Development of a novel scoring system for glaucoma risk based on demographic and laboratory factors using ChatGPT-4.

We developed a scoring system for assessing glaucoma risk using demographic and laboratory factors by employing a no-code approach (automated coding) using ChatGPT-4. Comprehensive health checkup data were collected from the Korea National Health and Nutrition Examination Survey. Using ChatGPT-4, logistic regression was conducted to predict glaucoma without coding or manual numerical processes, and the scoring system was developed based on the odds ratios (ORs). ChatGPT-4 also facilitated the no-code creation of an easy-to-use risk calculator for glaucoma. The ORs for the high-risk groups were calculated to measure performance. ChatGPT-4 automatically developed a scoring system based on demographic and laboratory factors, and successfully implemented a risk calculator tool. The predictive ability of the scoring system was comparable to that of traditional machine learning approaches. For high-risk groups with 1-2, 3-4, and 5 + points, the calculated ORs for glaucoma were 1.87, 2.72, and 15.36 in the validation set, respectively, compared with the group with 0 or fewer points. This study presented a novel no-code approach for developing a glaucoma risk assessment tool using ChatGPT-4, highlighting its potential for democratizing advanced predictive analytics, making them readily available for clinical use in glaucoma detection.

Multifaceted association of overweight and metabolically unhealthy with the risk of Barrett's esophagus in the UK Biobank cohort.

The association of overweight/obesity and metabolically unhealthy (MU) with the risk of developing Barrett's esophagus (BE) remains uncertain. We evaluated whether MU and overweight/obesity are associated with increased BE incidence and whether they have a synergistic impact on BE development. We analyzed the body mass index (BMI) and metabolic indicators at baseline of 402,510 individuals from the UK Biobank with no history of BE. Overweight/obesity and MU were defined as BMI ≥ 25.0 kg/m2 and presence of ≥ 1 MU indicators, respectively. Accordingly, the participants were categorized into four groups: (1) metabolically healthy non-overweight/obesity (MHNO), (2) metabolically unhealthy non-overweight/obesity (MUNO), (3) metabolically healthy overweight/obesity (MHO), and (4) metabolically unhealthy overweight/obesity (MUO). During a median follow-up of 13.5 years, 6195 (1.5%) individuals were newly diagnosed with BE. Among them, 39,281 (9.8%), 92,000 (22.9%), 25,297 (6.3%), and 245,932 (61.1%) individuals were classified as MHNO, MUNO, MHO, and MUO, respectively. In Cox regression analyses, both MU and overweight/obesity were independently associated with BE incidence. Moreover, BE incidence was significantly higher in the MUNO, MHO, and MUO groups, compared to the MHNO group. MU and overweight/obesity are independent risk factors for BE and have a synergistic effect on BE development.

Impact of Serum Creatinine- and Cystatin C-Based Sarcopenia Index on Renal Outcomes in Non-Dialysis-Dependent Chronic Kidney Disease Patients: Results From the KNOW-CKD Study.

OBJECTIVE: To evaluate the impact of the serum creatinine- and cystatin C-based new sarcopenia index (SI) on renal outcomes in non-dialysis-dependent patients with chronic kidney disease (CKD). METHODS: In this observational Korean Cohort Study for Outcome in Patients With CKD (KNOW-CKD), 1957 patients with CKD stage 1 to stage 4 were analyzed from 2011 to 2019. Men and women were separately assigned to quartile groups according to their SI. The primary outcome was a composite renal outcome consisting of 50% reduction in estimated glomerular filtration rate or end-stage kidney disease. With use of Fine and Gray subdistribution hazard models, the association between the SI and the primary outcome was analyzed. RESULTS: During a median follow-up of 6.0 (4.2 to 7.7) years, the primary composite renal outcome occurred in 528 (28.6%) patients within a median of 3.0 (1.8 to 5.0) years. In unadjusted and adjusted models, lower SI groups had a poor primary outcome compared with the highest group (quartile 4). The hazard ratios for quartiles 1, 2, and 3 compared with quartile 4 in the fully adjusted model were 4.47 (95% CI, 3.05 to 6.56; P<.001), 3.08 (95% CI, 2.13 to 4.48; P<.001), and 2.09 (95% CI, 1.45 to 3.01; P<.001), respectively. Restricted cubic spline regression analyses found a relatively inverse linear relationship between the SI and the composite renal outcome. CONCLUSION: The new SI is an independent predictor of renal outcomes. A low SI is associated with poor renal outcome.

Association between dietary magnesium intake and incident chronic kidney disease: a prospective observational cohort study.

BACKGROUND: Although serum magnesium deficiency is linked to higher cardiovascular disease risk, its association with chronic kidney disease (CKD) remains unclear. OBJECTIVES: This study aimed to evaluate the relationship between dietary magnesium intake and CKD development in adults with clinically normal kidney function. METHODS: The prospective observational cohort study evaluated 188,510 participants (median age, 57.0 y; female, 54.1%) from the UK Biobank. Dietary magnesium intake was assessed through a 24-h dietary recall questionnaire compromising a list of 206 foods and 32 beverages and categorized into quintiles. The primary outcome was incident CKD diagnosed through International Classification of Diseases-10 and Office of Population Censuses and Surveys 4 codes. Incident CKD, defined as estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2, was also assessed in a subcohort with creatinine follow-up data. RESULTS: The median magnesium intake amount per person was 323.2 mg/d [interquartile range (IQR): 269.4-382.7 mg/d]. During 1,826,038.1 person-years of follow-up (median: 9.6 y; IQR: 9.3-10.3 y), CKD developed in 5,878 participants. The incidence of CKD was progressively higher in participants with lower magnesium intake (2.8%, 2.8%, 3.0%, 3.2%, and 3.7% in Q5-Q1, respectively). Cox regression analysis revealed that the hazard ratios (HRs) for incident CKD increased in a stepwise manner toward lower magnesium intake quintiles {adjusted HR (95% confidence interval [CI])-Q4: 0.97 (0.89, 1.06); Q3: 1.05 (0.96, 1.14); Q2: 1.12 (1.03, 1.21); Q1: 1.30 (1.20, 1.41)} relative to Q5 (P-linearity < 0.001). Similar results were observed with eGFR-defined CKD outcome [adjusted HR (95% CI)-Q4: 1.09 (0.92, 1.28); Q3: 1.15 (0.98, 1.35); Q2: 1.21 (1.03, 1.42); Q1: 1.41 (1.20, 1.65) relative to Q5; P-linearity < 0.001]. CONCLUSIONS: Lower dietary magnesium intake was associated with higher risk of incident CKD in adults with clinically normal kidney function. Further controlled studies are required to establish the potential benefit of adequate magnesium intake.

Longitudinal dynamics of circulating tumor DNA for treatment monitoring in patients with breast cancer recurrence.

The prevalence and dynamics of circulating tumor DNA (ctDNA) in patients with breast cancer recurrence or de novo metastatic cancer were examined in a retrospective analysis of a prospective observational cohort. Twenty-three recurrent/metastatic breast cancer cases (8 locoregional, 15 distant metastasis) were enrolled, and sequential plasma samples were obtained. Anchor mutations were selected from the target sequencing of each patient's primary and/or metastatic tumor. An in-house developed assay (UHS assay) was employed for a tumor-informed ctDNA assay during treatment and follow-up. A median of three (range 1-5) anchor mutations per case were applied for ctDNA detection. ctDNA was detected in 14 (63.6%, 14/22) cases at the time of enrollment and 18 (78.5%, 18/23) cases during follow-up. More anchor mutations and higher tumor burden were significantly related to higher ctDNA positive rates (p-value 0.036, 0.043, respectively). The mean enriched variant allele frequency (eVAF) at each time point was significantly higher for stable or progressive disease responses (ANOVA test p-value < 0.001). Eight patients showed an increase in their ctDNA eVAF prior to clinical progression with a mean lead time of 6.2 months (range 1.5-11 months). ctDNA dynamics measured using personalized assay reflected the clinical course of breast cancer recurrence.

Association of residual ductal carcinoma in situ with breast cancer treatment outcomes after neoadjuvant chemotherapy according to hormone receptor status.

PURPOSE: This research aimed to clarify the impact of residual ductal carcinoma in situ(DCIS) in surgical specimens obtained after neoadjuvant chemotherapy(NAC) for breast cancer on the associated prognosis outcomes. METHODS: This retrospective study was performed on a cohort of 1,009 patients who achieved pCR following NAC for breast cancer and underwent subsequent breast surgery at a single institution between January 2008 and December 2019. Overall survival, local recurrence-free survival, distant metastasis-free survival, and disease-free survival of the residual and non-residual DCIS groups were the outcomes compared, with further subgroup analysis performed according to hormone receptor status. RESULTS: 260 individuals (25.8%) presented with residual DCIS. Based on a median follow-up of 54.0 months, no significant differences in outcomes were observed between the two groups. Patients with residual DCIS and hormone receptor-negative (HR-) breast cancer demonstrated a significant decrease in distant metastasis-free survival (p = 0.030) compared to those without residual DCIS. In the HR + cohort, no significant difference was observed between the two groups. Multivariate analysis of the HR- cohort demonstrated a significant association between residual DCIS and an elevated risk for distant recurrence (hazard ratio = 2.3, 95% confidence interval = 1.01-5.20, p = 0.047). CONCLUSIONS: Residual DCIS following NAC may impact breast cancer outcomes, particularly with respect to the occurrence of distant metastasis in HR- patients. Therefore, clinicians must vigilantly monitor patients with residual DCIS after NAC, and further research is needed to expand our understanding of the clinical implications of residual DCIS.

Evaluation of safety and operative time in tumescent-free robotic nipple-sparing mastectomy: a retrospective single-center cohort study.

Purpose: Tumescent in nipple-sparing mastectomy (NSM) has been reported to increase the risk of necrosis by impairing blood flow to the skin flap and nipple-areolar complex. At our institution, we introduced a tumescent-free robotic NSM using the da Vinci single-port system (Intuitive Surgical, Inc.). Methods: We conducted a retrospective analysis of patients who underwent tumescent-free robotic NSM between October 2020 and March 2023 at Asan Medical Center (Seoul, Korea). Clinicopathological characteristics, adverse events, and operative time were evaluated. Results: During the study period, 118 patients underwent tumescent-free robotic NSM. Thirty-one patients (26.3%) experienced an adverse event. Five patients (4.2%) were classified as grade III based on the Clavien-Dindo classification and required surgery. The mean total operative time was 467 minutes for autologous tissue reconstruction (n = 49) and 252 minutes for implants (n = 69). No correlation was found between the cumulative number of surgical cases and the breast operative time (P = 0.30, 0.52, 0.59 for surgeons A, B, C) for the 3 surgeons. However, a significant linear relationship (P < 0.001) was observed, with the operative time increasing by 13 minutes for every 100-g increase in specimen weight. Conclusion: Tumescent-free robotic NSM is a safe procedure with a feasible operative time and few adverse events.

Blood pressure control in diabetic kidney disease: a post-hoc analysis of the FANTASTIC trial.

BACKGROUND: The target blood pressure (BP) value is unclear for diabetic kidney disease (DKD). Therefore, we aimed to evaluate the effect of strict BP control or 'on treatment' BP on clinical outcomes in patients with DKD. METHODS: A post-hoc analysis of the prespecified secondary outcomes of the FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC) trial, a randomized multicenter double-blind phase III trial. Eligible patients were aged ≥ 19 years with DKD. We assigned 341 participants with DKD to BP control strategy (standard-systolic BP [SBP] < 140 mmHg versus strict-SBP < 130 mmHg). The outcome was the occurrence of cardiovascular events and renal events. Separate analyses were performed to compared the risk of outcome according to achieved average BP levels. RESULTS: A total of 341 participants were included in the analysis. Over a median follow-up of 2.8 years, cardiovascular/renal events were observed in 25 (7.3%) participants. Mean (SD) SBPs in the standard and strict BP control group were 140.2 (11.6) and 140.2 (11.9) mmHg, respectively. The strict BP control group did not show significantly reduced risk of cardiovascular/renal events (HR 1.32; 95% CI 0.60-2.92]). In the post-hoc analyses using achieved BP, achieved average SBP of 130-139 mmHg resulted in reduced risk of cardiovascular/renal events (HR 0.15; 95% CI 0.03-0.67) compared to achieved average SBP ≥ 140 mmHg, whereas further reduction in achieved average SBP < 130 mmHg did not impart additional benefits. CONCLUSION: In patients with DKD, targeting a SBP of less than 130 mmHg, as compared with less than 140 mmHg, did not reduce the rate of a composite of cardiovascular and renal events. Achieved SBP of 130-139 mmHg was associated with a decreased risk for the primary outcome in patients with DKD. TRIAL REGISTRATION: ClinicalTirals.gov Identifier: NCT02620306, registered December 3, 2015. ( https://clinicaltrials.gov/study/NCT02620306 ).

Comparison of automated corneal endothelial cell analysis in healthy and postoperative eyes with phakic intraocular lens: a cross-sectional study and literature review.

PURPOSE: Measurement of corneal endothelial cells is critical for postoperative evaluation of phakic intraocular lens (pIOL) surgery. However, inter-instrument differences in corneal endothelial cell density (ECD) after pIOL implantation have not yet been reported. This study aimed to compare automated corneal endothelial cell analysis between CellChek-20 (Konan Medical, Hyogo, Japan) and EM-4000 (Tomey, Nagoya, Japan) in healthy and postoperative eyes with pIOL. METHODS: We retrospectively analyzed 154 healthy and 236 postoperative eyes after pIOL surgery. Endothelial cell measurements were performed using CellChek-20 and EM-4000 with autofocusing and automated image analysis. ECD, percentage of hexagonal cells (HEX), coefficient of variation in cell size (CoV), and central corneal thickness (CCT) were compared between the two devices. RESULTS: The ECDs of the two devices were highly correlated in both healthy (Spearman's correlation coefficient [r] = 0.805; p < 0.001) and postoperative (r = 0.901; p < 0.001) groups. ECD from CellChek-20 was higher than EM-4000 in both healthy (mean difference = 228.9 cells/mm2; p < 0.001) and postoperative (mean difference = 115.6 cells/mm2; p < 0.001) groups. The CCT values also showed a strong correlation in healthy eyes (r = 0.974; p < 0.001) and in postoperative eyes (r = 0.936; p < 0.001); however, significant inter-instrument differences were observed. HEX and CV showed significant differences and relatively weak correlations (r < 0.7) between the two devices in both healthy and postoperative groups. CONCLUSION: The ECD values between the two instruments were correlated, but that of the CellChek-20 was significantly higher than that of the EM-4000 in both healthy and postoperative eyes after pIOL surgery. Most previous studies have also shown that the Konan software overestimated the ECD compared to other products in automatic measurement mode. The possibility of measurement bias should be considered when replacing equipment used for corneal endothelial cell measurements.

Uremic toxin indoxyl sulfate induces trained immunity via the AhR-dependent arachidonic acid pathway in end-stage renal disease (ESRD).

Trained immunity is the long-term functional reprogramming of innate immune cells, which results in altered responses toward a secondary challenge. Despite indoxyl sulfate (IS) being a potent stimulus associated with chronic kidney disease (CKD)-related inflammation, its impact on trained immunity has not been explored. Here, we demonstrate that IS induces trained immunity in monocytes via epigenetic and metabolic reprogramming, resulting in augmented cytokine production. Mechanistically, the aryl hydrocarbon receptor (AhR) contributes to IS-trained immunity by enhancing the expression of arachidonic acid (AA) metabolism-related genes such as arachidonate 5-lipoxygenase (ALOX5) and ALOX5 activating protein (ALOX5AP). Inhibition of AhR during IS training suppresses the induction of IS-trained immunity. Monocytes from end-stage renal disease (ESRD) patients have increased ALOX5 expression and after 6 days training, they exhibit enhanced TNF-α and IL-6 production to lipopolysaccharide (LPS). Furthermore, healthy control-derived monocytes trained with uremic sera from ESRD patients exhibit increased production of TNF-α and IL-6. Consistently, IS-trained mice and their splenic myeloid cells had increased production of TNF-α after in vivo and ex vivo LPS stimulation compared to that of control mice. These results provide insight into the role of IS in the induction of trained immunity, which is critical during inflammatory immune responses in CKD patients.

An epidermal growth factor receptor-targeting immunotoxin based on IgG shows potent antitumor activity against head and neck cancer.

The epidermal growth factor receptor (EGFR) is an important target for cancer therapies. Many head and neck cancer (HNC) cells have been reported to overexpress EGFR; therefore, anti-EGFR therapies have been attempted in patients with HNC. However, its clinical efficacy is limited owing to the development of drug resistance. In this study, we developed an EGFR-targeting immunotoxin consisting of a clinically proven anti-EGFR IgG (cetuximab; CTX) and a toxin fragment (LR-LO10) derived from Pseudomonas exotoxin A (PE) using a novel site-specific conjugation technology (peptide-directed photo-crosslinking reaction), as an alternative option. The immunotoxin (CTX-LR-LO10) showed specific binding to EGFR and properties of a typical IgG, such as stability, interactions with receptors of immune cells, and pharmacokinetics, and inhibited protein synthesis via modification of elongation factor-2. Treatment of EGFR-positive HNC cells with the immunotoxin resulted in apoptotic cell death and the inhibition of cell migration and invasion. The efficacy of CTX-LR-LO10 was evaluated in xenograft mouse models, and the immunotoxin exhibited much stronger tumor suppression than CTX or LR-LO10. Transcriptome analyses revealed that the immunotoxins elicited immune responses and altered the expression of genes related to its mechanisms of action. These results support the notion that CTX-LR-LO10 may serve as a new therapeutic agent targeting EGFR-positive cancers.

The association between transferrin saturation and all-cause mortality in chronic kidney disease: findings from Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease.

Background: Transferrin saturation (TSAT) has been used as an indicator of iron deficiency. However, there is no consensus regarding its optimal range for patient with chronic kidney disease (CKD). We aimed to analyze the effect of TSAT on the prognosis of patients with non-dialysis CKD (NDCKD). Methods: From 2011 to 2016, 2157 NDCKD patients with baseline TSAT measurements were followed for 10 years. Patients were divided into three groups based on baseline TSAT values: <25%, ≥25% and <45%, and ≥45%. All-cause mortality and 4-point major adverse cardiovascular events (MACE) were analyzed using multivariable Cox regression analysis. Other iron biomarkers and mortality were also analyzed. Results: During a mean follow-up of 7.1 ± 2.9 years, 182 of a total of 2,157 patients (8.4%) died. Compared with the TSAT ≥25% and <45% group, the TSAT <25% group showed significantly increased all-cause mortality (hazard ratio [HR], 1.44; 95% confidence interval (CI), 1.02-2.03; p = 0.04). The occurrence of 4-point MACE was significantly increased in univariable analysis in the TSAT <25% group (HR, 1.48; 95% CI, 1.02-2.15; p = 0.04), but it was not significant in the multivariable analysis (HR, 1.38; 95% CI, 0.89-2.15; p = 0.15). Tertile comparisons of the iron-to-log-ferritin ratio showed increased mortality in the first tertile group. Conclusion: TSAT <25% is an independent risk factor for all-cause mortality in patients with NDCKD and care should be taken to prevent TSAT values of <25%. Other indicators, such as serum iron and iron-to-log-ferritin ratio, may also be used to assess iron deficiency.

Adequacy of Dialysis and Incidence of Atrial Fibrillation in Patients Undergoing Hemodialysis.

BACKGROUND: Atrial fibrillation (AF) can lead to stroke, heart failure, and mortality and has a greater prevalence in dialysis patients than in the general population. Several studies have suggested that uremic toxins may contribute to the development of AF. However, the association between dialysis adequacy and incident AF has not been well established. METHODS: In this retrospective nationwide cohort study, we analyzed data from the Korean National Periodic Hemodialysis Quality Assessment from 2013 to 2015 of patients who received outpatient maintenance hemodialysis 3× a week. The main exposure was single pooled Kt/V (spKt/V), which is the dialysis adequacy index, and the primary outcome was the development of AF. For the primary analysis, patients were categorized into quartiles according to baseline spKt/V. The lowest quartile, representing the lowest adequacy, was used as the reference group. Fine-Gray subdistribution hazard models were used, treating all-cause mortality as a competing risk. RESULTS: Of 25 173 patients, the mean age was 60 (51-69) years, and 14 772 (58.7%) were men. During a median follow-up of 5.7 years, incident AF occurred in a total of 3883 (15.4%) patients. Participants with a higher spKt/V tended to have lower AF incidence. In survival analysis, a graded association was observed between the risk of incident AF and spKt/V quartiles: subdistribution hazard ratios and 95% CIs for the second, third, and the highest quartile compared with the lowest quartile were 0.90 (95% CI, 0.82-0.98), 0.84 (95% CI, 0.77-0.93), and 0.79 (95% CI, 0.72-0.88), respectively. CONCLUSIONS: This nationwide cohort study showed that a higher spKt/V is associated with a reduced risk of incident AF. These findings suggests that reducing uremic toxin burden through enhanced dialysis clearance may be associated with a lower risk of AF development in patients undergoing maintenance hemodialysis.

Volume control strategy and patient survival in sepsis-associated acute kidney injury receiving continuous renal replacement therapy: a randomized controlled trial with secondary analysis.

Optimal strategy for volume control and the clinical implication of achieved volume control are unknown in patients with sepsis-associated acute kidney injury (AKI) receiving continuous renal replacement therapy (CRRT). This randomized controlled trial aimed to compare the survival according to conventional or bioelectrical impedance analysis (BIA)-guided volume control strategy in patients with sepsis-associated AKI receiving CRRT. We also compared patient survival according to achieved volume accumulation rate ([cumulative fluid balance during 3 days × 100]/fluid overload measured by BIA at enrollment) as a post-hoc analysis. We randomly assigned patients to conventional volume control strategy (n = 39) or to BIA-guided volume control strategy (n = 34). There were no differences in 28-day mortality (HR, 1.19; 95% CI, 0.63-2.23) or 90-day mortality (HR, 0.99; 95% CI 0.57-1.75) between conventional and BIA-guided volume control group. In the secondary analysis, achieved volume accumulation rate was significantly associated with patient survival. Compared with the achieved volume accumulation rate of ≤ - 50%, the HRs (95% CIs) for the risk of 90-day mortality were 1.21 (0.29-5.01), 0.55 (0.12-2.48), and 7.18 (1.58-32.51) in that of - 50-0%, 1-50%, and > 50%, respectively. Hence, BIA-guided volume control in patients with sepsis-associated AKI receiving CRRT did not improve patient outcomes. In the secondary analysis, achieved volume accumulation rate was associated with patient survival.

The role of PCSK9 in glomerular lipid accumulation and renal injury in diabetic kidney disease.

AIMS/HYPOTHESIS: Glomerular lipid accumulation is a defining feature of diabetic kidney disease (DKD); however, the precise underlying mechanism requires further elucidation. Recent evidence suggests a role for proprotein convertase subtilisin/kexin type 9 (PCSK9) in intracellular lipid homeostasis. Although PCSK9 is present in kidneys, its role within kidney cells and relevance to renal diseases remain largely unexplored. Therefore, we investigated the role of intracellular PCSK9 in regulating lipid accumulation and homeostasis in the glomeruli and podocytes under diabetic conditions. Furthermore, we aimed to identify the pathophysiological mechanisms responsible for the podocyte injury that is associated with intracellular PCSK9-induced lipid accumulation in DKD. METHODS: In this study, glomeruli were isolated from human kidney biopsy tissues, and glomerular gene-expression analysis was performed. Also, db/db and db/m mice were used to perform glomerular gene-expression profiling. We generated DKD models using a high-fat diet and low-dose intraperitoneal streptozocin injection in C57BL/6 and Pcsk9 knockout (KO) mice. We analysed cholesterol and triacylglycerol levels within the kidney cortex. Lipid droplets were evaluated using BODIPY staining. We induced upregulation and downregulation of PCSK9 expression in conditionally immortalised mouse podocytes using lentivirus and siRNA transfection techniques, respectively, under diabetic conditions. RESULTS: A significant reduction in transcription level of PCSK9 was observed in glomeruli of individuals with DKD. PCSK9 expression was also reduced in podocytes of animals under diabetic conditions. We observed significantly higher lipid accumulation in kidney tissues of Pcsk9 KO DKD mice compared with wild-type (WT) DKD mice. Additionally, Pcsk9 KO mouse models of DKD exhibited a significant reduction in mitochondria number vs WT models, coupled with a significant increase in mitochondrial size. Moreover, albuminuria and podocyte foot process effacement were observed in WT and Pcsk9 KO DKD mice, with KO DKD mice displaying more pronounced manifestations. Immortalised mouse podocytes exposed to diabetic stimuli exhibited heightened intracellular lipid accumulation, mitochondrial injury and apoptosis, which were ameliorated by Pcsk9 overexpression and aggravated by Pcsk9 knockdown in mouse podocytes. CONCLUSIONS/INTERPRETATION: The downregulation of PCSK9 in podocytes is associated with lipid accumulation, which leads to mitochondrial dysfunction, cell apoptosis and renal injury. This study sheds new light on the potential involvement of PCSK9 in the pathophysiology of glomerular lipid accumulation and podocyte injury in DKD.

Demonstration of a low power and high-speed graphene/silicon heterojunction near-infrared photodetector.

The structure and process of the graphene/Si heterojunction near-infrared photodetector were optimized to enhance the operating speed limit. The introduction of a well-designed structure improved the rise time from 12.6 µs to 115 ns, albeit at the expense of the responsivity, which decreased from 1.25 A W-1 to 0.56 A W-1. Similarly, the falling time was improved from 38 µs to 288 ns with a sacrifice in responsivity from 1.25 A W-1 to 0.29 A W-1, achieved through the introduction of Ge-induced defect-recombination centers within the well. Through a judicious well design and the introduction of recombination defect centers, the minimum pulse width could be improved from 50.6 µs to 435 ns, facilitating 2 MHz operation. This represents more than 100 times increase compared to previously reported graphene and graphene/Si hybrid photodetectors.

Association between progression of coronary artery calcification and development of kidney failure with replacement therapy: Findings from KNOW-CKD study.

BACKGROUND AND AIMS: High coronary artery calcification (CAC) burden is a significant risk factor for adverse cardiovascular and kidney outcomes. However, it is unknown whether changes in the coronary atherosclerotic burden can accompany changes in kidney disease progression. Here, we evaluated the relationship between CAC progression and the risk of kidney failure with replacement therapy (KFRT). METHODS: We analyzed 1173 participants with chronic kidney disease (CKD) G1 to G5 without kidney replacement therapy from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Participants were categorized into three groups according to the change in the CAC score between enrollment and year 4 (non-progressors, ≤0 AU; moderate progressors, 1-199 AU; and severe progressors, ≥200 AU). The primary outcome was the development of KFRT. RESULTS: During a follow-up period of 4690 person-years (median, 4.2 years), the primary outcome occurred in 230 (19.6 %) participants. The incidence of KFRT was 37.6, 54.3, and 80.9 per 1000 person-years in the non-, moderate, and severe progressors, respectively. In the multivariable cause-specific hazard model, the hazard ratios (HRs) for the moderate and severe progressors were 1.71 (95 % confidence interval [CI], 1.02-2.87) and 2.55 (95 % CI, 1.07-6.06), respectively, compared with non-progressors. A different definition of CAC progression with a threshold of 100 AU yielded similar results in a sensitivity analysis. CONCLUSIONS: CAC progression is associated with an increased risk of KFRT in patients with CKD. Our findings suggest that coronary atherosclerosis changes increase the risk of CKD progression.