8th weeks. Twenty-four (42.1%) patients received topical corticosteroid alone; 33 (57.9%) patients received the combination of topical corticosteroid and silver sulfadiazine. In the 11th week, most grade 2 and 3 ARD had disappeared and 93.0% of the patients had ARD of grade 1 or lower. In the binary logistic regression model, we identified habitual smoking [odds ratio (OR): 5.2, 95% confidence interval (CI): 1.3–18.8, P = 0.012] and N2 to N3 nodal status (OR: 4.9, 95% CI: 1.6–15.4, P = 0.006) as independent predictors of grade 2 and 3 ARD. Conclusion The results show ARD is a major concern for patients with NPC treated with PBT, especially those with habitual smoking or advanced nodal status. Topical corticosteroid and silver sulfadiazine are effective for treating ARD induced by PBT.

To determine associations between lid wiper microvascular responses, lens fit, and comfort after 1 day of contact lens adaptation by neophytes.Functional slitlamp biomicroscopy was used to image the microvascular network of the upper tarsal conjunctiva, lid wiper, and bulbar conjunctiva. Fractal dimension was obtained to represent vessel density. Ultra-high-resolution optical coherence tomography was used to image the lens edge and fitting characteristics, including lens movement and lens-induced conjunctival indentation. Ocular comfort was rated using a 50-point visual analogue scale (VAS). Forty-nine healthy subjects without a history of contact lens wear were recruited. A contact lens was then fitted in the right eye. Imaging was taken at baseline and 6 hr after lens wear.The changes of VAS comfort score were negatively related to the changes of the vessel density in the lid-wiper (R 2 =0.18, P =0.002) and bulbar conjunctiva (R 2 =0.13, P =0.009). However, the changes of VAS were positively related to the changes in vessel density of the tarsal conjunctiva (R 2 =0.11, P =0.02). The changes of ocular microvasculature were not related to the objective metrics of the lens-fitting characteristics ( P0.05). Similarly, the changes in the VAS comfort score were not related to the objective metrics of the lens-fitting characteristics ( P0.05).Contact lens discomfort seemed to relate to lid wiper microvascular responses rather than fitting characteristics after 1 day of contact lens adaptation by neophytes.

PURPOSE Chemotherapy outcomes in older patients with Philadelphia (Ph) chromosome–negative B-acute lymphoblastic leukemia (ALL) are very poor. Here, we evaluated blinatumomab as induction and consolidation therapy followed by prednisone, vincristine, 6-mercaptopurine, and methotrexate (POMP) maintenance chemotherapy in this patient population. PATIENTS AND METHODS Patients were treated at National Clinical Trial Network sites. Eligibility criteria included age ≥ 65 years and newly diagnosed Ph chromosome–negative B-ALL. Patients received blinatumomab as induction for one-two cycles until attainment of response (complete remission (CR) and CR with incomplete count recovery). Patients then received three cycles of consolidation with blinatumomab followed by 18 months of POMP maintenance chemotherapy. Eight doses of intrathecal methotrexate were administered as central nervous system prophylaxis. RESULTS Twenty-nine eligible patients were enrolled. The median age was 75 years, and the median bone marrow blast count at diagnosis was 87%. Cytogenetic risk was poor in 10 patients (34%), and five of 14 patients (36%) tested had the Ph-like ALL gene signature. Nineteen patients (66%; 95% CI, 46 to 82) achieved CR. Kaplan-Meier 3-year disease-free survival and overall survival estimates were 37% (95% CI, 17 to 57) and 37% (95% CI, 20 to 55), respectively. CONCLUSION Blinatumomab was well tolerated and effective in the treatment of older patients with newly diagnosed Ph chromosome–negative B-ALL, including patients with poor-risk cytogenetics. The 3-year disease-free survival and overall survival results are encouraging and suggest that this approach should be further explored.

Rice is a recognized source of cadmium (Cd) exposure. In this study, a total of 102 rice samples were obtained from main producing rice regions of China, and the bioavailability of Cd in rice were assessed by using an in vitro digestion method combined with a Caco-2 cell monolayer model. The results revealed that the average (range of) concentration of Cd in the rice samples was 0.2840 (0.0123-2.4710) mg/kg, and the average (range of) bioavailability of Cd in the rice samples was 23.94% (7.47-39.73%). We analyzed the recent rice consumption data and calculated the target hazard quotients (THQs) to evaluate the noncarcinogenic health risk of Cd in rice consumption for adults and children, respectively. We suggested that the most of investigated regions showed low risks of Cd in rice for general population, and the regions of Cd in rice near the limit deserves might be attracted more attention after taking bioavailability into account. PRACTICAL APPLICATION: The cadmium content of rice itself will affect its corresponding bioavailability to a certain extent. By studying the in vitro bioavailability of cadmium rice with different pollution levels, it is helpful for the dose selection of animal experiments or toxicity tests, and finally, we may provide some references for the establishment of appropriate treatment scheme of rice Cd poisoning.

Concurrent chemoradiation therapy (CCRT) is the mainstay treatment for patients with nasopharyngeal carcinoma (NPC). Baroreflex impairment can be a late sequela in patients after neck radiotherapy. We hypothesized that cardiovascular autonomic dysfunction is a progressive process that can begin after CCRT and persists for a longer period.Cardiovascular autonomic function was assessed in 29 newly diagnosed patients with NPC using standardized measures including heart rate response to deep breathing (HRDB), Valsalva ratio (VR), baroreflex sensitivity (BRS), and analyses of heart rate variability (HRV), biomarkers of oxidative stress, and inflammation at three different time points (baseline, immediately after CCRT, and 9 years after enrollment). A healthy control group was recruited for the comparison.Although there was an aging effect on autonomic parameters in both groups during the 9 years of follow-up, the between-group comparison showed that there was a significant decrease in HRDB, VR, and HRV at the 9th year of follow-up in the NPC group. Repeated measures ANOVA after controlling for age and sex showed that both HRDB and triangle index of HRV had statistically significant differences between the two groups.Based on our results, cardiovascular autonomic dysfunction after CCRT is a progressive and dynamic process. Cardiovagal impairment occurs in the early phase and persists in decline, while adrenergic dysfunction is significant only after a 9-year follow-up. In contrast to the current opinion, our study showed that both afferent and efferent baroreflex pathways can be involved after CCRT.

Shang-Yu Chou,1 Hung-I Lu,2 Yen-Hao Chen,3 Chien-Ming Lo,2 Yun-Hsuan Lin,1 Tzu-Ting Huang,1 Fu-Min Fang,1 Li-Chun Chen,2 Yu Chen,2 Yi-Chun Chiu,4 Yeh-Pin Chou,4 Shau-Hsuan Li,3,&ast; Yu-Ming Wang1,5,&ast; 1Department of Radiation Oncology & Proton and Radiation Therapy Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 2Department of Thoracic & Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 3Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 4Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; 5School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan&ast;These authors contributed equally to this workCorrespondence: Yu-Ming Wang, Department of Radiation Oncology & Proton and Radiation Therapy Center, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 129, Ta-Pei Road, Niaosong Dist., Kaohsiung, 833, Taiwan, Tel +886-7-7317123 ext. 7000, Fax +886-7-7322813, Email scorpion@cgmh.org.tw Shau-Hsuan Li, Department of Hematology-Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, No. 123, Ta-Pei Road, Niaosong Dist., Kaohsiung, 833, Taiwan, Tel +886-7-7317123 ext. 8303, Fax +886-7-7322813, Email lee0624@cgmh.org.twPurpose: For locally advanced esophageal cancer, definitive concurrent chemoradiotherapy (CCRT) with a radiation dose of 50– 50.4 Gy/25-28 Fx is prescribed, followed by adjuvant esophagectomy for better local control or salvage treatment if locoregional recurrence occurs. However, radiation injury before surgery may delay wound healing. We performed cervical anastomosis directly inside the left supraclavicular fossa (SCF), the irradiation target for esophageal cancer. The significance of radiation injury in patients with cervical anastomotic leak (AL) remains unclear. Thus, we assessed the influence of radiation on cervical AL in patients undergoing preoperative CCRT followed by esophagectomy.Patients and Methods: We defined the SYC zone, a portion of the region overlapping the left SCF. The radiation dose to the SYC zone was analyzed and correlated with AL in patients with locally advanced esophageal squamous cell carcinoma (ESCC) who were administered preoperative CCRT (radiation dose with 50– 50.4 Gy/25-28 Fx to the primary esophageal tumor) followed by esophagectomy between October 2009 and January 2018. Receiver operating characteristic curve analysis and logistic regression were used to identify the optimal radiation factor to predict AL and the cutoff value.Results: The optimal radiation factor to predict AL was the mean dose to the SYC zone (area under the curve (AUC)=0.642), and the cutoff point of the mean dose was 48.55 Gray (Gy). For a mean SYC zone dose ≥ 48.55 Gy, the AL risk was sevenfold greater than that for < 48.55 Gy (OR = 7.805; 95% CI: 1.184 to 51.446; P value = 0.033).Conclusion: Recognizing the SYC zone as an organ at risk and performing radiation evaluation are meaningful. A reduced mean dose of the SYC zone below 48.55 Gy results in a lower cervical AL rate following esophagectomy.Keywords: esophageal squamous cell carcinoma, preoperative concurrent chemoradiotherapy, radiation therapy

Background Amyotrophic lateral sclerosis (ALS) associated with TAR DNA-binding protein 43 (TDP-43) aggregation has been considered as a lethal and progressive motor neuron disease. Recent studies have shown that both C-terminal TDP-43 (C-TDP-43) aggregates and oligomers were neurotoxic and pathologic agents in ALS and frontotemporal lobar degeneration (FTLD). However, misfolding protein has long been considered as an undruggable target by applying conventional inhibitors, agonists, or antagonists. To provide this unmet medical need, we aim to degrade these misfolding proteins by designing a series of proteolysis targeting chimeras (PROTACs) against C-TDP-43. Methods By applying filter trap assay, western blotting, and microscopy imaging, the degradation efficiency of C-TDP-43 aggregates was studied in Neuro-2a cells overexpressing eGFP-C-TDP-43 or mCherry-C-TDP-43. The cell viability was characterized by alarmarBlue assay. The beneficial and disaggregating effects of TDP-43 PROTAC were examined with the YFP-C-TDP-43 transgenic C. elegans by motility assay and confocal microscopy. The impact of TDP-43 PROTAC on C-TDP-43 oligomeric intermediates was monitored by fluorescence lifetime imaging microscopy and size exclusion chromatography in the Neuro-2a cells co-expressing eGFP-C-TDP-43 and mCherry-C-TDP-43. Results Four PROTACs with different linker lengths were synthesized and characterized. Among these chimeras, PROTAC 2 decreased C-TDP-43 aggregates and relieved C-TDP-43-induced cytotoxicity in Neuro-2a cells without affecting endogenous TDP-43. We showed that PROTAC 2 bound to C-TDP-43 aggregates and E3 ligase to initiate ubiquitination and proteolytic degradation. By applying advanced microscopy, it was further shown that PROTAC 2 decreased the compactness and population of C-TDP-43 oligomers. In addition to cellular model, PROTAC 2 also improved the motility of transgenic C. elegans by reducing the C-TDP-43 aggregates in the nervous system. Conclusions Our study demonstrated the dual-targeting capacity of the newly-designed PROTAC 2 against both C-TDP-43 aggregates and oligomers to reduce their neurotoxicity, which shed light on the potential drug development for ALS as well as other neurodegenerative diseases.

Establishing plantation forests significantly increases the carbon (C) storage of terrestrial ecosystems. However, how vegetation types affect the ecosystem C sequestration capacity is not completely clear. Here, a slash pine plantation (SPP), a Schima superba plantation (SSP), and a Masson pine plantation (MPP), which have been planted for 30 years, were selected in subtropical China. The C storage and distribution patterns of plant, litter, and soil were investigated and calculated. The ecosystem C density was 17.7, 21.6, and 15.3 kg m–2 for SPP, SSP, and MPP, respectively. Ecosystem C stocks were mainly contributed by tree aboveground (39.9–46.0%) and soil C stocks (41.6–44.2%). The ecosystem C density of SSP was higher than that of SPP and MPP, and significant differences were found among three plantations for both aboveground and underground C densities. The aboveground and underground ecosystem C storage of SSP was 27.4 and 53.4% higher than that of MPP, respectively. Meanwhile, root C storage of MPP was lower than that of SPP and SSP, while soil C storage of MPP was lower than that of SSP. In the understory layer, SPP had the highest C density, followed by MPP, and there was a significant difference in C density among three plantations. However, no significant difference was found for the ecosystem C distribution among three plantations. Our results show that vegetation types significantly affect C storage but not C distribution in forest ecosystems and establishing the broad-leaved plantation has the highest ecosystem C storage in the subtropics. This study provides a theoretical basis for us to choose appropriate forest management measures.

Background During the COVID-19 pandemic, it is vital for individuals to comply with the government’s prevention and control measures. This study aims to explore determinants of college students’ compliance behaviour during the COVID-19 pandemic. Methods This study conducted an online survey among 3,122 individuals aged 18 and above from March to November 2022 in China. Individuals’ compliance behaviour was divided into protective behaviour (that includes wearing a mask, maintaining a physical distance, and getting vaccinated) and restrictive behaviour (that includes offering health codes and a nucleic acid test certificate). Individuals’ compliance motivation was divided into calculated motivation (including the fear of being infected, the fear of being published, and previous experience of pandemic prevention) and normative motivation (including the sense of social responsibility and trust in government). We defined young people aged between 18 and 24 with a college degree as young elites, and constructed ordinary least squares linear regression to compare their compliance behaviour with young people without a college degree (young non-elites), and non-young people with a college degree (non-young elites). Results Almost three years after the outbreak of the pandemic, Chinese individuals retained a high degree of compliance with COVID-19 prevention and control policies, particularly with respect to the provision of health codes. Young elites were more compliant with getting vaccinated, wearing a mask, providing health codes and testing results than their counterparts. The sense of social responsibility and trust in government were the major drivers of young elites’ compliance behaviour during the pandemic. Young elites who were male, had a rural “hukou”, and were not a member of the China Communist Party were more compliant with COVID-19 prevention and control measures. Conclusion This study found that young elites in China had high policy compliance during the COVID-19 pandemic. These young elites’ compliance behaviour was driven by their sense of social responsibility and trust in government rather than the fear of being infected and the fear of being punished as a result of violating the regulations. We suggest that in the context of managing health crises, in stead of introducing punitive measures to enforce citizens to comply with the management measures, promoting citizens’ sense of social responsibility and building a trusting relationship with citizens contrite to the enhancement of citizens’ policy compliance.

Background: IL-33 is considered to be a multifunctional cytokine with dual functions. However, the clinicopathological and prognostic significance of IL-33 in cancer patients, especially hepatocellular carcinoma (HCC)，remains controversial. Therefore, we conducted 565 patients with HCC and 561 healthy controls and a meta-analysis to quantitatively evaluate the above problems. Methods: We collected the blood of 565 patients with HCC and 561 healthy controls. ELISA was used to detect the concentration of IL-33 and ST2 in the serum, and the RT-PCR method was used to detect the levels of IL-33 and ST2 mRNA content. Meanwhile, we collected comprehensive literature on IL-33 and clinical characteristics of cancer patients retrieved from PubMed, Web of Science and CNKI databases as of August 15, 2021. An odds ratio (OR) with a 95% confidence interval (CI) were used to estimate the impact through overall and stratified analysis. Results: Compared with the healthy control group, the levels of ST2 mRNA and serum in the peripheral blood of HCC patients increased(P0.05). In the meta-analysis section, at the level of tissue level, the overall analysis showed that the expression of IL-33 was positively correlated with tumor stage, histological grade, distant metastasis and tumor size. Compared with the low IL-33 expression, the 3-year overall survival (OS) rate (OR=3.467, P Conclusion: IL-33/ST2 is a useful predictive or prognostic biomarker in clinical evaluation, and may be used as a potential therapeutic target, but it needs a lot of research to verify.

This study aimed to evaluate whether the hybrid and biomechanically deformable image registration (DIR) algorithm of the RayStation treatment planning system would produce contour propagation and dose deformation errors in the head and neck due to the inclusion of adjuvant therapeutic fixtures. We analyzed the treatment plans of two groups of patients with head and neck cancer (Planx and Planp). Planx included photon beam therapy (5250cGy/25 sessions) and Planp involved proton beam therapy (1680cGy/8 sessions). We used two adjuvant treatment immobilization devices (immobilization) to scan computed tomography (CT) images: Planx included CTx and immobilizationx, and Planp included CTp and immobilizationp. Using the hybrid (Hy) and biomechanical (Bio) algorithms of the RayStation treatment planning system, we controlled the registration to analyze the contour propagation and dose deformation. The range of immobilization including the body contour is defined as Rim+b, and the range of only the body contour is defined as Rb. We generated four settings as follows: Hy_Rim+b, Bio_Rim+b, Hy_Rb, and Bio_Rb. We mapped organs at risk (OARs) to Planp by using contour propagation through the aforementioned four settings. Contour propagation uses the results of overlapping image display, the Dice similarity coefficient (DSC), and the contour drawn by the physician on Planp. We used the results shown in the overlapping images in the contour propagation and evaluated them with the DSC and the contour drawn by the physician in Planp. We mapped the received dose of OARs in Planx to Planp with dose deformation, and evaluated the percent dose difference [dose diff.(%)] between the four settings and Planx. In terms of contour propagation, the overlapping image of the horizontal section (transversal) showed that because the range set by Hy_Rim+b and Bio_Rim+b includes immobilization, Hy_Rim+b deforms in the oral cavity and esophagus area, and for Bio_Rim+b significant deformations around the body contour lead to misregistration. The Hy_Rb and Bio_Rb settings are not obviously deformed in the overlapping images. We assessed the consistency of dissemination of OARs contours by using the DSC. The average DSC of Hy_Rim+b and Bio_Rim+b is 0.63 and 0.32, respectively; the average DSC of Hy_Rb and Bio_Rb is 0.94 and 0.83, respectively. The results of the overlapping image and DSC evaluation showed that the two algorithms can reduce the error by excluding immobilization in the registration range of contour propagation. We found that the hybrid algorithm is superior to the biomechanical algorithm. In terms of dose deformation, the average dose differences of Hy_Rim+b and Bio_Rim+b in Planx are 13.15% and 17.82%, respectively, while those of Hy_Rb and Bio_Rb are 3.32% and 5.13%, respectively. We found that the average dose error of the hybrid algorithm is smaller than that of the biomechanical algorithm. Considering the setting where the registration range does or does not include immobilization, the average dose of OARs differs by 9.83% for the hybrid algorithm and 12.69% for the biomechanical algorithm. In conclusion, we found that the hybrid and biomechanical algorithms of the RayStation treatment planning system increase the error of contour propagation and dose deformation because the registration range includes head and neck immobilization. The results show that the hybrid algorithm is more suitable for the head and neck than the biomechanical algorithm. Therefore, we suggest using the hybrid algorithm for clinical planning of DIR, and excluding immobilization from taking the patient's body contour as the registration range.

Animal models play crucial roles in the rapid development of vaccines/drugs for the prevention and therapy of COVID-19, but current models have some deficits when studying the pathogenesis of SARS-CoV-2 on some special tissues or organs. Here, we generated a human ACE2 and SARS-CoV-2 NF/F knockin mouse line that constitutively expresses human ACE2 and specifically expresses SARS-CoV-2 N gene induced by Cre-recombinase. By crossing with Cre transgenic lines allowing for lung-specific and constitutive expression, we generated lung-specific (Sftpc-hACE2-NF/F) and constitutive SARS-CoV-2 N (EIIa-hACE2-NF/F) expressing mice. Upon intranasal infection with a SARS-CoV-2 GFP/ΔN strain which can only replicate in SARS-CoV-2 N expressed cells, we demonstrated that both the Sftpc-hACE2-NF/F and EIIa-hACE2-NF/F mice support viral replication. Consistent with our design, viral replication was limited to the lung tissues in Sftpc-hACE2-NF/F mice, while the EIIa-hACE2-NF/F mice developed infections in multiple tissues. Furthermore, our model supports different SARS-CoV-2 variants infection, and it can be successfully used to evaluate the effects of therapeutic monoclonal antibodies (Ab1F11) and antiviral drugs (Molnupiravir). Finally, to test the effect of SARS-CoV-2 infection on male reproduction, we generated Sertoli cell-specific SARS-CoV-2 N expressed mice by crossing with AMH-Cre transgenic line. We found that SARS-CoV-2 GFP/ΔN strain could infect Sertoli cells, led to spermatogenic defects due to the destruction of blood-testis barrier. Overall, combining with different tissue-specific Cre transgenic lines, the human ACE2 and SARS-CoV-2 NF/F line enables us to evaluate antivirals in vivo and study the pathogenesis of SARS-CoV-2 on some special tissues or organs.

Background: Up to 30% colorectal carcinoma (CRC) are inherited tendency. Lynch syndrome (LS) which is caused by mismatch repair (MMR) genes germline mutation, is the most prevalent form of hereditary CRC. Ethnical and regional differences would lead to diverse characteristics of LS. However, Studies of LS from China are few and with relatively small sample sizes. Method: Immunohistochemistry (IHC) testing for MMR deficiency (dMMR) is advocated to preliminarily screen LS in recent guidelines. This single center retrospective study from central China performed IHC to prescreen dMMR and analyze the patterns and characteristics of dMMR CRCs. Results: 12.0% (180/1505) CRCs had dMMR status in this study, they had the universal features such as younger diagnostic age, more proximal colon location, more poorly differentiated with an excess of mucinous type, advanced pT stage and lower pN stage (all P ＜ 0.05), but had larger tumor size and less perineural invasion (all P ＜ 0.05) compared with proficiency MMR CRCs, which were not reported before. Moreover, PMS2 deficiency (8.7%) was common in this study which was different from studies in Western. MLH1/PMS2, isolated PMS2, MSH2/MSH6 and isolated MSH6 were the most common deficiency patterns, and the MSH2/MSH6 subtype had the most often family history. Conclusion: This study demonstrated dMMR CRCs from central China had the similar general characteristics as reported studies, but had larger tumor size and less perineural invasion which were not reported before. What’s more, PMS2 deficiency (8.7%) was common in this study which was different from studies in Western.

CircRNAs are an important class of noncoding RNAs characterized by a covalently closed circular structure. CircRNAs have been proven to impact numerous cellular processes, where they conduct specialized biological activities.

Not available.

Background: Radiation-induced pulmonary fibrosis (RIPF) is a long-term complication of thoracic radiotherapy without effective treatment available. background: Radiation-induced pulmonary fibrosis (RIPF) is a long-term complication of thoracic radiotherapy, without effective treatment available. Objective: This study aimed to establish a RIPF mouse model and explore the therapeutic effects and mechanisms of recombinant human endostatin (Endostar). Methods: C57BL/6 mice received a 16-Gy dose of X-rays to the whole thorax with or without the administration of Endostar for 24 weeks. method: C57BL/6 mice received a 16-Gy dose of X-rays to the whole thorax with or without the administration of Endostar for 24 weeks. Results: Radiation-induced body weight loss was partially attenuated by Endostar (P Conclusion: Endostar could alleviate RIPF through decreased antiangiogenic activity and inhibition of the TGF-β1/Smad3/ERK pathway. conclusion: Endostar could alleviate RIPF through decreased antiangiogenic activity and inhibition of the TGF-β1/Smad3/ERK pathway.

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