Search

Background Kidney involvement frequently occurs in systemic lupus erythematosus (SLE), and its clinical manifestations are complicated. We profiled kidney involvement in SLE patients using deep learning based on data from the National Database of Designated Incurable Diseases of Japan. Methods We analyzed the cross-sectional data of 1655 patients with SLE whose Personal Clinical Records were newly registered between 2015 and 2017. We trained an artificial neural network using clinical data, and the extracted characteristics were evaluated using an autoencoder. We tested the difference of population proportions to analyze the correlation between the presence or absence of kidney involvement and that of other clinical manifestations. Results Data of patients with SLE were compressed in a feature space in which the anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibody titer, antinuclear antibody titer, or white blood cell count contributed significantly to distinguishing patients. Many SLE manifestations were accompanied by kidney involvement, whereas in a subgroup of patients with high anti-dsDNA antibody titers and low antinuclear antibody titers, kidney involvement was positively and negatively correlated with hemolytic anemia and inflammatory manifestations, respectively. Conclusion Although there are various combinations of SLE manifestations, our study revealed that some of them are specific to kidney involvement. SLE profiles extracted from the objective analysis will be useful for categorizing SLE manifestations.

Each transfer RNA (tRNA) is aminoacylated (charged) with a genetic codon-specific amino acid at its 3′ end. Charged tRNAs are primarily used for translation, whereas fluctuations in charged tRNA fractions are known to reflect cellular response to stress. Here we report the development of individual tRNA-acylation using PCR (i-tRAP), a convenient PCR-based method that can specifically quantify the individual tRNA charging ratio. In this i-tRAP method, demethylases remove base methylations which are problematic for reverse transcription reaction, and β-elimination reaction specifically removes the 3′ end of adenine residue in uncharged tRNA. Subsequent TaqMan MGB qRT-PCR can distinguish between cDNA of charged tRNA and uncharged tRNA. By using this method, we revealed that the charging ratio of tRNAGln(CUG) was changed in response to amino acid starvation and also the charging ratio of tRNAGln(CUG) in senescent cells was lower than in young cells under starvation conditions. i-tRAP can be applicable to the quantification of the charging ratio of various tRNAs, and provides a simple and convenient method for analyzing tRNA charging.

Background Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items. Methods Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder–decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood. Results Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort. Conclusions Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.

Background In this study, we investigated the mechanism by which excessive salt intake aggravates atherosclerosis by evaluating the changes in the gut microbiota, the expression of nutrient transporters in the gut, and the fatty acid composition in atherosclerosis. Results Sixteen-week-old male ApoE-deficient mice were either fed a high-fat, high-sucrose diet (HFHSD) or HFHSD, high-salt diet (HFHSD + 4%NaCl) for 8 weeks. The HFHSD + 4%NaCl group showed progression of atherosclerosis, and gut microbiota analysis revealed that this group had a reduced abundance of Allobaculum spp., Ruminococcaceae family, Lachnospiraceae family, and Alphaproteobacteria class compared to the HFHSD group. Furthermore, Cd36 gene expression levels were increased in the small intestine of the HFHSD + 4%NaCl group compared to those in the HFHSD group. The concentration of saturated fatty acids in serum and atherosclerotic lesions, was remarkably increased in the HFHSD + 4%NaCl group. Conclusions Dysbiosis induced by excessive salt intake increases the expression of long-chain fatty acid transporters in the intestinal tract, which increases the influx of saturated fatty acids into the body.

A certain number of patients with coronavirus disease 2019 (COVID-19), particularly those who test positive for SARS-CoV-2 in the serum, are hospitalized. Further, some even die. We examined the effect of blood adsorption therapy using columns that can eliminate SARS-CoV-2 on the improvement of the prognosis of severe COVID-19 patients.This study enrolled seven patients receiving mechanical ventilation. The patients received viral adsorption therapy using SARS-catch column for 3 days. The SARS-catch column was developed by immobilizing a specific peptide, designed based on the sequence of human angiotensin-converting enzyme 2 (hACE2), to an endotoxin adsorption column (PMX). In total, eight types of SARS-CoV-2-catch (SCC) candidate peptides were developed. Then, a clinical study on the effects of blood adsorption therapy using the SARS-catch column in patients with severe COVID-19 was performed, and the data in the present study were compared with historical data of severe COVID-19 patients.Among all SCC candidate peptides, SCC-4N had the best adsorption activity against SARS-CoV-2. The SARS-catch column using SCC-4N removed 65% more SARS-CoV-2 than PMX. Compared with historical data, the weaning time from mechanical ventilation was faster in the present study. In addition, the rate of negative blood viral load in the present study was higher than that in the historical data.The timely treatment with virus adsorption therapy may eliminate serum SARS-CoV-2 and improve the prognosis of patients with severe COVID-19. However, large-scale studies must be performed in the future to further assess the finding of this study (jRCTs052200134).

Introduction d-Serine, present only in trace amounts in humans, is now recognized as a biomarker of chronic kidney disease (CKD). CKD is heterogeneous in its original kidney diseases, whose diagnoses require kidney biopsy. In this study, we examined whether the intra-body dynamics of d-serine, indexed by its blood and urinary levels, reflects the origin of kidney diseases. Methods Patients with six kinds of kidney disease undergoing kidney biopsy were enrolled in a single center. Levels of d- and l-serine were measured using two-dimensional high-performance liquid chromatography. The associations between the origin of kidney diseases and the intra-body dynamics of d-serine were examined using multivariate cluster analyses. Results Unlike the non-CKD profile, patients with CKD showed broadly-distributed profiles of intra-body dynamics of d-serine. The plasma level of d-serine plays a key role in the detection of kidney diseases, whereas a combination of plasma and urinary levels of d-serine distinguished the origin of CKD, especially lupus nephritis. Conclusion Intra-body dynamics of d-serine have the potential to predict the origin of kidney diseases. Monitoring of d-serine may guide specific treatments for the origin of kidney diseases.

Ephrin type-A receptor 2 (EPHA2) is a receptor tyrosine kinase (RTK), whose over-expression has been observed in a variety of cancers, including breast cancer. EPHA2 expression may be causally related to tumorigenesis; therefore, it is important to understand how EPHA2 gene (EPHA2) expression is regulated. Here, we report that EPHA2 antisense RNA (EPHA2-AS), a natural antisense transcript, is an important modulator of EPHA2 mRNA levels. EPHA2-AS is a ∼1.8 kb long non-coding RNA (lncRNA) with a poly(A) tail that encodes two splice variants, EPHA2-AS1/2. They are constitutively expressed in a concordant manner with EPHA2 mRNA in human breast adenocarcinoma cell lines and in patient samples, with the highest levels detected in the triple-negative breast cancer (TNBC) subtype. The silencing of EPHA2-AS1/2 by a sense oligonucleotide or over-expression of an antisense oligoribonucleotide, which were both designed from the EPHA2 mRNA region (nt 2955–2974) targeted by AS1/2, showed that EPHA2-AS1/2 modulated EPHA2 mRNA levels by interacting with the specific AS1/2-complementary region in the mRNA. The EPHA2-AS1/2 did not prevent microRNAs from acting on the relevant microRNA response elements shared by EPHA2-AS1/2 and EPHA2 mRNA. Our studies demonstrate a crucial role played by EPHA2-AS1/2 in modulating EPHA2 mRNA levels, and hence production of EPHA2 protein, a key oncogenic RTK that contributes to the tumorigenesis of TNBC cells.

d-Amino acids are the recently detected enantiomers of l-amino acids. Accumulating evidence points their potential in solving the long-standing critical problems associated with the management of both chronic and acute kidney diseases. This includes estimating kidney function, early diagnosis and prognosis of chronic kidney disease, and disease monitoring. Among the d-amino acids, d-serine levels in the blood are strongly correlated with the glomerular filtration rate and are useful for estimating the function of the kidney. Urinary d-serine also reflects other conditions. The kidney proximal tubule reabsorbs serine with chiral-selectivity, with d-serine being reabsorbed much less efficiently than l-serine, and urinary excretion of d-serine is sensitive to the presence of kidney diseases. Therefore, assessing the intra-body dynamics of d-serine by measuring its level in blood and urinary excretion can be used to detect kidney diseases and assess pathophysiology. This new concept, the intra-body dynamics of d-serine, can be useful in the comprehensive management of kidney disease.

This study is the first research to present a detailed assessment of core loss, copper loss and magnetic flux density of the interior permanent magnet synchronous motor (IPMSM) with pulse-amplitude modulation (PAM) inverter under different excitation angles in both no-load and load conditions. The PAM method automatically controls the amplitude of changeable DC-link voltage, and the excitation angle for switches in the inverter is varied from 120° to 180° according to a 12-step switching pattern designed particularly for the PAM-based inverter of IPMSM. For reference purpose, the pulse-width modulation excitation with a very high voltage modulation index is performed. Various conditions with changes in speed and torque are examined. Experimental results show that harmonic components produced by the PAM inverter in the IPMSM current, voltage and magnetic flux density have large effects on the motor core and copper losses; physics-based explanations and insights are also presented. The PAM under 135° excitation angle has an excellent performance in reducing IPMSM core and copper losses since it can significantly decrease the harmonic components in motor current, voltage and magnetic flux density. Furthermore, simulations using the finite element method are conducted to validate the experimental results of IPMSM core loss with the PAM excitations.

Since the outbreak of coronavirus disease 2019 (COVID-19), biomarkers for evaluating severity, as well as supportive care to improve clinical course, remain insufficient. We explored the potential of d-amino acids, rare enantiomers of amino acids, as biomarkers for assessing disease severity and as protective nutrients against severe viral infections. In mice infected with influenza A virus (IAV) and in patients with severe COVID-19 requiring artificial ventilation or extracorporeal membrane oxygenation, blood levels of d-amino acids, including d-alanine, were reduced significantly compared with those of uninfected mice or healthy controls. In mice models of IAV infection or COVID-19, supplementation with d-alanine alleviated severity of clinical course, and mice with sustained blood levels of d-alanine showed favorable prognoses. In severe viral infections, blood levels of d-amino acids, including d-alanine, decrease, and supplementation with d-alanine improves prognosis. d-Alanine has great potentials as a biomarker and a therapeutic option for severe viral infections.

Bacterial flora has clinical significance for the host. The metabolic environment created by this flora influences immunotherapy in urothelial carcinoma. However, there are no reports on the clinical significance of bacterial flora in the host bloodstream. We aimed to clarify the correlation between extracellular vesicle (EV)-derived blood microflora information and tumor immunological status in urothelial carcinoma (UC) patients. Serum samples were collected from 20 healthy donors, 50 patients with localized UC, and 31 patients with metastatic UC (mUC) who had undergone pembrolizumab treatment. Bacterial DNA in EVs was extracted from each sample. Metagenomic sequencing was performed after amplification of the V1-V2 region of the bacterial 16S rRNA gene. Using the matched tumor tissue and serum samples, we revealed that the smaller amount of peripheral EVs carrying Firmicutes DNA was significantly correlated with the higher number of infiltrating T cells within tumor tissues (CD3; p = 0.015, CD4; p = 0.039, CD8; p = 0.0084) and the higher expression of activation markers on their surface (ICOS on both CD4; p = 0.0013 and CD8 T cells; p = 0.016 and 4-1BB on CD4 T cells; p = 0.016). In terms of circulating metabolic information, L-Ser and L-Pro levels, which play important roles in T cell expansion and proliferation, were significantly higher in the Firmicutes-low group (p = 0.010). All of the patients with higher Firmicutes abundance had disease progression without any clinical response (p = 0.026) and significantly inferior prognosis for pembrolizumab therapy (p = 0.035). This is the first study on the importance of peripheral bacterial EVs in cancer patients treated with cancer immunotherapy.

Drug repositioning (DR) is an effective way for developing drugs for rare and intractable diseases (RIDs). Preparation of the ontology is essential for drug development in RIDs, in which disease names have been inconsistently used worldwide. Ontology-based analysis of clinical trial data revealed that DR occurs actively in RIDs. Drugs and their target genes are keys to explore repositionable drugs, because shared target genes between diseases indicate a common mechanism of drug action. This approach visualizes a DR landscape that facilitates drug development. Here, we review the current situation of ontology in RIDs, the trends in drug development, and an efficient strategy for DR based on drug target gene information.

BACKGROUND: The diagnosis of diabetic nephropathy (DN), the major cause of ESKD, requires kidney biopsy. d-Serine, present only in trace amounts in humans, is a biomarker for kidney diseases and shows potential to distinguish the origin of kidney diseases, whose diagnoses usually require kidney biopsy. We extended this concept and examined the potential of d-serine in the diagnosis of DN. METHODS: We enrolled patients with biopsy sample–proven DN and primary GN (minimal change disease and IgA nephropathy) and participants without kidney disease. A total of 388 participants were included in this study, and d-serine levels in blood and urine were measured using two-dimensional high-performance liquid chromatography, and urinary fractional excretion (FE) of d-serine was calculated. Using data from 259 participants, we developed prediction models for detecting DN by logistic regression analyses, and the models were validated in 129 participants. RESULTS: A d-serine blood level of >2.34 μM demonstrated a high specificity of 83% (95% CI, 70% to 93%) for excluding participants without kidney diseases. In participants with a d-serine blood level >2.34 μM, the threshold of 47% in FE of d-serine provided an optimal threshold for the detection of DN (AUC, 0.85 [95% CI, 0.76 to 0.95]; sensitivity, 79% [95% CI, 61% to 91%]; specificity, 83% [95% CI, 67% to 94%]). This plasma-high and FE-high profile of d-serine in combination with clinical factors (age, sex, eGFR, and albuminuria) correctly predicted DN with a sensitivity of 91% (95% CI, 72% to 99%) and a specificity of 79% (95% CI, 63% to 80%), and outperformed the model based on clinical factors alone in the validation dataset (P

Background: D-Serine, a long-term undetected enantiomer of serine, is a biomarker that reflects kidney function and disease activity. The physiological functions of D-serine have been unclear. Methods: Dynamics of D-serine was assessed by measuring D-serine in human samples of living kidney donors using two-dimensional high-performance liquid chromatography, and by auto-radiographic studies in mice. Effects of D-serine on kidney were examined by gene expression profiling and metabolic studies using unilateral nephrectomy mice, and genetically modified cells. Results: Unilateral nephrectomy in human living kidney donors decreases urinary excretion and thus increases the blood level of D-serine. D-Serine is quickly and dominantly distributed to the kidney upon injection in mice, suggesting that the kidney is a main target organ. Treatment of D-serine at low dose promotes the enlargement of remnant kidney in mouse model. Mechanistically, D-serine activates the cell cycle for tissue remodeling through an mTOR-related pathway. Conclusions: D-Serine is a physiological molecule that promotes kidney remodeling. Besides its function as a biomarker, D-serine has a physiological activity that influences kidney function.

Background: This study compares and clarifies the changes in intestinal flora resulting from the continuous consumption of two types of matcha.Methods: Healthy adults will consume two types of matcha tea for four weeks, and differences in the intestinal microflora before and after drinking will be compared. Gut microbiota will be identified using next-generation sequencing (NGS). Phylogenetic classification of the enterobacteria will be performed based on sequence similarities. The relative proportions of the classified enterobacteria to the total nucleotide sequences will be compared between the samples obtained from the two groups consuming different matcha.Discussion: The continuous consumption of matcha may improve dysbiosis and prevent atherosclerosis. The effects may vary according to the type of matcha used.Trial registration:The study was registered with university hospital medical information network (UMIN) (UMIN000040303), and all participants gave their written informed consent. Registered 1 November 2020, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000045982.

The aim of the present study was to examine whether dietary salt restriction guidance is beneficial for dietary salt restriction and lowering of home blood pressure in patients with diabetes with excessive salt intake. We performed an intervention trial of 37 people with type 2 diabetes and excessive salt intake. National registered dietitians provided dietary salt restriction guidance to each patient at the start of the study. All participants were instructed to perform triplicate morning and evening home blood pressure measurements using home blood pressure telemonitoring system. Daily salt intake at 2 months and 6 months was significantly lower than that at baseline; the difference was 0.8 [95% confidence interval (CI): 0.2-1.4, p = 0.009] g and 0.7 (95% CI: 0.1-1.3, p = 0.009) g, respectively. Morning systolic blood pressure at 2 months and 6 months was significantly lower than that at baseline; the difference was 2.7 (95% CI: 0.2-5.1, p = 0.034) mmHg and 5.8 (95% CI: 0.5-11.1, p = 0.034) mmHg, respectively. This intervention study revealed, for the first time, that dietary salt restriction guidance provided by a national registered dietitian is beneficial for reducing daily salt intake and home blood pressure in people with diabetes with excessive salt intake.

We experienced a case of a 36-year-old female with rapidly progressive glomerulonephritis (RPGN) due to anti-neutrophil cytoplasmic antibody (ANCA)-associated nephritis and systemic lupus erythematosus (SLE) nephritis. Chiral amino acid metabolomics revealed a prominent profile of d-serine in this patient. At the fulminant period of RPGN, the level of plasma d-serine, a potential biomarker in CKD that reflects actual glomerular filtration ratio (GFR), was extremely high. On the other hand, urinary fractional excretion (FE) of d-serine, which was usually much higher than that of l-isoform, was 0% in this patient. These abnormal d-serine profiles normalized in response to the intensive treatment. Normalizations of blood d-serine levels were in parallel with those of blood creatinine levels and potentially reflect the recovery of GFR. FE of d-serine increased transiently before the normalization of d-serine profile, suggesting that kidney promotes urinary excretion of d-serine for the normalization of plasma d-serine level. These unexplored clinical features of d-serine well reflected the clinical course of this patient. Blood d-serine level can also serve as a biomarker in acute kidney injury (AKI) or RPGN, and, in combination with FE of d-serine, may render the clinical practitioners to judge the efficacy of intensive treatments. Electronic supplementary material The online version of this article (10.1007/s13730-019-00411-6) contains supplementary material, which is available to authorized users.

D-Amino acids, long-term undetected enantiomers of L-amino acids, are now emerging as potential biomarkers, especially for kidney diseases. Management of chronic kidney disease (CKD), a global problem with its high prevalence and poor prognosis, is currently unsatisfactory due to the difficulty in estimating kidney function and in early detection of diseases. We now show that intra-body dynamics of D-serine reflect kidney function and diseases. The blood level of D-serine correlated well with the actual glomerular filtration ratio, a key kidney function. This correlation was compatible with those of conventional kidney markers, and blood level of D-serine was relatively unaffected by such clinical factors as body size. The balance between excretion and reabsorption of amino acids by the kidney was controlled with chiral selectivity, and the reabsorption of D-serine was sensitive to the presence of CKD. The combination of blood level and urinary dynamics of D-serine effectively distinguished CKD from non-CKD. These lines of evidence provide new insights into the enantioselective amino acid dynamics in the human body that reflect disease pathophysiology. D-Serine may serve as a vital biomarker that suppress CKD onset through the precise assessment of kidney function and the diagnosis of CKD.

Drug development for rare and intractable diseases has been challenging for decades due to the low prevalence and insufficient information on these diseases. Drug repositioning is increasingly being used as a promising option in drug development. We aimed to analyze the trend of drug repositioning and inter-disease drug repositionability among rare and intractable diseases. We created a list of rare and intractable diseases based on the designated diseases in Japan. Drug information extracted from clinical trial data were integrated with information of drug target genes, which represent the mechanism of drug action. We obtained 753 drugs and 551 drug target genes from 8307 clinical trials for 189 diseases or disease groups. Trend analysis of drug sharing between a disease pair revealed that 1676 drug repositioning events occurred in 4401 disease pairs. A score, Rgene, was invented to investigate the proportion of drug target genes shared between a disease pair. Annual changes of Rgene corresponded to the trend of drug repositioning and predicted drug repositioning events occurring within a year or two. Drug target gene-based analyses well visualized the drug repositioning landscape. This approach facilitates drug development for rare and intractable diseases.

Background In continuous renal replacement therapy (CRRT), administration of anticoagulants is necessary for achieving a certain level of filter lifetime. Generally, anticoagulant doses are controlled to keep activated partial thromboplastin time and other indicators within a certain target range, regardless of the membrane materials used for the filter. However, in actual clinical practice, the filter lifetime varies significantly depending on the membrane material used. The objective of this study was to demonstrate that the minimum anticoagulant dose necessary for prolonging the filter lifetime while reducing the risk of hemorrhagic complications varies depending on the type of membrane. Methods In three beagles, hemodiafiltration was performed with hemofilters using polysulfone (PS), polymethylmethacrylate (PMMA), and AN69ST membranes separately. The minimum dose of nafamostat mesylate (NM) that would allow for 6 h of hemodiafiltration (required dose) was investigated for each membrane material. Results The NM doses required for 6 h of hemodiafiltration were 2 mg/kg/h for the PS membrane, 6 mg/kg/h for the PMMA membrane, and 6 mg/kg/h for the AN69ST membrane. Conclusion For hemodiafiltration performed in beagles, the required NM dose varied for each filter membrane material. Using the optimal anticoagulant dose for each membrane material would allow for safer CRRT performance.

HLA genotype-clinical phenotype correlations are not established for multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We studied HLA-DRB1/DPB1 genotype–phenotype correlations in 528 MS and 165 NMOSD cases using Japan MS/NMOSD Biobank materials. HLA-DRB1*04:05, DRB1*15:01 and DPB1*03:01 correlated with MS susceptibility and DRB1*01:01, DRB1*09:01, DRB1*13:02 and DPB1*04:01 were protective against MS. HLA-DRB1*15:01 was associated with increased optic neuritis and cerebellar involvement and worsened visual and pyramidal functional scale (FS) scores, resulting in higher progression index values. HLA-DRB1*04:05 was associated with younger onset age, high visual FS scores, and a high tendency to develop optic neuritis. HLA-DPB1*03:01 increased brainstem and cerebellar FS scores. By contrast, HLA-DRB1*01:01 decreased spinal cord involvement and sensory FS scores, HLA-DRB1*09:01 decreased annualized relapse rate, brainstem involvement and bowel and bladder FS scores, and HLA-DRB1*13:02 decreased spinal cord and brainstem involvement. In NMOSD, HLA-DRB1*08:02 and DPB1*05:01 were associated with susceptibility and DRB1*09:01 was protective. Multivariable analysis revealed old onset age, long disease duration, and many relapses as independent disability risks in both MS and NMOSD, and HLA-DRB1*15:01 as an independent risk only in MS. Therefore, both susceptibility and protective alleles can influence the clinical manifestations in MS, while such genotype–phenotype correlations are unclear in NMOSD.

Direct hemoperfusion was useful for the treatment of phenobarbital poisoning. It decreased the blood levels of phenobarbital and improved the level of consciousness., Aim Phenobarbital overdose can cause coma and even death. The consciousness disturbance is often prolonged due to its long half‐life. In this study, we investigated the efficacy of direct hemoperfusion (DHP) for the removal of phenobarbital by measuring the blood levels of phenobarbital. Methods Study subjects included five patients with phenobarbital poisoning who were transferred to our hospital. Direct hemoperfusion was carried out in three of the five patients (six times in total), and the elimination rate was calculated by measuring the blood levels before and after DHP. Furthermore, the disappearance rate of phenobarbital without DHP was calculated in all five patients (seven times in total) for comparison with the elimination rate. Results The elimination rate of phenobarbital with DHP was significantly higher than the disappearance rate without DHP． Conclusion This study suggests that early introduction of DHP should be considered as a treatment option for phenobarbital poisoning.

Current-mode control is used in Switched-Mode Power Supplies (SMPSs) due to its high stability and quick response. Moreover, peak current-mode control, as one of the current-mode control techniques is often used due to its ease of design and capability of overcurrent protection. However, peak current-mode control sometimes makes output oscillations in certain conditions. Accordingly, SMPSs designers often use slope compensation to prevent output oscillation. However, it has some challenges such as design complexity and delayed response. Therefore, in this research, the authors derived a conditional expression to replace the use of slope compensation based on multi-cycle digital control. The proposed quantity along with its derivation is provided in this manuscript. Furthermore, the carried-out investigations validate its applicability.