ETV5 promotes lupus pathogenesis and follicular helper T cell differentiation by inducing osteopontin expression.

Follicular helper T (TFH) cells mediate germinal center reactions to generate high affinity antibodies against specific pathogens, and their excessive production is associated with the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus (SLE). ETV5, a member of the ETS transcription factor family, promotes TFH cell differentiation in mice. In this study, we examined the role of ETV5 in the pathogenesis of lupus in mice and humans. T cell-specific deletion of Etv5 alleles ameliorated TFH cell differentiation and autoimmune phenotypes in lupus mouse models. Further, we identified SPP1 as an ETV5 target that promotes TFH cell differentiation in both mice and humans. Notably, extracellular osteopontin (OPN) encoded by SPP1 enhances TFH cell differentiation by activating the CD44-AKT signaling pathway. Furthermore, ETV5 and SPP1 levels were increased in CD4+ T cells from patients with SLE and were positively correlated with disease activity. Taken together, our findings demonstrate that ETV5 is a lupus-promoting transcription factor, and secreted OPN promotes TFH cell differentiation.

Crystal Nucleation in Supercooled Atomic Liquids.

The liquid-to-solid phase transition is a complex process that is difficult to investigate experimentally with sufficient spatial and temporal resolution. A key aspect of the transition is the formation of a critical seed of the crystalline phase in a supercooled liquid, that is, a liquid in a metastable state below the melting temperature. This stochastic process is commonly described within the framework of classical nucleation theory, but accurate tests of the theory in atomic and molecular liquids are challenging. Here, we employ femtosecond x-ray diffraction from microscopic liquid jets to study crystal nucleation in supercooled liquids of the rare gases argon and krypton. Our results provide stringent limits to the validity of classical nucleation theory in atomic liquids, and offer the long-sought possibility of testing nonclassical extensions of the theory.

Clinical Outcomes of Solid Organ Transplant Recipients Hospitalized with COVID-19: A Propensity Score-Matched Cohort Study.

BACKGROUND: Solid-organ transplant recipients (SOTRs) receiving immunosuppressive therapy are expected to have worse clinical outcomes from coronavirus disease 2019 (COVID-19). However, published studies have shown mixed results, depending on adjustment for important confounders such as age, variants, and vaccination status. MATERIALS AND METHODS: We retrospectively collected the data on 7,327 patients hospitalized with COVID-19 from two tertiary hospitals with government-designated COVID-19 regional centers. We compared clinical outcomes between SOTRs and non-SOTRs by a propensity score-matched analysis (1:2) based on age, gender, and the date of COVID-19 diagnosis. We also performed a multivariate logistic regression analysis to adjust other important confounders such as vaccination status and the Charlson comorbidity index. RESULTS: After matching, SOTRs (n=83) had a significantly higher risk of high-flow nasal cannula use, mechanical ventilation, acute kidney injury, and a composite of COVID-19 severity outcomes than non-SOTRs (n=160) (all P <0.05). The National Early Warning Score was significantly higher in SOTRs than in non-SOTRs from day 1 to 7 of hospitalization (P for interaction=0.008 by generalized estimating equation). In multivariate logistic regression analysis, SOTRs (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.12-4.11) and male gender (OR, 2.62; 95% CI, 1.26-5.45) were associated with worse outcomes, and receiving two to three doses of COVID-19 vaccine (OR, 0.43; 95% CI, 0.24-0.79) was associated with better outcomes. CONCLUSION: Hospitalized SOTRs with COVID-19 had a worse prognosis than non-SOTRs. COVID-19 vaccination should be implemented appropriately to prevent severe COVID-19 progression in this population.

Tau propagation in the brain olfactory circuits is associated with smell perception changes in aging.

The direct access of olfactory afferents to memory-related cortical systems has inspired theories about the role of the olfactory pathways in the development of cortical neurodegeneration in Alzheimer's disease (AD). In this study, we used baseline olfactory identification measures with longitudinal flortaucipir and PiB PET, diffusion MRI of 89 cognitively normal older adults (73.82 ± 8.44 years; 56% females), and a transcriptomic data atlas to investigate the spatiotemporal spreading and genetic vulnerabilities of AD-related pathology aggregates in the olfactory system. We find that odor identification deficits are predominantly associated with tau accumulation in key areas of the olfactory pathway, with a particularly strong predictive power for longitudinal tau progression. We observe that tau spreads from the medial temporal lobe structures toward the olfactory system, not the reverse. Moreover, we observed a genetic background of odor perception-related genes that might confer vulnerability to tau accumulation along the olfactory system.

Clinical Value of Single-Projection Angiography-Derived FFR in Noninfarct-Related Artery.

BACKGROUND: The Murray law-based quantitative flow ratio (µFR) is an emerging technique that requires only 1 projection of coronary angiography with similar accuracy to quantitative flow ratio (QFR). However, it has not been validated for the evaluation of noninfarct-related artery (non-IRA) in acute myocardial infarction (AMI) settings. Therefore, our study aimed to evaluate the diagnostic accuracy of µFR and the safety of deferring non-IRA lesions with µFR >0.80 in the setting of AMI. METHODS: µFR and QFR were analyzed for non-IRA lesions of patients with AMI enrolled in the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction), consisting of fractional flow reserve (FFR)-guided percutaneous coronary intervention and angiography-guided percutaneous coronary intervention groups. The diagnostic accuracy of µFR was compared with QFR and FFR. Patients were classified by the non-IRA µFR value of 0.80 as a cutoff value. The primary outcome was a vessel-oriented composite outcome, a composite of cardiac death, non-IRA-related myocardial infarction, and non-IRA-related repeat revascularization. RESULTS: µFR and QFR analyses were feasible in 443 patients (552 lesions). µFR showed acceptable correlation with FFR (R=0.777; P<0.001), comparable C-index with QFR to predict FFR ≤0.80 (µFR versus QFR: 0.926 versus 0.961, P=0.070), and shorter total analysis time (mean, 32.7 versus 186.9 s; P<0.001). Non-IRA with µFR >0.80 and deferred percutaneous coronary intervention had a significantly lower risk of vessel-oriented composite outcome than non-IRA with performed percutaneous coronary intervention (3.4% versus 10.5%; hazard ratio, 0.37 [95% CI, 0.14-0.99]; P=0.048). CONCLUSIONS: In patients with multivessel AMI, µFR of non-IRA showed acceptable diagnostic accuracy comparable to that of QFR to predict FFR ≤0.80. Deferred non-IRA with µFR >0.80 showed a lower risk of vessel-oriented composite outcome than revascularized non-IRA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02715518.

Design of High Affinity Binders to Convex Protein Target Sites.

While there has been progress in the de novo design of small globular miniproteins (50-65 residues) to bind to primarily concave regions of a target protein surface, computational design of minibinders to convex binding sites remains an outstanding challenge due to low level of overall shape complementarity. Here, we describe a general approach to generate computationally designed proteins which bind to convex target sites that employ geometrically matching concave scaffolds. We used this approach to design proteins binding to TGFßRII, CTLA-4 and PD-L1 which following experimental optimization have low nanomolar to picomolar affinities and potent biological activity. Co-crystal structures of the TGFßRII and CTLA-4 binders in complex with the receptors are in close agreement with the design models. Our approach provides a general route to generating very high affinity binders to convex protein target sites.

Social context modulates multibrain broadband dynamics and functional brain-to-brain coupling in the group of mice.

Although mice are social, multiple animals' neural activities are rarely explored. To characterise the neural activities during multi-brain interaction, we simultaneously recorded local field potentials (LFP) in the prefrontal cortex of four mice. The social context and locomotive states predominately modulated the entire LFP structure. The power of lower frequency bands-delta to alpha-were correlated with each other and anti-correlated with gamma power. The high-to-low-power ratio (HLR) provided a useful measure to understand LFP changes along the change of behavioural and locomotive states. The HLR during huddled conditions was lower than that during non-huddled conditions, dividing the social context into two. Multi-brain analyses of HLR indicated that the mice in the group displayed high cross-correlation. The mice in the group often showed unilateral precedence of HLR by Granger causality analysis, possibly comprising a hierarchical social structure. Overall, this study shows the importance of the social environment in brain dynamics and emphasises the simultaneous multi-brain recordings in social neuroscience.

Effects of Pulsed Radiofrequency Duration in Patients With Chronic Lumbosacral Radicular Pain: A Randomized Double-Blind Study.

OBJECTIVES: We hypothesized that the duration of pulsed radiofrequency (PRF) application may affect the effectiveness of PRF in patients with chronic lumbosacral radicular pain (LRP). MATERIALS AND METHODS: In this prospective, double-blind, randomized study, 68 patients were randomly allocated to two groups: a 6-minute group, in which PRF was applied at 42 °C for 2 minutes followed by a 2-minute pause, repeated three times; and a 12-minute group, with a continuous application at 42 °C for 12 minutes. The total application time in each group was equal. After PRF, 2 to 3 mL of 1% lidocaine with 5 mg of dexamethasone was injected. The primary outcome was the intensity of leg pain measured using a numerical rating scale (NRS) three months after the procedure. The secondary outcomes were intensities of leg and back pain, the Oswestry Disability Index (ODI), the Medication Quantification Scale III (MQS), the Global Perceived Effect of Satisfaction (GPES), and the incidence of adverse events during follow-up. Primary and secondary outcomes were analyzed using a linear mixed-effect model in the modified intention-to-treat population. RESULTS: Each group comprised 34 patients. Three patients in each group did not receive the allocated intervention owing to alleviation of pain. The estimated NRS mean of leg pain at three months was 4.0 (95% CI, 3.2-4.9) and 4.5 (95% CI, 3.6-5.4) in the 6- and 12-minute groups, respectively, with no significant difference between groups (estimated mean difference, -0.5; 95% CI, -1.8 to 0.8; p = 0.436). Regarding the intensities of leg and back pain, ODI, MQS, and GPES, there was no significant difference between the two groups except for GPES at six months. No adverse events were observed in the groups. CONCLUSIONS: Among patients with chronic LRP, a prolonged PRF application of 12 minutes, compared with 6 minutes, caused no significant difference in leg pain intensity. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number under the Clinical Trial Registry of Korea for the study is KCT0003850; https://cris.nih.go.kr.

Complete Obstruction, a Real Risk Factor: A Comprehensive Study on Obstruction in Stage IIA Colon Cancer With Propensity Score Matching Analysis.

MICROABSTRACT: This study evaluates the prognostic significance of obstructions in stage IIA colon cancer, distinguishing between partial and complete obstructions. It employs a retrospective review of 1914 patients with propensity score matching to analyze oncologic outcomes. Findings reveal complete obstruction as a significant risk factor for poorer outcomes, emphasizing the necessity for further research to refine treatment strategies, particularly regarding the efficacy of adjuvant chemotherapy across obstruction types. BACKGROUND: This study examined the prognostic impact of obstructions in stage IIA colon cancer. The analysis specifically differentiated partial and complete obstructions, analyzing their distinct influences of both on oncologic outcomes. MATERIALS AND METHODS: A retrospective review was conducted of stage IIA colon cancer cases with the presence of an obstruction. Patients were stratified by whether it was partial or complete based on the severity of obstruction. Propensity score matching was employed to control for confounders. RESULTS: Among 1914 consecutive patients diagnosed with stage IIA colon cancer, 758 patients (597 patients with partial obstruction, 161 patients with complete obstruction) exhibited obstruction, while 1156 patients had no obstruction. The median follow-up period was 126 months. Complete obstruction was associated with poorer disease-free survival (Hazard ratio (HR) = 1.785, P < .001) and overall survival (HR = 1.853, P = .001). This trend persisted after propensity score matching, patients with complete obstruction showing a worsened disease-free survival (HR = 1.666, P = .028) and overall survival (HR = 1.732, P = .041). Adjuvant chemotherapy showed improved outcomes overall, but its efficacy varied across obstruction types. CONCLUSION: Differentiating between complete and partial obstructions in stage IIA colon cancer is an important clinical distinction, as our findings suggest that complete obstruction is a significant risk factor for poorer oncologic outcomes. While adjuvant chemotherapy generally improves prognosis in stage IIA colon cancer, the correlation of obstruction type with its efficacy remains uncertain, necessitating further research to refine treatment strategies.

CILP2 is a potential biomarker for the prediction and therapeutic target of peritoneal metastases in colorectal cancer.

Peritoneal metastases (PM) in colorectal cancer (CRC) is associated with a dismal prognosis. Identifying and exploiting new biomarkers, signatures, and molecular targets for personalised interventions in the treatment of PM in CRC is imperative. We conducted transcriptomic profiling using RNA-seq data generated from the primary tissues of 19 CRC patients with PM. Using our dataset established in a previous study, we identified 1422 differentially expressed genes compared to non-metastatic CRC. The profiling demonstrated no differential expression in liver and lung metastatic CRC. We selected 12 genes based on stringent criteria and evaluated their expression patterns in a validation cohort of 32 PM patients and 84 without PM using real-time reverse transcription-polymerase chain reaction. We selected cartilage intermediate layer protein 2 (CILP2) because of high mRNA expression in PM patients in our validation cohort and its association with a poor prognosis in The Cancer Genome Atlas. Kaplan-Meier survival analysis in our validation cohort demonstrated that CRC patients with high CILP2 expression had significantly poor survival outcomes. Knockdown of CILP2 significantly reduced the proliferation, colony-forming ability, invasiveness, and migratory capacity and downregulated the expression of molecules related to epithelial-mesenchymal transition in HCT116 cells. In an in vivo peritoneal dissemination mouse knockdown of CILP2 also inhibited CRC growth. Therefore, CILP2 is a promising biomarker for the prediction and treatment of PM in CRC.

Distinct Characteristics and Changes in Liver Function of Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab for more than 1 Year.

Purpose: Since 2020, Atezolizumab plus bevacizumab (Ate/Bev) has been the standard first-line therapy for unresectable hepatocellular carcinoma (HCC), but long-term treatment studies are limited. This study evaluated the clinical characteristics and effects of Ate/Bev for over 1 year. Materials and Methods: This study included patients with unresectable HCC treated with first-line Ate/Bev between May 2020 and April 2022. Those receiving Ate/Bev for 1 year or more were classified as the long-term treatment group. Results: Of 246 patients, 69 (28.0%) were in the long-term treatment group, which comprised more proportions of intrahepatic tumor burden <25%, ECOG 0, and a lower proportion of portal vein tumor thrombosis than the short-term treatment group. The long-term treatment group had a higher incidence of atezolizumab-related thyroid dysfunction (31.9% vs. 10.7%, p<0.001; median time to onset [mTTO]: 2.8 months), dermatologic toxicity (29.0% vs. 14.7%, p=0.017; mTTO: 3.3 months), bevacizumab-related hypertension (44.9% vs. 22.0%, p=0.001; mTTO: 4.2 months), and proteinuria (69.6% vs. 38.4%, p<0.001; mTTO: 6.8 months), compared to the short-term treatment group. Regarding liver function in the long-term treatment group, patients initially classified as Child-Pugh class A decreased from 87% to 75.4%, and albumin-bilirubin grade 1 decreased from 68.1% to 50.7% after 1 year of treatment. Conclusion: The Ate/Bev long-term treatment group had a lower intrahepatic tumor burden, less portal vein tumor thrombosis, and better performance status and liver function at baseline. Atezolizumab-related immunological adverse events emerged relatively early in treatment compared to the bevacizumab-related. Additionally, some patients demonstrated liver function deterioration during long-term Ate/Bev treatment.

Impact of Intravascular Imaging-Guided Stent Optimization According to Clinical Presentation in Patients Undergoing Complex PCI.

BACKGROUND: It is unclear whether the beneficial effects of intravascular imaging-guided stent optimization vary by clinical presentation during complex percutaneous coronary intervention (PCI). OBJECTIVES: In this prespecified, stratified subgroup analysis from RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance versus Angiography-Guidance on Clinical Outcomes After Complex PCI), we sought to compare the outcomes between intravascular imaging vs angiography guidance according to clinical presentation. METHODS: Patients with complex coronary artery lesions were randomly assigned to undergo either intravascular imaging-guided PCI or angiography-guided PCI in a 2:1 ratio. The primary endpoint was target vessel failure (TVF), which is a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. RESULTS: Of 1,639 patients, 832 (50.8%) presented with acute coronary syndrome (ACS) and 807 (49.2%) with chronic coronary syndrome. During a median follow-up of 2.1 years (Q1-Q3: 1.4-3.0 years), there was no significant interaction between the treatment effect of intravascular imaging and clinical presentation (P for interaction = 0.19). Among patients with ACS, the incidences of TVF were 10.4% in the intravascular imaging group and 14.6% in the angiography group (HR: 0.74; 95% CI: 0.48-1.15; P = 0.18). Among patients with CCS, the incidences of TVF were 5.0% in the intravascular imaging group and 10.4% in the angiography group (HR: 0.46; 95% CI: 0.27-0.80; P = 0.006). Achieving stent optimization by intravascular imaging resulted in a reduced risk of TVF among patients with ACS who were randomly assigned to intravascular imaging-guided PCI for complex coronary lesions (optimized vs unoptimized, 6.5% vs 14.1%; HR: 0.49; 95% CI: 0.27-0.87; P = 0.02) but not those with CCS (5.4% vs 4.7%, HR: 1.18; 95% CI: 0.53-2.59; P = 0.69). CONCLUSIONS: No significant interaction was observed between the benefits of intravascular imaging and clinical presentation in the risk of TVF. Stent optimization by intravascular imaging was particularly important for ACS patients. (Intravascular Imaging- Versus Angiography-Guided Percutaneous Coronary Intervention For Complex Coronary Artery Disease [RENOVATE]; NCT03381872).

SARS-CoV-2 Mpro responds to oxidation by forming disulfide and NOS/SONOS bonds.

The main protease (Mpro) of SARS-CoV-2 is critical for viral function and a key drug target. Mpro is only active when reduced; turnover ceases upon oxidation but is restored by re-reduction. This suggests the system has evolved to survive periods in an oxidative environment, but the mechanism of this protection has not been confirmed. Here, we report a crystal structure of oxidized Mpro showing a disulfide bond between the active site cysteine, C145, and a distal cysteine, C117. Previous work proposed this disulfide provides the mechanism of protection from irreversible oxidation. Mpro forms an obligate homodimer, and the C117-C145 structure shows disruption of interactions bridging the dimer interface, implying a correlation between oxidation and dimerization. We confirm dimer stability is weakened in solution upon oxidation. Finally, we observe the protein's crystallization behavior is linked to its redox state. Oxidized Mpro spontaneously forms a distinct, more loosely packed lattice. Seeding with crystals of this lattice yields a structure with an oxidation pattern incorporating one cysteine-lysine-cysteine (SONOS) and two lysine-cysteine (NOS) bridges. These structures further our understanding of the oxidative regulation of Mpro and the crystallization conditions necessary to study this structurally.

Efficacy of Integrated Risk Score Using Omics-Based Biomarkers for the Prediction of Acute Rejection in Kidney Transplantation: A Randomized Prospective Pilot Study.

Acute rejection (AR) is critical for long-term graft survival in kidney transplant recipients (KTRs). This study aimed to evaluate the efficacy of the integrated risk score of omics-based biomarkers in predicting AR in KTRs. This prospective, randomized, controlled, multicenter, pilot study enrolled 40 patients who recently underwent high-immunologic-risk kidney transplantation (KT). Five omics biomarkers were measured, namely, blood mRNA (three-gene signature), urinary exosomal miRNA (three-gene signature), urinary mRNA (six-gene signature), and two urinary exosomal proteins (hemopexin and tetraspanin-1) at 2 weeks and every 4 weeks after KT for 1 year. An integrated risk score was generated by summing each biomarker up. The biomarker group was informed about the integrated risk scores and used to adjust immunosuppression, but not the control group. The outcomes were graft function and frequency of graft biopsy. Sixteen patients in the biomarker group and nineteen in the control group completed the study. The mean estimated glomerular filtration rate after KT did not differ between the groups. Graft biopsy was performed in two patients (12.5%) and nine (47.4%) in the biomarker and control groups, respectively, with the proportion being significantly lower in the biomarker group (p = 0.027). One patient (6.3%) in the biomarker group and two (10.5%) in the control group were diagnosed with AR, and the AR incidence did not differ between the groups. The tacrolimus trough level was significantly lower in the biomarker group than in the control group at 1 year after KT (p = 0.006). Integrated omics biomarker monitoring may help prevent unnecessary or high-complication-risk biopsy and enables tailored immunosuppression by predicting the risk of AR in KTRs.

Sinonasal seromucinous hamartoma: a single institution case series combined with a narrative review of the literature.

PURPOSE: This study aimed to investigate the clinical and histopathological characteristics of sinonasal seromucinous hamartomas (SHs). METHODS: Eight patients with sinonasal SH and treated at a tertiary hospital between November 2005 and September 2023 were included. Additionally, a systematic review of published articles was conducted, analyzing 48 cases of SH described in the literature. RESULTS: Among the eight patients treated at our institution, tumors originated from the posterior nasal cavity in four patients and middle turbinate and middle meatus were the primary origin in two patients each. Coexistence of inflammatory nasal polyps (NPs) was observed in four cases. Histopathologically, four patients exhibited focal respiratory epithelial adenomatoid hamartoma (REAH) features, and low-grade dysplasia was found in one patient. A combined analysis with previous literature revealed that 46.3% of all cases originated in the anterior nasal cavity. The proportions of cases accompanied by NPs and those with focal REAH features were 20.5% and 39.1%, respectively. Additionally, the frequencies of cases exhibiting dysplastic features (5.4%) and recurrence (2.1%) were low. Remarkably, tumors originating from the anterior region tended to have a higher frequency of dysplasia than those originating from the posterior region, although this difference was not statistically significant (p = 0.0996). CONCLUSION: Patients with sinonasal SH showed favorable treatment outcomes following surgical resection. Focal REAH features and accompanying NPs were frequently observed. A substantial proportion of cases originate in the anterior nasal cavity, and these tumors may exhibit a high tendency for dysplasia.

Autophagy caused by oxidative stress promotes TGF-ß1-induced epithelial-to-mesenchymal transition in human peritoneal mesothelial cells.

Epithelial-to-mesenchymal transition (EMT) is one of the main causes of peritoneal fibrosis. However, the pathophysiological mechanisms of EMT, specifically its relationship with autophagy, are still unknown. This study aimed to evaluate the role of autophagy in transforming growth factor-beta 1 (TGF-ß1)-induced EMT in human peritoneal mesothelial cells (HPMCs). Primary cultured HPMCs were treated with TGF-ß1 (2 and 5 ng/mL) and changes in autophagy markers and the relationship between autophagy and EMT were evaluated. We also identified changes in EMT- and autophagy-related signaling pathways after autophagy and NADPH oxidase 4 (NOX4) inhibition. TGF-ß1 increased the generation of NOX4 and reactive oxygen species (ROS) in HPMCs, resulting in mitochondrial damage. Treatment with GKT137831 (20 µM), a NOX1/4 inhibitor, reduced ROS in the mitochondria of HPMC cells and reduced TGF-ß1-induced mitochondrial damage. Additionally, the indirect inhibition of autophagy by GKT137831 (20 µM) downregulated TGF-ß1-induced EMT, whereas direct inhibition of autophagy using 3-methyladenine (3-MA) (2 mM) or autophagy-related gene 5 (ATG5) gene silencing decreased the TGF-ß1-induced EMT in HPMCs. The suppressor of mothers against decapentaplegic 2/3 (Smad2/3), autophagy-related phosphoinositide 3-kinase (PI3K) class III, and protein kinase B (Akt) pathways, and mitogen-activated protein kinase (MAPK) signaling pathways, such as extracellular signal-regulated kinase (ERK) and P38, were involved in TGF-ß1-induced EMT. Autophagy and NOX4 inhibition suppressed the activation of these signaling pathways. Direct inhibition of autophagy and its indirect inhibition through the reduction of mitochondrial damage by upstream NOX4 inhibition reduced EMT in HPMCs. These results suggest that autophagy could serve as a therapeutic target for the prevention of peritoneal fibrosis in patients undergoing peritoneal dialysis.

Anuria after kidney transplantation diagnosed as early recurrence of focal segmental glomerulosclerosis combined with acute calcineurin inhibitor nephrotoxicity: a case report and literature review.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that sometimes recurs in patients after kidney transplantation (KT) and increases the risk of graft loss. Proteinuria is a common early sign of recurrent FSGS, but an abrupt decrease in urine volume is rare. Herein, we report a patient with early recurrence of FSGS with anuria following KT. CASE PRESENTATION: A 55-year-old man with end-stage kidney disease caused by primary FSGS experienced anuria on postoperative day 2 following deceased donor KT. Laboratory results revealed that serum tacrolimus trough levels were consistently elevated at the time of anuria. At first, we considered acute calcineurin inhibitor (CNI) nephrotoxicity based on graft biopsy on light microscopy, laboratory findings, and clinical courses. However, the allograft function did not recover even after discontinuation of CNI, and recurrent FSGS was diagnosed 2 weeks later on electron microscopy. A total of 13 sessions of plasmapheresis and two administrations of rituximab (375 mg/m2) were required to treat recurrent FSGS. The patient achieved a partial response, and the spot urine protein-to-creatinine ratio decreased from 15.5 g/g creatinine to 5.2 g/g creatinine. At 5 months following KT, the serum creatinine level was stable at 1.15 mg/dL. CONCLUSIONS: These findings highlight that anuria can occur in cases of early recurrence of FSGS combined with acute CNI nephrotoxicity.

Multi-modal Neuroimaging Phenotyping of Mnemonic Anosognosia in the Aging Brain.

BACKGROUND: Unawareness is a behavioral condition characterized by a lack of self-awareness of objective memory decline. In the context of Alzheimer's Disease (AD), unawareness may develop in predementia stages and contributes to disease severity and progression. Here, we use in-vivo multi-modal neuroimaging to profile the brain phenotype of individuals presenting altered self-awareness of memory during aging. METHODS: Amyloid- and tau-PET (N = 335) and resting-state functional MRI (N = 713) imaging data of individuals from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4)/Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study were used in this research. We applied whole-brain voxel-wise and region-of-interest analyses to characterize the cortical intersections of tau, amyloid, and functional connectivity networks underlying unawareness in the aging brain compared to aware, complainer and control groups. RESULTS: Individuals with unawareness present elevated amyloid and tau burden in midline core regions of the default mode network compared to aware, complainer or control individuals. Unawareness is characterized by an altered network connectivity pattern featuring hyperconnectivity in the medial anterior prefrontal cortex and posterior occipito-parietal regions co-locating with amyloid and tau deposition. CONCLUSIONS: Unawareness is an early behavioral biomarker of AD pathology. Failure of the self-referential system in unawareness of memory decline can be linked to amyloid and tau burden, along with functional network connectivity disruptions, in several medial frontal and parieto-occipital areas of the human brain.

Lack of self-awareness of cognitive changes, such as memory decline, occurs in people who later go on to develop Alzheimer's disease. In the present study, we investigated various characteristics of the brains of people who were unaware they were experiencing memory loss and likely to develop Alzheimer's disease due to their age. We identified individuals with low performance in memory tests and a lack of sense of their memory decline. Compared to aware individuals, they had more deposits of proteins known to be present at higher levels in people with Alzheimer's disease. The results of this investigation suggest that unawareness of memory decline is an early behavioral sign that a person might develop Alzheimer's disease. This knowledge might enable such people to be more easily identified in the future, and treatments to be started sooner.

Designing a highly near infrared-reflective black nanoparticles for autonomous driving based on the refractive index and principle.

HYPOTHESIS: The development of highly NIR reflective black single-shell hollow nanoparticles (BSS-HNPs) can overcome the Light Detection and Ranging (LiDAR) sensor limitations of dark-tone materials. The crystalline phase of TiO2 and the refractive index can be controlled by calcination temperature. The formation of hollow structure and the refractive index is expected to simultaneously increase the light reflection and LiDAR detectability. EXPERIMENTS: The BSS-HNPs are synthesized using the sol-gel method, calcination, NaBH4 reduction, and etching to form a hollow structure with true blackness. The computational bandgap calculation is conducted to determine the bandgap energy (Eg) of the white and black TiO2 with different crystalline structures. The blackness of the as-synthesized materials is determined by the Commission on Illumination (CIE) L*a*b* color system. FINDINGS: The hydrophilic nature of BSS-HNPs enables the formulation of hydrophilic paints, allowing the mono-layer coating. With the synergistic effects of hollow structure and the refractive index, BSS-HNPs manifested superb NIR reflectance at LiDAR detection wavelengths. The high detectability, blackness, and hollow structure of BSS-HNPs can expand the variety of LiDAR-detectable dark-tone materials.

Intravascular Imaging-Guided Optimization of Complex Percutaneous Coronary Intervention by Sex: A Subgroup Analysis of the RENOVATE-COMPLEX-PCI Trial.

Importance: There have been heterogeneous results related to sex differences in prognosis after percutaneous coronary artery intervention (PCI) for complex coronary artery lesions. Objective: To evaluate potential differences in outcomes with intravascular imaging-guided PCI of complex coronary artery lesions between women and men. Design, Setting, and Participants: This prespecified substudy evaluates the interaction of sex in the investigator-initiated, open-label, multicenter RENOVATE-COMPLEX-PCI randomized clinical trial, which demonstrated the superiority of intravascular imaging-guided PCI compared with angiography-guided PCI in patients with complex coronary artery lesions. The trial was conducted at 20 sites in Korea. Patients with complex coronary artery lesions undergoing PCI were enrolled between May 2018 and May 2021, and the median (IQR) follow-up period was 2.1 (1.4-3.0) years. Data were analyzed from December 2022 to December 2023. Interventions: After diagnostic coronary angiography, eligible patients were randomly assigned in a 2:1 ratio to receive intravascular imaging-guided PCI or angiography-guided PCI. The choice and timing of the intravascular imaging device were left to the operators' discretion. Main Outcomes and Measures: The primary end point was target vessel failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Secondary end points included individual components of the primary end point. Results: Of 1639 included patients, 339 (20.7%) were women, and the mean (SD) age was 65.6 (10.2) years. There was no difference in the risk of the primary end point between women and men (9.4% vs 8.3%; adjusted hazard ratio [HR], 1.39; 95% CI, 0.89-2.18; P = .15). Intravascular imaging-guided PCI tended to have lower incidence of the primary end point than angiography-guided PCI in both women (5.2% vs 14.5%; adjusted HR, 0.34; 95% CI, 0.15-0.78; P = .01) and men (8.3% vs 11.7%; adjusted HR, 0.72; 95% CI, 0.49-1.05; P = .09) without significant interaction (P for interaction = .86). Conclusions and Relevance: In patients undergoing complex PCI, compared with angiographic guidance, intravascular imaging guidance was associated with similar reduction in the risk of target vessel failure among women and men. The treatment benefit of intravascular imaging-guided PCI showed no significant interaction between treatment strategy and sex. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.