Five Karenia species along the Chinese coast: With the description of a new species, Karenia hui sp. nov. (Kareniaceae, Dinophyta).

Dinoflagellates within the genus Karenia are well known for their potential to cause harmful algal blooms and induce detrimental ecological consequences. In this study, five Karenia species, Karenia longicanalis, Karenia papilionacea, Karenia mikimotoi, Karenia selliformis, and a new species, Karenia hui sp. nov., were isolated from Chinese coastal waters. The new species exhibits the typical characteristics of the genus Karenia, including a linear apical groove and butanoyl-oxyfucoxanthin as the major accessory pigment. It is distinguished from the other Karenia species by a wide-open sulcal intrusion onto the epicone, a conical epicone with an apical crest formed by the rim of the apical groove, and a hunchbacked hypocone. It is most closely related to Karenia cristata, with a genetic divergence of 3.16 % (22 bp out of 883 bp of LSU rDNA). Acute toxicity tests indicated that the five Karenia species from China are all toxic to marine medaka Oryzias melastigma. Karenia selliformis and K. hui were very toxic to O. melastigma, resulting in 100 % mortality within 4 h and 24 h, respectively. Further analysis by high-performance liquid chromatography revealed that four species, K. selliformis, K. longicanalis, K. papilionacea and K. mikimotoi were capable of producing Gymnodimine-A (GYM-A). The highest GYM-A content was in K. selliformis (strain HK-43), in which the value was 889 fg/cell. No GYM-A was detected in the new species K. hui, however and its toxin remains unknown. Below we provide a comprehensive report of the morphology, phylogeny, pigment composition, and toxicity profiles of Karenia species along the Chinese coast. These findings contribute new insights for monitoring of Karenia species, with important toxicological and ecological implications.

Label-free and ultrasensitive detection of environmental lead ions based on spatially localized DNA nanomachines driven by hyperbranched hybridization chain reaction.

A label-free fluorescent sensing strategy for the rapid and highly sensitive detection of Pb2+ was developed by integrating Pb2+ DNAzyme-specific cleavage activity and a tetrahedral DNA nanostructure (TDN)-enhanced hyperbranched hybridization chain reaction (hHCR). This strategy provides accelerated reaction rates because of the highly effective collision probability and enriched local concentrations from the spatial confinement of the TDN, thus showing a higher detection sensitivity and a more rapid detection process. Moreover, a hairpin probe based on a G-triplex instead of a G-quadruplex or chemical modification makes hybridization chain reaction more controlled and flexible, greatly improving signal amplification capacities and eliminating labeled DNA probes. The enhanced reaction rates and improved signal amplification efficiency endowed the biosensors with high sensitivity and a rapid response. The label-free detection of Pb2+ based on G-triplex combined with thioflavin T can be achieved with a detection limit as low as 1.8 pM in 25 min. The proposed Pb2+-sensing platform was also demonstrated to be applicable for Pb2+ detection in tap water, river water, shrimp, rice, and soil samples, thus showing great potential for food safety and environmental monitoring.

Construction of machine learning models for recognizing comorbid anxiety in epilepsy patients based on their clinical and quantitative EEG features.

BACKGROUND: This study aimed to construct prediction models for the recognizing of anxiety disorders (AD) in patients with epilepsy (PWEs) by combining clinical features with quantitative electroencephalogram (qEEG) features and using machine learning (ML). METHODS: Nineteen clinical features and 20-min resting-state EEG were collected from 71 PWEs comorbid with AD and another 60 PWEs without AD who met the inclusion-exclusion criteria of this study. The EEG were preprocessed and 684 Phase Locking Value (PLV) and 76 Lempel-Ziv Complexity (LZC) features on four bands were extracted. The Fisher score method was used to rank all the derived features. We constructed four models for recognizing AD in PWEs, whether PWEs based on different combinations of features using eXtreme gradient boosting (XGboost) and evaluated these models using the five-fold cross-validation method. RESULTS: The prediction model constructed by combining the clinical, PLV, and LZC features showed the best performance, with an accuracy of 96.18%, precision of 94.29%, sensitivity of 98.33%, F1-score of 96.06%, and Area Under the Curve (AUC) of 0.96. The Fisher score ranking results displayed that the top ten features were depression, educational attainment, α_P3LZC, α_T6-PzPLV, α_F7LZC, ß_Fp2-O1PLV, θ_T4-CzPLV, θ_F7-PzPLV, α_Fp2LZC, and θ_T4-PzPLV. CONCLUSIONS: The model, constructed by combining the clinical and qEEG features PLV and LZC, efficiently identified the presence of AD comorbidity in PWEs and might have the potential to complement the clinical diagnosis. Our findings suggest that LZC features in the α band and PLV features in Fp2-O1 may be potential biomarkers for diagnosing AD in PWEs.

Outcomes of intermediate or high-risk CMML patients treated with hypomethylating agents combined with venetoclax: A single center experience.

Chronic myelomonocytic leukemia (CMML) treatment remains a pressing clinical challenge. We conducted a retrospective analysis on 52 CMML cases, exploring the effectiveness of combining venetoclax (Vene) with hypomethylating agents (HMAs). The study's findings show promise: the HMAs plus Vene group (n = 13, 53.8%) demonstrated superior overall response rates compared to the HMA monotherapy (mono) group (n = 19, 31.6%) and HMA plus arsenic trioxide group (n = 9, 22.2%) by the second cycle, and notably higher response rates (53.8% vs. 15.7%, p = 0.04) compared to the HMA mono group after four cycles. Over a median follow-up of 14.7 months, the HMAs plus Vene group exhibited significantly lower cumulative mortality (23.1%) compared to the other two groups (p = 0.003 and p = 0.008, respectively). Furthermore, this group displayed extended overall survival compared to the others. The study also delved into the molecular mechanisms, revealing significant BCL2 mRNA overexpression in patients with CMML. These findings suggest the potential for HMAs combined with Vene therapy in CMML but emphasize the necessity for further prospective studies to determine its precise role in managing CMML.

Determining effect of seagrass-mediated CO2 flux on the atmospheric cooling potential of a subtropical intertidal seagrass meadow.

Atmospheric greenhouse gas (GHG) emissions from seagrass meadows that determine the ecosystem atmospheric cooling effect have rarely been quantified. This study measured the simultaneous fluxes direct to the atmosphere of three GHGs (CO2, CH4 and N2O) within a Halophila beccarii seagrass meadow and an adjacent unvegetated bare intertidal flat, and their relationships to seagrass abundance and relevant soil parameters. The results showed that seasonal variation in seagrass abundance was strongly linked with the CO2 exchange rate. The CH4 and N2O fluxes were similarly low at both sites and comparable between winter and summer. The global warming potential of CH4 and N2O reduced the ecosystem CO2 uptake by only 5 % at the seagrass site. The results indicated that the H. beccarii meadow had a stronger atmospheric cooling effect than the bare flat and that the seagrass-mediated CO2 flux in this oligotrophic seagrass meadow primarily determined the atmospheric cooling effect.

The Preparation of Monomer Casting Polyamide 6/Thermotropic Liquid Crystalline Polymer Composite Materials with Satisfactory Miscibility.

It is highly expected to develop a simple and effective method to reinforce polyamide 6 (PA6) to enlarge its application potential. This is challenging because of frequently encountered multi-component phase separations. In this paper, we propose a novel method to solve this issue, essentially comprising two steps. Firstly, a kind of poly (amide-block-aramid) block copolymers, i.e., thermotropic liquid crystalline polymer (TLCP)-polyamide 6 (TLCP-PA6), that contains both rigid aromatic liquid crystal blocks, and flexible alkyl blocks were synthesized. It is unique in that TLCP is chemically linked with PA6, which is advantageous in excellent chemical and physical miscibility with the precursors of monomer casting polyamide 6 (MCPA6), i.e., ε-caprolactam. Secondly, such newly synthesized block copolymer TLCP-PA6 was dissolved in the melting ε-caprolactam, and followed by in situ polymerization to obtain composite polymer blends, i.e., MCPA6/TLCP-PA6. The thermodynamic, morphological, and crystalline properties of MCPA6/TLCP-PA6 can be easily manipulated by tailoring the loading ratios between TLCP-PA6 and ε-caprolactam. Especially, at the optimized condition, such MCPA6/TLCP-PA6 blends show an excellent miscibility. Systematic characterizations, including nuclear magnetic resonance (NMR), Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimeter (DSC), and polarizing optical microscope (POM), were performed to confirm these statements. In view of these results, it is anticipated that the overall mechanical properties of such PA6-based polymer composites will be satisfactory, which should enable applications in the modern plastic industry and other emerging areas, such as wearable fabrics.

Fine root densities of grasses and perennial sugarcane significantly reduce stream channel erosion in southern China.

Stream Channel (SC) erosion results in immense soil and nutrient losses and eutrophication of downstream lakes and rivers. Among other factors, the lack of vegetation cover within SCs and on adjacent soils can accelerate soil and nutrient losses. The combined impact of perennial sugarcane plantation and grass cover on increasing SC erosion losses have not been previously studied. Current study determined SC erosion and associated nutrient losses and clarified the effect of grass roots within SCs and the ratooned sugarcane grown on adjacent lands in Nala watershed in southern subtropics of China. Six SCs in two sub-watersheds (SW1 and SW2) surveyed after revegetation during 2019 were compared with initial survey conducted in 2017 and 2018. The SC erosion was significantly (P < 0.05) reduced by 84.2% (5.19 ± 2.16 Mg ha-1) in entire watershed in 2019 compared to 2018 (43.9 ± 15.2 Mg ha-1). It notably decreased by 99.23% and 96.50% in SC-1-3 at SW1 and SC2-3 at SW2, respectively. Total N and P losses decreased by 84.9% and 82.5%, respectively, in entire watershed. The decreases in SC erosion and nutrient losses are attributed to increasing vegetative cover (R2 = 0.7543, P < 0.001), and grass root densities of <1 mm (R2 = 0.7543, P < 0.001), 1-2 mm (R2 = 0.7051, P < 0.001) and >2 mm (R2 = 0.5746, P < 0.001). Principal component regression analysis confirmed that root densities of SC grasses, perennial sugarcane, and organic matter had positive impacts on controlling SC erosion and consequent nutrient losses.

Neoadjuvant systemic therapy in patients undergoing nephroureterectomy for urothelial cancer: a multidisciplinary systematic review and critical analysis.

INTRODUCTION: The benefit of neoadjuvant systemic therapy (NAST) is not yet supported by randomized controlled trials in upper tract urothelial carcinoma (UTUC), but the evidence is increasing. This narrative systematic review was conducted to evaluate the available evidence on the role of NAST in patients undergoing radical nephroureterectomy (RNU) for UTUC. EVIDENCE ACQUISITION: We searched for all relevant articles or conference abstracts published and indexed in PubMed, Embase, and Scopus on July 19, 2021. The study was reported according to the PRISMA criteria and designed within the PICOS framework. We included studies comparing patients with non-metastatic UTUC who received neoadjuvant chemotherapy (NAC) or immunotherapy (NAI) with patients who underwent definitive surgery alone or surgery plus adjuvant systemic therapy. Prospective uncontrolled studies were also included. EVIDENCE SYNTHESIS: We identified 27 reports (NAC, N.=24 and NAI, N.=3) published between 2010 and 2021. Twenty of the 24 studies on NAC were retrospective comparative analyses, whereas the remaining four were prospective single-arm studies. One of the three NAI studies exclusively enrolled patients with UTUC. NAC was associated with improved survival and better pathological response relative to surgery alone, but there was no clear advantage when compared to surgery plus adjuvant chemotherapy. Overall, the drug-induced toxicity and risk of disease progression were acceptable but the inherent bias across study designs, inadequate reporting and heterogeneous definition of primary outcomes render it difficult to synthesize results, compare centers, and inform practice. CONCLUSIONS: The current level of evidence supporting NAST for UTUC is relatively low and the inability to predict responsiveness and thereby pinpoint the optimal candidates remains a major challenge. There is a need to compare NAST to adjuvant therapies using clearly defined primary endpoints as minimum reporting standards developed by a multidisciplinary team.

Development and validation of a multi-parameter nomogram for predicting prostate cancer: a retrospective analysis from Handan Central Hospital in China.

Background: To explore the possible predicting factors related to prostate cancer and develop a validated nomogram for predicting the probability of patients with prostate cancer. Method: Clinical data of 697 patients who underwent prostate biopsy in Handan Central Hospital from January 2014 to January 2020 were retrospectively collected. Cases were randomized into two groups: 80% (548 cases) as the development group, and 20% (149 cases) as the validation group. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for prostate cancer. The nomogram prediction model was generated using the finalized independent risk factors. Decision curve analysis (DCA) and the area under receiver operating characteristics curve (ROC) of both development group and validation group were calculated and compared to validate the accuracy and efficiency of the nomogram prediction model. Clinical utility curve (CUC) helped to decide the desired cut-off value for the prediction model. The established nomogram with Prostate Cancer Prevention Trial Derived Cancer Risk Calculator (PCPT-CRC) and other domestic prediction models using the entire study population were compared. Results: The independent risk factors determined through univariate and multivariate logistic regression analyses were: age, tPSA, fPSA, PV, DRE, TRUS and BMI. Nomogram prediction model was developed with the cut-off value of 0.31. The AUC of development group and validation group were 0.856 and 0.797 respectively. DCA exhibits consistent observations with the findings. Through validating our prediction model as well as other three domestic prediction models based on the entire study population of 697 cases, our prediction model demonstrated significantly higher predictive value than all the other models. Conclusion: The nomogram for predicting prostate cancer can facilitate more accurate evaluation of the probability of having prostate cancer, and provide better ground for prostate biopsy.

Perampanel add-on therapy for drug-refractory epilepsy: A single-center retrospective study based on 6-month treatment outcomes in Central China.

OBJECTIVE: To systematically evaluate the efficacy, tolerability and retention of perampanel (PER) for treating drug-refractory epilepsy (DRE), and to investigate the independent factors affecting efficacy and retention. We hope this will provide clinicians with guidelines for the use of PER to treat patients with DRE. METHODS: We conducted a single-center retrospective observational study of patients with DRE who received PER as add-on therapy at the Epilepsy Center of the People's Hospital of Henan Province, China, between 2020 Mar. and 2021 Sep. We collected clinical data from these patients. The observation period was 6 months. The observation endpoint is the drug response and retention rate at 6 months of PER use. Regression analyses were used to compare the differences in efficacy and retention rates, respectively. RESULTS: Clinical data were obtained for 72 patients with DRE (mean duration of treatment: 10.6 months). At 6 months, 25% of patients (n = 18) were seizure free; 18.1% of patients (n = 13) remained seizure free for 6 months after the addition of PER. 22.2% of patients (n = 16) had a response (One of the patients was withdrawn 5 months after adding PER due to financial difficulties). The retention rate of PER at 6 months was 77.8%. Adverse effects tended to be dominated by neuropsychiatric symptoms. Multifactorial logistic regression analysis showed significant differences in whether the baseline seizure frequency exceeded 4 seizures/month (OR = 0.232, 95%CI: 0.077-0.702, p = 0.01) and whether the number of previously failed ASMs exceeded 3 (OR = 0.316; 95%CI:0.109-0.920, p = 0.035). This indicates that the risk of experiencing a nonresponse is higher with a higher baseline seizure frequency as well as with a higher number of previous ASM failures. Therefore, a baseline frequency exceeding four seizures/month and more than three previous ASM failures were independent influencing factors for PER addition treatment for patients with DRE. Multifactorial COX regression showed that patients with DRE due to infection had a lower retention rate (OR = 15.957, 95% CI: 3.692-68.972, P < 0.001) than patients with DRE due to other noninfectious etiologies. Patients with DRE who only had a single seizure type (OR = 0.053, 95% CI:0.006-0.476, P = 0.009), and patients who did not have cognitive impairment (OR = 134.253, 95% CI:5.623-3205.104, P = 0.002) showed longer durations of PER use. Infection-related epilepsy etiology, experiencing multiple types of seizures, and with cognitive impairment were independent influencing factors on PER use retention in patients with DRE. CONCLUSION: Our study demonstrated the efficacy of PER for reducing seizure frequency in patients with DRE and found significant differences in efficacy and retention rate, respectively. This provides a basis for assessing the expected efficacy and duration of use of PER for patients with DRE.

Adverse Events of Immune Checkpoint Inhibitors Therapy for Urologic Cancer Patients in Clinical Trials: A Collaborative Systematic Review and Meta-analysis.

CONTEXT: Therapies based on immune checkpoint inhibitors (ICIs) are transforming the treatment landscape of urologic oncology. Nevertheless, an exhaustive overview of the toxicity spectrum of these novel therapies has yet to be provided. OBJECTIVE: To comprehensively investigate the incidence and profile of ICI therapy-related adverse events (AEs) across urologic cancers. EVIDENCE ACQUISITION: We searched for all clinical trials investigating the role of ICI therapy published between January 2010 and September 2021. Studies involving urologic cancers with reported overall incidence or tabulated data of treatment-related AEs (trAEs) or immune-related AEs (irAEs) were included. A systematic review and meta-analysis was performed after protocol registration in PROSPERO (CRD42021276435). EVIDENCE SYNTHESIS: We identified 2638 records, of which 92 studies (including 22942 participants) met the inclusion criteria. The pooled overall incidence was 81.6% (95% confidence interval [CI] 78.0-84.7) for any-grade trAEs and 29.3% (95% CI 24.9-34.1) for grade ≥3 trAEs. The pooled overall incidence was 34.3% (95% CI 28.5-40.7) for any-grade irAEs and 10.2% (95%CI 8.2-12.7) for grade ≥3 irAEs. On a multivariable analysis, cancer type, therapy combination, clinical settings (perioperative vs advanced/metastatic), and drug exposure were independently associated with the occurrence of trAEs or irAEs. The overall rate of treatment-related mortality was 0.94% (140 of 14 899 participants), with pneumonitis (9.3%), pneumonia (7.9%), and respiratory failure (7.1%) being the most common causes. Immune-related mortality occurred in 0.26% (28 of 10 723) patients, with pneumonitis (35.7%), hepatic failure (10.7%), and hepatitis (7.1%) being most common. CONCLUSIONS: Our study provides a comprehensive overview of ICI-associated AEs in urologic cancer patients. The spectrum and incidence of AEs vary across cancer types, ICI types, clinical settings, and therapy combinations. These findings provide important guidance to clinicians in counseling and management of patients with urologic cancers. PATIENT SUMMARY: A high proportion of patients experience immune checkpoint inhibitor-associated toxicity. Physician and patient education is critical for early recognition and proper management.

An integrative prediction algorithm of drug-refractory epilepsy based on combined clinical-EEG functional connectivity features.

OBJECTIVE: Although the use of antiepileptic drugs (AEDs) is routine, 30-40% of patients with epilepsy (PWEs) experience drug resistance. Thus, early identification of AED resistance will help optimize treatment regimens and improve patients' prognoses. However, there have been few studies on this topic to date. Here, we try to establish an integrative prediction model of AED resistance for drug-naive PWEs, and to identify the clinical and Electroencephalogram (EEG) factors that affect their outcomes. METHODS: One hundred sixty-four PWEs naive to AEDs treated at a tertiary care center from January 2014 to June 2020 were retrospectively analyzed. A total of 113 of these patients were well controlled and 53 were drug refractory with regular AED treatment for more than one year. Eighty clinical characteristics and 684 EEG functional connectivity variables based on phase lag index before drug initiation were identified. Overall, 80% of each group was chosen to establish a support vector machine (SVM) model with ten-fold cross validation, and the other 20% were used to evaluate the model's performance. Absolute weight value was used to rank the features that had impacts on classification. RESULTS: An integrative algorithm was modeled to predict AED resistance for drug-naive PWEs by SVM based on clinical characteristics and EEG functional connectivity values. The model had an accuracy of 94% [95% confidence interval (CI) 0.85-1.0], sensitivity of 95% [95% CI 0.82-1.0], specificity of 93% [95% CI 0.77-1.0], and an area under the curve (AUC) of 0.98 [95% CI 0.91-1.0]. The p values of accuracy, sensitivity specificity and AUC were calculated as 0.001, 0.001, 0.01 and 0.001, respectively. The δ band fromT4-FZ and T3-PZ, α band from T3-T6 and ß band from F7-CZ and FP2-F3 were the top five EEG features that impacted the SVM classifier. CONCLUSION: We constructed an integrative prediction algorithm of AED resistance for drug-naive PWEs. Its utility in clinical settings should be evaluated in the future.

Association Between Stress Hyperglycemia Ratio and In-hospital Outcomes in Elderly Patients With Acute Myocardial Infarction.

Backgrounds: Emerging evidence suggests that stress hyperglycemia ratio (SHR), an index of relative stress hyperglycemia, is of great prognostic value in acute myocardial infarction (AMI), but current evidence is limited in elderly patients. In this study, we aimed to assess whether SHR is associated with in-hospital outcomes in elderly patients with AMI. Methods: In this retrospective study, patients who were aged over 75 years and diagnosed with AMI were consecutively enrolled from 2015, January 1st to 2019, December 31th. Admission blood glucose and glycosylated hemoglobin (HbA1C) during the index hospitalization were used to calculate SHR. Restricted quadratic splines, receiver-operating curves, and logistic regression were performed to evaluate the association between SHR and in-hospital outcomes, including in-hospital all-cause death and in-hospital major adverse cardiac and cerebrovascular events (MACCEs) defined as a composite of all-cause death, cardiogenic shock, reinfarction, mechanical complications of MI, stroke, and major bleeding. Results: A total of 341 subjects were included in this study. Higher SHR levels were observed in patients who had MACCEs (n = 69) or death (n = 44) during hospitalization. Compared with a SHR value below 1.25, a high SHR was independently associated with in-hospital MACCEs (odds ratio [OR]: 2.945, 95% confidence interval [CI]: 1.626-5.334, P < 0.001) and all-cause death (OR: 2.871 95% CI: 1.428-5.772, P = 0.003) in univariate and multivariate logisitic analysis. This relationship increased with SHR levels based on a non-linear dose-response curve. In contrast, admission glucose was only associated with clinical outcomes in univariate analysis. In subgroup analysis, high SHR was significantly predictive of worse in-hospital clinical outcomes in non-diabetic patients (MACCEs: 2.716 [1.281-5.762], P = 0.009; all-cause death: 2.394 [1.040-5.507], P = 0.040), but the association was not significant in diabetic patients. Conclusion: SHR might serve as a simple and independent indicator of adverse in-hospital outcomes in elderly patients with AMI, especially in non-diabetic population.

Stress Induced Hyperglycemia in the Context of Acute Coronary Syndrome: Definitions, Interventions, and Underlying Mechanisms.

Elevation of glucose level in response to acute coronary syndrome (ACS) has been recognized as stress induced hyperglycemia (SIH). Plenty of clinical studies have documented that SIH occurs very common in patients hospitalized with ACS, even in those without previously known diabetes mellitus. The association between elevated blood glucose levels with adverse outcome in the ACS setting is well-established. Yet, the precise definition of SIH in the context of ACS remains controversial, bringing confusions about clinical management strategy. Several randomized trials aimed to evaluate the effect of insulin-based therapy on outcomes of ACS patients failed to demonstrate a consistent benefit of intensive glucose control. Mechanisms underlying detrimental effects of SIH on patients with ACS are undetermined, oxidative stress might play an important role in the upstream pathways leading to subsequent harmful effects on cardiovascular system. This review aims to discuss various definitions of SIH and their values in predicting adverse outcome in the context of ACS, as well as the effect of intensive glucose control on clinical outcome. Finally, a glimpse of the underlying mechanisms is briefly discussed.

Genetic analysis using targeted next-generation sequencing of sporadic Chinese patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Inherited dilated cardiomyopathy (DCM) contributes to approximately 25% of idiopathic DCM cases, and the proportion is even higher in familial DCM patients. Most studies have focused on familial DCM, whereas the genetic profile of sporadic DCM in Chinese patients remains unknown. METHODS: Between June 2018 and September 2019, 24 patients diagnosed with idiopathic DCM without a family history were included in the present study. All patients underwent genetic screening for 80 DCM-related genes using targeted next-generation sequencing. RESULTS: By in silico analysis, 10 of 99 detected variants were considered pathogenic or likely-pathogenic, including seven TTN truncating variants (TTNtv), one in-frame deletion in TNNT2, one missense mutation in RBM20, and one frameshift deletion variant in FLNC. Of these variants, eight are reported for the first time. CONCLUSIONS: Using targeted next-generation sequencing, potential genetic causes of idiopathic DCM were identified. Sarcomere mutations remained the most common genetic cause of inherited DCM in this cohort of sporadic Chinese DCM.

Pure retroperitoneoscopic extravesical standardized seeable (PRESS) excision of distal ureter and bladder cuff in radical nephroureterectomy: step-by-step technique.

BACKGROUND: Concerns have been raised regarding the management of bladder cuff with these minimally invasive approaches. The aim of this study was to describe a modified radical nephroureterectomy (RNU) with pure retroperitoneoscopic extravesical standardized seeable (PRESS) bladder cuff excision (BCE) and to assess its outcomes based on a novel concept of intraoperative "trifecta." METHODS: Twenty-four patients with upper urinary tract urothelial carcinoma underwent retroperitoneoscopic RNU from August 2017 to August 2019. A modified RNU with PRESS BCE and lymph node dissection (LND) was performed. Descriptive analysis of patients' characteristics, surgical technique, perioperative outcomes, and follow-up data was performed. BCE trifecta was defined as en-bloc excision, mucosa-to-mucosa reliable closure and no urine spillage. RESULTS: In 23 out of 24 cases (95.8%) the procedure was successfully completed. One patient was converted to open distal ureterectomy with a Gibson incision due to peritoneum rupture during dissection of the distal ureter. BCE trifecta was achieved in 95.7% (22/23) cases of all patients finished with PRESS technique. Median OT was 260 min (IQR: 220-305) with median EBL of 100 mL (IQR: 100-250). Median OT for distal ureterectomy was 52 min (IQR: 40-69). No positive surgical margin occurred. Median postoperative hospital stay was 6 d (IQR: 5-7). Median follow-up time was 7 mo (IQR: 5-17). One patient (4.3%) experienced bladder recurrence and no patient developed distant metastasis or died of the disease. CONCLUSIONS: Herein, we demonstrate a standardized retroperitoneoscopic RNU technique that is safe and reproducible, enabling the visual confirmation of complete BCE and facilitating LND. BCE trifecta should be a routine goal in minimally invasive RNU. Prospective comparison with the standard open surgical technique is warranted.

EEG-Driven Prediction Model of Oxcarbazepine Treatment Outcomes in Patients With Newly-Diagnosed Focal Epilepsy.

Objective: Antiseizure medicine (ASM) is the first choice for patients with epilepsy. The choice of ASM is determined by the type of epilepsy or epileptic syndrome, which may not be suitable for certain patients. This initial choice of a particular drug affects the long-term prognosis of patients, so it is critical to select the appropriate ASMs based on the individual characteristics of a patient at the early stage of the disease. The purpose of this study is to develop a personalized prediction model to predict the probability of achieving seizure control in patients with focal epilepsy, which will help in providing a more precise initial medication to patients. Methods: Based on response to oxcarbazepine (OXC), enrolled patients were divided into two groups: seizure-free (52 patients), not seizure-free (NSF) (22 patients). We created models to predict patients' response to OXC monotherapy by combining Electroencephalogram (EEG) complexities and 15 clinical features. The prediction models were gradient boosting decision tree-Kolmogorov complexity (GBDT-KC) and gradient boosting decision tree-Lempel-Ziv complexity (GBDT-LZC). We also constructed two additional prediction models, support vector machine-Kolmogorov complexity (SVM-KC) and SVM-LZC, and these two models were compared with the GBDT models. The performance of the models was evaluated by calculating the accuracy, precision, recall, F1-score, sensitivity, specificity, and area under the curve (AUC) of these models. Results: The mean accuracy, precision, recall, F1-score, sensitivity, specificity, AUC of GBDT-LZC model after five-fold cross-validation were 81%, 84%, 91%, 87%, 91%, 64%, 81%, respectively. The average accuracy, precision, recall, F1-score, sensitivity, specificity, AUC of GBDT-KC model with five-fold cross-validation were 82%, 84%, 92%, 88%, 83%, 92%, 83%, respectively. We used the rank of absolute weights to separately calculate the features that have the most significant impact on the classification of the two models. Conclusion: (1) The GBDT-KC model has the potential to be used in the clinic to predict seizure-free with OXC monotherapy. (2). Electroencephalogram complexity, especially Kolmogorov complexity (KC) may be a potential biomarker in predicting the treatment efficacy of OXC in newly diagnosed patients with focal epilepsy.

Predicting seizure freedom with AED treatment in newly diagnosed patients with MRI-negative epilepsy: A large cohort and multicenter study.

OBJECTIVE: We developed and validated a prediction score for predicting the probability of 6-month and 12-month seizure freedom of antiepileptic drug (AED) treatment in newly diagnosed patients with magnetic resonance imaging (MRI)-negative epilepsy. METHODS: The development cohort included 543 consecutive patients from the Epilepsy Center of Henan Provincial People's Hospital, while the validation cohorts included 493 consecutive patients in two independent cohorts. Univariate analysis and a forward and backward elimination of multivariate Cox regression analysis were used to select predictive factors. The performance of the score was evaluated with C-index, calibration plots, and decision curve analysis. The risk stratification was also performed. RESULTS: The score included five routinely available predictors including Circadian rhythms, Electroencephalography before AED treatment, Neuropsychiatric disorders, Perinatal brain injury, and History of central nervous system infection (CENPH score). When applied to the external validation cohort, the score showed good discrimination with C-index (development group: 0.83; validation group: 0.78), and calibration plots indicated well calibration, as well as the decision curve analysis showed good predictive accuracy and clinical values in four cohorts. The points of the score were categorized to the following three probability levels for predicting seizure freedom: high probability (0-83.11 points), medium probability (83.11-122.71 points), and low probability (>122.71 points). And online calculator was established to make this score easily applicable in clinical practice. CONCLUSIONS: We established a simple, practical, and evidence-based prediction score for predicting seizure freedom with AEDs to aid in the clinical consultation and treatment decision for the newly diagnosed patients with MRI-negative epilepsy.

Fabricating Covalent Organic Framework Capsules with Commodious Microenvironment for Enzymes.

Enzyme immobilization has been demonstrated to be a favorable protocol to promote industrialization of biomacromolecules. Despite tremendous efforts to develop new strategies and materials to realize this process, maintaining enzyme activity is still a formidable challenge. Herein we created a sacrificial templating method, using metal-organic frameworks (MOFs) as sacrificial templates to construct hollow covalent organic framework (COF) capsules for enzyme encapsulation. This strategy can provide a capacious microenvironment to unleash enzyme molecules. The improved conformational freedom of enzymes, enhanced mass transfer, and protective effect against the external environment ultimately boosted the enzymatic activities. We also found that this strategy possesses high versatility that is suitable for diverse biomacromolecules, MOF templates, and COF capsules. Moreover, the dimensions, pore sizes, and shell thickness of COF capsules can be conveniently tuned, allowing for customizing bioreactors for specific functions. For example, coencapsulation of different enzymes with synergistic functions were successfully demonstrated using this bioreactor platform. This study not only opens up a new avenue to overcome the present limitations of enzymatic immobilization in porous matrixes but also provides new opportunities for construction of biomicrodevices or artificial organelles based on crystalline porous materials.

Identification of insulin gene variants in patients with neonatal diabetes in the Chinese population.

AIMS/INTRODUCTION: Neonatal diabetes mellitus is created by alterations in the genes responsible for beta-cell mass and/or function. The present study aimed to evaluate the genetic variants in the insulin gene (INS) in four Chinese infants aged <12 months with diabetes onset, and to explore the clinical and genetic characteristics of permanent neonatal diabetes mellitus caused by INS mutations. MATERIALS AND METHODS: The complete coding sequences of KCNJ11, ABCC8 and INS were detected using Sanger sequencing. The pathogenicity of the mutations was determined based on the American College of Medical Genetics and Genomics, and the structure of wild-type and mutant proteins was predicted using the web-based tool, Phyre2. RESULTS: One novel mutation (p.I99_C100insSI) and three previously reported variants (p.G32S, p.R89C and p.C96R) in INS were identified in four infants with early-onset diabetes. All the mutations in the four patients were de novo. Except for mutation R89C, which causes permanent neonatal diabetes mellitus through the addition of an additional cysteine residue at the cleavage site of the A chain and C-peptide, the other three mutations affected disulfide bonds. The patients had diabetes with marked hyperglycemia or diabetic ketoacidosis, and were then treated with exogenous insulin. Mutations in crucial regions of the INS might give rise to diabetes with varying severity. CONCLUSIONS: This study enriches our awareness of the mutant spectrum in INS, and suggests the important role of INS in the development of permanent neonatal diabetes mellitus.