Quantitative PCR for early detection of human cytomegalovirus end-organ disease in immunocompetent host: A retrospective single-center study.

BACKGROUND: Tissue-invasive end-organ disease (EOD) caused by cytomegalovirus (CMV) is less frequently reported in immunocompetent patients compared to immunocompromised patients. In this study, we investigated the association between CMV viremia and CMV end-organ disease in immunocompetent patients. METHODS: Adult patients (≥18 years old) with CMV viremia were screened from January 2010 to June 2022. The primary outcome was the presence of CMV EOD. Risk factors associated with CMV EOD were analyzed, and a receiver operating characteristic curve was plotted to determine the most accurate cutoff value of the CMV titer for the prediction of CMV EOD. RESULTS: Among the 106 immunocompetent patients with CMV viremia, 31 exhibited CMV EOD. Gastrointestinal tract disease was the most common. The log10 value of the CMV titer was significantly associated with the occurrence of CMV EOD in immunocompetent patients with CMV viremia. The optimal cut-off CMV titer for the prediction of CMV EOD was 749 IU/mL. CONCLUSIONS: Our study suggests the potential association between high CMV titers and the development of CMV end-organ diseases and describes the diagnostic performance and utility of quantitative PCR as a surrogate marker for predicting the occurrence of CMV EOD in immunocompetent patients.

Association between intraoperative tidal volume and postoperative acute kidney injury in non-cardiac surgical patients using a propensity score-weighted analysis.

Acute kidney injury (AKI) is related to adverse clinical outcomes. Therefore, identifying patients at increased risk of postoperative AKI and proactively providing appropriate care is crucial. However, only a limited number of modifiable risk factors have been recognized to mitigate AKI risk. We retrospectively analyzed adult patients who underwent endotracheal intubation and mechanical ventilation of more than 2 h during non-cardiac surgery at Seoul National University Hospital from January 2011 to November 2022. Patients were grouped into low- or high-tidal volume groups based on their intraoperative tidal volume relative to their predicted body weight (PBW) of 8 ml/kg. The association between intraoperative tidal volume and postoperative AKI was evaluated using inverse probability of treatment weighting (IPTW), adjusting for various preoperative confounders. Among the 37,726 patients included, the incidence of postoperative AKI was 4.1%. The odds of postoperative AKI risk were significantly higher in the high-tidal volume group than in the low-tidal volume group before and after IPTW (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.08-1.32, P = 0.001 and OR: 1.10, 95% CI 1.02-1.19, P = 0.010, respectively). In the multivariable logistic regression analysis after IPTW, a high tidal volume was independently associated with an increased risk of postoperative AKI (OR: 1.21, 95% CI 1.12-1.30, P < 0.001). In this propensity score-weighted analysis, an intraoperative high tidal volume of more than 8 ml/kg PBW was significantly associated with an increased risk of postoperative AKI after IPTW in non-cardiac surgical patients. Intraoperative tidal volume showed potential as a modifiable risk factor for preventing postoperative AKI.

Brain activations elicited during task-switching generalize beyond the task: A partial least squares correlation approach to combine fMRI signals and cognition.

An underlying hypothesis for broad transfer from cognitive training is that the regional brain signals engaged during the training task are related to the transfer tasks. However, it is unclear whether the brain activations elicited from a specific cognitive task can generalize to performance of other tasks, esp. in normal aging where cognitive training holds much promise. In this large dual-site functional magnetic resonance imaging (fMRI) study, we aimed to characterize the neurobehavioral correlates of task-switching in normal aging and examine whether the task-switching-related fMRI-blood-oxygen-level-dependent (BOLD) signals, engaged during varieties of cognitive control, generalize to other tasks of executive control and general cognition. We therefore used a hybrid blocked and event-related fMRI task-switching paradigm to investigate brain regions associated with multiple types of cognitive control on 129 non-demented older adults (65-85 years). This large dataset provided a unique opportunity for a data-driven partial least squares-correlation approach to investigate the generalizability of multiple fMRI-BOLD signals associated with task-switching costs to other tasks of executive control, general cognition, and demographic characteristics. While some fMRI signals generalized beyond the scanned task, others did not. Results indicate right middle frontal brain activation as detrimental to task-switching performance, whereas inferior frontal and caudate activations were related to faster processing speed during the fMRI task-switching, but activations of these regions did not predict performance on other tasks of executive control or general cognition. However, BOLD signals from the right lateral occipital cortex engaged during the fMRI task positively predicted performance on a working memory updating task, and BOLD signals from the left post-central gyrus that were disengaged during the fMRI task were related to slower processing speed in the task as well as to lower general cognition. Together, these results suggest generalizability of these BOLD signals beyond the scanned task. The findings also provided evidence for the general slowing hypothesis of aging as most variance in the data were explained by low processing speed and global low BOLD signal in older age. As processing speed shared variance with task-switching and other executive control tasks, it might be a possible basis of generalizability between these tasks. Additional results support the dedifferentiation hypothesis of brain aging, as right middle frontal activations predicted poorer task-switching performance. Overall, we observed that the BOLD signals related to the fMRI task not only generalize to the performance of other executive control tasks, but unique brain predictors of out-of-scanner performance can be identified.

Impact of Respiratory Bacterial Findings on Patients with Chronic Pulmonary Aspergillosis.

Background: Distinct bacterial strains may affect the prognosis of patients with chronic respiratory diseases. However, little is known about the clinical significance of respiratory bacteria in patients with chronic pulmonary aspergillosis (CPA), a progressive and debilitating disease caused by Aspergillus spp. Objectives: This study aimed to analyze data obtained from CPA patients and their sputum or bronchial washing samples and investigate the prevalence and composition of respiratory bacteria and clinical implications. Patients and Methods. We retrospectively reviewed the data of patients diagnosed with CPA between March 2019 and February 2023 in a tertiary referral hospital. We assessed the clinical characteristics and overall and pneumonia-specific survival rates of patients with CPA based on the presence of bacteria. Results and Conclusions. We included 142 patients with CPA. The most commonly identified bacteria were Klebsiella pneumoniae (22.5%), followed by Pseudomonas aeruginosa (21.8%) and Escherichia coli (4.2%). Patients with isolated bacteria had a higher prevalence of older age, female sex, diabetes, and a history of extrathoracic malignancy than those without isolated bacteria (P = 0.024, 0.013, 0.021, and 0.034, respectively). Furthermore, over a median follow-up of 11 (4-21) months, the pneumonia-specific mortality rate was 13.4% (19/142), which was higher in patients with isolated bacteria than in those without (P = 0.045, log-rank test). Particularly, patients with the presence of P. aeruginosa had a significantly higher mortality rate from pneumonia than those without the presence of P. aeruginosa (adjusted hazard ratio, 3.34; P = 0.015). In conclusion, CPA patients with isolated bacteria, especially P. aeruginosa, showed higher mortality rates due to pneumonia. Performing tests to identify bacteria in the lower respiratory tract of patients with CPA may be helpful in predicting future prognosis. Further studies are required to validate these findings in diverse ethnic groups.

Educational Attainment Moderates Task-State Control Network Connectivity Relations to Response Conflict Among Healthy Older Adults.

OBJECTIVES: Older adult executive function varies widely due to brain and cognitive aging. Variance in older adult executive function is linked to increased response conflict from cognitive and brain aging. Cognitive reserve (CR) is a theoretical protective mechanism that lessens brain aging's impact on cognition and is associated with greater educational attainment. Recent work in rest-state functional magnetic resonance imaging (fMRI) suggests CR proxies moderate the relationship between functional connectivity (FC) and cognitive performance. Brain network FC in "control networks," including the salience (SN), dorsal attention and frontoparietal networks, are associated with cognitive processes in older adults. CR is hypothesized to maintain cognitive processing in part through changes in how brain networks respond to cognitive demands. However, it is unclear how CR proxies like educational attainment are related to control network FC during performance when cognitive demands are increased relative to rest. Because CR is expressed more in those with higher education, we hypothesized stronger control network FC would relate to better performance, where this relationship would be strongest among the most educated. METHODS: We collected flanker task data during fMRI to assess the impact of a CR proxy (i.e., educational attainment) on response conflict among older adult subjects (n = 42, age = 65-80). RESULTS: Linear mixed-effects models showed more educated older adults with greater SN-FC had a smaller flanker effect (i.e., less influence of distractors; p < .001) during task performance. DISCUSSION: For the first time, we show that educational attainment moderates the relationship between task-state SN-FC and executive function among older adults.

Characteristics and biomarkers associated with mortality in COVID-19 patients presenting to the emergency department.

This study aimed to investigate the diverse clinical manifestations and simple early biomarkers predicting mortality of COVID-19 patients admitted to the emergency department (ED). A total of 710 patients with COVID-19 were enrolled from 6,896 patients presenting to the ED between January 2022 and March 2022. During the study period, a total of 478 patients tested positive for COVID-19, among whom 222 (46.4%) presented with extrapulmonary manifestations of COVID-19; 49 (10.3%) patients displayed gastrointestinal manifestations, followed by neurological (n = 41; 8.6%) and cardiac manifestations (n = 31; 6.5%). In total, 54 (11.3%) patients died. A Cox proportional hazards model revealed that old age, acute kidney injury at presentation, increased total leukocyte counts, low platelet counts, decreased albumin levels, and increased LDH levels were the independent predictors of mortality. The albumin levels exhibited the highest area under the curve in receiver operating characteristic analysis, with a value of 0.860 (95% confidence interval, 0.796-0.875). The study showed the diverse clinical presentations and simple-to-measure prognostic markers in COVID-19 patients presenting to the ED. Serum albumin levels can serve as a novel and simple early biomarker to identify COVID-19 patients at high risk of death.

The Effects of Computerized Cognitive Training in Older Adults' Cognitive Performance and Biomarkers of Structural Brain Aging.

OBJECTIVES: Cognitive training (CT) has been investigated as a means of delaying age-related cognitive decline in older adults. However, its impact on biomarkers of age-related structural brain atrophy has rarely been investigated, leading to a gap in our understanding of the linkage between improvements in cognition and brain plasticity. This study aimed to explore the impact of CT on cognitive performance and brain structure in older adults. METHODS: One hundred twenty-four cognitively normal older adults recruited from 2 study sites were randomly assigned to either an adaptive CT (n = 60) or a casual game training (active control, AC, n = 64). RESULTS: After 10 weeks of training, CT participants showed greater improvements in the overall cognitive composite score (Cohen's d = 0.66, p < .01) with nonsignificant benefits after 6 months from the completion of training (Cohen's d = 0.36, p = .094). The CT group showed significant maintenance of the caudate volume as well as significant maintained fractional anisotropy in the left internal capsule and in left superior longitudinal fasciculus compared to the AC group. The AC group displayed an age-related decrease in these metrics of brain structure. DISCUSSION: Results from this multisite clinical trial demonstrate that the CT intervention improves cognitive performance and helps maintain caudate volume and integrity of white matter regions that are associated with cognitive control, adding to our understanding of the changes in brain structure contributing to changes in cognitive performance from adaptive CT. CLINICAL TRIAL REGISTRATION: NCT03197454.

Energy Metabolism in Human Pluripotent Stem and Differentiated Cells Compared Using a Seahorse XF96 Extracellular Flux Analyzer.

Evaluating cell metabolism is crucial during pluripotent stem cell (PSC) differentiation and somatic cell reprogramming as it affects cell fate. As cultured stem cells are heterogeneous, a comparative analysis of relative metabolism using existing metabolic analysis methods is difficult, resulting in inaccuracies. In this study, we measured human PSC basal metabolic levels using a Seahorse analyzer. We used fibroblasts, human induced PSCs, and human embryonic stem cells to monitor changes in basal metabolic levels according to cell number and determine the number of cells suitable for analysis. We evaluated normalization methods using glucose and selected the most suitable for the metabolic analysis of heterogeneous PSCs during the reprogramming stage. The response of fibroblasts to glucose increased with starvation time, with oxygen consumption rate and extracellular acidification rate responding most effectively to glucose 4 hours after starvation and declining after 5 hours of starvation. Fibroblasts and PSCs achieved appropriate responses to glucose without damaging their metabolism 2∼4 and 2∼3 hours after starvation, respectively. We developed a novel method for comparing basal metabolic rates of fibroblasts and PSCs, focusing on quantitative analysis of glycolysis and oxidative phosphorylation using glucose without enzyme inhibitors. This protocol enables efficient comparison of energy metabolism among cell types, including undifferentiated PSCs, differentiated cells, and cells undergoing cellular reprogramming, and addresses critical issues, such as differences in basal metabolic levels and sensitivity to normalization, providing valuable insights into cellular energetics.

SIRT1 ISGylation accelerates tumor progression by unleashing SIRT1 from the inactive state to promote its deacetylase activity.

ISG15 is an interferon-stimulated ubiquitin-like protein (UBL) with multifaceted roles as a posttranslational modifier in ISG15 conjugation (ISGylation). However, the mechanistic consequences of ISGylation in cancer have not been fully elucidated, largely due to a lack of knowledge on the ISG15 target repertoire. Here, we identified SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, as a new target for ISGylation. SIRT1 ISGylation impairs the association of SIRT1 with its negative regulator, deleted in breast cancer 1 (DBC1), which unleashes SIRT1 from its inactive state and leads to an increase in its deacetylase activity. Importantly, SIRT1 ISGylation promoted lung cancer progression and limited lung cancer cell sensitivity to DNA damage-based therapeutics in vivo and in vitro models. The levels of ISG15 mRNA and protein were significantly higher in lung cancer tissues than in adjacent normal tissues. Accordingly, elevated expression of SIRT1 and ISG15 was associated with poor prognosis in lung cancer patients, a finding that could be translated for lung cancer patient stratification and disease outcome evaluation. Taken together, our findings provide a mechanistic understanding of the regulatory effect of SIRT1 ISGylation on tumor progression and therapeutic efficacy in lung cancer.

A Comparison of Short-Term Outcomes after Surgical Treatment of Multilevel Degenerative Cervical Myelopathy in the Geriatric Patient Population: An Analysis of the National Surgical Quality Improvement Program Database 2010-2020.

STUDY DESIGN: Retrospective review of the American College of Surgeons-National Surgical Quality Improvement Program database from 2010 to 2020. PURPOSE: To compare the short-term complication rates of anterior cervical decompression and fusion (ACDF), posterior cervical laminoplasty (LP), and posterior cervical laminectomy and fusion (PCF) in a geriatric population. OVERVIEW OF LITERATURE: The geriatric population in the United States has increased significantly. Degenerative cervical myelopathy (DCM) is caused by cervical spinal stenosis, and its prevalence increases with age. Therefore, the incidence of multilevel DCM requiring surgical intervention is likely to increase. ACDF, LP, and PCF are the most commonly used surgical techniques for treating multilevel DCM. However, there is uncertainty regarding the optimal surgical technique for the decompression of DCM in geriatric patients. METHODS: Patients aged 65 years who had undergone either multilevel ACDF, LP, or PCF for the treatment of DCM were analyzed. Additional analysis was performed by standardizing the data for the American Society of Anesthesiologists classification scores and preoperative functional status. RESULTS: A total of 23,129 patients were identified. Patients with ACDF were younger, more often female, and preoperatively healthier than those in the other two groups. The estimated postoperative mortality and morbidity, mean operation time, and length of hospital stay were the lowest for ACDF, second lowest for LP, and highest for PCF. The readmission and reoperation rates were comparable between ACDF and LP; however, both were significantly lower than PCF. CONCLUSIONS: PCF is associated with the highest risk of mortality, morbidity, unplanned reoperation, and unplanned readmission in the short-term postoperative period in patients aged 65 years. In contrast, ACDF carries the lowest risk. However, some disease-specific factors may require posterior treatment. For these cases, LP should be included in the preoperative discussion when determining the ideal surgical approach for geriatric patients.

Intraoperative Normal Saline Administration and Acute Kidney Injury in Patients Undergoing Liver Transplantation.

BACKGROUND: Normal saline is still used in patients undergoing living donor liver transplantation (LDLT) with normonatremia. We investigated whether the normal saline administered during LDLT is associated with the increased risk of acute kidney injury (AKI) compared with the balanced crystalloids. METHODS: We reviewed 1011 cases undergoing LDLT. The primary exposure variable was normal saline administered intraoperatively compared with the balanced crystalloid. To compare the risk of AKI after adjusting for potential confounders of baseline characteristics and surgical parameters, a propensity score matching analysis was performed. As a sensitivity analysis, ordinal logistic regression analysis was performed for AKI using inverse probability of treatment weighting (IPTW). RESULTS: The incidence of AKI was significantly higher in the saline group (n = 88/174, 50.6%) than in the balanced group (n = 67/174, 38.5%) after matching (P = .010). The incidence of stage 2 or 3 AKI was also significantly higher in the saline group (n = 26/174, 14.9%) than in the balanced group (n = 43/174, 24.7%) after matching (P = .022). The length of hospital stay was significantly longer in the saline group than in the balanced group after matching. Ordinal logistic regression analysis using IPTW showed that the saline group showed a significant association of saline administration with the risk of AKI (odds ratio 1.23, 95% CI 1.05-1.28, P = .013). CONCLUSION: Our propensity score analysis using propensity score matching and IPTW showed that normal saline administration during LDLT is associated with a high risk of postoperative AKI and longer hospital stays. However, our results should be interpreted carefully due to the relatively long period of data collection.

The feasibility of MR elastography with transpelvic vibration for localization of focal prostate lesion.

We aimed to evaluate the feasibility of MR elastography (MRE) using a transpelvic approach. Thirty-one patients who underwent prostate MRE and had a pathological diagnosis were included in this study. MRE was obtained using a passive driver placed at the umbilicus and iliac crests. The shear stiffness, clinical data, and conventional imaging findings of prostate cancer and benign prostatic hyperplasia (BPH) were compared. Inter-reader agreements were evaluated using the intraclass coefficient class (ICC). Prostate MRE was successfully performed for all patients (100% technical success rate). Nineteen cancer and 10 BPH lesions were visualized on MRE. The mean shear stiffness of cancer was significantly higher than that of BPH (5.99 ± 1.46 kPa vs. 4.67 ± 1.54 kPa, p = 0.045). One cancer was detected on MRE but not on conventional sequences. Six tiny cancer lesions were not visualized on MRE. The mean size of cancers that were not detected on MRE was smaller than that of cancers that were visible on MRE (0.8 ± 0.3 cm vs. 2.3 ± 1.8 cm, p = 0.001). The inter-reader agreement for interpreting MRE was excellent (ICC = 0.95). Prostate MRE with transpelvic vibration is feasible without intracavitary actuators. Transpelvic prostate MRE is reliable for detecting focal lesions, including clinically significant prostate cancer and BPH.

Polymorphic Self-Assembly with Procedural Flexibility for Monodisperse Quaternary Protein Structures of DegQ Enzymes.

As large molecular tertiary structures, some proteins can act as small robots that find, bind, and chaperone target protein clients, showing the potential to serve as smart building blocks in self-assembly fields. Instead of using such intrinsic functions, most self-assembly methodologies for proteins aim for de novo-designed structures with accurate geometric assemblies, which can limit procedural flexibility. Here, a strategy enabling polymorphic clustering of quaternary proteins, exhibiting simplicity and flexibility of self-assembling paths for proteins in forming monodisperse quaternary cage particles is presented. It is proposed that the enzyme protomer DegQ, previously solved at low resolution, may potentially be usable as a threefold symmetric building block, which can form polyhedral cages incorporated by the chaperone action of DegQ in the presence of protein clients. To obtain highly monodisperse cage particles, soft, and hence, less resistive client proteins, which can program the inherent chaperone activity of DegQ to efficient formations of polymorphic cages, depending on the size of clients are utilized. By reconstructing the atomic resolution cryogenic electron microscopy DegQ structures using obtained 12- and 24-meric clusters, the polymorphic clustering of DegQ enzymes is validated in terms of soft and rigid domains, which will provide effective routes for protein self-assemblies with procedural flexibility.

Multicentre validation of a machine learning model for predicting respiratory failure after noncardiac surgery.

BACKGROUND: Postoperative respiratory failure is a serious complication that could benefit from early accurate identification of high-risk patients. We developed and validated a machine learning model to predict postoperative respiratory failure, defined as prolonged (>48 h) mechanical ventilation or reintubation after surgery. METHODS: Easily extractable electronic health record (EHR) variables that do not require subjective assessment by clinicians were used. From EHR data of 307,333 noncardiac surgical cases, the model, trained with a gradient boosting algorithm, utilised a derivation cohort of 99,025 cases from Seoul National University Hospital (2013-9). External validation was performed using three separate cohorts A-C from different hospitals comprising 208,308 cases. Model performance was assessed by area under the receiver operating characteristic (AUROC) curve and area under the precision-recall curve (AUPRC), a measure of sensitivity and precision at different thresholds. RESULTS: The model included eight variables: serum albumin, age, duration of anaesthesia, serum glucose, prothrombin time, serum creatinine, white blood cell count, and body mass index. Internally, the model achieved an AUROC of 0.912 (95% confidence interval [CI], 0.908-0.915) and AUPRC of 0.113. In external validation cohorts A, B, and C, the model achieved AUROCs of 0.879 (95% CI, 0.876-0.882), 0.872 (95% CI, 0.870-0.874), and 0.931 (95% CI, 0.925-0.936), and AUPRCs of 0.029, 0.083, and 0.124, respectively. CONCLUSIONS: Utilising just eight easily extractable variables, this machine learning model demonstrated excellent discrimination in both internal and external validation for predicting postoperative respiratory failure. The model enables personalised risk stratification and facilitates data-driven clinical decision-making.

Purely self-rectifying memristor-based passive crossbar array for artificial neural network accelerators.

Memristor-integrated passive crossbar arrays (CAs) could potentially accelerate neural network (NN) computations, but studies on these devices are limited to software-based simulations owing to their poor reliability. Herein, we propose a self-rectifying memristor-based 1 kb CA as a hardware accelerator for NN computations. We conducted fully hardware-based single-layer NN classification tasks involving the Modified National Institute of Standards and Technology database using the developed passive CA, and achieved 100% classification accuracy for 1500 test sets. We also investigated the influences of the defect-tolerance capability of the CA, impact of the conductance range of the integrated memristors, and presence or absence of selection functionality in the integrated memristors on the image classification tasks. We offer valuable insights into the behavior and performance of CA devices under various conditions and provide evidence of the practicality of memristor-integrated passive CAs as hardware accelerators for NN applications.

Randomized controlled trial of the effect of general anesthetics on postoperative recovery after minimally invasive nephrectomy.

BACKGROUND: General anesthetic techniques can affect postoperative recovery. We compared the effect of propofol-based total intravenous anesthesia (TIVA) and desflurane anesthesia on postoperative recovery. METHODS: In this randomized trial, 150 patients undergoing robot-assisted or laparoscopic nephrectomy for renal cancer were randomly allocated to either the TIVA or desflurane anesthesia (DES) group. Postoperative recovery was evaluated using the Korean version of the Quality of Recovery-15 questionnaire (QoR-15K) at 24 h, 48 h, and 72 h postoperatively. A generalized estimating equation (GEE) was performed to analyze longitudinal QoR-15K data. Fentanyl consumption, pain severity, postoperative nausea and vomiting, and quality of life three weeks after discharge were also compared. RESULTS: Data were analyzed for 70 patients in each group. The TIVA group showed significantly higher QoR-15K scores at 24 and 48 h postoperatively (24 h: DES, 96 [77, 109] vs. TIVA, 104 [82, 117], median difference 8 [95% CI: 1, 15], P = 0.029; 48 h: 110 [95, 128] vs. 125 [109, 130], median difference 8 [95% CI: 1, 15], P = 0.022), however not at 72 h (P = 0.400). The GEE revealed significant effects of group (adjusted mean difference 6.2, 95% CI: 0.39, 12.1, P = 0.037) and time (P < 0.001) on postoperative QoR-15K scores without group-time interaction (P = 0.051). However, there were no significant differences in other outcomes, except for fentanyl consumption, within the first 24 h postoperatively. CONCLUSIONS: Propofol-based TIVA showed only a transient improvement in postoperative recovery than desflurane anesthesia, without significant differences in other outcomes.

Modifying Kohlrausch's Law to Describe Nonaqueous Electrolytes for Lithium-Ion Batteries.

To develop next-generation lithium-ion batteries with enhanced stability and safety, it is crucial to understand the physicochemical principles of nonaqueous electrolytes. Kohlrausch's law describes a linear decrease in the molar conductivity (Λ) with respect to the square root of the molarity of strong electrolytes at lower concentrations. This empirical law explains the impeded ionic mobility at higher concentrations due to ionic interactions, i.e., relaxation and asymmetric effects. However, this law does not hold at higher concentrations due to the ionic association that alleviates the ionic interactions and retards the decrease in the Λ. Especially, the anomalously stagnant decrease in the Λ near the solubility limit has not been clearly explained, calling for the consideration of other concentration-dependent factors such as the mean activity coefficient (γ±), viscosity (η), and dielectric constant (ε). Herein, we develop a systematic method to modify Kohlrausch's law. First, we install the ionic association constant, and the theoretical estimation is compared with the experimental results to induce the correction function that is related with the previously neglected concentration-dependent factors. Thus, the induced correction function was close to the rectified linear unit (ReLU) function, which has been widely used in the field of artificial intelligence. The modified Kohlrausch's law with the ReLU-type correction function provides a highly precise and reliable data fitting, and the fitted parameters showed clear concentration dependency and straightforward interpretability. As a result, this method effectively generalized Kohlrausch's law for nonaqueous electrolytes at higher concentrations up to the solubility limit of 3.0-3.5 M. Moreover, the modified Kohlrausch's law inspired us to discover the physical origins of the anomalously stagnant Λ profiles near the solubility limit; and the most relevant physical origin of the anomaly was the concentration dependency of the γ± and η, which grow exponentially above a critical concentration.