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Brain metastases (BM) is common in non-small-cell lung cancer (NSCLC) patients. Immune checkpoint inhibitors (ICIs) have gradually become a routine treatment for NSCLC BM patients. Currently, three PD-1 inhibitors (pembrolizumab, nivolumab and cemiplimab), one PD-L1 inhibitor (atezolizumab) and one CTLA-4 inhibitor (ipilimumab) have been approved for the first-line treatment of metastatic NSCLC. It is still controversial whether PD-L1, tumor infiltrating lymphocytes, and tumor mutation burden can be used as predictive biomarkers for immune checkpoint inhibitors in NSCLC patients with BM. In addition, clinical data on NSCLC BM were inadequate. Here, we review the theoretical basis and clinical data for the application of ICIs in the therapy of NSCLC BM.

Purpose: Available evidence indicates that kinetochore-localized astrin/SPAG5-binding protein (KNSTRN) is an oncogene in skin carcinoma. This study aimed to evaluate the prognostic value of KNSTRN in lung adenocarcinoma (LUAD) underlying the Cancer Genome Atlas (TCGA) database. Methods: The relationship between clinicopathological features and KNSTRN was analyzed with the Wilcoxon signed-rank test and logistic regression. The clinicopathological characteristics associated with overall survival (OS) were evaluated using Cox regression and the Kaplan-Meier method. Gene ontology (GO) analysis, gene set enrichment analysis (GSEA), and single-sample GSEA (ssGSEA) were performed using TCGA data. Results: The KNSTRN expression level was found to be significantly higher in LUAD tissue than in normal lung tissue. Also, it correlated significantly with advanced clinicopathological characteristics. The Kaplan-Meier survival curve revealed a significant relationship of high expression of KNSTRN with poor OS in patients with LUAD. The multivariate Cox regression hazard model demonstrated the KNSTRN expression level as an independent prognostic factor for patients with LUAD. GO and GSEA analyses indicated the involvement of KNSTRN in cell cycle checkpoints, DNA replication, and G2-M checkpoint M phase. Based on ssGSEA analysis, KNSTRN had a positive relationship with Th2 cells and CD56dim natural killer cells. The KNSTRN expression levels in several types of immune cells were significantly different. Conclusion: The findings suggested that the increased expression level of KNSTRN was significantly associated with the progression of LUAD and could also serve as a novel prognostic biomarker for patients with LUAD.

Brain metastasis (BM) is a common malignant event in lung cancer. Here, we recruited 33 lung cancer patients with brain oligo-metastasis to explore the genomic features and tumor immune microenvironment (TIME) of the lung and BM independently. For genomic profiling, targeted sequencing was performed. We found that high-frequent ZFHX3 occurred in the lung (40%) and brain tumor (28%), which might relate to brain metastasis event; the vast majority of patients had lesions-shared mutations in primary tumor and BM, confirming the common clonal events; and EGFR was the most frequently clonal gene in both lung and BM, indicating its driver capability. To characterize TIME status, we also sequenced the T cell receptor (TCR) repertoires and performed immunohistochemistry (IHC) on CD8+ tumor-infiltrating lymphocytes (TILs) and PD-L1 expression in 28 patients who had paired samples. Through the comparison, the TCR clonality of BM was higher than lung tumor, indicating the distinct pattern of the stronger oligoclonal T cell expansion in BM; the primary tumor had a higher TMB than oligo-BM (13.9 vs 8.7 mutations, p = 0.019); CD8 + TILs of BM were significantly lower than lung tumor (10% vs 30%, p = 0.015), revealing the lower level of cytotoxic T cell infiltration; BM showed statistically equivalent level of PD-L1 compared with lung tumor (p = 0.722). We further investigated the potential biomarkers associated with overall survival (OS) after brain surgery. We found that higher TCR clonality was related to prolonged OS in EGFR-treated patients (HR 0.175, p p = 0.034). More CD8+ TILs were an independently positive indicator for OS, in EGFR-treated (HR 0.160, p = 0.001) and non-EGFR-treated patients (HR 0.308, p = 0.009). These findings provide a meaningful molecular and clinical understanding of lung carcinoma and brain oligo-metastasis.

Alcohol-related liver disease is a major public health burden, and the gut microbiota is an important contributor to disease pathogenesis. The aim of the present study is to characterize functional alterations of the gut microbiota and test their performance for short-term mortality prediction in patients with alcoholic hepatitis. We integrated shotgun metagenomics with untargeted metabolomics to investigate functional alterations of the gut microbiota and host co-metabolism in a multicenter cohort of patients with alcoholic hepatitis. Profound changes were found in the gut microbial composition, functional metagenome, serum, and fecal metabolomes in patients with alcoholic hepatitis compared with nonalcoholic controls. We demonstrate that in comparison with single omics alone, the performance to predict 30-day mortality was improved when combining microbial pathways with respective serum metabolites in patients with alcoholic hepatitis. The area under the receiver operating curve was higher than 0.85 for the tryptophan, isoleucine, and methionine pathways as predictors for 30-day mortality, but achieved 0.989 for using the urea cycle pathway in combination with serum urea, with a bias-corrected prediction error of 0.083 when using leave-one-out cross validation. Conclusion: Our study reveals changes in key microbial metabolic pathways associated with disease severity that predict short-term mortality in our cohort of patients with alcoholic hepatitis.

The efficacy of whole-body vibration for functional improvement in stroke patients remains controversial. We conduct a systematic review and meta-analysis to explore the influence of whole-body vibration on functional improvement in stroke patients.We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through June 2018 for randomized controlled trials (RCTs) assessing the effect of whole-body vibration on functional improvement in stroke patients. This meta-analysis is performed using the random-effect model.Eight RCTs are included in the meta-analysis. Overall, compared with control group for stroke patients, whole-body vibration has no positive impact on 6 min walk test (6MWT) distance (standard mean difference (Std. MD)=−0.28; 95% confidence interval (CI)=−0.66 to 0.11; P=0.16), timed-up-and-go (TUG) test (Std. MD=0.15; 95% CI=−0.54 to 0.84; P=0.67), Fugl-Meyer assessment (Std. MD=0.33; 95% CI=−0.23 to 0.89; P=0.25), Berg Balance Scale (Std. MD=0.19; 95% CI=−0.43 to 0.80; P=0.55), and activities specific balance (ABC) scale (Std. MD=−0.22; 95% CI=−0.62 to 0.17; P=0.26).Whole-body vibration shows no notable influence on 6MWT distance, TUG test, Fugl-Meyer assessment, Berg Balance Scale, and ABC scale in stroke patients.

Liver cirrhosis is a major cause of morbidity and mortality worldwide. The most common chronic liver diseases in western countries are alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). Although these diseases have different causes, liver fibrosis develops via shared mechanisms. The liver and intestinal microbiome are linked by the portal vein and have bidirectional interactions. Changes in the intestinal microbiome contribute to the pathogenesis and progression of liver diseases including ALD, NAFLD, viral hepatitis and cholestatic disorders, based on studies in patients and animal models. Intestinal microbial dysbiosis has been associated with liver cirrhosis and its complications. We review the mechanisms by which alterations in the microbiome contribute to liver fibrosis and discuss microbiome-based treatment approaches.

Diabetic kidney disease (DKD), as the most common complication of diabetes mellitus (DM), is the major cause of end-stage renal disease (ESRD). Renal interstitial fibrosis is a crucial metabolic change in the late stage of DKD, which is always considered to be complex and irreversible. In this review, we discuss the pathological mechanisms of diabetic renal fibrosis and discussed some signaling pathways that are closely related to it, such as the TGF-β, MAPK, Wnt/β-catenin, PI3K/Akt, JAK/STAT, and Notch pathways. The cross-talks among these pathways were then discussed to elucidate the complicated cascade behind the tubulointerstitial fibrosis. Finally, we summarized the new drugs with potential therapeutic effects on renal fibrosis and listed related clinical trials. The purpose of this review is to elucidate the mechanisms and related pathways of renal fibrosis in DKD and to provide novel therapeutic intervention insights for clinical research to delay the progression of renal fibrosis.

Traditional Chinese medicine (TCM) prescriptions lack standardization due to the complex composition of the prescribed herbs, the unclear mechanism of the formulas, and a lack of scientific data to support the dose-response relationship. Here, we proposed a new clinical strategy of dosage modification for TCM prescriptions to evaluate the clinical efficacy and guide the clinical medication. This study used two TCM prescriptions for the treatment of newly diagnosed type 2 diabetes mellitus (T2DM) to explore the key indications and the most appropriate critical values of dosage modification by analyzing two randomized controlled trials (RCTs). In this study, the indications refer to a change in the indicators from baseline at a certain time point (week 4, week 8, week 12), which could predict the change in outcome indicators, and the critical values refer to the change ranges closely related to the decrease in HbA1c at week 12. In Study 1, the correlation analysis between the change range of indicators at three time points (weeks 4, 8, and 12) from baseline and the decrease in HbA1c at week 12 from baseline (HbA1c 012) was carried out to screen the related indications. Next, we evaluate the related indications and the respective critical values to determine the key indicators, indications, and the most appropriate critical value. We conducted a correlation between the change range of key indicators (obtained from the result of Study 1) at three time points from baseline and HbA1c 012 to screen the key indications in the drug group, high-dose group, and low-dose group in Study 2. Key indications with critical values were determined to investigate the most appropriate critical value in the three groups separately. In Study 1, the key indicator was FBG, the key indication was FBG 04, and the most appropriate critical value was 0.5 mmol/L. In Study 2, the key indication was FBG 04 and the most appropriate critical value was 0.6 mmol/L in the drug group. In the high-dose group, the key indication was FBG 04, and the most appropriate critical value was 0.3 mmol/L. In the low-dose group, the key indication was FBG08, and the most appropriate critical value was 0.1 mmol/L. In addition, we summarized a verification strategy for dosage modification.

Panax ginseng C.A.Mey. has been widely consumed as food/diet supplements from natural sources, and its therapeutic properties have also aroused widespread concern. Therapeutic properties of Panax ginseng C.A.Mey. such as anti-inflammatory, ameliorating chronic inflammation, enhancing the immunity, resisting the oxidation again, and regulating the glucose and lipid metabolism have been widely reported. Recent years, lots of interesting studies have reported the potential use of Panax ginseng C.A.Mey. in the management of DKD. DKD has become the leading cause of end-stage renal disease worldwide, which increases the risk of premature death and poses a serious financial burden. Although DKD is somehow controllable with different drugs such as Angiotensin-Converting Enzyme Inhibitors (ACEI), Angiotensin Receptor Blockers (ARB) and lowering-glucose agents, modern dietary changes associated with DKD have facilitated research to assess the preventive and therapeutic merits of diet supplements from natural sources as medicine including Panax ginseng C.A.Mey. Findings from many scientific evidences have suggested that Panax ginseng C.A.Mey. can relieve the pathological status in cellular and animal models of DKD. Moreover, a few studies showed that alleviation of clinical phenotype such as reducing albuminuria, serum creatinine and renal anemia in DKD patients after application or consumption of Panax ginseng C.A.Mey.. Therefore, this review aims to discuss the effectiveness of Panax ginseng C.A.Mey. as medicine for targeting pathological phenotypes in DKD from a pharmacological perspective. This review will provide new insights into the potential understanding use of Panax ginseng C.A.Mey. in the management of DKD in clinical settings.

Graphical abstract Abbreviation: SARS-CoV-2: Severe acute respiratory syndrome coronavirus 2; COVID-19: Coronavirus Disease 2019., Highlights • TCM could reduce the all-cause mortality in COVID-19 patients. • TCM could inhibit virus replication and transcription of SARS-CoV-2. • TCM can attenuate the cytokine storm and immune deficiency caused by the SARS-CoV-2., Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the third coronavirus causing serious human disease to spread across the world in the past 20 years, after SARS and Middle East respiratory syndrome. As of mid-September 2020, more than 200 countries and territories have reported 30 million cases of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, including 950,000 deaths. Supportive treatment remains the mainstay of therapy for COVID-19. The World Health Organization reported that four candidate drugs, including remdesivir, are ineffective or have little effect on COVID-19. According to China News, 90 % of Chinese patients with COVID-19 use traditional Chinese medicine (TCM), with an effectiveness rate of 80 %, and no deterioration in patient condition. We have compiled the direct evidence of TCM treatment for COVID-19 as of December 31, 2020. We describe the advantages of TCM in the treatment of COVID-19 based on clinical evidence and the required methods for its clinical use. TCM can inhibit virus replication and transcription, prevent the combination of SARS-CoV-2 and the host, and attenuate the cytokine storm and immune deficiency caused by the virus infection. The cooperation of many countries is required to establish international guidelines regarding the use of TCM in patients with severe COVID-19 from other regions and of different ethnicities. Studies on the psychological abnormalities in patients with COVID-19, and medical staff, is lacking; it is necessary to provide a complete chain of evidence to determine the efficacy of TCM in the related prevention, treatment, and recovery. This study aims to provide a reference for the rational use of TCM in the treatment of COVID-19.

Objective. The purpose of this study was to investigate the feasibility of applying handcrafted radiomics (HCR) and deep learning-based radiomics (DLR) for the accurate preoperative classification of glioblastoma (GBM) and solitary brain metastasis (BM). Methods. A retrospective analysis of the magnetic resonance imaging (MRI) data of 140 patients (110 in the training dataset and 30 in the test dataset) with GBM and 128 patients (98 in the training dataset and 30 in the test dataset) with BM confirmed by surgical pathology was performed. The regions of interest (ROIs) on T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and contrast-enhanced T1WI (T1CE) were drawn manually, and then, HCR and DLR analyses were performed. On this basis, different machine learning algorithms were implemented and compared to find the optimal modeling method. The final classifiers were identified and validated for different MRI modalities using HCR features and HCR + DLR features. By analyzing the receiver operating characteristic (ROC) curve, the area under the curve (AUC), accuracy, sensitivity, and specificity were calculated to evaluate the predictive efficacy of different methods. Results. In multiclassifier modeling, random forest modeling showed the best distinguishing performance among all MRI modalities. HCR models already showed good results for distinguishing between the two types of brain tumors in the test dataset (T1WI, AUC = 0.86; T2WI, AUC = 0.76; T1CE, AUC = 0.93). By adding DLR features, all AUCs showed significant improvement (T1WI, AUC = 0.87; T2WI, AUC = 0.80; T1CE, AUC = 0.97; p < 0.05 ). The T1CE-based radiomic model showed the best classification performance (AUC = 0.99 in the training dataset and AUC = 0.97 in the test dataset), surpassing the other MRI modalities ( p < 0.05 ). The multimodality radiomic model also showed robust performance (AUC = 1 in the training dataset and AUC = 0.84 in the test dataset). Conclusion. Machine learning models using MRI radiomic features can help distinguish GBM from BM effectively, especially the combination of HCR and DLR features.

Objective To establish a nude mouse model of photoaging and study the therapeutic effect of a concentrated growth factor preparation (CGF) on skin photoaging. Methods CGF was prepared from blood from Sprague–Dawley rats. A skin photoaging nude mouse model was developed using UV irradiation combined with the photosensitizer, 8-methoxypsoralen. Mice were divided randomly into seven groups (n = 6 per group): normal control, photoaging, mock treatment, saline treatment, CGF treatment, Filoca 135HA treatment, and plasma skin regeneration system irradiation (the latter two were positive controls). Body weight and skin appearance were observed and pathological changes were determined by hematoxylin and eosin staining. Fiber elasticity was evaluated by Weigert staining. Expression levels of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase 1 (MMP1) were determined by immunohistochemistry. Results A mouse model with typical features of photoaging skin was successfully developed. CGF significantly improved the skin appearance, wrinkle scores, pathological changes, and fiber elasticity, and increased PCNA and decreased MMP1 expression levels in photoaging mice, comparable to the two positive controls. Conclusion CGF can improve the symptoms of skin photoaging in mice, suggesting that it may have applications in the treatment of skin aging in humans.

Background Diabetic retinopathy (DR) is the leading cause of blindness in many countries. The current treatment for non-proliferative DR (NPDR) using Western medicine (WM) alone is insufficient. At present, the combination of NPDR treatment with traditional Chinese medicine (TCM) and WM is universally applied. We aimed to evaluate the effectiveness and safety of TCM as an add-on for NPDR using a systematic review and meta-analysis. Method Data from randomized controlled trials (RCTs) of TCM for NPDR treatment along with WM before July 6, 2019, were collected from the China National Knowledge Infrastructure, Wanfang Database, China Biomedical Database, Pubmed, Embase, and Cochrane Library. Relevant data were extracted by two reviewers. I2 statistics was adopted to appraise heterogeneity. If I2 Result Eighteen RCTs (1522 patients) were included based on the inclusion and exclusion criteria. The results showed that compared with WM alone, TCM (including Compound Xueshuantong Capsule, Qiming Granule, and others) combined with WM for NPDR could improve the overall effiicacy [n = 1686, RR 1.24 (1.18,1.30), P I2 = 0%], and reduce the influence of risk factors related to NPDR, such as glycated hemoglobin level [n = 360, MD − 0.85 (− 1.28, − 0.41), P = 0.0001, I2 = 72%], triglyceride (P P = 0.0008). Moreover, no serious adverse events were reported. Conclusion Compared with WM alone, TCM + WM could significantly improve NPDR and also reduce the correlation levels of risk factors, such as hyperglycemia, dyslipidemia. However, the small sample included in the study might lead to a publication bias, and therefore, our results should be treated with caution.

Radiation-induced optic neuropathy (RION) is a devastating complication following external beam radiation therapy (EBRT) that leads to acute vision loss. To date, no efficient, available treatment for this complication, due partly to the lack of understanding regarding the developmental processes behind RION. Here, we report radiation caused changes in mitochondrial dynamics by regulating the mitochondrial fission proteins dynamin-related protein 1 (Drp1) and fission-1 (Fis1). Concurrent with an excessive production of reactive oxygen species (ROS), both neuronal injury and visual dysfunction resulted. Further, our findings delineate an important mechanism by which cyclin-dependent kinase 5 (Cdk5)-mediated phosphorylation of Drp1 (Ser616) regulates defects in mitochondrial dynamics associated with neuronal injury in the development of RION. Both the pharmacological inhibition of Cdk5 by roscovitine and the inhibition of Drp1 by mdivi-1 inhibited mitochondrial fission and the production of ROS associated with radiation-induced neuronal loss. Taken together, these findings may have clinical significance in preventing the development of RION.

Bac kground Diabetic retinopathy (DR) is the leading cause of blindness in many countries. The current treatment of non-proliferative DR (NPDR) with Western medicine (WM) alone are still insufficient. At present, the treatment of NPDR with the combination of traditional Chinese medicine (TCM) and WM is universally applied, and we would evaluate the effectiveness and safety of TCM as an additional drug for NPDR with systematic reviews and meta-analysis. Method Data before July 6, 2019 were searched as randomized controlled trials (RCTs) of TCM for the treatment of NPDR with WM, which were collected from China National Knowledge Infrastructure , Wanfang Database , China Biomedical Database , Pubmed , Embase and Cochrane Library . Relevant data was extracted by two reviewers respectively. I 2 statistics was adopted to appraise the heterogeneity, if I 2 Result 18 RCTs (1522 patients) were included according to the inclusion criteria. The results showed that compared with WM, TCM (including Compound Xueshuantong Capsule, Qiming Granule, and others)+ WM for NPDR could improve overall efficiency [n=1686,RR1.24(1.18,1.30), P Conclusion Compared with WM alone, TCM+WM could significantly improve NPDR, and also reduced the correlation levels of risk factors, considering the sample size and the number of patients included in the study, there might be publication bias, so the corresponding results should be treated with caution.

Background: Diabetic nephropathy (DN), which affects more than 40% of diabetic patients, is still the main cause of end-stage renal disease in most countries. Prescription containing Astragalus Membranaceus (AM) in the treatment of early stage DN with significant effect, but the mechanism is unclear, which we would explore based on network pharmacology.Method: First, we searched the database of China National Knowledge Internet, Wanfang Database, Chinese Biomedical Literature Database, PubMed, EMBASE, Cochrane database about the randomized, single (double) blind, controlled clinical studies of prescription containing AM in the treatment of DN, determined the effectiveness of prescription containing AM in the treatment of DN. Then, the effective components of AM in Traditional Chinese Medicine systems taxonomy database and analysis platform (TCMSP), Traditional Chinese medicine integrated database (TCMID) and Bioinformatics analysis tool for molecular mechanism of traditio Internal Chinese medicine (BATMAN-TCM) database were searched. According to the oral utilization ≥ 30% and drug-like ≥0.18, the effective components were screened. PubChem and health information technology (HIT) databases were searched for query validation targets and Simplified molecular input line entry specification (SMILES) of the effective ingredients, and Swisstarget prediction database was used to obtain prediction targets (possibility > 0). Drugbank, transient triple differential (TTD), and DisGeNET were searched for the targets related to DN. Finally, the data were integrated by the Cytoscape software, the drug-target-disease network was drawn, the protein interaction network was drawn with String database, and the signal pathway enrichment analysis was carried out with ClueGO.Result: The results showed that prescription containing AM could effectively reduce the urinary protein excretion rate [95% md-43.30 (- 57.00, - 29.61)]. 51 active components, 396 verified targets and 2330 predicted targets were searched. A total of 120 DN related targets were retrieved. 21 targets were found with Cytoscape. The main pathways were Interleukin-4 and 13 signaling, Activation of Matrix Metalloproteinases, EPH-Ephrin signaling.Conclusion: Prescription containing AM could effectively reduce the urinary protein excretion rate of DN patients. We speculated that AM mainly treated DN by regulating Angiotensin-converting enzyme (ACE), Vascular endothelial growth factor A (VEGFA), Janus Kinase 1 (JAK1), and interleukin-4 (IL-4) and interleukin-13 (IL-13) signaling, activation of matrix metalloproteins, ephrin signaling and other signaling pathways based on network pharmacology, which would be verified by animal experiments or in vitro experiments in the later.

PURPOSE: We evaluated the feasibility of using an automatic segmentation tool to delineate cardiac substructures from noncontrast computed tomography (CT) images for cardiac dosimetry and toxicity analyses for patients with non-small cell lung cancer (NSCLC) after radiotherapy. METHODS AND MATERIALS: We used an in-house developed multi-atlas segmentation tool to delineate 11cardiac substructures, including the whole heart, four heart chambers, and six greater vessels, automatically from the averaged 4D-CT planning images of 49 patients with NSCLC. Two experienced radiation oncologists edited the auto-segmented contours. Times for automatic segmentation and modification were recorded. The modified contours were compared with the auto-segmented contours in terms of Dice similarity coefficient (DSC) and mean surface distance (MSD) to evaluate the extent of modification. Differences in dose-volume histogram (DVH) characteristics were also evaluated for the modified versus auto-segmented contours. RESULTS: The mean automatic segmentation time for all 11 structures was 7–9 min. For the 49 patients, the mean DSC values (±SD) ranged from 0.73±0.08 to 0.95±0.04, and the mean MSD values ranged from 1.3±0.6 mm to 2.9±5.1mm. Overall, the modifications were small; the largest modifications were in the pulmonary vein and the inferior vena cava. The heart V30 (volume receiving dose ≥30 Gy) and the mean dose to the whole heart and the four heart chambers were not different for the modified versus the auto-segmented contours based on the statistically significant condition of p

To evaluate aesthetic outcomes in patients with bilateral trapezius hypertrophy treated by botulinum toxin type A (BTxA) injection for aesthetic reconstruction of the upper trapezius. From May 2015 to May 2016, 30 women with a short neck shape resulting from bilateral trapezius hypertrophy were treated with botulinum toxin type A (BTxA) injection at the most affected area of the upper trapezius. Pre- and postoperative values of SACDF (irregularly shaped area of the four points A, C, D, and F) and SACDE (irregularly shaped area of the four points A, C, D, and E), responses to patients’ and doctors’ Global Aesthetic Improvement Scale (GAIS) questionnaires for neck aesthetic assessment, as well as reported adverse events, were recorded and analyzed. Duration of follow-up ranged from 4 to 12 months. Subjects experienced non-severe adverse events and complete recovery after a single BTxA injection. In patients’ GAIS questionnaires, “very much improved” accounted for 53%, “much improved” accounted for 13%, and “improved” accounted for 27%. In doctors’ GAIS questionnaires, “very much improved” accounted for 27%, “much improved” accounted for 33%, “improved” accounted for 33%, and “no change” accounted for 7%. The overall degree of improvement was high. Statistically significant differences were observed with respect to the “very much improved” response to GAIS questionnaires between patients and doctors (P = 0.035). A single injection of BTxA for aesthetic reconstruction of the upper trapezius is safe and effective in patients with bilateral trapezius hypertrophy. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The incidence of measles in Yunnan Province among vaccine target-age children has decreased markedly after attaining and sustaining high 2-dose coverage of measles containing vaccine (MCV) through routine immunization services and supplementary immunization activities (SIAs). Most cases of measles now occur among adults. In 2015, we investigated a measles outbreak among adults to determine transmission patterns and the potential role of nosocomial transmission.We enhanced measles surveillance using retrospective active case search. We conducted case investigations to determine sources of infection and routes of transmission; laboratory testing included serologic and molecular diagnostic methods.Twenty-two outbreak-associated cases of measles were identified; most (86.36%) were among individuals 20 to 39 years of age (range, 7 months to 43 years). We interviewed 19 individuals who had acquired measles. The first 3 cases were infected in Tibet; 12 (63%) were hospital-acquired infections; 2 (11%) were community-acquired; and 2 (11%) were family-contact cases. We conducted outbreak response immunization (ORI) that provided MCV without regard to vaccination status; 10,596 residents between 20 and 40 years of age were vaccinated. A serological survey conducted during the ORI showed that 84% of the 20-40 year-olds were immune to measles prior to vaccination. Post-vaccination serological testing showed 100% were immune.Despite high population immunity among children and adolescents, imported measles virus transmission occurred among adults in a provincial cross-border area. Nosocomial transmission and measles immunity gaps among adults poses a threat to measles elimination and highlights the strategy of targeting adults during ORI to outbreaks with adult-to-adult transmission.

Background: The urgency of the 2019 novel coronavirus outbreak has led to demand of effective antiviral agents Preliminary experiment indicated that Arbidol co

Excessive alcohol consumption is associated with hepatic steatosis and dysregulation of the gut microbiota in patients with alcohol use disorder. However, how gut microbiota responds when patients stop drinking has not been well studied. In this study, we use shotgun metagenomic sequencing to elucidate the alterations in the functional capacity of gut microbiota in patients with alcohol use disorder when they stop drinking for two-weeks. Sensitive microbial pathways to alcohol abstinence were identified in alcohol use disorder patients. Further, we found the functional microbial responses to alcohol abstinence were different in alcohol use disorder patients with different degree of hepatic steatosis. Our results provide insights into the link between functional alterations of the gut microbiota and steatosis associated with alcohol consumption.

BACKGROUND: Fucosyltransferase 2 (Fut2)-mediated intestinal α1-2-fucosylation is important in maintaining a symbiotic host-microbiota relationship and can protect against several pathogens. Intestinal dysbiosis is an important factor for the progression of experimental ethanol-induced liver disease, but the role of Fut2 in modulating the intestinal glycocalyx during alcohol-associated liver disease is unknown. We investigated the role of Fut2-mediated intestinal α1-2-fucosylation for the development of alcohol-associated liver disease. METHODS: Immunohistochemistry staining was applied to evaluate α1-2-fucosylation in duodenal biopsies from patients with alcohol use disorder. Wild type (WT) and Fut2 deficient littermate mice were subjected to Lieber DeCarli models of chronic ethanol administration and the chronic-binge ethanol diet (NIAAA model). RESULTS: Intestinal α1-2-fucosylation was down-regulated in patients with alcohol use disorder. Lack of α1-2-fucosylation in Fut2 deficient mice exacerbates chronic ethanol-induced liver injury, steatosis and inflammation without affecting ethanol metabolism. Dietary supplementation of the α1-2-fucosylated glycan 2’-fucosyllactose ameliorates ethanol-induced liver disease in Fut2 deficient mice in the NIAAA model. Despite no direct effects on growth of Enterococcus faecalis in vitro, intestinal α1-2-fucosylation reduces colonization of cytolysin-positive E. faecalis in the intestine of ethanol-fed mice. CONCLUSIONS: Intestinal α1-2-fucosylation acts as a host protective mechanism against ethanol-induced liver disease. 2’-FL is an oligosaccharide naturally present in human milk that could be considered as therapeutic agent for alcohol-associated liver disease.

Background: To evaluate the diagnostic value of Epstein–Barr virus (EBV) DNA in nasopharyngeal carcinoma (NPC) patients with locoregional or distant recurrence. Methods: Articles related to the diagnosis of recurrent or metastatic NPC by the detection of EBV DNA in plasma or serum were retrieved from different databases. Sensitivity, specificity, summary receiver operating characteristic (SROC) curves, and likelihood ratios were pooled to assess the diagnostic value of individual diagnostic tests. Results: This meta-analysis pooled 25 eligible studies including 2496 patients with NPC. The sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (−LR) of EBV DNA in the diagnosis of NPC were 0.858 (95% confidence interval (CI): 0.801–0.901), 0.890 (95% CI: 0.866–0.909), 7.782 (95% CI: 6.423–9.429) and 0.159 (95% CI: 0.112–0.226), respectively. The diagnostic odds ratio (DOR) was 48.865 (95% CI: 31.903–74.845). The SROC for EBV DNA detection was 0.93 (95% CI: 0.90–0.95). Conclusion: The detection of EBV DNA for the diagnosis of recurrent or metastatic NPC has good sensitivity and specificity and might be helpful in monitoring recurrent or metastatic NPC.

e14011 Background: Leptomeningeal metastasis (LM) is the deadliest complication of lung cancer. No standard therapy for the LM harbor non-sensitive epidermal growth factor receptor (EGFR)-mutant|(neither E19 del, E21 p.L858R nor E18 p. G719X mutation ). Previous studies showed cetuximab held the potential for treating the EGFR mutants who had failed 2 or more lines of standard cytotoxic chemotherapy and reversible EGFR TKIs. Methods: We screen the lung cancer patients with LM treated with Cetuximab-based regimen from July 1st, 2020 to Dec 31th 2020. The medical records were retrospectively reviewed and analyzed. Results: Three lung cancer patients with LM were included. All of them were heavily pretreated with various TKIs, chemotherapy, or/and with antiangiogenesis and PD-1 antibodies. When they were referred to our department, all these patients were in severe medical conditions. Case 1 has severe multiple cranial nerve impairment with cauda equina syndrome and massive malignant pleural effusion. Case 2 has intensively violent headaches with vomit and lumbosacral pain due to more than 500mm H2O of intracranial hypertension. Case 3 has acute pancreatitis due to oppressive obstruction of pancreatic duct by multiple metastatic tumors. The molecule test of tumor tissue or liquid from malignant pleural fluid have revealed E20 p.C797S in cis with p.T790M accompanied E19 del of EGFR gene in case 1, E21 p. R831H with E19 p.L747P of EGFR gene in case 2, and E20 p.S768_D770dup of EGFR gene in case 3, respectively. Their therapies were changed to cetuximab combined with TKI of afatinib or osimertinib, and local treatment including local radiation, intraventricular pemetrexed administration, or with intrathoracic drain. The disease control rate (DCR) was 100% of one partial remission (PR) and two stable disease (SD). The intracranial response was also observed in all the 3 patients showing CSF cytology turning negative or enhanced meningeal disappearance in MRI image with obviously relieved headache or/and improved cranial nerve palsy. The performance status of two patients was largely improved from Karnofsky Performance Status (KPS) scoring 20 to 90 and 50, respectively, and that of the other patient was stable with KPS scoring 50. The side effect is manageable skin rashes (grade II-III). Until this abstract was written, all the 3 patients were still alive. Conclusions: Cetuximab-based systemic therapy combined with local treatment demonstrated preliminary clinical activity in the rare EGFR-mutant lung cancer with LM who have already undergone heavily previous therapy, warranting further investigation.

e21017 Background: Lung adenocarcinoma (LUAD) occupies the most of non-small cell lung cancer (NSCLC) and shows promising response to PD-1 immunotherapy, but immune escape will cause treatment failure indicating poor prognosis. TWEAK (Tumor necrosis factor-related weak inducer of apoptosis, also known as TNFSF12) combining with its receptor FN14 (fibroblast growth factor–inducible 14) mediates crucial innate and adaptive immune pathways to promote the progression of multiple autoimmune diseases. So we assumed that TWEAK is a prognostic predictor and related with tumor-infiltrating immune cells (TIICs) in LUAD. Methods: TWEAK expression of LUAD was primarily investigated in The Cancer Immunome Atlas (TCIA) and then validated in Tumor Immune Estimation Resource (TIMER) databases. We assessed the effect of TWEAK on the survival via the Kaplan-Meier plotter, GEPIA2 (gene expression profiling interactive analysis) and PrognoScan databases. The relation between TWEAK and TIICs was explored in TIMER and TCIA, as well as the correlation of TWEAK and FN14 was analyzed in TIMER and GEPIA2. Results: Low TWEAK expression was significantly associated with poor relapse-free survival (RFS) (HR = 0.62, 95% CI = 0.4~0.97, logrank P = 0.035) and overall survival (OS) (HR = 0.61, 95% CI = 0.46~0.83, logrank P = 0.0012) in LUAD from Kaplan-Meier plotter. Similar impacts of TWEAK on the survival were validated in GEPIA2 and four independent cohorts from PrognoScan (jacob-00182-CANDF, GSE13213, jacob-00182-MSK and GSE31210). Moreover, reduced TWEAK expression was closely related with the paucity of TIICs which contributed to poor OS, including central memory CD8 T cells, plasmacytoid dendritic cells, activated CD8 T cells, monocytes, T follicular helper cells, immature B cells and eosinophils. In addition, TWEAK expression was positively related with the expression level of FN14 in both GEPIA2(R = 0.13, P= 0.0031) and TIMER (partial.cor = 0.212, P= 2.04e-06). Conclusions: Low TWEAK expression maybe indicate poor prognosis in LUAD, and correlated with the impaired infiltration of immune cells in the tumor region. The defective TWEAK/FN14 pathway possibly accounts for these observations, but the underlying mechanism needs to be further explored.

Ethnopharmacological relevance Sophora alopecuroides L., which is called Kudouzi in China, is a medicinal plant distributed in Western and Central Asia, especially in China, and has been used for decades to treat fever, bacterial infection, heart disease, rheumatism, and gastrointestinal diseases. Aim of the review This review aims to provide up-to-date information on S. alopecuroides, including its botanical characterization, medicinal resources, traditional uses, phytochemistry, pharmacological research, and toxicology, in exploring future therapeutic and scientific potentials. Materials and methods The information related to this article was systematically collected from the scientific literature databases including PubMed, Google Scholar, Web of Science, Science Direct, Springer, China National Knowledge Infrastructure, published books, PhD and MS dissertations, and other web sources, such as the official website of Flora of China and Yao Zhi website ( https://db.yaozh.com/ ). Results A total of 128 compounds, such as alkaloids, flavonoids, steroids, and polysaccharides, were isolated from S. alopecuroides. Among these compounds, the effects of alkaloids, such as matrine and oxymatrine, were extensively studied and developed into new drugs. S. alopecuroides and its active components had a wide range of pharmacological activities, such as anticancer, antiviral, anti-inflammatory, antimicrobial, analgesic, and neuroprotective functions, as well as protective properties against pulmonary fibrosis and cardiac fibroblast proliferation. Conclusions As an important traditional Chinese medicine, modern pharmacological studies have demonstrated that S. alopecuroides has prominent bioactivities, especially on gynecological inflammation and hepatitis B, and anticancer activities. These activities provide prospects for novel drug development for cancer and some chronic diseases. Nevertheless, the comprehensive evaluation, quality control, understanding of the multitarget network pharmacology, long-term in vivo toxicity, and clinical efficacy of S. alopecuroides require further detailed research.

To establish botulinum toxin-A (BTX-A) rejuvenation as an innovative technique to treat facial sagging with descent of the mid and lower face in Asian females. Between March 2016 and March 2017, 512 female patients with facial sagging were treated with regional platysma BTX-A injection. Droplet injection into the dermis was performed. Among the patients, 192 were recruited into our retrospective study. Eligible patients were divided into a pre-senile group (28–39 years old) and a senile group (> 40 years old). We analyzed the patient/physician-graded improvement, the mean scores of the 5-point improvement scale, and any reported complications. The overall degree of both patient- and physician-graded mid-face aesthetic improvement was very high. Improvement ratings reached 97.92% for patients and 94.79% for physicians. Improvement ratings were significantly greater in the pre-senile group compared to the senile group (p

Background Primary amoebic meningoencephalitis (PAM), caused by Naegleria fowleri, is a rare protozoan infectious disease in China. A fatality rate of over 95% had been reported due to extremely rapid disease progression in the USA and other countries. Rapid and precise identification of the causative agent is very important to clinicians for guiding their choices for administering countermeasures in the clinic. In this report, we applied the next-generation sequencing (NGS) method to rapidly show that N. fowleri was the causative agent of a fatal case involving a 42-year-old man with severe PAM disease, the first reported in mainland China. Case presentation A 42-year old male in a deep coma was admitted to Shenzhen Third People’s Hospital, a special medical care unit with expertise in infectious diseases. Increased intracranial pressure was detected. The cerebrospinal fluid (CSF) sample was found to be red and cloudy with increased leukocyte and protein levels. While bacterial cultures with CSF were negative, N. fowleri was determined to be the causative agent with NGS. Amphotericin B (AmB), a drug with anti-amoeba activity, was used immediately, but the treatment came too late and the patient died 2 days after the NGS confirmation. Conclusion In this paper, we reported a case of PAM disease for the first time in mainland China. NGS was used for rapid diagnosis and provided guidance for prescribing medications. However, the patient died due to a late admission amid advanced PAM disease. Early detection of N. fowleri is necessary in order to select effective drug treatments and control the disease progression. Despite the negative survival outcome, NGS was shown to be a promising method of rapid and precise identification of N. fowleri. Electronic supplementary material The online version of this article (10.1186/s12879-018-3261-z) contains supplementary material, which is available to authorized users.

Microfinance offers poor people access to basic financial services such as loans, savings, money transfer services and micro insurance. Corruption happens in microfinance area and the FCPA applies to it. In China, micro finance and social enterprises have developed for year; however, the government corruption poses a chilling climate for the flourish of microfinance and the innovation of private capital. Chinese government took measures to fight corruption and via the government’s action. Corruption problems became more tangible and more controllable.

Background: The bi-directional solid fermentation product extract of Trametes robiniophila Murr (Huaier) with Radix Isatidis (TIF) has been shown to have good anti-tumor activity. However, the mechanisms of this activity are still unknown. In the present study, we aimed to investigate its inhibitory effect on both SK-BR-3 and MDA-MB-231 cells, and explore the possible mechanisms of its anti-cancer effect in vitro. Methods: The experiment comprised a control group, Radix Isatidis group, Huaier group, and TIF group. The cell viability was measured by MTT and the distribution of cell cycle and apoptosis levels were analyzed by flow cytometry. Cell scratch, Transwell, and adhesion assays were used to measure the effects of the test compounds on the migration, invasion, and adhesion capability of SK-BR-3 and MDA-MB-231 cells. The effects of TIF on the mRNA and protein expression related to apoptosis and migration were measured by using semi-quantitative RT-PCR and western blotting. Results: TIF strongly inhibited the cell proliferation of the SK-BR-3 and MDA-MB-231 cells in a time-dependent manner and induced G2/M arrest and apoptosis. Furthermore, TIF significantly inhibited the proliferation, migration, invasion, and adhesion capabilities of SK-BR-3 and MDA-MB-231 cells. Compared with other treatments, the anticancer effect of TIF were stronger in MDA-MB-231 cells. Semi-quantitative RT-PCR suggested that TIF may upregulate the expression of p53 and caspase-3 to inhibit cell proliferation, and downregulate the expression of MMP-9/Snail and MMP-9/MMP-2 to inhibit the migration, invasion, and adhesion capabilities of SK-BR-3 and MDA-MB-231 cells. Western blotting results showed that TIF increased the expression of p53 protein and decreased the expression of MMP-9 protein in SK-BR-3 and MDA-MB-231 cells. Conclusion: The results indicated that the bi-directional solid fermentation may enhance the efficacy of Huaier in MDA-MB-231 cells and that TIF may be an effective complementary medicine for cancer treatment. Keywords: Apoptosis, Breast cancer, Fermentation, Huaier

Youyi Dai,1 Huaxin Duan,2,3 Chaojun Duan,4 Hong Zhu,1 Rongrong Zhou,1 Haiping Pei,5 Liangfang Shen1 1Department of Oncology, Xiangya Hospital, Central South University, 2Department of Oncology, Hunan Provincial People’s Hospital, 3Department of Oncology, The First Affiliated Hospital of Hunan Normal University, 4Institute of Medical Sciences, Xiangya Hospital, Central South University, 5Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, People’sRepublic of China Abstract: Colorectal cancer (CRC) has become a major public health problem, ranking as the third most common type of cancer. Our previous study has revealed that TCF21 is frequently silenced by promoter hypermethylation in both CRC cell lines and primary CRC, with TCF21 methylation being significantly correlated with lymph node invasion. In this study, we further analyze the expression of TCF21 in CRC tissues and investigate the role of TCF21 in CRC invitro and in vivo. We also explore the possible pathway regulated by TCF21. We thus demonstrate that decreased levels of TCF21 are associated with the pathological stage, clinical stage and lymph node metastasis, indicating a poor prognosis in CRC patients; overexpression of TCF21 inhibits cell proliferation, migration and invasion in the colorectal cell lines HCT116 and HT29. Furthermore, TCF21 functions as a tumor suppressor probably through inactivation of PI3K/AKT signaling and inhibition of MMPs. Our results suggest that enhancement of TCF21 levels may be a potential strategy to facilitate the prevention and treatment of CRC in the clinic. Keywords: colorectal cancer, TCF21, prognosis, PI3K/AKT signaling, MMPs

Human facial aesthetics relies on the classification of facial features and standards of attractiveness. However, there are no widely accepted quantitative criteria for facial attractiveness, particularly for Chinese Han faces. Establishing quantitative standards of attractiveness for facial landmarks within facial types is important for planning outcomes in cosmetic plastic surgery. The aim of this study was to determine quantitatively the criteria for attractiveness of eight female Chinese Han facial types. A photographic database of young Chinese Han women’s faces was created. Photographed faces (450) were classified based on eight established types and scored for attractiveness. Measurements taken at seven standard facial landmarks and their relative proportions were analyzed for correlations to attractiveness scores. Attractive faces of each type were averaged via an image-morphing algorithm to generate synthetic facial types. Results were compared with the neoclassical ideal and data for Caucasians. Morphological proportions corresponding to the highest attractiveness scores for Chinese Han women differed from the neoclassical ideal. In our population of young, normal, healthy Han women, high attractiveness ratings were given to those with greater temporal width and pogonion–gonion distance, and smaller bizygomatic and bigonial widths. As attractiveness scores increased, the ratio of the temporal to bizygomatic widths increased, and the ratio of the distance between the pogonion and gonion to the bizygomatic width also increased slightly. Among the facial types, the oval and inverted triangular were the most attractive. The neoclassical ideal of attractiveness does not apply to Han faces. However, the proportion of faces considered attractive in this population was similar to that of Caucasian populations. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Avionics is confronted with transitioning from a federated avionics architecture to an Integrated Modular Avionics (IMA) architecture. IMA architectures utilize shared, configurable computing, communication, and I/O resources to increase system scalability. Therefore, resources scheduling becomes a critical issue for IMA. This paper focuses on the process scheduling. We use preemption threshold scheduling strategy to improve process scheduling performance, and propose a two-stage tabu algorithm to optimize the preemption threshold and the priority respectively. Firstly, we investigate a convergence criterion to stop iteration of level-i busy period which is used to calculate the worse-case response time. Secondly, we propose the difference analysis method based on weight to evaluate the optimal schedule. Finally, we propose TS-preemption threshold and priority optimization algorithm to obtain the near-optimal assignment of the priority and the preemption threshold. The experiment results of different sizes of process scheduling problems illustrate the validity and effectivity of the algorithm.

To develop and validate a set of atlases for auto-contouring cardiac substructures.Eight radiation oncologists manually and independently delineated 15 cardiac substructures from noncontrast CT images of 6 patients by referring to their respective fused contrast CT images. Individual contours were fused together for each structure, edited by 2 physicians, and became atlases to delineate other 6 patients. The auto-delineated contours of the 6 additional patients became templates for manual contouring. These 12 patients with well-defined contours composed the final atlases for multi-atlas segmentation.The average time for manually contouring the 15 cardiac substructures was about 40min. Inter-observer variability was small for the heart, the chambers, and the aorta compared with that for other structures that were not clearly distinguishable in CT images. The mean dice similarity coefficient and mean surface distance of auto-segmented contours were within one standard deviation of expert contouring variability. Good agreement between auto-segmented and manual contours was observed for the heart, the chambers, and the great vessels. Independent validation on other 19 patients showed reasonable agreement for the heart chambers.A set of cardiac atlases was created for auto-contouring from noncontrast CT images. The accuracy of auto-contouring for the heart, chambers, and great vessels was validated for potential clinical use.

Past research on queuing has identified social justice as an important determinant of consumers’ waiting experiences. In queuing settings, people’s perception of social justice is affected by whether the principle of first in and first out (FIFO) has been violated. However, even when service follows the FIFO principle, waiting time may still differ from one consumer to another for various reasons. For instance, a consumer who happens to arrive in the queue after a large group of people may have to wait longer than average. In this research, it is argued that, aside from and independent of the FIFO principle, consumers also care about whether everyone spends an approximately equal amount of time waiting before availing of the product or service. When consumers perceive that they have spent more time waiting than others and when they can attribute this injustice to the service provider, they will be less satisfied with the waiting experience. It is also proposed that adherence to the FIFO principle is a more salient concern to consumers (thus termed “first-order” justice), and equal waiting time (“second-order” justice) matters only when first-order justice is not an issue. Three studies support the predictions. © 2008 Wiley Periodicals, Inc.

We propose that consumers’ investment decisions involve processes of promotion and prevention regulation that are managed across separate mental accounts, with different financial products seen as representative of promotion versus prevention. Consistent with this hypothesis, we show that (a) investors are differentially sensitive to gains and losses and differentially risk seeking depending on the financial products being considered and (b) that these phenomena occur because of strong associations between financial products and promotion versus prevention. Therefore, investors’ goals may be determined by the investment opportunities under evaluation rather than being independent of these opportunities, as is assumed in standard finance theory.

For the past fifteen years, automotive safety engineers have mainly relied on the Control Volume (CV) approach to simulate airbag deployment. The CV approach assumes that the gas is uniformly distributed in an inflated bag and therefore the airbag fabric is subject to uniform pressure. This assumption is true only when the airbag is fully deployed, and therefore makes CV approach inappropriate for Out-of-Position (OOP) safety analysis in which an occupant is in close proximity to the air bag module when it deploys, and therefore airbag-occupant interaction occurs before the bag is fully inflated. This paper describes the theory and validation of a new airbag simulation tool, an ALE-based (Arbitrary-Lagrange-Eulerian) approach. This tool, developed by Livermore Software Technology Corporation (LSTC), is aimed at using ALE as a CFD (Computational Fluid Dynamics) tool to model the gas flow inside a deploying airbag and the interaction between the airbag and the inflator gas. The validation of this methodology is performed through comparing the simulation results with test results of various test setup and airbag design.Copyright © 2007 by ASME

This paper presents an occupant-first approach, which allows for the simultaneous consideration of vehicle structure and the design of the occupant restraint system in the early stages. There are many difficulties in solving this problem, such as the large number of design variables, the large number of constraints and the highly non-linear nature of the occupant's responses. An efficient genetic algorithm (GA) is applied to deal with the challenges involved in the optimal design of the vehicle target pulse and the occupant restraint system. The methodology is demonstrated through a vehicle design problem. The results show that the occupant-first approach is effective and the GA is a valuable optimisation tool which can be used to achieve design targets.

In this research we examine the motivational influence of regulatory focus on revealed time preference. Drawing on regulatory focus research, we hypothesize an interaction effect between regulatory focus and valence such that, compared with prevention focus, promotion focus is associated with lower discount rate in the gain domain and a higher discount rate in the loss domain. This prediction was tested in three laboratory experiments where participants revealed their preference for intertemporal tradeoffs among hypothetical monetary rewards or payments. The data provide strong empirical support for the hypothesized interaction effect. These results highlight the importance of incorporating motivational influences in theoretical treatment of time discounting. The implications of the present research for the marketing of certain financial products that involve intertemporal tradeoffs (such as loans) are also discussed.