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(1) Background: Urinary tract infection (UTI) is a leading cause of emergency department visits and hospital admissions. Despite many studies identifying UTI-related risk factors for bacteremia or sepsis, a significant gap remains in developing predictive models for in-hospital mortality or the necessity for emergent intensive care unit admission in the emergency department. This study aimed to construct interpretable machine learning models capable of identifying patients at high risk for critical outcomes. (2) Methods: This was a retrospective study of adult patients with urinary tract infection (UTI), extracted from the Medical Information Mart for Intensive Care IV Emergency Department (MIMIC-IV-ED) database. The critical outcome is defined as either in-hospital mortality or transfer to an intensive care unit within 12 h. ED visits were randomly partitioned into a 70%/30% split for training and validation. The extreme gradient boosting (XGBoost), random forest (RF), and support vector machine (SVM) algorithms were constructed using variables selected from the stepwise logistic regression model. The XGBoost model was then compared to the traditional model and clinical decision rules (CDRs) on the validation data using the area under the curve (AUC). (3) Results: There were 3622 visits among 3235 unique patients diagnosed with UTI. Of the 2535 patients in the training group, 836 (33%) experienced critical outcomes, and of the 1087 patients in the validation group, 358 (32.9%) did. The AUCs for different machine learning models were as follows: XGBoost, 0.833; RF, 0.814; and SVM, 0.799. The XGBoost model performed better than others. (4) Conclusions: Machine learning models outperformed existing traditional CDRs for predicting critical outcomes of ED patients with UTI. Future research should prospectively evaluate the effectiveness of this approach and integrate it into clinical practice.

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Establishing a safe exposure level from epidemiological studies while providing direct hazard characterization in humans often faces uncertainty in causality, especially cross-sectional data. With advances in molecular epidemiology, it is reasonable to integrate identified intermediate biomarkers into health risk assessment. In this study, by considering the mediation of the oxidative stress marker malondialdehyde (MDA), we explored the exposure threshold of melamine on the early renal injury marker N-acetyl-ß-D glucosaminidase (NAG). The benchmark dose (BMD) was derived from model averaging of the composite direct effect of melamine exposure and the indirect effect through the mediation of MDA on NAG levels. As illustrative examples, we analyzed 309 adult patients with calcium urolithiasis and 80 occupational workers for the corresponding exposure thresholds. The derived threshold was subpopulation-dependent, with the one-sided lower bound BMDL10 for the patients with urolithiasis with (without) the mediator MDA for the patients with kidney stones and the occupational workers being 0.88 (0.96) µg/kg_bw/day and 22.82 (18.09) µg/kg_bw/day, respectively. The derived threshold levels, considering the oxidative stress marker MDA, were consistent with those without adjusting for the mediation effect. However, the study outcomes were further supported by the suggested mechanism pathway. The threshold for the patients with urolithiasis was up to two orders lower than the current tolerable daily intake level of 200 µg/kg_bw/day recommended by the WHO (EFSA).

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Background and Objectives: In patients with urolithiasis-related obstructive pyelonephritis (UROP), sepsis represents a critical and concerning complication that can substantially increase the mortality rate. This study aimed to identify the risk factors for sepsis in UROP patients and to develop a predictive nomogram model. Materials and Methods: We analyzed data from 148 patients who met the UROP criteria and were admitted to Chang Gung Memorial Hospital between 1 January 2016 and 31 December 2021. The primary outcome evaluated was the incidence of sepsis, as defined by the most recent Sepsis-3 guidelines. To identify potential risk factors for sepsis, we employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression technique. Subsequently, we utilized multivariable logistic regression to construct the predictive model. Results: There was a total of 102 non-sepsis cases and 46 sepsis cases. Risk factors for sepsis in multivariable analysis were a history of diabetes mellitus (DM) (OR = 4.24, p = 0.007), shock index (SI) (×10-1) (OR = 1.55, p < 0.001), C-reactive protein (CRP) (mg/dL) (OR = 1.08, p = 0.005), and neutrophil to lymphocyte ratio (NLR) (×10) (OR = 1.58, p = 0.007). The nomogram exhibited an area under the receiver operating characteristic curve of 0.890 (95% CI 0.830-0.949). Conclusions: Our study demonstrated that patients with UROP who have DM, higher SI, higher NLR, and elevated CRP levels are significantly more likely to develop sepsis. These insights may aid in risk stratification, and it is imperative that clinicians promptly initiate treatment for those identified as high risk.

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The worldwide prevalence and incidence rates of end-stage renal disease have been increasing, and the trend is pronounced in Taiwan. This is especially evident in southern Taiwan, where the wet-bulb globe temperature (WBGT) is consistently higher than in other regions. The association between kidney function and WBGT has not been fully investigated. Therefore, the aim of this study was to evaluate the association between estimated glomerular filtration rate (eGFR) and WBGT and variations in this association across different geographic regions in Taiwan. We used the Taiwan Biobank (TWB) to obtain data on community-dwelling individuals, linked these data with WBGT data obtained from the Central Weather Bureau and then processed the data using a machine learning model. WBGT data were recorded during the working period of the day from 8:00 a.m. to 5:00 p.m. These data were then compiled as 1-year, 3-year and 5-year averages, recorded prior to the survey year of the TWB of each participant. We identified 114 483 participants who had WBGT data during 2012-2020. Multivariable analysis showed that, in northern Taiwan, increases in 1- and 3-year averages of WBGT during the working period (ß = -0.092, P = .043 and ß = -0.193, P < .001, respectively) were significantly associated with low eGFR. In southern Taiwan, increases in 1-, 3- and 5-year averages of WBGT during the working period (ß = -0.518, P < .001; ß = -0.690, P < .001; and ß = -0.386, P = .001, respectively) were gnificantly associated with low eGFR. These findings highlight the importance of heat protection for people working outdoors or in high-temperature environments as a measure to prevent negative impacts on kidney function. Moreover, we observed that in southern Taiwan, every 1°C increase in WBGT had a greater impact on the decrease in eGFR compared with other regions in Taiwan.

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The incidence and prevalence of dialysis in Taiwan are high compared to other regions. Consequently, mitigating chronic kidney disease (CKD) and the worsening of kidney function have emerged as critical healthcare priorities in Taiwan. Heat stress is known to be a significant risk factor for CKD and kidney function impairment. However, differences in the impact of heat stress between males and females remains unexplored. We conducted this retrospective cross-sectional analysis using data from the Taiwan Biobank (TWB), incorporating records of the wet bulb globe temperature (WBGT) during midday (11 AM-2 PM) and working hours (8 AM-5 PM) periods based on the participants' residential address. Average 1-, 3-, and 5-year WBGT values prior to the survey year were calculated and analyzed using a geospatial artificial intelligence-based ensemble mixed spatial model, covering the period from 2010 to 2020. A total of 114,483 participants from the TWB were included in this study, of whom 35.9% were male and 1053 had impaired kidney function (defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2). Multivariable analysis revealed that in the male participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 â„ƒ increase were significantly positively associated with eGFR < 60 ml/min/1.73 m2 (odds ratio [OR], 1.096, 95% confidence interval [CI] = 1.002-1.199, p = 0.044 for 1 year; OR, 1.093, 95% CI = 1.000-1.196, p = 0.005 for 3 years; OR, 1.094, 95% CI = 1.002-1.195, p = 0.045 for 5 years). However, significant associations were not found for the working hours period. In the female participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 â„ƒ increase were significantly negatively associated with eGFR < 60 ml/min/1.73 m2 (OR, 0.872, 95% CI = 0.778-0.976, p = 0.018 for 1 year; OR, 0.874, 95% CI = 0.780-0.978, p = 0.019 for 3 years; OR, 0.875, 95% CI = 0.784-0.977, p = 0.018 for 5 years). In addition, during the working hours period, the 1-, 3-, and 5-year average WBGT values per 1 â„ƒ increase were also significantly negatively associated with eGFR < 60 ml/min/1.73 m2 (OR, 0.856, 95% CI = 0.774-0.946, p = 0.002 for 1 year; OR, 0.856, 95% CI = 0.774-0.948, p = 0.003 for 3 years; OR, 0.853, 95% CI = 0.772-0.943, p = 0.002 for 5 years). In conclusion, our results revealed that increased WBGT was associated with impaired kidney function in males, whereas increased WBGT was associated with a protective effect against impaired kidney function in females. Further studies are needed to elucidate the exact mechanisms underlying these sex-specific differences.

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BACKGROUND: Vibrio is a genus of Gram-negative bacteria found in various aquatic environments, including saltwater and freshwater. Vibrio bacteremia can lead to sepsis, a potentially life-threatening condition in which the immune system enters overdrive in response to the disease, causing widespread inflammation and damage to tissues and organs. V. vulnificus had the highest case fatality rate (39%) of all reported foodborne infections in the United States and a high mortality rate in Asia, including Taiwan. Numerous scoring systems have been created to estimate the mortality risk in the emergency department (ED). However, there are no specific scoring systems to predict the mortality risk of Vibrio bacteremia. Therefore, this study modified the existing scoring systems to better predict the mortality risk of Vibrio bacteremia. METHODS: Cases of Vibrio bacteremia were diagnosed based on the results from at least one blood culture in the ED. Patient data were extracted from the electronic clinical database, covering January 2012 to December 2021. The primary outcome was in-hospital mortality.This study used univariate and multivariate analyses to evaluate the mortality risk. RESULTS: This study enrolled 36 patients diagnosed with Vibrio bacteremia, including 23 males (63.9%) and 13 females (36.1%), with a mean age of 65.1 ± 15.7 years. The in-hospital mortality rate amounted to 25% (9/36), with 31.5% in V. vulnificus (6/19) and 17.6% in V. non-vulnificus (3/17). The non-survivors demonstrated higher MEDS (10.3 ± 2.4) than the survivors (6.2 ± 4.1) (p = 0.002). Concerning the qSOFA, the survivors scored 0.3 ± 0.5, and the non-survivors displayed a score of 0.6 ± 0.7 (p = 0.387). The AUC of the ROC for the MEDS and qSOFA was 0.833 and 0.599, respectively. This study modified the scoring systems with other predictive factors, including BUN and pH. The AUC of the ROC for the modified MEDS and qSOFA reached up to 0.852 and 0.802, respectively. CONCLUSION: The MEDS could serve as reliable indicators for forecasting the mortality rate of patients grappling with Vibrio bacteremia. This study modified the MEDS and qSOFA to strengthen the predictive performance of mortality risk for Vibrio bacteremia. We advocate the prompt initiation of targeted therapeutic interventions and judicious antibiotic treatments to curb fatality rates.

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BACKGROUND: Procalcitonin (PCT) has garnered attention as a potential diagnostic biomarker for infection in cancer patients. We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy of procalcitonin (PCT) and to compare it with C-reactive protein (CRP) in adult non-neutropenic cancer patients with suspected infection. METHODS: A systematic literature search was performed in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials to identify all relevant diagnostic accuracy studies. Original articles reporting the diagnostic accuracy of PCT for infection detection in adult patients with solid or hematological malignancies were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, area under the hierarchical summary receiver operator characteristic (HSROC) curve, and corresponding 95% confidence interval (CI) were calculated. RESULTS: Seven studies were included in the meta-analysis. The pooled sensitivity and specificity of PCT were 60% (95% CI [45-74%]) and 78% (95% CI [69-86%]). The diagnostic odds ratio was estimated at 5.47 (95% CI [2.86-10.46]). Three studies compared the diagnostic accuracies of PCT and CRP. The pooled sensitivity and specificity values for PCT were 57% (95% CI [26-83%]) and 75% (95% CI [68-82%]), and those for CRP were 67% (95% CI [35-88%]) and 73% (95% CI [69-77%]). The pooled sensitivity and specificity of PCT and CRP did not differ significantly (p = 0.61 and p = 0.63). The diagnostic accuracy of PCT was similar to that of CRP as measured by the area under the HSROC curve (0.73, CI = 0.61-0.91 vs. 0.74, CI = 0.61-0.95, p = 0.93). CONCLUSION: While elevated PCT levels can be indicative of potential infection, they should not be solely relied upon to exclude infection. We recommend not using the PCT test in isolation; Instead, it should be carefully interpreted in the context of clinical findings.

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BACKGROUND: Aeromonas species, Gram-negative, non-sporulating, facultative, and anaerobic bacilli, widely distributed in aquatic environments, derive various infections, including bacteremia. Most of these infections were opportunistic and found in patients with predisposing conditions. Among the infections, bacteremia remains with notable mortality, reported from 15% to 45%. However, predicting systems for assessing the mortality risk of this disease have yet to be investigated. We aimed to validate the performance of specific predictive scoring systems to assess the clinical outcomes of Aeromonas bacteremia and applied the revised systems to predict mortality risk. METHODS: A retrospective observational study reviewed patients with bacteremia caused by Aeromonas spp. based on at least one positive blood culture sample collected in the emergency department from January 2012 to December 2020. The outcome was in-hospital mortality. We used seven predictive scoring systems to predict the clinical outcome. According to the effectiveness in predicting mortality, we revised three of the seven predictive scoring systems by specific characteristics to refine their risk-predicting performances. RESULTS: We enrolled 165 patients with bacteremia caused by Aeromonas spp., including 121 males (73.3%) and 44 females (26.7%), with a mean age of 66.1 ± 14.9 years and an average length of hospital stay of 12.4 ± 10.9 days. The overall mortality rate was 32.7% (54/165). The non-survivors had significantly higher scores in MEDS (6.7 ± 4.2 vs. 12.2 ± 3.3, p < 0.001), NEWS (4.0 ± 2.8 vs. 5.3 ± 3.0, p = 0.008), and qSOFA (0.3 ± 0.6 vs. 0.6 ± 0.7, p = 0.007). Regarding mortality risk prediction, the MEDS demonstrated the best predictive power with AUC of ROC measured up to 0.834, followed by NEWS (0.626) and qSOFA (0.608). We revised the MEDS, NEWS, and qSOFA by hemoglobin and lactate. We found that the revised scores had better powerful performance, including 0.859, 0.767, and 0.691 of the AUC of ROC, if the revised MEDS ≥10, revised NEWS ≥8, and revised qSOFA ≥2, respectively. CONCLUSIONS: MEDS, NEWS, and qSOFA were good tools for predicting outcomes in patients with Aeromonas spp. bacteremia. The revised MEDS, NEWS, and qSOFA demonstrated more powerful predicting performance than the original scoring systems. We suggested that patients with higher scores in revised MEDS (≥10), revised NEWS (≥8), and revised qSOFA (≥2) received early goal-directed therapy and appropriate broad-spectrum antibiotic treatment as early as possible to reduce mortality.

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CONTEXT: Type 2 diabetes (T2D) is the major contributor to chronic kidney disease and end-stage kidney disease (ESKD). The influence of trimethylamine N-oxide (TMAO) on kidney outcomes in T2D remains unclear. OBJECTIVE: To examine the association between fasting serum TMAO levels and adverse kidney outcomes in patients with T2D. METHODS: Between October 2016 and June 2020, patients with T2D were recruited and monitored every 3 months until December 2021. Serum TMAO levels were assessed using liquid chromatography-mass spectrometry. The primary kidney outcomes were doubling of serum creatinine levels or progression to ESKD necessitating dialysis; the secondary kidney outcome was a rapid 30% decline in estimated glomerular filtration rate within 2 years. All-cause mortality was also evaluated. RESULTS: Among the 440 enrolled patients with T2D, those in the highest serum TMAO tertile (≥0.88 µM) were older, had a longer diabetes duration, elevated blood urea nitrogen, and lower estimated glomerular filtration rate. Over a median follow-up period of 4 years, 26 patients (5.9%) had a doubling of serum creatinine level or progression to ESKD. After propensity score weighting, the patients in the highest serum TMAO tertile had a 6.45-fold increase in the risk of doubling of serum creatinine levels or progression to ESKD and 5.86-fold elevated risk of rapid decline in kidney function compared with those in the lowest tertile. Additionally, the stepwise increase in serum TMAO was associated with all-cause mortality. CONCLUSION: Patients with T2D with elevated circulating TMAO levels are at higher risk of doubling serum creatinine, progressing to ESKD, and mortality. TMAO is a potential biomarker for kidney function progression and mortality in patients with T2D.

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The prevalence of patients with primary aldosteronism (PA) is about 5%-15% in hypertensive patients, and it is common cause of secondary hypertension in clinical practice. Two major causes of PA are noted, namely bilateral adrenal hyperplasia and aldosterone-producing adenoma, and the general diagnosis is based on three steps: (1) screening, (2) confirmatory testing, and (3) subtype differentiation (Figure 1). The recommendation for screening patients is at an increased risk of PA, here we focus on which patients should be screened for PA, not only according to well-established guidelines but for potential patients with PA. We recommend screening for 1) patients with resistant or persistent hypertension, 2) hypertensive patients with hypokalemia (spontaneous or drug-induced), 3) young hypertensive patients (age <40 years), and 4) all hypertensive patients with a history of PA in first-degree relatives. Moreover, we suggest screening for 1) hypertensive patients themselves or first-degree relatives with early target organ damage, such as stroke and other diseases, 2) all hypertensive patients with a concurrent adrenal incidentaloma, 3) hypertensive patients with obstructive sleep apnea, 4) hypertensive patients with atrial fibrillation unexplained by structural heart defects and/or other conditions resulting in the arrhythmia, 5) hypertensive patients with anxiety and other psychosomatic symptoms, and 6) hypertensive patients without other comorbidities to maintain cost-effectiveness.

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Chronic kidney diseases (CKD) is an important public health issue worldwide, and diabetes mellitus is the main cause of CKD. Having sufficient disease knowledge and good self-care behavior both help to prevent the progression of diabetes mellitus and CKD. This cross-sectional study enrolled 181 type 2 diabetic patients with CKD from July 2017 to October 2017. Perceived Kidney Knowledge survey and structured questionnaires of self-care behavior were used to measure perceived disease knowledge and CKD Self-Care (CKDSC) scales respectively with the determinants analyzed by linear regression. Meanwhile, socio-demographic information, kidney function and laboratory data were collected. Of 181 enrolled patients, the mean age was 66.8 ±â€…9.7 years, 59.1% were male and the mean estimated glomerular filtration rate was 33.1 ±â€…23.1 mL/min/1.73 m2. The mean scores of CKDSC and perceived disease knowledge were 63.2 and 22.4, respectively. High scores of disease knowledge were significantly correlated with low glycated hemoglobin (P = .03) and high scores of overall self-care behavior (P = .03) and aspects of self-care behavior, including diet (P = .003), exercise (P = .02), and home blood pressure monitoring (P = .04). The relationship between young age and high scores of disease knowledge was found (P = .001); however, old age was significantly associated with high scores of overall self-care behavior (P < .001) while additionally, married patients had high scores of regular medication behavior (P = .03). Our findings identified the significant factors correlated with disease knowledge and self-care behavior in type 2 diabetic patients with CKD. Healthcare givers should establish personalized health education plans to improve perceived disease knowledge and self-care behavior.

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BACKGROUND: The in-hospital mortality of cardiogenic shock (CS) remains high (28% to 45%). As a result, several studies developed prediction models to assess the mortality risk and provide guidance on treatment, including CardShock and IABP-SHOCK II scores, which performed modestly in external validation studies, reflecting the heterogeneity of the CS populations. Few articles established predictive scores of CS based on Asian people with a higher burden of comorbidities than Caucasians. We aimed to describe the clinical characteristics of a contemporary Asian population with CS, identify risk factors, and develop a predictive scoring model. METHODS: A retrospective observational study was conducted between 2014 and 2019 to collect the patients who presented with all-cause CS in the emergency department of a single medical center in Taiwan. We divided patients into subgroups of CS related to acute myocardial infarction (AMI-CS) or heart failure (HF-CS). The outcome was all-cause 30-day mortality. We built the prediction model based on the hazard ratio of significant variables, and the cutoff point of each predictor was determined using the Youden index. We also assessed the discrimination ability of the risk score using the area under a receiver operating characteristic curve. RESULTS: We enrolled 225 patients with CS. One hundred and seven patients (47.6%) were due to AMI-CS, and ninety-eight patients among them received reperfusion therapy. Forty-nine patients (21.8%) eventually died within 30 days. Fifty-three patients (23.55%) presented with platelet counts < 155 × 103/µL, which were negatively associated with a 30-day mortality of CS in the restrictive cubic spline plot, even within the normal range of platelet counts. We identified four predictors: platelet counts < 200 × 103/µL (HR 2.574, 95% CI 1.379-4.805, p = 0.003), left ventricular ejection fraction (LVEF) < 40% (HR 2.613, 95% CI 1.020-6.692, p = 0.045), age > 71 years (HR 2.452, 95% CI 1.327-4.531, p = 0.004), and lactate > 2.7 mmol/L (HR 1.967, 95% CI 1.069-3.620, p = 0.030). The risk score ended with a maximum of 5 points and showed an AUC (95% CI) of 0.774 (0.705-0.843) for all patients, 0.781 (0.678-0.883), and 0.759 (0.662-0.855) for AMI-CS and HF-CS sub-groups, respectively, all p < 0.001. CONCLUSIONS: Based on four parameters, platelet counts, LVEF, age, and lactate (PEAL), this model showed a good predictive performance for all-cause mortality at 30 days in the all patients, AMI-CS, and HF-CS subgroups. The restrictive cubic spline plot showed a significantly negative correlation between initial platelet counts and 30-day mortality risk in the AMI-CS and HF-CS subgroups.

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Vascular stenosis is a late radiation complication that develops in long-term survivors of nasopharyngeal carcinoma. Vertebral arteries (VAs) are major vessels responsible for posterior circulation. In this study, we evaluated the feasibility of VA-sparing volumetric modulated arc therapy (VMAT) techniques. A total of 20 patients with nasopharyngeal carcinoma treated by a TrueBeam linear accelerator were enrolled in this study. The original VMAT plan was designed without the contouring of VAs as organs at risk (OARs). The same image set of the original VMAT plan was used to contour the VAs for each patient. A new VA-sparing VMAT plan was developed by avoiding VAs as OARs. Finally, a paired t-test was used to compare the dosimetric differences. The VA-sparing VMAT plan had similar target coverage and dose to those of other OARs. The VA-sparing plan yielded a significantly low VA dose from 53 to 40 Gy, with V35Gy changing from 97% to 56%, V50Gy changing from 67% to 35%, and V63Gy changing from 15% to approximately 7%-10% (p < 0.001 for all comparisons). VAs should be correctly identified as OARs. Photon VMAT with VA sparing can help substantially decrease the VA dose.

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Cryptococcal infection is usually diagnosed in immunocompromised individuals and those with meningeal involvement, accounting for most cryptococcosis. Cryptococcemia indicates a poor prognosis and prolongs the course of treatment. We use the scoring systems to predict the mortality risk of cryptococcal fungemia. This was a single hospital-based retrospective study on patients diagnosed with cryptococcal fungemia confirmed by at least one blood culture collected from the emergency department covering January 2012 and December 2020 from electronic medical records in the Taichung Veterans General Hospital. We enrolled 42 patients, including 28 (66.7%) males and 14 (33.3%) females with a mean age of 63.0 ± 19.7 years. The hospital stay ranged from 1 to 170 days (a mean stay of 44.4 days), and the overall mortality rate was 64.3% (27/42). In univariate analysis, the AUC of ROC for MEWS, RAPS, qSOFA, MEWS plus GCS, REMS, NEWS, and MEDS showed 0.833, 0.842, 0.848, 0.846, 0.846, 0.878, and 0.905. In the multivariate Cox regression analysis, all scoring systems, older age, lactate, MAP, and DBP, indicated significant differences between survivor and non-survivor groups. Our results show that all scoring systems could apply in predicting the outcome of patients with cryptococcal fungemia, and the MEDS displays the best performance. We recommend a further large-scale prospective study for patients with cryptococcal fungemia.

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Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, resulting in a huge socio-economic impact. Kidney is a highly complex organ and the pathogenesis underlying kidney organization involves complex cell-to-cell interaction within the heterogeneous kidney milieu. Advanced single-cell RNA sequencing (scRNA-seq) could reveal the complex architecture and interaction with the microenvironment in early DKD. We used scRNA-seq to investigate early changes in the kidney of db/m mice and db/db mice at the 14th week. Uniform Manifold Approximation and Projection were applied to classify cells into different clusters at a proper resolution. Weighted gene co-expression network analysis was used to identify the key molecules specifically expressed in kidney tubules. Information of cell-cell communication within the kidney was obtained using receptor-ligand pairing resources. In vitro model, human subjects, and co-detection by indexing staining were used to identify the pathophysiologic role of the hub genes in DKD. Among four distinct subsets of the proximal tubule (PT), lower percentages of proliferative PT and PT containing AQP4 expression (PTAQP4+) in db/db mice induced impaired cell repair activity and dysfunction of renin-angiotensin system modulation in early DKD. We found that ferroptosis was involved in DKD progression, and ceruloplasmin acted as a central regulator of the induction of ferroptosis in PTAQP4+. In addition, lower percentages of thick ascending limbs and collecting ducts with impaired metabolism function were also critical pathogenic features in the kidney of db/db mice. Secreted phosphoprotein 1 (SPP1) mediated pathogenic cross-talk in the tubular microenvironment, as validated by a correlation between urinary SPP1/Cr level and tubular injury. Finally, mesangial cell-derived semaphorin 3C (SEMA3C) further promoted endothelium-mesenchymal transition in glomerular endothelial cells through NRP1 and NRP2, and urinary SEMA3C/Cr level was positively correlated with glomerular injury. These data identified the hub genes involved in pathophysiologic changes within the microenvironment of early DKD.

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Taiwan had the high incidence of chronic kidney disease (CKD) worldwide. Our objective was to examine associations between daily exposure of phthalates and melamine, two common nephrotoxins, and kidney damage risk in a well-established nationwide cohort. Study subjects were from Taiwan Biobank (TWB) with existing data of questionnaire and biochemical examinations. Average daily intake (ADI) levels of melamine and seven parental phthalates, including DEHP (di-2-ethylhexylphthalate), DiBP (Dibutyl phthalate), DnBP (Di-n-butyl phthalate), BBzP (Butyl benzyl phthalate), DEP (Diethyl phthalate), and DMP (Dimethyl phthalate) were estimated using a creatinine excretion-based model from urine melamine and 10 phthalate metabolites. Urine microalbumin to creatinine ratio (ACR) was used to represent for the outcome of kidney damage. Two statistical strategies were used: First, a weighted quantile sum (WQS) regression model to select the most important exposure variables of ADI levels of phthalates and melamine associated with ACR; Second, to examine effects of those most important exposure variables on ACR in multivariable linear regression models. In total, 1153 eligible adults were left for analyses. Of them, 591 (51.3%) and 562 (48.7%) were men and women, respectively, with a median age of 49 years old. By WQS, a significant and positive association was found between ADI of melamine and phthalates and ACR (ß = 0.14, p = 0.002). ADI levels of melamine had the highest weight (0.57), followed by DEHP (0.13). Next, examining the two most important exposures in association with ACR, we found that the higher the melamine and DEHP intakes, the higher the ACR levels were found. An interaction effect was also found between melamine and DEHP intakes on urine ACR (p = 0.015). This result was more prominent in men (p = 0.008) than in women (p = 0.651). Environmental co-exposure of melamine and DEHP can potentially affect ACR in the community-dwelling Taiwanese adult population.

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Repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS) have been proven effective non-invasive treatments for patients with drug-resistant major depressive disorder (MDD). However, some depressed patients do not respond to these treatments. Therefore, the investigation of reliable and valid brain oscillations as potential indices for facilitating the precision of diagnosis and treatment protocols has become a critical issue. The current review focuses on brain oscillations that, mostly based on EEG power analysis and connectivity, distinguish between MDD and controls, responders and non-responders, and potential depression severity indices, prognostic indicators, and potential biomarkers for rTMS or iTBS treatment. The possible roles of each biomarker and the potential reasons for heterogeneous results are discussed, and the directions of future studies are proposed.

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BACKGROUND: Extended field-of-view (eFOV) methods have been proposed to generate larger demonstration FOVs for computed tomography (CT) simulators with a limited scanning FOV (sFOV) size in order to ensure accurate dose calculation and patient collision avoidance. Although the efficacy of these strategies has been evaluated for photon applications, the effect of stopping power ratio (SPR) estimation on proton therapy has not been studied. This study investigated the effect of an eFOV approach on the accuracy of SPR to water estimation in homogeneous and heterogeneous phantoms. MATERIALS AND METHODS: To simulate patient geometries, tissue-equivalent material (TEM) and customized extension phantoms were used. The TEM phantom supported various rod arrangements through predefined holes. Images were reconstructed to three FOV sizes using a commercial eFOV technique. A single-energy CT stoichiometric method was used to generate Hounsfield unit (HU) to SPR (HU-to-SPR) conversion curves for each FOV. To investigate the effect of rod location in the sFOV and eFOV regions, eight TEM rods were placed at off-center distances in the homogeneous phantom and scanned individually. Similarly, 16 TEM rods were placed in the heterogeneous TEM phantom and scanned simultaneously. RESULTS: The conversion curves derived from the sFOV and eFOV data were identical. The average SPR differences of soft-tissue, bone, and lung materials for rods placed at various off-center locations were 3.3%, 4.8%, and 39.6%, respectively. In the heterogeneous phantom, the difference was within 1.0% in the absence of extension. However, in the presence of extension, the difference increased to 2.8% for all rods, except for lung materials, whose difference was 4.8%. CONCLUSIONS: When an eFOV method is used, the SPR variation in phantoms considerably increases for all TEM rods, especially for lung TEM rods. This phenomenon may substantially increase the uncertainty of HU-to-SPR conversion. Therefore, image reconstruction with a standard FOV size is recommended.

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The impact of melamine exposure on kidney outcomes in type 2 diabetes mellitus (T2D) patients remains unclear. In this prospective cohort study, 561 T2D patients during October 2016 and June 2020 were enrolled and followed until December 2021. Baseline one-spot urinary corrected melamine levels were measured by LC-MS/MS. Average daily intake (ADI) of melamine represented environmental melamine exposure in daily life, and was estimated using urinary corrected melamine level by creatinine excretion (CE)-based model. Primary kidney outcomes were defined as doubling of serum creatinine levels or end stage kidney disease (ESKD), and secondary kidney outcomes included rapid decline in kidney function as estimated glomerular filtration rate (eGFR) decline >5 ml/min/1.73 m2/year. Baseline median urinary corrected melamine levels and estimated DI of melamine were 0.8 µg/mmol and 0.3 µg/kg/day in 561 T2D patients. During 3.7 years of follow-up, urinary corrected melamine level was positively correlated with reaching composite outcomes of either doubling of serum creation levels or ESKD and rapid decline in kidney function. Those with the highest quartile of urinary corrected melamine had 2.96-fold risk of composite outcomes of either doubling of serum creation levels or ESKD and 2.47-fold risk of eGFR decline >5 ml/min/1.73 m2/year. Estimated ADI of melamine also had significant correlation with adverse kidney outcomes. Furthermore, the positive relationship between melamine exposure and rapid decline in kidney function was only found in T2D patients with male, baseline eGFR ≥60 ml/min/1.73 m2 or glycated hemoglobin ≤7%. In conclusion, melamine exposure is significantly associated with adverse kidney outcomes in T2D patients, especially in those with male, well sugar control or good baseline kidney function.

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(1) Background: Non-alcoholic fatty liver disease (NAFLD) is a major global health concern. The increasing prevalence of NAFLD has been related to type 2 diabetes mellitus (T2D). However, the relationship between short-chain fatty acids (SCFAs) and NAFLD severity is ambiguous in T2D subjects. This study aimed to explore the association of SCFAs with the severity of NAFLD in T2D patients. (2) Methods: We employed echography to examine the severity of hepatic steatosis. The serum levels of nine SCFAs, namely, formate, acetate, propionate, butyrate, isobutyrate, methylbutyrate, valerate, isovalerate, and methylvalerate, were measured using gas chromatography mass spectrometry. (3) Results: A total of 259 T2D patients was enrolled in this cross-sectional study. Of these participants, 117 with moderate to severe NAFLD had lower levels of formate, isobutyrate, and methylbutyrate than the 142 without NAFLD or with mild NAFLD. Lower circulating levels of isobutyrate and methylbutyrate were associated with an increased severity of NAFLD. A relationship between NAFLD severity and circulating isobutyrate and methylbutyrate levels was found independently of a glycated hemoglobin (HbA1C) level of 7.0%. (4) Conclusion: Circulating levels of isobutyrate and methylbutyrate were significantly and negatively correlated with NAFLD severity in the enrolled T2D patients. SCFAs may be related to NAFLD severity in T2D patients.

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