An effective AI model for automatically detecting arteriovenous fistula stenosis.

In this study, a novel artificial intelligence (AI) model is proposed to detect stenosis in arteriovenous fistulas (AVFs) using inexpensive and non-invasive audio recordings. The proposed model is a combination of two new input features based on short-time Fourier transform (STFT) and sample entropy, as well as two associated classification models (ResNet50 and ANN). The model's hyper-parameters were optimized through the use of the design of the experiment (DOE). The proposed AI model demonstrates high performance with all essential metrics, including sensitivity, specificity, accuracy, precision, and F1-score, exceeding 0.90 at detecting stenosis greater than 50%. These promising results suggest that our approach can lead to new insights and knowledge in this field. Moreover, the robust performance of our model, combined with the affordability of the audio recording device, makes it a valuable tool for detecting AVF stenosis in home-care settings.

Correlation between breath ammonia and blood urea nitrogen levels in chronic kidney disease and dialysis patients.

Previous studies have shown that breath ammonia (breath-NH3) concentration is associated with blood urea nitrogen (BUN) levels. However, interindividual variations in breath-NH3 concentrations were observed. Thus, the present study aimed to assess the effect of oral cavity conditions on breath-NH3 concentration and to validate whether the measurement of breath-NH3 concentration is feasible in clinical settings. A total of 125 individuals, including patients with stage 3 to 5 chronic kidney disease (CKD3-5), those on dialysis, and healthy participants, were recruited. A nanostructured sensor was used to detect breath-NH3 concentrations. Pre- and post-gargling as well as pre- and post-hemodialysis (HD) breath-NH3, salivary pH, and salivary urea levels were measured. Breath-NH3, salivary urea, salivary pH, and BUN levels were positively correlated to each other. Breath-NH3 concentrations were associated with BUN levels (r = 0.43, p < 0.001) and were significantly higher in CKD3-5 (p < 0.005) and dialysis patients (p < 0.001) than in healthy participants. Higher correlation coefficients were noted between breath-NH3 concentrations and BUN levels during follow-up (r = 0.59-0.94, p < 0.05). When the cutoff value of breath-NH3 was set at 523.65 ppb, its sensitivity and specificity in predicting CKD (BUN level >24 mg dl-1) were 87.6% and 80.9%, respectively. Breath-NH3 concentrations decreased after HD (p < 0.001) and immediately after gargling (p < 0.01). Breath-NH3 concentration, which was affected by gargling, was correlated to BUN level. The measurement of breath-NH3 concentration using the nanostructured device may be used as a tool for CKD detection and personalized point-of-care for CKD and dialysis patients. The current study had a small sample size. Thus, further studies with a larger cohort must be conducted to validate the effect of oral factors on breath-NH3 concentration and to validate the benefit of breath-NH3 measurement.

A low-cost, portable and easy-operated salivary urea sensor for point-of-care application.

Salivary urea was reported to be a useful biomarker to reflect the blood urea nitrogen in chronic kidney disease patients. However, as a new biomarker, enormous clinical trials are required to define the intended-use and to verify the specification. In this report, we demonstrated a low-cost easy-operated real-time sensing system (optical fiber-urea-sensing, OFUS, system) to detect salivary urea. We aim to make the system easily reproduced by the community to stimulate abundant clinical tests worldwide. The OFUS system is composed of a simple three-dimensional printed tank to link with two optical fibers, one connecting with a commercial light-emitting diode to deliver the input light signal, the other connecting with a commercial cadmium sulfide photo-conductive cell to detect the sensing signal. To allow on-site detection without any sample pretreatment, only 1 µl saliva is needed to be mixed with 10 µl urease solution and 90 µl pH indicator solution in the reaction tank and the detection time is only 20 s. A stable and reproducible calibration curve can be easily built with a detection range as 24-300 mg/dL. The OFUS system successfully detected saliva with added synthetic urea and samples from chronic kidney disease patients. A good agreement between the OFUS system and the commercial kit was obtained. A good correlation between salivary urea and the blood urea nitrogen was also confirmed.

A Versatile Method to Enhance the Operational Current of Air-Stable Organic Gas Sensor for Monitoring of Breath Ammonia in Hemodialysis Patients.

Point-of-care (POC) application for monitoring of breath ammonia (BA) in hemodialysis (HD) patients has emerged as a promising noninvasive health monitoring approach. In this context, many organic gas sensors have been reported for BA detection. However, one of the major challenges for its integration with affordable household POC application is to achieve stable performance for accuracy and high operational current at low voltage for low-cost read-out circuitry. Herein, we exploited the stability of the Donor-Acceptor polymer on the cylindrical nanopore structure to realize the sensors with a high sensitivity and stability. Then, we proposed a double active layer (DL) strategy that exploits an ultrathin layer of Poly(3-hexylthiophene-2,5-diyl) (P3HT) to serve as a work function buffer to enhance the operational current. The DL sensor exhibits a sustainable enhanced operational current of microampere level and a stable sensing response even with the presence of P3HT layer. This effect is carefully examined with different aspects, including vertical composition profile of DL configuration, lifetime testing on different sensing layer, morphological analysis, and the versatility of the DL strategy. Finally, we utilize the DL sensor to conduct a tracing of BA concentration in two HD patients before and after HD, and correlate it with the blood urea nitrogen (BUN) levels. A good correlation coefficient of 0.96 is achieved. Moreover, the feasibility of DL sensor integrated into a low-cost circuitry was also verified. The results demonstrate the potential of this DL strategy to be used to integrate organic sensor for affordable household POC devices.

Organic Gas Sensor with an Improved Lifetime for Detecting Breath Ammonia in Hemodialysis Patients.

In this work, a TFB (poly[(9,9-dioctylfluorenyl-2,7-diyl)-co-(4,4'-(N-(4-s-butylphenyl)diphenylamine)]) sensor with a cylindrical nanopore structure exhibits a high sensitivity to ammonia in ppb-regime. The lifetime and sensitivity of the TFB sensor were studied and compared to those of P3HT (poly(3-hexylthiophene)), NPB (N,N'-di(1-naphthyl)-N,N'-diphenyl-(1,1'-biphenyl)-4,4'-diamine), and TAPC (4,4'-cyclohexylidenebis[N,N-bis(4-methylphenyl) benzenamine]) sensors with the same cylindrical nanopore structures. The TFB sensor outstands the others in sensitivity and lifetime and it shows a sensing response (current variation ratio) of 13% to 100 ppb ammonia after 64 days of storage in air. A repeated sensing periods testing and a long-term measurement have also been demonstrated for the test of robustness. The performance of the TFB sensor is stable in both tests, which reveals that the TFB sensor can be utilized in our targeting clinical trials. In the last part of this work, we study the change of ammonia concentration in the breath of hemodialysis (HD) patients before and after dialysis. An obvious drop of breath ammonia concentration can be observed after dialysis. The reduction of breath ammonia is also correlated with the reduction of blood urea nitrogen (BUN). A correlation coefficient of 0.82 is achieved. The result implies that TFB sensor may be used as a real-time and low cost breath ammonia sensor for the daily tracking of hemodialysis patients.

Increased serum levels of betatrophin in pancreatic cancer-associated diabetes.

Long-standing diabetes or glucose intolerance is recognized as a crucial event in the process of pancreatic cancer. Betatrophin, a novel liver-derived hormone, promotes ß-cell proliferation and improves glucose intolerance. However, the relationship between betatrophin and PDAC-associated diabetes is not fully understood. To evaluate the serum betatrophin levels in PDAC-associated diabetes, a total 105 Taiwanese subjects including 15 healthy subjects, and 12 patients having PDAC with normal glucose tolerance (PDAC-NGT), 12 patients having PC with impaired glucose tolerance (PDAC-IGT), and 66 patients having PC with diabetes mellitus (PDAC-DM) were enrolled for this study. Serum betatrophin and carbohydrate antigen 19-9 (CA19-9) levels were analyzed by enzyme-linked immunosorbent assay (ELISA). Compared to healthy subjects, PDAC patients had higher levels of betatrophin and CA19-9. Consistently, betatrophin protein was significantly expressed in pancreatic ductal of PDAC-associated DM patients using immunohistochemistry (IHC) method. Furthermore, multivariate regression analysis showed the betatrophin was significantly and positively independent with T category (ß= 0.605, P=0.010), serum albumin (ß= 0. 423, P=0.021), lipase (ß= 0.292, P=0.039), and blood urea nitrogen (BUN) (ß= 0.303, P=0.040). Further, the betatrophin was three folds of having PDAC-associated diabetes with the highest odds ratio [OR=3.39; 95% CI (1.20-9.57); P=0.021) and receiver operating characteristic (ROC) curve analysis showed that AUC value of betarophin was 0.853 which is slightly larger than AUC value of CA19-9 (0.792) in PDAC-DM patients. Interestingly, AUC value of betarophin plus CA19-9 was 0.988 in PDAC-DM patients. Therefore, betatrophin combined CA19-9 may serve as a potential biomarker for PDAC-associated diabetes.

Higher serum betatrophin level in type 2 diabetes subjects is associated with urinary albumin excretion and renal function.

BACKGROUND: Betatrophin is a newly identified liver-derived hormone that is associated with glucose homeostasis and lipid metabolism. Although dysregulated lipid metabolism results in diabetic nephropathy (DN) development in patients with type 2 diabetes mellitus (T2DM), it is not understood whether betatrophin is associated with urinary albumin excretion and renal function. METHODS: Based on albumin/creatinine ratio (ACR), 109 T2DM patients were divided into normoalbuminuria (ACR <30 mg/g), microalbuminuria (ACR between 30 and 300 mg/g), and macroalbuminuria (ACR > 300 mg/g). Serum betatrophin levels of 109 T2DM patients and 32 healthy subjects were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum level of betatrophin was significantly increased in T2DM patients with normoalbuminuria, microalbuminuria, and macroalbuminuria as compared with healthy subjects (P < 0.001). Serum betatrophin level was positively correlated with sex, duration of diabetes, systolic blood pressure (SBP), body mass index (BMI), ACR, and triglyceride, whereas it was inversely correlated with estimated glomerular filtration rate (eGFR), total cholesterol, and high-density lipoprotein cholesterol (HDL-C) (P < 0.001). Furthermore, multivariate regression analysis showed the betatrophin was significantly and positively independent with triglyceride and low-density lipoprotein cholesterol (LDL-C) (P < 0.05), whereas it was inversely independent with eGFR, total cholesterol, and low-density lipoprotein cholesterol (HDL-C) (P < 0.05). In addition, the betatrophin had higher odds of having DN [odds ratio (OR) = 5.65, 95 % confidence interval (CI) 2.17-14.57, P < 0.001]. CONCLUSION: Betatrophin is significantly increased in T2DM patients with different stages of albuminuria. Betatrophin may be a novel endocrine regulator involved in DN development.