Crystalline CdS/amorphous Cd(OH)2 Composite for Electrochemical CO2 Reduction to CO in a Wide Potential Window.

Electrochemical CO2 reduction is a promising method for converting atmospheric CO2 into valuable low-carbon chemicals. In this study, a crystalline cadmium sulfide/amorphous cadmium hydroxide composite was successfully deposited on the carbon paper substrate surface by in-situ chemical bath deposition (named as c-CdS/a-Cd(OH)2/CP electrodes) for the efficient electrochemical CO2 reduction to produce CO. The c-CdS/a-Cd(OH)2/CP electrode exhibited high CO Faradaic efficiencies (>90%) under a wide potential window of 1.0 V, with the highest value reaching ~100% at the applied potential ranging from -2.16 V to -2.46 V vs. ferrocene/ferrocenium (Fc/Fc+), superior to the crystalline counterpart c-CdS/CP and c-CdS/c-Cd(OH)2@CP electrodes. Meanwhile, the CO partial current density reached up to 154.7 mA cm-2 at -2.76 V vs. Fc/Fc+ on the c-CdS/a-Cd(OH)2/CP electrode. The excellent performance of this electrode was mainly ascribed to its special three-dimensional structure and the introduction of a-Cd(OH)2. These structures could provide more active sites, accelerate the charge transfer, and enhance adsorption of *COOH intermediates, thereby improving the CO selectivity. Moreover, the electrolytes consisting of 1-butyl-3-methylimidazolium tetrafluoroborate and acetonitrile also enhanced the reaction kinetics of electrochemical CO2 reduction to CO.

Prevalence of inappropriateness of elemene injection for hospitalized cancer patients: a multicenter retrospective study.

Background: Elemene injection could provide clinical benefit for the treatment of various cancers, but the clinical evidence is weak. Thus, its wide use in China has raised concerns about the appropriateness of its use. Methods: This was a multicenter retrospective study to evaluate the prevalence of inappropriateness of elemene injection for hospitalized cancer patients. Patients who met the inclusion criteria were retrospectively included, and demographic characteristics were extracted from the hospital information systems. The inappropriateness of elemene injection use was assessed using the preset criteria, and the prevalence was calculated. Multivariate logistic analysis was applied to identify any factors associated with inappropriate use. Results: A total of 275 patients were included in the analysis. The median age was 62 years, and 30.9% were females. The most common cancer was lung cancer (24.0%), and 68.2% of the patients were receiving chemotherapy. The overall prevalence of inappropriateness was 61.8%. The most common reason for inappropriateness was inappropriate indications, and the second was inappropriate doses. Age and oncological department were significant risk factors associated with inappropriate use, while lung cancer, liver cancer and admission to cardiothoracic surgery were associated with a low risk of inappropriate use. Conclusion: The prevalence of inappropriateness among hospitalized elemene injection users was high. More efforts, especially those to improve the appropriateness of indications, should be made to improve the rational use of elemene, as well as other complementary medicines. Physicians should take caution to avoid inappropriate use when prescribing drugs with limited clinical evidence.

Chinese Society of Cardiology guidelines on the diagnosis and treatment of adult fulminant myocarditis.

Fulminant myocarditis is an acute diffuse inflammatory disease of myocardium. It is characterized by acute onset, rapid progress and high risk of death. Its pathogenesis involves excessive immune activation of the innate immune system and formation of inflammatory storm. According to China's practical experience, the adoption of the "life support-based comprehensive treatment regimen" (with mechanical circulation support and immunomodulation therapy as the core) can significantly improve the survival rate and long-term prognosis. Special emphasis is placed on very early identification,very early diagnosis,very early prediction and very early treatment.

A Retrospective Real-World Study of Prognostic Factors Associated With EGFR Mutated Lung Cancer With Leptomeningeal Metastasis.

OBJECTIVE: To analyze the factors associated with EGFR-mutated lung cancer with leptomeningeal metastasis (LM) in the real world that affects the prognosis of patients. MATERIALS AND METHODS: The clinical data of 123 patients with advanced EGFR mutated lung cancer combined with LM treated at Henan Cancer Hospital and confirmed by histology between January 2016 and December 2020 were retrospectively collected, and all patients were followed up until September 2021. Analyze the median overall survival (mOS) time of patients with clinical characteristics and treatment factors to explore the factors influencing the prognosis of lung cancer patients with LM. RESULTS: A total of 123 patients with EGFR-mutated lung cancer and LM were included in this study. Overall, patients with exon 19 deletion (19del) in the classical mutation of the EGFR gene had a prolonged mOS compared to patients with exon 21 L858R mutation (21L858R) (30.1 months vs. 26.0 months); patients with primary LM (mOS 21.2 months) had a significantly shorter mOS than those with secondary LM (mOS 28.3 months); mOS was also significantly shorter in patients with combined brain metastases (mOS of 25.4 months) than in patients without combined brain metastases (mOS of 33.4 months); Patients treated with tyrosine kinase inhibitors (TKI) combined with antiangiogenic therapy (bevacizumab) experienced delayed onset of LM (mOS1: 19.4 months vs. 13.9 months), and prolonged survival after LM compared with those treated with EGFR-TKI alone (mOS2: 14.5 months vs. 10.0 months); There is no survival benefit to the patients treated with EGFR-TKI combined with chemotherapy compared to the patients treated with EGFR-TKI alone. CONCLUSION: Among NSCLC-LM patients with EGFR mutation, receiving EGFR-TKI combined with antiangiogenic therapy may result in a better survival benefit. The factors of primary LM, combined brain metastasis may be prognostic factors for poor OS.

Electrocatalytic Activity of CO2 Reduction to CO on Cadmium Sulfide Enhanced by Chloride Anion Doping.

The electrocatalytic CO2 reduction (ECR) to produce valuable fuel is a promising process for addressing atmospheric CO2 emissions and energy shortages. In this study, Cl-anion doped cadmium sulfide structures were directly fabricated on a nickel foam surface (Cl/CdS-NF) using an in situ hydrothermal method. The Cl-anion doping could significantly improve ECR activity for CO production in ionic liquid and acetonitrile mixed solution, compared to pristine CdS. The highest Faradaic efficiency of CO is 98.1 % on a Cl/CdS-NF-2 cathode with an excellent current density of 137.0 mA cm-2 at -2.25 V versus ferrocene/ferrocenium (Fc/Fc+ , all potentials are versus Fc/Fc+ in this study). In particular, CO Faradaic efficiencies remained above 80 % in a wide potential range of -2.05 V to -2.45 V and a maximum partial current density (192.6 mA cm-2 ) was achieved at -2.35 V. The Cl/CdS-NF-2, with appropriate Cl anions, displayed abundant active sites and a suitable electronic structure, resulting in outstanding ECR activity. Density functional theory calculations further demonstrated that Cl/CdS is beneficial for increasing the adsorption capacities of *COOH and *H, which can enhance the activity of the ECR toward CO and suppress the hydrogen evolution reaction.

Herbal medicine and gut microbiota: exploring untapped therapeutic potential in neurodegenerative disease management.

The gut microbiota that exists in the human gastrointestinal tract is incredibly important for the maintenance of general health as it contributes to multiple aspects of host physiology. Recent research has revealed a dynamic connection between the gut microbiota and the central nervous system, that can influence neurodegenerative diseases (NDs). Indeed, imbalances in the gut microbiota, or dysbiosis, play a vital role in the pathogenesis and progression of human diseases, particularly NDs. Herbal medicine has been used for centuries to treat human diseases, including NDs. These compounds help to relieve symptoms and delay the progression of NDs by improving intestinal barrier function, reducing neuroinflammation, and modulating neurotransmitter production. Notably, herbal medicine can mitigate the progression of NDs by regulating the gut microbiota. Therefore, an in-depth understanding of the potential mechanisms by which herbal medicine regulates the gut microbiota in the treatment of NDs can help explain the pathogenesis of NDs from a novel perspective and propose novel therapeutic strategies for NDs. In this review, we investigate the potential neuroprotective effects of herbal medicine, focusing on its ability to regulate the gut microbiota and restore homeostasis. We also highlight the challenges and future research priorities of the integration of herbal medicine and modern medicine. As the global population ages, access to this information is becoming increasingly important for developing effective treatments for these diseases.

Evidence mapping of clinical practice guidelines on nutritional management for pressure injuries and their quality.

CONTEXT: The safety and efficacy of nutritional management for pressure injuries (PIs) have been the subjects of ongoing interest. Some evidence demonstrated that nutrition is essential for skin and tissue viability, supporting tissue repair for healing the pressure injury. OBJECTIVE: This investigation aimed to systematically review clinical practice guidelines (CPGs) for the nutritional management of PIs and furnish an evidence map to assess research trends and CPG gaps. METHODS: The PubMed, Embase, and guidelines databases, and society websites were searched for CPGs for the nutritional management of PIs. The basic recommendations for the nutritional management of PIs, method quality, and reporting CPGs quality were identified and imported into Excel. Four researchers independently elucidated each CPG's quality via the Appraisal of Guidelines for Research & Evaluation (AGREE) II instrument and the Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist. All bubble charts were generated using Excel software. RESULTS: This review included 12 CPGs with a combined 23 recommendations. The nutrition screening and assessment were summarized on the basis of the PI recommendations for 6 major items, 12 items on nutrition management, and 3 on PI education. The assessed CPGs had mixed quality, and the highest score ± standard deviation based on the clarity of presentation was 83.46 ± 7.62, whereas the lowest mean score based on AGREE II applicability was 53.31 ± 16.90. Field 1 (basic information) in the RIGHT checklist had the greatest reporting rate (68.06%), whereas field 5 (review and quality assurance) had the lowest CPGs quality (41.67%). CONCLUSION: This investigation furnishes an evidence map and provides new perspectives on the CPGs for the nutritional management of PIs. However, the CPGs included still need improvement, especially in the applicability and editorial independence domains.

The Efficacy of Erector Spinae Plane Block for Thoracoscopic Surgery: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The efficacy of erector spinae plane block for thoracoscopic surgery remains controversial. We conducted a systematic review and meta-analysis to explore the impact of erector spinae plane block on thoracoscopic surgery. METHODS: We searched the PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through February 2022 for randomized controlled trials (RCTs), assessing the effect of erector spinae plane block on thoracoscopic surgery. This meta-analysis was performed using the random-effect model. RESULTS: Seven RCTs, involving 439 patients, are included in the meta-analysis. Overall, compared with the control group for thoracoscopic surgery, erector spinae plane block (ESPB) results in significantly reduced pain scores at 1 h (standard mean difference (SMD) = -4.26; 95% confidence interval (CI) = -7.63 to -0.88; p = 0.01), 4 h (SMD = -4.08; 95% CI = -4.56 to -3.60; p < 0.00001), 8 h (SMD = -4.13; 95% CI = -4.62 to -3.65; p < 0.00001), and postoperative anesthesia consumption (SMD = -3.04; 95% CI = -4.58 to -1.50; p = 0.0001) and can decrease the incidence of nausea and vomiting (odd ratio (OR) = 0.18; 95% CI = 0.08 to 0.39; p < 0.001). CONCLUSIONS: ESPB can substantially enhance pain relief for thoracoscopic surgery.

The Riddle of the Sphinx: Progress in Leptomeningeal Metastasis of Non-Small Cell Lung Cancer.

Leptomeningeal metastasis (LM) is a serious complication of advanced non-small cell lung cancer (NSCLC), and the incidence of LM has been increasing yearly in recent times. There is no consensus on the best treatment modality for LM, which underscores a difficult problem in the management of advanced NSCLC patients. The existing treatments include molecular targeted therapy, systemic chemotherapy, local radiotherapy, antivascular tumor therapy, intrathecal chemotherapy, and immunotherapy, but their efficacy is not satisfactory. In this article, we briefly describe the clinical manifestations, diagnosis, and treatment of NSCLC-LM and discuss progress regarding evaluation of the efficacy of LM treatment to better provide a necessary reference for clinical practice and clinical trial evaluation.

Cd/Cd(OH)2 Nanosheets Enhancing the Electrocatalytic Activity of CO2 Reduction to CO.

Electric-driven conversion of carbon dioxide (CO2 ) to carbon monoxide (CO) under mild reaction conditions offers a promising approach to mitigate the greenhouse effect and the energy crisis. Surface engineering is believed to be one of the prospective methods for enhancing the electrocatalytic activity of CO2 reduction. Herein, hydroxyl (OH) groups were successfully introduced to cadmium nanosheets to form cadmium and cadmium hydroxide nanocomposites (i. e. Cd/Cd(OH)2 nanosheets) via a facile two-step method. The as-prepared Cd/Cd(OH)2 /CP (CP indicates carbon paper) electrode displays excellent electrocatalytic activity for CO2 reduction to produce CO. The Faradaic efficiency of CO reaches 98.3 % and the current density achieves 23.8 mA cm-2 at -2.0 V vs. Ag/Ag+ in a CO2 -saturated 30 wt% 1-butyl-3-methylimidazole hexafluorophosphate ([Bmim]PF6 )-65 wt% acetonitrile (CH3 CN)-5 wt% water (H2 O) electrolyte. And the CO partial current density can reach up to 71.6 mA cm-2 with the CO Faradaic efficiency of more than 85 % at -2.3 V vs. Ag/Ag+ , which stands out against Cd/CP, Cd(OH)2 /CP, and Cd/CdO/CP electrodes. The excellent electrocatalytic performance of the Cd/Cd(OH)2 /CP electrode can be attributed to its unique structural properties, suitable OH groups, perfect interaction with electrolyte, abundant active sites and fast electron transfer rate.

Evaluating the Antioxidant Properties of the Leaves and Stems of Alpinia oxyphylla In Vitro and Its Growth-Promoting, Muscle Composition Change, and Antioxidative Stress Function on Juvenile Litopenaeus vannamei.

Alpinia oxyphylla is a homology of medicine and food. This study aims to investigate the dominant chemical composition and explore the antioxidant properties of the ethanol extract of the leaves and stems of A. oxyphylla (AOE) on juvenile shrimp, Litopenaeus vannamei. An in vitro test showed that AOE and its dominant chemical composition procyanidin B-2 (1) and epicatechin (2) presented DPPH and ABTS radical scavenging activities. A shrimp feeding supplement experiment revealed that shrimp growth parameters and muscle composition were improved significantly when fed with a 200 mg/Kg AOE additive. Meanwhile, the activities of antioxidant enzymes (CAT, GSH-Px, SOD, and T-AOC) in serum and the liver and the expression of related genes (LvMn-SOD, LvCAT, LvproPo, and LvGSH-Px) were enhanced with various degrees in different AOE additive groups while the content of MDA was significantly decreased. Moreover, the antioxidative effect of AOE additive groups on shrimp was also observed in an acute ammonia nitrogen stress test.

Should the trough concentration of vancomycin be abandoned in therapeutic drug monitoring? A multicentre, retrospective study of critically ill patients without any form of dialysis.

BACKGROUND: There are conflicts in guideline recommendations about the value and range of vancomycin trough concentration during therapeutic drug monitoring (TDM). This multicentre, retrospective study was conducted to explore the usefulness of trough concentration in specific patients who were critically ill and without any form of dialysis. METHODS: Patient information from five centres was retrospectively collected and the 24-hour area under the curve (AUC) was estimated by a Bayesian method. Patients were categorised into four groups according to trough concentration: < 10, 10-15, 15-20 and > 20 mg/L, and the corresponding AUC was analysed. A multivariable logistic regression model was used to investigate the relationship between trough concentration and AUC. RESULTS: Overall, 645 trough concentrations available from 416 patients were included in this study. The results indicated that the AUC was always < 400 mg/L∙h or > 600 mg/L∙h in the < 10 or > 20 mg/L groups, whereas the ratios of vancomycin AUC target attainment (400-600 mg/L∙h) were 48.8% and 92.3% in the 10-15 mg/L and 15-20 mg/L groups, respectively. Augmented renal clearance, low daily dose and non-q12h administration were found to be independent risk factors associated with AUC target non-attainment for patients with trough concentrations of 10-15 mg/L. CONCLUSION: Vancomycin trough concentration is a good marker of AUC for critically ill adults without any form of dialysis. However, AUC-guided TDM may be needed for patients with trough concentrations of 10-15 mg/L, especially for those with risk factors.

Advances in the Treatment of Rare Epidermal Growth Factor Receptor Mutations in Advanced Nonsmall-Cell Lung Cancer.

Epidermal growth factor receptor (EGFR) mutations are common driver genes in nonsmall-cell lung cancer and have different sensitivities to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). EGFR is divided into classic mutations and rare mutations. Classic mutations are well known, but the understanding of rare mutations is not sufficient. In this article, we summarize the clinical research and treatment progress of rare mutations for different EGFR-TKIs and provide a basis for clinical treatment decisions.

ErbB2-upregulated HK1 and HK2 promote breast cancer cell proliferation, migration and invasion.

ErbB2 is overexpressed in 15-20% of breast cancer, which is associated with malignancy and poor prognosis. We previously reported that ErbB2 supports malignant progression of breast cancer by upregulating lactate dehydrogenase A (LDHA), an important enzyme in glycolysis. However, whether ErbB2 promotes breast cancer progression through other glycolytic enzymes remains unclear. Hexokinase 1 (HK1) and hexokinase 2 (HK2) are the first rate-limiting enzymes of glycolysis and both of them are increased in breast cancer. Here, we aim to investigate whether ErbB2 upregulates HK1 and HK2 and the role of HK1 and HK2 in the malignant progression of ErbB2-overexpressing breast cancer. In current study, we found that the mRNA level of ErbB2 was positively correlated with that of HK1 and HK2, respectively. Moreover, ErbB2 upregulated the protein levels of HK1 and HK2 in breast cancer cells. We also found that both siHK1 and siHK2 significantly inhibited the proliferation, migration and invasion of ErbB2-overexpressing breast cancer cells. Taken together, our findings suggested that ErbB2 promoted the malignant progression of breast cancer cells by upregulating HK1 and HK2, and HK1 and HK2 might serve as promising therapeutic targets for ErbB2-overexpressing breast cancer.

Cerebral small-vessel disease at high altitude: A comparison of patients from plateau and plain.

Background and purpose: Cerebral small-vessel disease (CSVD) is prevalent worldwide and one of the major causes of stroke and dementia. For patients with CSVD at high altitude, a special environmental status, limited information is known about their clinical phenotype and specific neuroimaging change. We investigated the clinical and neuroimaging features of patients residing at high altitude by comparing with those in the plain, trying to explore the impact of high altitude environment on CSVD. Methods: Two cohorts of CSVD patients from the Tibet Autonomous Region and Beijing were recruited retrospectively. In addition to the collection of clinical diagnoses, demographic information and traditional vascular risk factors, the presence, location, and severity of lacunes and white matter hyperintensities were assessed by manual counting and using age-related white matter changes (ARWMC) rating scale. Differences between the two groups and influence of long-term residing in the plateau were analyzed. Results: A total of 169 patients in Tibet (high altitude) and 310 patients in Beijing (low altitude) were enrolled. Fewer patients in high altitude group were found with acute cerebrovascular events and concomitant traditional vascular risk factors. The median (quartiles) ARWMC score was 10 (4, 15) in high altitude group and 6 (3, 12) in low altitude group. Less lacunes were detected in high altitude group [0 (0, 4)] than in low altitude group [2 (0, 5)]. In both groups, most lesions located in the subcortical (especially frontal) and basal ganglia regions. Logistic regressions showed that age, hypertension, family history of stroke, and plateau resident were independently associated with severe white matter hyperintensities, while plateau resident was negatively correlated with lacunes. Conclusion: Patients of CSVD residing at high altitude showed more severe WMH but less acute cerebrovascular events and lacunes in neuroimaging, comparing to patients residing at low altitude. Our findings suggest potential biphasic effect of high altitude on the occurrence and progression of CSVD.

Patterns and Trends in Pharmacological Treatment for Outpatients with Postherpetic Neuralgia in Six Major Areas of China, 2015-2019.

The aim of this study was to assess the patterns and trends of pharmacological treatment for outpatients with postherpetic neuralgia (PHN) in China in the period 2015-2019. Prescription data for outpatients with PHN were extracted from the database of the Hospital Prescription Analysis Program of China according to the inclusion criteria. The trends in yearly prescriptions and corresponding costs were analyzed and stratified by drug class and specific drugs. A total of 19,196 prescriptions from 49 hospitals in 6 major regions of China were included for analysis. The yearly prescriptions increased from 2534 in 2015 to 5676 in 2019 (p = 0.027), and the corresponding expenditures increased from CNY 898,618 in 2015 to CNY 2,466,238 in 2019 (p = 0.027). Gabapentin and pregabalin are the most commonly used drugs for PHN, and more than 30% of these two drugs were combined with mecobalamin. Opioids were the second most frequently prescribed drug class, and oxycodone accounted for the largest share of the cost. Topical drugs and TCAs are rarely used. The frequent use of pregabalin and gabapentin was in accordance with current guidelines; however, the use of oxycodone raised concerns about rationality and economic burden. The results of this study may benefit the allocation of medical resources and management for PHN in China and other countries.

Metabolites, gene expression, and gut microbiota profiles suggest the putative mechanisms via which dietary creatine increases the serum taurine and g-ABA contents in Megalobrama amblycephala.

A 90-day experiment was conducted to explore the effects of creatine on growth performance, liver health status, metabolites, and gut microbiota in Megalobrama amblycephala. There were 6 treatments as follows: control (CD, 29.41% carbohydrates), high carbohydrate (HCD, 38.14% carbohydrates), betaine (BET, 1.2% betaine + 39.76% carbohydrates), creatine 1 (CRE1, 0.5% creatine + 1.2% betaine + 39.29% carbohydrates), creatine 2 (CRE2, 1% creatine + 1.2% betaine + 39.50% carbohydrates), and creatine 3 (CRE3, 2% creatine + 1.2% betaine + 39.44% carbohydrates). The results showed that supplementing creatine and betaine together reduced the feed conversion ratio significantly (P < 0.05, compared to CD and HCD) and improved liver health (compared to HCD). Compared with the BET group, dietary creatine significantly increased the abundances of Firmicutes, Bacteroidota, ZOR0006, and Bacteroides and decreased the abundances of Proteobacteria, Fusobacteriota, Vibrio, Crenobacter, and Shewanella in the CRE1 group. Dietary creatine increased the content of taurine, arginine, ornithine, γ-aminobutyric acid (g-ABA), and creatine (CRE1 vs. BET group) and the expression of creatine kinase (ck), sulfinoalanine decarboxylase (csad), guanidinoacetate N-methyltransferase (gamt), glycine amidinotransferase (gatm), agmatinase (agmat), diamine oxidase1 (aoc1), and glutamate decarboxylase (gad) in the CRE1 group. Overall, these results suggested that dietary supplementation of creatine (0.5-2%) did not affect the growth performance, but it altered the gut microbial composition at the phylum and genus levels, which might be beneficial to the gut health of M. amblycephala; dietary creatine also increased the serum content of taurine by enhancing the expressions of ck and csad and increased the serum content of g-ABA by enhancing the arginine content and the expressions of gatm, agmat, gad, and aoc1.

Clinical and prognostic characteristics of cerebral venous thrombosis at high altitude: a single-center retrospective study of Tibet.

OBJECTIVE: Data regarding diagnosis, management, and prognosis of patients with cerebral venous thrombosis (CVT) from high altitude are limited. The aim of the present study is to identify the clinical features, risk factors, and outcomes of cerebral venous thrombosis (CVT) in Tibet. METHODS: We retrospectively included patients with a diagnosis of CVT consecutively admitted to Tibet Autonomous Region People's Hospital between July 2015, and September 2022. The risk factors, clinical and radiological presentations, treatment and outcomes were analyzed. RESULTS: A total of 38 patients with CVT were included in this study. The median age was 31 years, and females accounted for 63.2%. Patients of Tibetan nationality accounted for 71.1% (n = 27) and the median altitude of residence in Tibet was 3800 m (3657, 4054). Headache was the most common symptom (92.1%). The most common risk factors of CVT were infection in the past 4 weeks (34.2%) and pregnancy or puerperium (23.7%). Lateral sinus (transverse and/or sigmoid sinus) (68.4%) and superior sagittal sinus (55.3%) were the most commonly involved. The D-dimer increased in 31 patients (81.6%). All three patients who died in hospital and during follow-up had risk factor of recent infection. Favorable outcome at follow-up with a median length of 454 days (189, 1059) was observed in 85.3% of patients. CONCLUSIONS: CVT at high altitude is more common in young patients and women, with various clinical manifestations and risk factors. Recent infection is the most common risk factor and may increase the mortality of CVT at high altitude. The long-term prognosis of CVT at high altitude is favorable.