Transition of intracranial aneurysmal wall enhancement from high to low wall shear stress mediation with size increase: A hemodynamic study based on 7T magnetic resonance imaging.

Background: Wall shear stress (WSS) has been proved to be related to the formation, development and rupture of intracranial aneurysms. Aneurysm wall enhancement (AWE) on magnetic resonance imaging (MRI) can be caused by inflammation and have confirmed its relationship with low WSS. High WSS can also result in inflammation but the research of its correlation with AWE is lack because of the focus on large aneurysms limited by 3T MRI in most previous studies.This study aimed to assess the potential association between high or low WSS and AWE in different aneuryms. Especially the relationship between high WSS and AWE in small aneurysm. Methods: Forty-three unruptured intracranial aneurysms in 42 patients were prospectively included for analysis. 7.0 T MRI was used for imaging. Aneurysm size was measured on three-dimensional time-of-flight (TOF) images. Aneurysm-to-pituitary stalk contrast ratio (CRstalk) was calculated on post-contrast black-blood T1-weighted fast spin echo sequence images. Hemodynamics were assessed by four-dimensional flow MRI. Results: The small aneurysms group had more positive WSS-CRstalk correlation coefficient distribution (dome: 78.6 %, p = 0.009; body: 50.0 %, p = 0.025), and large group had more negative coefficient distribution (dome: 44.8 %, p = 0.001; body: 69.0 %, p = 0.002). Aneurysm size was positively correlated with the significant OSI-CRstalk correlation coefficient at the dome (p = 0.012) and body (p = 0.010) but negatively correlated with the significant WSS-CRstalk correlation coefficient at the dome (p < 0.001) and body (p = 0.017). Conclusion: AWE can be mediated by both high and low WSS, and translate from high WSS- to low WSS-mediated pathways as size increase. Additionally, AWE may serve as an indicator of the stage of aneurysm development via different correlations with hemodynamic factors.

Efficacy of traditional Chinese medicine versus angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and their combinations in the treatment of IgA nephropathy: a systematic review and network meta-analysis.

Background: IgA nephropathy (IgAN), a condition posing a significant threat to public health, currently lacks a specific treatment protocol. Research has underscored the potential benefits of traditional Chinese medicine (TCM) for treating IgAN. Nevertheless, the effectiveness of various intervention strategies, such as combining TCM with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs), lacks a comprehensive systematic comparison. Therefore, this study aimed to conduct a network meta-analysis to assess the clinical efficacy of ACEIs, ARBs, TCM, and their combinations in treating IgAN to offer novel insights and approaches for the clinical management of IgAN. Methods: A systematic review conducted until November 2023 included relevant literature from databases such as PubMed, Embase, Cochrane, Web of Science, Scopus, CNKI, and Wanfang. Two independent researchers screened and assessed the data for quality. Network and traditional meta-analyses were performed using Stata 18.0 and RevMan 5.3 software, respectively. Outcome measures included 24-h urinary protein quantification (24 hpro), estimated glomerular filtration rate (eGFR), serum creatinine (Scr), blood urea nitrogen (BUN), and adverse event incidence rates (ADRs). Forest plots, cumulative ranking probability curves (SUCRA), and funnel plots generated using Stata 18.0 facilitated a comprehensive analysis of intervention strategies' efficacy and safety. Results: This study included 72 randomized controlled trials, seven interventions, and 7,030 patients. Comparative analysis revealed that ACEI + TCM, ARB + TCM combination therapy, and TCM monotherapy significantly reduced the levels of 24 hpro, eGFR, Scr, and BUN compared to other treatment modalities (p < 0.05). TCM monotherapy demonstrated the most favorable efficacy in reducing eGFR levels (SUCRAs: 78%), whereas the combination of ARB + TCM reduced Scr, 24 hpro, and BUN levels (SUCRAs: 85.7%, 95.2%, and 87.6%, respectively), suggesting that ARB + TCM may represent the optimal intervention strategy. No statistically significant differences were observed among the various treatment strategies in terms of ADR (p > 0.05). Conclusion: The combination of ACEI or ARB with TCM demonstrated superior efficacy compared to ACEI/ARB monotherapy in the treatment of IgAN without any significant ADRs. Therefore, combination therapies can be used to enhance therapeutic outcomes based on individual patient circumstances, highlighting the use of TCM as a widely applicable approach in clinical practice. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023476674.

Identification of a novel KCNT2 variant in a family with developmental and epileptic encephalopathies: a case report and literature review.

Background: Developmental and epileptic encephalopathies (DEEs) are a group of heterogeneous neurodevelopmental diseases characterized mainly by developmental delay/intellectual disability and early-onset epilepsy. Researchers have identified variations in the KCNT2 gene (OMIM* 610044) as the cause of DEE type 57 (MIM# 617771). Case presentation: We report in this study a 46-year-old woman who presented with early-onset epilepsy, intellectual disability, hypertrichosis, coarse facial features, and short stature. Besides, there were four other affected individuals in her family history, including two elder brothers, a younger brother, and their mother. We collected blood samples from the proband, her two affected brothers, and her clinically normal daughter for genetic analysis. Clinical exome sequencing revealed a novel heterozygous variant in the KCNT2 gene (NM_198503: c.188G>A, p.Arg63His) in the proband and her two affected brothers, while her daughter did not carry this variant. Furthermore, we reviewed all 25 patients identified in the literature with KCNT2 variants and compared their phenotypes. Conclusion: Epilepsy and intellectual disability/developmental delay occur in almost all patients with KCNT2 variants. KCNT2-relevant DEEs partially overlap with the clinical phenotypes of KATP channel diseases, particularly in hypertrichosis and distinctive coarse facial features.

Retracted: Expression of TP53, BCL-2, and VEGFA Genes in Esophagus Carcinoma and its Biological Significance.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Wei Wei, Yanqin Wang, Xiaoming Yu, Lan Ye, Yuhua Jiang, Yufeng Cheng. Expression of TP53, BCL-2, and VEGFA Genes in Esophagus Carcinoma and its Biological Significance. Med Sci Monit, 2015; 21: 3016-3022. DOI: 10.12659/MSM.894640.

JinChan YiShen TongLuo Formula ameliorate mitochondrial dysfunction and apoptosis in diabetic nephropathy through the HIF-1α-PINK1-Parkin pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The JinChan YiShen TongLuo (JCYSTL) formula, a traditional Chinese medicine (TCM), has been used clinically for decades to treat diabetic nephropathy (DN). TCM believes that the core pathogenesis of DN is "kidney deficiency and collateral obstruction," and JCYSTL has the effect of "tonifying kidney and clearing collateral," thus alleviating the damage to kidney structure and function caused by diabetes. From the perspective of modern medicine, mitochondrial damage is an important factor in DN pathogenesis. Our study suggests that the regulation of mitophagy and mitochondrial function by JCYSTL may be one of the internal mechanisms underlying its good clinical efficacy. AIM OF THE STUDY: This study aimed to investigate the mechanisms underlying the renoprotective effects of JCYSTL. MATERIALS AND METHODS: Unilateral nephrectomy combined with low-dose streptozotocin intraperitoneally injected in a DN rat model and high glucose (HG) plus hypoxia-induced HK-2 cells were used to explore the effects of JCYSTL on the HIF-1α/mitophagy pathway, mitochondrial function and apoptosis. RESULTS: JCYSTL treatment significantly decreased albuminuria, serum creatinine, blood urea nitrogen, and uric acid levels and increased creatinine clearance levels in DN rats. In vitro, medicated serum containing JCYSTL formula increased mitochondrial membrane potential (MMP); improved activities of mitochondrial respiratory chain complexes I, III, and IV; decreased the apoptotic cell percentage and apoptotic protein Bax expression; and increased anti-apoptotic protein Bcl-2 expression in HG/hypoxia-induced HK-2 cells. The treatment group exhibited increased accumulation of PINK1, Parkin, and LC3-II and reduced P62 levels in HG/hypoxia-induced HK-2 cells, whereas in PINK1 knockdown HK-2 cells, JCYSTL did not improve the HG/hypoxia-induced changes in Parkin, LC3-II, and P62. When mitophagy was impaired by PINK1 knockdown, the inhibitory effect of JCYSTL on Bax and its promoting effect on MMP and Bcl-2 disappeared. The JCYSTL-treated group displayed significantly higher HIF-1α expression than the model group in vivo, which was comparable to the effects of FG-4592 in DN rats. PINK1 knockdown did not affect HIF-1α accumulation in JCYSTL-treated HK-2 cells exposed to HG/hypoxia. Both JCYSTL and FG-4592 ameliorated mitochondrial morphological abnormalities and reduced the mitochondrial respiratory chain complex activity in the renal tubules of DN rats. Mitochondrial apoptosis signals in DN rats, such as increased Bax and Caspase-3 expression and apoptosis ratio, were weakened by JCYSTL or FG-4592 administration. CONCLUSION: This study demonstrates that the JCYSTL formula activates PINK1/Parkin-mediated mitophagy by stabilizing HIF-1α to protect renal tubules from mitochondrial dysfunction and apoptosis in diabetic conditions, presenting a promising therapy for the treatment of DN.

Diagnosis of intracranial aneurysms by computed tomography angiography using deep learning-based detection and segmentation.

BACKGROUND: Detecting and segmenting intracranial aneurysms (IAs) from angiographic images is a laborious task. OBJECTIVE: To evaluates a novel deep-learning algorithm, named vessel attention (VA)-Unet, for the efficient detection and segmentation of IAs. METHODS: This retrospective study was conducted using head CT angiography (CTA) examinations depicting IAs from two hospitals in China between 2010 and 2021. Training included cases with subarachnoid hemorrhage (SAH) and arterial stenosis, common accompanying vascular abnormalities. Testing was performed in cohorts with reference-standard digital subtraction angiography (cohort 1), with SAH (cohort 2), acquired outside the time interval of training data (cohort 3), and an external dataset (cohort 4). The algorithm's performance was evaluated using sensitivity, recall, false positives per case (FPs/case), and Dice coefficient, with manual segmentation as the reference standard. RESULTS: The study included 3190 CTA scans with 4124 IAs. Sensitivity, recall, and FPs/case for detection of IAs were, respectively, 98.58%, 96.17%, and 2.08 in cohort 1; 95.00%, 88.8%, and 3.62 in cohort 2; 96.00%, 93.77%, and 2.60 in cohort 3; and, 96.17%, 94.05%, and 3.60 in external cohort 4. The segmentation accuracy, as measured by the Dice coefficient, was 0.78, 0.71, 0.71, and 0.66 for cohorts 1-4, respectively. VA-Unet detection recall and FPs/case and segmentation accuracy were affected by several clinical factors, including aneurysm size, bifurcation aneurysms, and the presence of arterial stenosis and SAH. CONCLUSIONS: VA-Unet accurately detected and segmented IAs in head CTA comparably to expert interpretation. The proposed algorithm has significant potential to assist radiologists in efficiently detecting and segmenting IAs from CTA images.

Selective C-H Halogenation of Alkenes and Alkynes Using Flavin-Dependent Halogenases.

Single component flavin-dependent halogenases (FDHs) possess both flavin reductase and FDH activity in a single enzyme. We recently reported that the single component FDH AetF catalyzes site-selective bromination and iodination of a variety of aromatic substrates and enantioselective bromolactonization and iodoetherification of styrenes bearing pendant carboxylic acid or alcohol substituents. Given this inherent reactivity and selectivity, we explored the utility of AetF as catalyst for alkene and alkyne C-H halogenation. We find that AetF catalyzes halogenation of a range of 1,1-disubstituted styrenes, often with high stereoselectivity. Despite the utility of haloalkenes for cross-coupling and other applications, accessing these compounds in a stereoselective manner typically requires functional group interconversion processes, and selective halogenation of 1,1'-disubstituted olefins remains rare. We also establish that AetF and homologues of this enzyme can halogenate terminal alkynes. Mutagenesis studies and deuterium kinetic isotope effects are used to support a mechanistic proposal involving covalent catalysis for halogenation of unactivated alkynes by AetF homologues. These findings expand the scope of FDH catalysis and continue to show the unique utility of single component FDHs for biocatalysis.

Asprosin contributes to nonalcoholic fatty liver disease through regulating lipid accumulation and inflammatory response via AMPK signaling.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a primary contributor to liver-related morbidity and mortality. Asprosin has been reported to be implicated in NAFLD. AIMS: This work is to illuminate the effects of Asprosin on NAFLD and the possible downstream mechanism. MATERIALS & METHODS: The weight of NAFLD mice induced by a high-fat diet was detected. Quantitative reverse-transcription polymerase chain reaction (RT-qPCR) examined serum Asprosin expression. RT-qPCR and western blot analysis examined Asprosin expression in mice liver tissues. Intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) were implemented. Biochemical kits tested liver enzyme levels in mice serum and liver tissues. Hematoxylin and eosin staining evaluated liver histology. Liver weight was also tested and oil red O staining estimated lipid accumulation. RT-qPCR and western blot analysis analyzed the expression of gluconeogenesis-, fatty acid biosynthesis-, fatty acid oxidation-, and inflammation-associated factors. Besides, western blot analysis examined the expression of AMP-activated protein kinase (AMPK)/p38 signaling-associated factors. In palmitic acid (PA)-treated mice hepatocytes, RT-qPCR and western blot analysis examined Asprosin expression. Lipid accumulation, gluconeogenesis, fatty acid biosynthesis, fatty acid oxidation, and inflammation were appraised again. RESULTS: Asprosin was overexpressed in the serum and liver tissues of NAFLD mice and PA-treated mice hepatocytes. Asprosin interference reduced mice body and liver weight, improved glucose tolerance and diminished liver injury in vivo. Asprosin knockdown alleviated lipid accumulation and inflammatory infiltration both in vitro and in vivo. Additionally, Asprosin absence activated AMPK/p38 signaling and AMPK inhibitor Compound C reversed the impacts of Asprosin on lipid accumulation and inflammatory response. CONCLUSION: Collectively, Asprosin inhibition suppressed lipid accumulation and inflammation to obstruct NAFLD through AMPK/p38 signaling.

From Diabetic Nephropathy to End-Stage Renal Disease: The Effect of Chemokines on the Immune System.

Background: Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD), and there is growing evidence to support the role of immunity in the progression of DN to ESRD. Chemokines and chemokine receptors (CCRs) can recruit immune cells to sites of inflammation or injury. Currently, no studies have reported the effect of CCRs on the immune environment during the progression of DN to ESRD. Methods: Differentially expressed genes (DEGs) from the GEO database were identified in DN patients versus ESRD patients. GO and KEGG enrichment analyses were performed using DEGs. A protein-protein interaction (PPI) network was constructed to identify hub CCRs. Differentially expressed immune cells were screened by immune infiltration analysis, and the correlation between immune cells and hub CCRs was also calculated. Result: In this study, a total of 181 DEGs were identified. Enrichment analysis showed that chemokines, cytokines, and inflammation-related pathways were significantly enriched. Combining the PPI network and CCRs, four hub CCRs (CXCL2, CXCL8, CXCL10, and CCL20) were identified. These hub CCRs showed an upregulation trend in DN patients and a downregulation trend in ESRD patients. Immune infiltration analysis identified a variety of immune cells that underwent significant changes during disease progression. Among them, CD56bright natural killer cell, effector memory CD8 T cell, memory B cell, monocyte, regulatory T cell, and T follicular helper cell were significantly associated with all hub CCR correlation. Conclusion: The effect of CCRs on the immune environment may contribute to the progression of DN to ESRD.

Gene mutation landscape of a rare patient with acute megakaryoblastic leukemia after treatment of intracranial germ cell tumor.

Introduction: It was first reported that germ cell tumor patients suffer from hematologic malignancies 37 years ago. Since then, the number of relevant reports has increased each year, with most cases being mediastinal germ cell tumor. Theories have been proposed to explain this phenomenon, including a shared origin of progenitor cells, the effects of treatment, and independent development. However, up to now, no widely accepted explanation exists. The case with acute megakaryoblastic leukemia and intracranial germ cell tumor has never been reported before and the association is far less known. Methods: We used whole exome sequencing and gene mutation analysis to study the relationship between intracranial germ cell tumor and acute megakaryoblastic leukemia of our patient. Results: We report a patient who developed acute megakaryoblastic leukemia after treatment for an intracranial germ cell tumor. Through whole exome sequencing and gene mutation analysis, we identified that both tumors shared the same mutation genes and mutation sites, suggesting they originated from the same progenitor cells and differentiated in the later stage. Discussion: Our findings provide the first evidence supporting the theory that acute megakaryoblastic leukemia and intracranial germ cell tumor has the same progenitor cells.

Morphological features predicting in-stent stenosis after pipeline implantation for unruptured intracranial aneurysm.

Purpose: Elongation denotes the regularity of an aneurysm and parent artery. This retrospective research study was conducted to identify the morphological factors that could predict postoperative in-stent stenosis (ISS) after Pipeline Embolization Device (PED) implantation for unruptured intracranial aneurysms (UIAs). Methods: Patients with UIA and treated with PED at our institute between 2015 and 2020 were selected. Preoperative morphological features including both manually measured shape features and radiomics shape features were extracted and compared between patients with and without ISS. Logistic regression analysis was performed for factors associated with postoperative ISS. Results: A total of 52 patients (18 men and 34 women) were involved in this study. The mean angiographic follow-up time was 11.87 ± 8.26 months. Of the patients, 20 of them (38.46%) were identified with ISS. Multivariate logistic analysis showed that elongation (odds ratio = 0.008; 95% confidence interval, 0.001-0.255; p = 0.006) was an independent risk factor for ISS. The area under the curve (AUC) of the receiver operating characteristic curve(ROC) was 0.734 and the optimal cut-off value of elongation for ISS classification was 0.595. The sensitivity and specificity of prediction were 0.6 and 0.781, respectively. The ISS degree of elongation of less than 0.595 was larger than the ISS degree of elongation of more than 0.595. Conclusion: Elongation is a potential risk factor associated with ISS after PED implantation for UIAs. The more regular an aneurysm and parent artery, the less likelihood of an ISS occurrence.

The incidence and predictors of in-stent stenosis after pipeline flow-diverter stenting for intracranial aneurysm treatment.

Background and purpose: Data on in-stent stenosis (ISS) following the flow diverter (FD) implantation method are scarce and inconsistent. In the present study, we sought to determine the incidence of ISS and identify the factors that predict its severity via the use of ordinal logistic regression. Methods: A retrospective review of our center's electronic database was conducted to identify all patients with intracranial aneurysms (IAs) who received pipeline embolization device (PED) implantation between 2016 and 2020. Patient demographics, aneurysm characteristics, procedural information, and clinical and angiographic outcomes were reviewed. ISS was quantitatively assessed on angiographic follow-ups and graded as mild (<25%), moderate (25-50%), or severe (>50%). Ordinal logistic regression was conducted to determine the predictors of stenosis severity. Results: A total of 240 patients with 252 aneurysms treated in 252 procedures were enrolled in this study. ISS has been detected in 135 (53.6%) lesions, with a mean follow-up time of 6.53 ± 3.26 months. The ISS was mild in 66 (48.9%) cases, moderate in 52 (38.5%) cases, and severe in 17 (12.6%) cases. All patients were asymptomatic, except for two of them with severe stenosis who presented with symptoms of acute cerebral thrombosis. Ordinal logistic regression identified that younger age and a longer procedure duration were independent predictors of a higher likelihood of ISS. Conclusion: ISS is a common angiographic finding after PED implantation for IAs and is presented as a largely benign course through long-term follow-up. Patients who were younger in age and had a longer procedure duration were found to be at a greater risk of developing ISS.

Asymmetric catalysis by flavin-dependent halogenases.

In nature, flavin-dependent halogenases (FDHs) catalyze site-selective chlorination and bromination of aromatic natural products. This ability has led to extensive efforts to engineer FDHs for selective chlorination, bromination, and iodination of electron rich aromatic compounds. On the other hand, FDHs are unique among halogenases and haloperoxidases that exhibit catalyst-controlled site selectivity in that no examples of enantioselective FDH catalysis in natural product biosynthesis have been characterized. Over the past several years, our group has established that FDHs can catalyze enantioselective reactions involving desymmetrization, atroposelective halogenation, and halocyclization. Achieving high activity and selectivity for these reactions has required extensive mutagenesis and mitigation of problems resulting from hypohalous acid generated during FDH catalysis. The single-component flavin reductase/FDH AetF is unique among the wild type enzyme we have studied in that it provides high activity and selectivity toward several asymmetric transformations. These results highlight the ability of FDH active sites to tolerate different substrate topologies and suggest that they could be useful for a broad range of oxidative halogenations.

Long-term outcomes and dynamic changes of in-stent stenosis after Pipeline embolization device treatment of intracranial aneurysms.

BACKGROUND: Flow diverters have revolutionized the treatment of intracranial aneurysms. However, the delayed complications associated with flow diverter use are unknown. OBJECTIVE: To evaluate the incidence, severity, clinical outcomes, risk factors, and dynamic changes associated with in-stent stenosis (ISS) after treatment with a Pipeline embolization device (PED). METHODS: Patients who underwent PED treatment between 2015 and 2020 were enrolled. The angiographic, clinical, and follow-up data of 459 patients were independently reviewed by four neuroradiologists to identify ISS. Binary logistic regression was conducted to determine ISS risk factors, and an ISS-time curve was established to demonstrate dynamic changes in ISS after PED implantation. RESULTS: Of the 459 treated patients, 69 (15.0%) developed ISS. At follow-up, nine patients (2.0%) with ISS demonstrated reversal, while 18 (3.9%) developed parental artery occlusion. A total of 380 patients (82.8%) achieved complete aneurysm occlusion (O'Kelly-Marotta grade D). Patients with posterior-circulation aneurysm (OR=2.895, 95% CI (1.732 to 4.838; P<0.001) or balloon angioplasty (OR=1.992, 95% CI 1.162 to 3.414; P=0.037) were more likely to develop ISS. Patients aged >54 years (OR=0.464, 95% CI 0.274 to 0.785; P=0.006) or with a body mass index of >28 kg/m2 (OR=0.427, 95% CI 0.184 to 0.991; P=0.026) had a lower ISS risk. Intimal hyperplasia initiated by PED placement peaked within 1 year after the procedure, rarely progressed after 12 months, and tended to reverse within 24 months. CONCLUSIONS: ISS is a common, benign, and self-limiting complication of PED implantation in the Chinese population.

Clinical Outcomes and Risk Factors for Death following Carbapenem-Resistant Klebsiella pneumoniae Infection in Solid Organ Transplant Recipients.

Infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) are associated with significant morbidity and mortality. Among solid organ transplant recipients (SOTRs), clinical outcomes and risk factors for death following such infections remain not well documented. A single-center retrospective study was performed. All SOTRs with a CRKP infection at the First Affiliated Hospital of Zhengzhou University between 1 January 2018 and 31 December 2021 were included. Multivariable Cox regression was performed to determine risk factors for death following CRKP infection. We identified 94 SOTRs with CRKP infection, with a median age of 50 years old. CRKP infections resulted in 38.3% of overall 30-day mortality. On multivariable analysis, independent risk factors for death following CRKP infection included older age (hazard ratio [HR], 1.044; 95% confidence interval [CI], 1.007 to 1.083; P = 0.02), allograft failure (HR, 3.962; 95% CI, 1.628 to 9.644; P = 0.002), and septic shock (HR, 8.512; 95% CI, 3.294 to 21.998; P < 0.001). Receiving appropriate targeted therapy was associated with a reduced hazard of death (HR, 0.245; 95% CI, 0.111 to 0.543; P = 0.001). Our study characterized the clinical features and mortality in SOTRs with CRKP infection. The protective effects of appropriate targeted therapy highlight the importance of assessing how antibiotic choices affect the clinical outcomes among SOTRs. IMPORTANCE Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are increasingly identified in solid organ transplant recipients (SOTRs), but data on the clinical outcomes and risk factors for death following such infections remain limited. Here, we reported CRKP infection was associated with 38.3% of overall 30-day mortality in SOTRs. Independent risk factors for death after CRKP infection included older age, allograft failure, and septic shock. Appropriate targeted therapy was important for alleviating the impact of CRKP infections on these SOTRs.

Automated anatomical labeling of the intracranial arteries via deep learning in computed tomography angiography.

Background and purpose: Anatomical labeling of the cerebral vasculature is a crucial topic in determining the morphological nature and characterizing the vital variations of vessels, yet precise labeling of the intracranial arteries is time-consuming and challenging, given anatomical structural variability and surging imaging data. We present a U-Net-based deep learning (DL) model to automatically label detailed anatomical segments in computed tomography angiography (CTA) for the first time. The trained DL algorithm was further tested on a clinically relevant set for the localization of intracranial aneurysms (IAs). Methods: 457 examinations with varying degrees of arterial stenosis were used to train, validate, and test the model, aiming to automatically label 42 segments of the intracranial arteries [e.g., 7 segments of the internal carotid artery (ICA)]. Evaluation metrics included Dice similarity coefficient (DSC), mean surface distance (MSD), and Hausdorff distance (HD). Additionally, 96 examinations containing at least one IA were enrolled to assess the model's potential in enhancing clinicians' precision in IA localization. A total of 5 clinicians with different experience levels participated as readers in the clinical experiment and identified the precise location of IA without and with algorithm assistance, where there was a washout period of 14 days between two interpretations. The diagnostic accuracy, time, and mean interrater agreement (Fleiss' Kappa) were calculated to assess the differences in clinical performance of clinicians. Results: The proposed model exhibited notable labeling performance on 42 segments that included 7 anatomical segments of ICA, with the mean DSC of 0.88, MSD of 0.82 mm and HD of 6.59 mm. Furthermore, the model demonstrated superior labeling performance in healthy subjects compared to patients with stenosis (DSC: 0.91 vs. 0.89, p < 0.05; HD: 4.75 vs. 6.19, p < 0.05). Concurrently, clinicians with model predictions achieved significant improvements when interpreting the precise location of IA. The clinicians' mean accuracy increased by 0.04 (p = 0.003), mean time to diagnosis reduced by 9.76 s (p < 0.001), and mean interrater agreement (Fleiss' Kappa) increased by 0.07 (p = 0.029). Conclusion: Our model stands proficient for labeling intracranial arteries using the largest CTA dataset. Crucially, it demonstrates clinical utility, helping prioritize the patients with high risks and ease clinical workload.

The Single-Component Flavin Reductase/Flavin-Dependent Halogenase AetF is a Versatile Catalyst for Selective Bromination and Iodination of Arenes and Olefins.

Flavin-dependent halogenases (FDHs) natively catalyze selective halogenation of electron rich aromatic and enolate groups. Nearly all FDHs reported to date require a separate flavin reductase to supply them with FADH2 , which complicates biocatalysis applications. In this study, we establish that the single component flavin reductase/flavin dependent halogenase AetF catalyzes halogenation of a diverse set of substrates using a commercially available glucose dehydrogenase to drive its halogenase activity. High site selectivity, activity on relatively unactivated substrates, and high enantioselectivity for atroposelective bromination and bromolactonization was demonstrated. Site-selective iodination and enantioselective cycloiodoetherification was also possible using AetF. The substrate and reaction scope of AetF suggest that it has the potential to greatly improve the utility of biocatalytic halogenation.

Bifurcated Aneurysm Location Predicts In-Stent Stenosis After Neuroform-EZ Stent-Assisted Coiling for Intracranial Aneurysm.

Background and Purpose: The Neuroform EZ stent system (Boston Scientific Corporation, Fremont, CA, United States) is a fourth-generation intracranial aneurysm stent designed specifically for the cerebrovasculature to support aneurysm treatment. In this study, we analyzed our consecutive series of patients with aneurysm treated with the Neuroform EZ stent, with special attention to the occurrence of in-stent stenosis (ISS). Methods: A retrospective review of our center's electronic database was conducted to identify all patients with intracranial aneurysms who underwent aneurysm treatment with the Neuroform EZ stent between January 2016 and October 2018. Patients with at least one digital subtraction angiography (DSA) follow-up in our hospital were enrolled in this study. In-stent stenosis (ISS) was graded as mild (<2-5%), moderate (25-50%), or severe (>50%). Results: The study included 114 patients (78 women, 68.4%; median age 57.2 ± 9 years) with a total of 116 aneurysms. Of the 116 lesions, 20 were identified with ISS (17.2%) at a mean follow-up of 6.9 ± 1.7 months, and ISS was mild in 30% (6/20), moderate in 50% (10/20), and severe in 20% (4/20). No patients were symptomatic or required further intervention. Patients who developed ISS were younger than those without ISS (52.6 ± 7.8 vs. 57.9 ± 9; p = 0.016). The proportion of aneurysms located at the artery bifurcation was significantly higher in patients with stenosis than located at the sidewall artery (37.9 vs. 10.3%; p = 0.002). In the multivariable analysis, the patients' age (OR = 0.94; 95% CI 0.88-0.998; p = 0.02) and bifurcated aneurysm location (OR = 4.59; 95% CI 1.54-13.67; p = 0.006) were independent predictors of ISS. Conclusions: In this retrospective study, the incidence of ISS after Neuroform EZ stent placement was 17.2%, and all the ISS cases were asymptomatic. Patients with younger age and bifurcated aneurysm location are more likely to develop ISS. Although Neuroform EZ stent is particularly suitable for bifurcated aneurysms, the ISS for this location should be focused upon.

Renal Protective Effects of Melatonin in Animal Models of Diabetes Mellitus-Related Kidney Damage: A Systematic Review and Meta-Analysis.

Diabetic nephropathy (DN)-chronic kidney damage caused by hyperglycemia-eventually develops into end-stage renal disease (ESRD). Melatonin is a powerful antioxidant that has a wide range of biological activities. Potentially helpful effects of melatonin on diabetic kidney disease have been found in several studies. However, its protective mechanisms are not clear and remain to be explored. In this review (CRD42021285429), we conducted a meta-analysis to estimate the effects and relevant mechanisms of melatonin for diminishing renal injuries in diabetes mellitus models. The Cochrane Library, PubMed, and EMBASE databases up to September 2021 were used. Random- or fixed-effects models were used for calculating the standardized mean difference (SMD) or 90% confidence interval (CI). The risk of bias was estimated using the SYRCLE's RoB tool. Statistical analysis was conducted with RevMan. A total of 15 studies including 224 animals were included in the analysis. The experimental group showed a remarkable decrease in serum creatinine (P = 0.002), blood urea nitrogen (P = 0.02), and urinary albumin excretion rate (UAER) (P < 0.00001) compared with the control group, while the oxidative stress index improved. The experimental group also showed a remarkable increase in superoxide dismutase (P = 0.21), glutathione (P < 0.0001), and catalase (P = 0.04) and a remarkable decrease in MDA (P < 0.00001) content compared with the control group. We concluded that melatonin plays a role in renal protection in diabetic animals by inhibiting oxidative stress. Moreover, it should be noted that fasting blood glucose was reduced in the experimental group compared with the control group. The kidney and body weights of the animals were not decreased in the diabetic animal model compared with the control group.