Enhancing healthcare process analysis through object-centric process mining: Transforming OMOP common data models into object-centric event logs.

OBJECTIVES: This study aims to enhance the analysis of healthcare processes by introducing Object-Centric Process Mining (OCPM). By offering a holistic perspective that accounts for the interactions among various objects, OCPM transcends the constraints of conventional patient-centric process mining approaches, ensuring a more detailed and inclusive understanding of healthcare dynamics. METHODS: We develop a novel method to transform the Observational Medical Outcomes Partnership Common Data Models (OMOP CDM) into Object-Centric Event Logs (OCELs). First, an OMOP CDM4PM is created from the standard OMOP CDM, focusing on data relevant to generating OCEL and addressing healthcare data's heterogeneity and standardization challenges. Second, this subset is transformed into OCEL based on specified healthcare criteria, including identifying various object types, clinical activities, and their relationships. The methodology is tested on the MIMIC-IV database to evaluate its effectiveness and utility. RESULTS: Our proposed method effectively produces OCELs when applied to the MIMIC-IV dataset, allowing for the implementation of OCPM in the healthcare industry. We rigorously evaluate the comprehensiveness and level of abstraction to validate our approach's effectiveness. Additionally, we create diverse object-centric process models intricately designed to navigate the complexities inherent in healthcare processes. CONCLUSION: . Our approach introduces a novel perspective by integrating multiple viewpoints simultaneously. To the best of our knowledge, this is the inaugural application of OCPM within the healthcare sector, marking a significant advancement in the field.

Genetic analysis of porcine parvoviruses detected in South Korean wild boars.

Porcine parvovirus 1 (PPV1) is a major cause of reproductive failure in pigs. To date, six additional porcine parvoviruses (PPV2-PPV7) have been identified. In this study, we detected 11 PPV1 strains, five PPV3 strains, three PPV4 strains, six PPV5 strains, five PPV6 strains, and one PPV7 strain in Korean wild boars. PPV1, -3, and -5, and PPV6 from Korean wild boars harbor conserved motifs within the Ca2+ binding loop and the catalytic center of the PLA1 motif. Intra-species recombination among PPV7 strains was also identified. Genetic characterization revealed that PPV1 from Korean wild boars may be similar to virulent PPV strains.

Metrological sensitivity improvement of through-focus scanning optical microscopy by controlling illumination coherence.

We investigate the influence of the degree of illumination coherence on through-focus scanning optical microscopy (TSOM) in terms of metrological sensitivity. The investigation reveals that the local periodicity of the target object is a key structural parameter to consider when determining the optimal degree of illumination coherence for improved metrological sensitivity. The optimal coherence conditions for the TSOM inspection of several target objects are analyzed through numerical simulation.

Genetic characterization of bovine coronavirus in Vietnam.

A maximum clade credibility tree constructed using the full-length spike (S) and hemagglutinin-esterase genes revealed that Vietnamese Bovine coronavirus (BCoV) strains belong to a single cluster (C1); therefore, they might share a common origin with Cuban and Chinese BCoV strains. The omega values of cluster 1 (C1) and cluster 2 (C2) were 0.15734 and 0.11613, respectively, and naive empirical bayes analysis identified two amino acid positions (179 and 501) in the S protein in C1 and three amino acid positions (113, 501, and 525) in that of C2 that underwent positive selection (p > 99%). The evolutionary rate of C1 was estimated to be 7.6206 × 10-4 substitutions/site/year, and the most recent common ancestor (tMRCA) of Vietnamese BCoVs was estimated to date back to 1962 (95% HPD 1950-1973). The effective population sizes of C1 and C2 underwent a rapid reduction after 2000 and 2004, respectively.

Through-focus scanning optical microscopy with the Fourier modal method.

We propose a Fourier modal method (FMM) based through-focus scanning optical microscopy (TSOM) featuring sub-nano scale measurement tolerance. TSOM is very recently conceptualized non-destructive optical metrology technique just at the beginning stage of research. Nowadays the reliability and feasibility of TSOM concept is subject to controversy. We experimentally demonstrate stable nano-scale metrology of the FMM-based TSOM for the verification of the TSOM metrology and provide a numerical tool for true nano-meter scale TSOM through devising the FMM based TSOM scheme. By considering the illumination light parameters of incidence angle, polarization, degree of coherence, illumination numerical aperture, and collection numerical apertures in the FMM modeling of TSOM image acquisition, we reach precise agreement between the calculated and experimentally measured TSOM images. The essential elements of the FMM based TSOM for achieving high-level consistency are elucidated.

A novel strain of porcine deltacoronavirus in Vietnam.

Two porcine deltacoronavirus (PDCoV) strains (Binh21 and HaNoi6) were isolated from two pig farms in North Vietnam. Phylogenetic analysis of the complete genomes and the Spike and Membrane genes revealed that the two Vietnam PDCoVs belong to the same lineage as PDCoVs from Thailand and Laos; however, the N genes belonged to the same lineage as PDCoVs from the USA, Korea, China, and Hong Kong. The recombination detection program subsequently identified the major parent (S5011 strain) and minor parent (HKU15-44 strain) of the two Vietnam PDCoV strains (p < 0.01).

Characterization and Spike Gene Analysis of a Candidate Attenuated Live Bovine Coronavirus Vaccine.

The bovine coronavirus (BCoV) KBR-1 strain, obtained from calf diarrhea samples collected in 2017, belongs to group GIIa. To attenuate this strain, it was subcultured continuously (up to 79 times) in HRT-18 cells, followed by 80-120 passages in MDBK cells. The KBR-1-p120 strain harvested from MDBK cells at passage 120 harbored 13 amino acid mutations in the spike gene. Additionally, the KBR-1-p120 strain showed a high viral titer and cytopathogenic effects in MDBK cells. Seven-day-old calves (negative for BCoV antigen and antibodies) that did not consume colostrum were orally inoculated with the attenuated candidate strain (KBR-1-p120), or with KBR-1 passaged 10 times (KBR-1-p10) in HRT-18 cells. Calves inoculated with KBR-1-p10 had a low diarrhea score, and BCoV RNA was detected at 3-7 days post-inoculation (DPI). The virus was also present in the duodenum, jejunum, and ileum at autopsy; however, calves inoculated with KBR-1-p120 had low levels of BCoV RNA in feces at 4-6 DPI, and no diarrhea. In addition, an extremely small amount of BCoV RNA was present in the jejunum and ileum at autopsy. The small intestines of calves inoculated with KBR-1-p120 were emulsified and used to infect calves two more times, but pathogenicity was not recovered. Therefore, the KBR-1-p120 strain has potential as a live vaccine candidate.

Efficacy of an orally administered classical swine fever live marker vaccine (Flc-LOM-BErns strain) in pigs.

In several countries, classical swine fever (CSF) has not been detected in domestic pigs, but has been detected in wild boars, making the disease difficult to control. To overcome this problem, we inoculated pigs with a CSF live marker vaccine (Flc-LOM-BErns strain), which has "distinguish infection from vaccinated animals (DIVA)" function, to determine whether it is suitable as an oral vaccine specifically for wild boars. Pigs inoculated intramuscularly or orally with the Flc-LOM-BErns vaccine were challenged 2 or 4 weeks later, respectively, with virulent CSFV. Pigs administered the oral Flc-LOM-BErns strain (105.0 and 6.0 TCID50/dose), and those vaccinated intramuscularly (103.0 TCID50/dose), had normal numbers of leukocytes and normal body temperature. Also, they generated protective neutralizing antibodies and anti-BVDV Erns antibodies. In addition, all pigs in these groups survived, with no CSFV RNA detected in feces, spleen, or other organs. Thus, the Flc-LOM-BErns vaccine shows excellent safety and efficacy, while having DIVA function and suitability for oral inoculation.

Spike Gene Analysis and Prevalence of Porcine Epidemic Diarrhea Virus from Pigs in South Korea: 2013-2022.

From late 2013-2022, 1131 cases of porcine epidemic diarrhea (PED) were reported to the Korean Animal Health Integrated System (KAHIS). There were four major outbreaks from winter to spring (2013-2014, 2017-2018, 2018-2019, and 2021-2022), with the main outbreaks occurring in Chungnam (CN), Jeonbuk (JB), and Jeju (JJ). Analysis of the complete spike (S) gene of 140/1131 KAHIS PEDV cases nationwide confirmed that 139 belonged to the G2b genotype and 1 to the G2a genotype. Among them, two strains (K17GG1 and K17GB3) were similar to an S INDEL isolated in the United States (strain OH851), and 12 strains had deletions (nucleotides (nt) 3-99) or insertions (12 nt) within the S gene. PEDVs in JJ formed a regionally independent cluster. The substitution rates (substitutions/site/year) were as follows: 1.5952 × 10-3 in CN, 1.8065 × 10-3 in JB, and 1.5113 × 10-3 in JJ. A Bayesian skyline plot showed that the effective population size of PEDs in JJ fell from 2013-2022, whereas in CN and JB it was maintained. Genotyping of 340 Korean PEDV strains, including the 140 PEDVs in this study and 200 Korean reference strains from GenBank, revealed that only the highly pathogenic non-INDEL type (G2b) was dominant from 2020 onwards. Therefore, it is predicted that the incidence of PED will be maintained by the G2b (non-INDEL) genotype.

Rescue of a Live-Attenuated Porcine Epidemic Diarrhea Virus HSGP Strain Using a Virulent Strain and a Partially Attenuated Strain.

In South Korea in 2013, the G1-based vaccine failed to prevent an outbreak of G2b-type porcine epidemic diarrhea virus (PEDV), which is more pathogenic than the traditional G1-type strain, thereby allowing the virus to spread. In 2017 and 2018, field samples were cultured sequentially on Vero cells to isolate HS (virulent) and SGP-M1 (partially attenuated) strains, respectively, of the G2b type. The HS strain harbors a single amino acid (aa) change and two aa deletions in the N-terminal domain of S1 (55I56G57E→55K56Δ57Δ). The SGP-M1 strain harbors a seven aa deletion in the C-terminal domain of S2 (1380~1386ΔFEKVHVQ). By co-infecting various animal cells with these two strains (HS and SGP-M1), we succeeded in cloning strain HSGP, which harbors the mutations present in the two original viruses. The CPE pattern of the HSGP strain was different from that of the HS and SGP-M1 strains, with higher viral titers. Studies in piglets showed attenuated pathogenicity of the HSGP strain, with no clinical symptoms or viral shedding, and histopathologic lesions similar to those in negative controls. These findings confirm that deletion of specific sequences from the S gene attenuates the pathogenicity of PEDV. In addition, HSGP strains created by combining two different strains have the potential for use as novel attenuated live vaccine candidates.

Phylogenetic Analysis of G and P Genotypes of Bovine Group A Rotavirus Strains Isolated from Diarrheic Vietnam Cows in 2017 and 2018.

This study aimed to investigate the genetic diversity of G- and P-type bovine RVAs (BoRVAs) prevalent in Vietnam. Between 2017 and 2018, the prevalence of BoRVAs detected in diarrhea samples from 8 regions was as low as 1.9% (11/582). The prevalence of the G-type was 45.5% for G6 and 18.2% for G10; however, 36.3% remain unidentified. Interestingly, all BoRVAs were investigated as P[11], and there was no diversity within this P-type. Geographically, the G6 and G10 types were not identified in any specific area; rather, they occurred in both Northern and Southern Vietnam. G6P[11] and G10P[11], which are combined G- and P-types, were identified in 71.4% and 28.6% of BoRVA-positive samples, respectively. Phylogenetic tree analysis revealed that the G6-type detected in Vietnamese cows is similar to strains derived from China, Japan, and Korea, whereas the G10 type is closely related to the Chinese strain. In addition, the P11 strain detected in Vietnamese cows is similar to the Spanish and Chinese strains. The BoRVA-positive rate was higher in cows aged less than 2 months (3.2%, 3/94) than in those aged 2 months or more (1.6%, 8/488). In summary, we detected the presence of G6P11 and G10P11 BoVRAs on Vietnamese cow farms, and found that they were more predominant in young calves than in older cows.

Safety and Immunogenicity of Chimeric Pestivirus KD26_E2LOM in Piglets and Calves.

A chimeric pestivirus (KD26_E2LOM) was prepared by inserting the E2 gene of the classical swine fever virus (CSFV) LOM strain into the backbone of the bovine viral diarrhea virus (BVDV) KD26 strain. KD26_E2LOM was obtained by transfecting the cDNA pACKD26_E2LOM into PK-15 cells. KD26_E2LOM chimeric pestivirus proliferated to titers of 106.5 TCID50/mL and 108.0 TCID50/mL at 96 h post-inoculation into PK-15 cells or MDBK cells, respectively. It also reacted with antibodies specific for CSFV E2 and BVDV Erns, but not with an anti-BVDV E2 antibody. Piglets (55-60 days old) inoculated with a high dose (107.0 TCID50/mL) of KD26_E2LOM produced high levels of CSFV E2 antibodies. In addition, no co-habiting pigs were infected with KD26_E2LOM; however, some inoculated pigs excreted the virus, and the virus was detected in some organs. When pregnant sows were inoculated during the first trimester (55-60 days) with a high dose (107.0 TCID50/mL) of KD26_E2LOM, anti-CSFV E2 antibodies were produced at high levels; chimeric pestivirus was detected in one fetus and in the ileum of one sow. When 5-day-old calves that did not consume colostrum received a high dose (107.0 TCID50/mL) of KD26_E2LOM, one calf secreted the virus in both feces and nasal fluid on Day 2. A high dose of KD26_E2LOM does not induce specific clinical signs in most animals, does not spread from animal to animal, and generates CSFV E2 antibodies with DVIA functions. Therefore, chimeric pestivirus KD26_E2LOM is a potential CSFV live marker vaccine.

Real-world experience of angiotensin receptor neprilysin inhibitor on the glucose-lowering effect.

We investigated the effect of angiotensin receptor neprilysin inhibitor (ARNI) on glycemic control in Korean patients. This retrospective cohort study was conducted at a single tertiary hospital. We compared the HbA1c level reduction between the ARNI and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) in chronic heart failure patients with diabetes. We also examined whether the target HbA1c level was reached and the time to start insulin between the two groups. Over the study period, ARNI did not significantly lower the HbA1c level after adjusting confounding factors compared to ACEIs or ARBs. However, as a result of a simple comparison using Mann-Whitney U test, ARNI group showed significant decrease in HbA1c at 6, 12, and 24 months compared to ACEIs or ARBs group (p = 0.003, 0.009, and 0.026, respectively). The initiation of insulin was delayed in the ARNI group, but this difference was not significant based on the result of hazard ratio, but cumulative incidence was significantly lower in the ARNI group. In the real world, the blood glucose-control effects of ARNI were not superior to those of ACEIs or ARBs. However, long-term studies are needed as ARNI use increases to obtain more statistically significant results.

Sodium-Glucose Cotransporter-2 Inhibitors Could Help Delay Renal Impairment in Patients with Type 2 Diabetes: A Real-World Clinical Setting.

This study compared the renoprotective effects of sodium−glucose cotransporter-2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors in patients with type 2 diabetes mellitus (T2DM). We performed a retrospective cohort study using electronic medical records of patients with T2DM. The primary outcome was the first occurrence of an estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 after the index date. We analyzed changes in repeatedly measured laboratory data, such as eGFR and serum uric acid (SUA). We included 2396 patients (1198 patients in each group) in the present study. The rate of renal events was significantly lower in the SGLT2 inhibitors group than that in the DPP-4 inhibitors group (hazard ratio, 0.46; 95% CI, 0.29 to 0.72; p = 0.0007). The annual mean change in the eGFR was significantly smaller in the SGLT2 inhibitors group than that in the DPP-4 inhibitors group, with a between-group difference of 0.86 ± 0.18 mL/min/1.73 m2 per year (95% CI, 0.49 to 1.23; p < 0.0001). Moreover, the mean change in SUA was lower in the SGLT2 inhibitors group. Considering the lower incidence of renal impairment, the slower decline in eGFR, and reduced SUA, SGLT2 inhibitors could help delay renal impairment in patients with T2DM.

Haplotype of Wild Korean Boars Infected by Classical Swine Fever Virus Subgenotype 2.1d.

Classical swine fever virus (CSFV) is one of the major pathogens that causes severe economic damage to the swine industry. Circulation of CSFV in wild boars carries the potential risk of reintroducing the virus into CSFV-free pig farms. This study carried out a genetic analysis of CSFV isolates from wild boars and analyzed the mtDNA haplotypes of the wild boars. Blood samples (n = 2140) from wild Korean boars captured in 2020 were subjected to qRT-PCR to detect CSFV, which was classified as subgenotype 2.1d based on phylogenetic analysis. CSFV had been detected in wild boars only in northern regions (Gangwon and Gyeonggi) of South Korea between 2011 and 2019. However, CSFV was identified in wild boars in the more southern regions (Chungbuk and Gyeongbuk) in 2020. Based on mitochondrial DNA analysis, all wild boars with CSFV were haplotype 01 (H01). Thus, we presume that the H01 haplotype is more susceptible to CSFV. In the future, infection of wild boars by CSFV is expected to occur intermittently every year, and we predict that most wild boars infected with CSFV will be haplotype H01.

Isolation and Genetic Characterization of a Bovine Coronavirus KBR-1 Strain from Calf Feces in South Korea.

Bovine coronavirus (BCoV) causes severe diarrhea in neonatal calves, winter dysentery in adult cattle, and respiratory disease in feedlot cattle, resulting in economic losses. A total of 16/140 calf diarrheic feces samples collected in South Korea between 2017 and 2018 were positive for BCoV. Phylogenetic analysis of the complete spike and hemagglutinin/esterase genes revealed that the 16 Korean BCoV strains belonged to group GIIa along with Korean strains isolated after 2000, whereas Korean BCoV strains isolated before 2000 belonged to group GI. Mice and goats inoculated with an inactivated KBR-1 strain (isolated from this study) generated higher antibody titers (96 ± 13.49 and 73 ± 13.49, respectively) when mixed with the Montanide01 adjuvant than when mixed with the Carbopol or IMS1313 adjuvants. Viral antigens were detected in the large intestine, jejunum, and ileum of calves inoculated with inactivated KBR-1 vaccine (104.0 TCID50/mL) at 14 days of post-challenge (DPC). However, no viral antigens were detected in calves vaccinated with a higher dose of inactivated KBR-1 strain (106.0 TCID50/mL) at 14 DPC, and they had high antibody titers and stable diarrhea scores. Currently, the group GIIa is prevalent in cows in South Korea, and although further research is needed in the future, the recently isolated KBR-1 strain has potential value as a new vaccine candidate.

Prevalence of Bovine Viral Diarrhea Virus Infections in Pigs on Jeju Island, South Korea, from 2009-2019 and Experimental Infection of Pigs with BVDV Strains Isolated from Cattle.

On Jeju Island, South Korea, pigs have not been vaccinated against classical swine fever (CSF) since 1999. Analysis of bovine viral diarrhea virus (BVDV) isolated from pigs on Jeju Island between 2009 and 2019 identified five BVDV-1a strains and one BVDV-1b strain. These BVDV types were shown to be the same types as BVDV strains isolated from neighboring cow farms. BVDV antibody-positive pigs (both BVDV-1 and -2) were also detected at 54 of 168 pig farms during this period. In pig infection experiments using BVDV-1a and -2a strains isolated from neighboring cow farms, BVDV-1a was detected in the blood of one of four pigs infected at both 6 and 35 days post-infection (dpi) and in the blood of two of the four pigs at 28 dpi. Pigs showed higher anti-BVDV-1 titers (5.5 ± 1.5 log2) at 35 dpi. BVDV-2a was detected in the blood of one of four pigs infected with this virus at 28 dpi only, and lower antibody titers (2.75 ± 0.75 log2) were seen in these pigs at 35 dpi. While BVDV infection is not particularly pathogenic in pigs, it is still important to monitor porcine BVDV infections due to a differential diagnosis of CSFV.

Genetic Diversity of Porcine Group A Rotavirus Strains from Pigs in South Korea.

Porcine group A rotavirus (PoRVA; family, Reovirideae) strains cause acute viral gastroenteritis in piglets (especially suckling and weaned pigs), resulting in significant economic losses. In this study, we analyzed the VP7 and VP4 genes of PoRVA isolated between 2014 and 2018 from domestic pigs in South Korea to investigate the prevalence of predominant circulating genotypes (G and P types). The prevalence of the PoRVA antigen in the diarrheic fecal samples was 14.1% (53/377). Further genetic characterization of the VP7 and VP4 genes of 53 PoRVA isolates identified six different G-genotypes and five different P genotypes. The G4 and G9 genotypes were the most common (each 39.6%) in PoRVA-positive pigs, followed by P[7] and P[6] (33.9% and 30.1%, respectively). Because the G5 and G9 genotype vaccines are currently mainly used in South Korea, this result provides valuable epidemiological information about the genetic characteristics of PoRVA circulating on domestic pig farms. Development of a novel PoRVA vaccine that targets the current strains circulating in South Korea may be required for more effective virus control on pig farms.

Genetic Diversity of Bovine Group A Rotavirus Strains Circulating in Korean Calves during 2014 and 2018.

The purpose of this study was to investigate annual changes in BoRVA strains by examining the VP4 and VP7 genes of rotaviruses in Korean calves. Between 2014 and 2018, 35 out of 138 samples of calf diarrhea feces collected nationwide were positive for BoRVA. Further genetic characterization of the VP7 and VP4 genes of 35 BoRVA isolates identified three different G-genotypes (G6, G8, and G10) and two different P genotypes (P[5] and P[11]). The G6 genotype was most common (94.3%) in BoRVA-positive calves, followed by the P[5] genotype (82.9%). Four genotypes comprised combinations of VP4 and VP7: 80% were G6P[5], 14.2% were G6P[11], 2.9% were G8P[5], and 2.9% were G10P[11]. Susceptibility to infection was highest in calves aged < 10 days (35%) and lowest in calves aged 30−50 days (15.4%). The data presented herein suggest that the G6P[5] genotype is the main causative agent of diarrhea in Korean calves. In addition, it is predicted that G6P[5] will continue to act as a major cause of diarrhea in Korean calves.

Real-time three-dimensional tracking of single vesicles reveals abnormal motion and pools of synaptic vesicles in neurons of Huntington's disease mice.

Although defective synaptic transmission was suggested to play a role in neurodegenerative diseases, the dynamics and vesicle pools of synaptic vesicles during neurodegeneration remain elusive. Here, we performed real-time three-dimensional tracking of single synaptic vesicles in cortical neurons from a mouse model of Huntington's disease (HD). Vesicles in HD neurons had a larger net displacement and radius of gyration compared with wild-type neurons. Vesicles with high release probability (Pr) were interspersed with low-Pr vesicles in HD neurons, whereas high-Pr vesicles were closer to fusion sites than low-Pr in wild-type neurons. Non-releasing vesicles in HD neurons had an abnormally high prevalence of irregular oscillatory motion. These abnormal dynamics and vesicle pools were rescued by overexpressing Rab11, and the abnormal irregular oscillatory motion was rescued by jasplakinolide. Our studies reveal the abnormal dynamics and pools of synaptic vesicles in the early stages of HD, suggesting a possible pathogenic mechanism of neurodegenerative diseases.