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Background This study aimed to determine the proportion of organ donors suitable for donation after circulatory death and investigate the current process followed by critical care physicians for declaring circulatory death to establish organ donation. Methods This observational study involved potential organ donors who had recently died after discontinuation of life support. We conducted an online survey of intensivists to determine how these deaths were confirmed. Results Among the 177 patients who died after withdrawal of life-sustaining treatment across 19 intensive care units in 11 institutions, 49 (27.7%) were considered potential donors. According to general medical criteria for organ donation, 20 (11.3%) patients were identified as medically suitable donors. Notably, 116 (73.9%) patients exhibited a flat electrocardiogram within 5 min after the loss of pulse. In the survey, 90 physicians (59.2%) agreed to implement the concept of the 5-min no-touch period for the declaration of circulatory death. Conclusions This study found that 11.3% of the patients who died following the withdrawal of life-sustaining treatment in the intensive care units were identified as suitable donors after circulatory death. Most of critical care physicians agree with the concept of a 5-min no-touch period for the declaration of circulatory death., (© 2024. The Author(s).)

The armed conflict in Tigray, which spanned from November 2020 to November 2022, along with the accompanying siege, led to the near-total collapse of Tigray's healthcare system. Type 1 Diabetes Mellitus, the most common chronic condition in children, requires significant lifestyle adjustments, including daily insulin injections, regular glucose monitoring, and dietary modifications; all of which are severely impacted by war and siege. This study compared Type 1 diabetes care for children at the Ayder Comprehensive Specialized Hospital, Tigray, during the conflict and siege period with that of the pre-war period. We conducted a retrospective cross-sectional survey, analyzing data from September 2019 to August 2020 (pre-war period) and comparing it with data from September 2021 to August 2022 (war and siege period). Descriptive statistics, including frequencies and percentages, were employed, and Pearson's or Spearman's correlation analyses were used to evaluate correlations where appropriate. We identified 143 pediatric patients admitted (56 during the pre-war period and 87 during the war and siege period), with a mean age of 109 months in both periods. During the war and siege, a higher proportion of diabetes admissions were due to diabetic ketoacidosis (DKA) (90%) compared to the pre-war period (75%). In the pre-war period, the most common trigger for DKA was infections (35%), while in the war and siege period, it shifted to malnutrition (47%), infections (46%), lack of access to healthcare facilities (31%), and running out of medicines (24%). Complications such as death, renal failure, cerebral edema, and shock were more prevalent during the war and siege periods. The case fatality rate was significantly higher during the war and siege (9%) compared to the pre-war period (0%), correlating strongly with the severity of DKA, the degree of hypokalemia, the presence of complications, and admission during the war and siege. Our study showed the negative impact of war and siege on diabetes care in children demonstrating a high rate of DKA admissions with increased severity, complications, malnutrition, and case fatality rates. People with diabetes especially type 1 deserve great attention during such a crisis as the lack of insulin could lead to severe complications including death., (© 2024. The Author(s).)

The rapid response system (RRS) is associated with a reduction in in-hospital mortality. This study aimed to determine the characteristics and outcomes of patients transferred to the intensive care unit (ICU) by a rapid response team (RRT). This retrospective, multicenter cohort study included patients from nine hospitals in South Korea. Adult patients who were admitted to the general ward (GW) and required RRS activation were included. Patients with do-not-resuscitate orders and without lactate level or Sequential Organ Failure Assessment score were excluded. A total of 8228 patients were enrolled, 3379 were transferred to the ICU. The most common reasons for RRT activation were respiratory distress, sepsis and septic shock. The number of patients who underwent interventions, the length of hospital stays, 28-day mortality, and in-hospital mortality were higher in the ICU group than in the GW group. Factors that could affect both 28-day and in-hospital mortality included the severity score, low PaO 2 /FiO 2 ratio, higher lactate and C-reactive protein levels, and hospitalization time prior to RRT activation. Patients admitted to the ICU after RRT activation generally face more challenging clinical situations, which may affect their survival outcomes., (© 2024. The Author(s).)

Iron overload causes cognitive impairment in thalassemia patients. The gut-brain axis plays an important role in cognitive function. However, the association between gut/blood microbiome, cognition, and iron burden in thalassemia patients has not been thoroughly investigated. We aimed to determine those associations in thalassemia patients with different blood-transfusion regimens. Sixty participants: healthy controls, transfusion-dependent thalassemia (TDT) patients, and non-transfusion-dependent (NTDT) patients, were recruited to evaluate iron overload, cognition, and gut/blood microbiome. TDT patients exhibited greater iron overload than NTDT patients. Most thalassemia patients developed gut dysbiosis, and approximately 25% of the patients developed minor cognitive impairment. Increased Fusobacteriota and Verrucomicrobiota with decreased Fibrobacterota were observed in both TDT and NTDT groups. TDT patients showed more abundant beneficial bacteria: Verrucomicrobia. Iron overload was correlated with cognitive impairment. Increased Butyricimonas and decreased Paraclostridium were associated with higher cognitive function. No trace of blood microbiota was observed. Differences in blood bacterial profiles of thalassemia patients and controls were insignificant. These findings suggest iron overload plays a role in the imbalance of gut microbiota and impaired cognitive function in thalassemia patients. Harnessing probiotic potential from those microbes could prevent the gut-brain disturbance in thalassemia patients., (© 2024. The Author(s).)

This paper aims to examine the potential link between maternal COVID-19 infection during pregnancy and the increased risk of congenital heart disease (CHD) in newborns. A comparative analysis was conducted involving two groups: mothers infected with COVID-19 during pregnancy and a control group. Data on maternal characteristics, pregnancy-related complications, and newborn outcomes were collected and analyzed. Additionally, the annual incidence rates of CHD from 2020 to 2023 were evaluated to assess trends over time. No significant differences were found between the COVID-19 cases and the control group in terms of maternal age, BMI, gravidity, parity, use of assisted reproductive technology, adverse obstetric history, or complications during pregnancy, including diabetes mellitus, preeclampsia, and thyroid abnormalities. For newborn outcomes, there were no significant differences in sex distribution, rate of cesarean delivery, Apgar scores, or birth weight. However, a significantly higher prevalence of cardiac ultrasound abnormalities was observed in the COVID-19 group (10.08%) compared to the control group (4.13%, p = 0.012). Further analysis revealed that the majority of cardiac abnormalities in the COVID-19 group occurred in mothers infected before 8 weeks of pregnancy. The annual incidence rates of CHD showed a significant increase during the COVID-19 pandemic, with the highest rate in 2023 (5.46%) compared to previous years. Maternal COVID-19 infection during pregnancy may adversely affect the development of the newborn's heart. This could be due to the inflammatory response caused by the viral infection or other pathological processes. The findings underscore the importance of vigilant prenatal care and early detection of cardiac abnormalities during the pandemic and suggest the need for further research to explore potential mechanisms and intervention strategies., (© 2024. The Author(s).)

This study aimed to evaluate the 1-year mortality rate among older patients with COVID-19 discharged from hospital and to identify risk factors associated with this outcome. Using a COVID-19 dataset from the Korean National Health Insurance System, this study's evaluation period spanned from October 8, 2020, through December 31, 2021. The primary outcome was the 1-year mortality rate following hospital discharge. A logistic regression model was employed for multivariable analysis to estimate the odds ratios for the outcomes, and the Kaplan-Meier method was used to analyze differences in 1-year survival rates. Among the 66,810 COVID-19 patients aged 60 years or older who were hospitalized during the study period, the in-hospital mortality rate was 4.8% (n = 3219). Among the survivors (n = 63,369), the 1-year mortality rate was 4.9% (n = 3093). Non-survivors, compared to survivors, were significantly older (79.2 ± 9.5 vs. 68.9 ± 7.8, P < 0.001) and exhibited a lower rate of COVID-19 vaccination (63.0% vs. 91.7%, P < 0.001). Additionally, non-survivors experienced a higher incidence of organ dysfunction, along with a greater proportion of required mechanical ventilation (14.6% vs. 1.0%, P < 0.001) and extracorporeal membrane oxygenation (4.0% vs. 0.1%, P < 0.001). Multivariable logistic regression analysis identified older age, male sex, cardiovascular disease, immunosuppression, organ dysfunction, illness severity, and corticosteroid use during hospitalization as factors associated with death within 1 year after hospital discharge. However, vaccination was found to have a long-term protective effect against death among COVID-19 survivors. The 1-year mortality rate after hospital discharge for older COVID-19 patients was comparable to the in-hospital mortality rate for these patients in Korea. The long-term mortality rate among hospitalized older COVID-19 patients was influenced by demographic factors and the severity of illness experienced during hospitalization., (© 2024. The Author(s).)

Liver-expressed antimicrobial peptide 2 (LEAP2) is a peptide that counteracts the hunger hormone ghrelin-induced functions. Recently, we showed that vertical sleeve gastrectomy (VSG) did not alter the serum LEAP2 concentration in individuals with obesity. Here, we investigated the effects of VSG in both chow diet (CD)-fed and high-fat diet (HFD)-fed mice. In CD-fed mice, VSG increased plasma LEAP2 levels and hepatic Leap2 mRNA levels while decreasing body weight, blood glucose levels, and ghrelin levels. Intraperitoneal (ip) administration of ghrelin reversed these changes. These effects were found in both male and female mice. In contrast, VSG or weight loss in HFD-induced obese mice decreased LEAP2 levels. After fasting, the plasma LEAP2 concentration was in the following order: hepatic vein > abdominal aorta > portal vein. A high glucose concentration robustly increased the plasma LEAP2 concentration in the hepatic vein and abdominal aorta but not in the portal vein. In addition, corn oil or palmitate increased LEAP2 expression and secretion. The increase in LEAP2 levels after the meal tolerance test was delayed in the human subjects with diabetes. Our data suggest that various factors (metabolic, hormonal, and nutritional) regulate LEAP2, and the liver is the predominant site for the production and secretion of LEAP2. Furthermore, the interaction between ghrelin and LEAP2 is involved in the pathogenesis of obesity and diabetes., (© 2024. The Author(s).)

This study aimed to explore the impact of PM 2.5 exposure on survival, post-operative outcomes, and tumor recurrence in resectable non-small cell lung cancer (NSCLC) patients. The study cohort comprised 587 patients at Chiang Mai University Hospital between January 1, 2010, and December 31, 2017. Patients were categorized based on their residents' average PM 2.5 concentration into two groups: exposed (PM 2.5 ≥ 25 µg/m3 annual mean) and unexposed (PM 2.5 < 25 µg/m3 annual mean). The exposed group had 278 patients, while the unexposed group had 309 patients. Baseline differences in gender and surgical approach were observed between the groups. Multivariable regression analysis revealed that patients in the exposed group had a higher risk of death (HR 1.44, 95% CI, 1.08-1.89, p = 0.012). However, no significant associations were found between PM 2.5 and post-operative pulmonary complications (RR 1.12, 95% CI, 0.60-2.11, p = 0.718), in-hospital mortality (RR 1.98, 95% CI, 0.40-9.77, p = 0.401), and tumor recurrence (HR 1.12, 95% CI, 0.82-1.51, p = 0.483). In conclusion, a PM 2.5 concentration ≥ 25 µg/m3 annual mean was associated with decreased overall survival and a potential increase in in-hospital mortality among resectable NSCLC patients. Larger studies with extended follow-up periods are required to validate these findings., (© 2024. The Author(s).)

The association between self-rated health (SRH) and the development of atrial fibrillation (AF) in the general population remains underexplored. We reviewed the data of 9,895 participants in the Ansung-Ansan cohort study, a community-based Korean study. SRH was categorised as 'poor', 'fair', or 'good'. A newly developed AF was identified through biennial electrocardiography examinations and/or a self-reported history of physician-determined diagnoses. Over a median follow-up of 11 years, 149 patients (1.5%) developed AF. Compared with the 'good' group, the 'poor' group exhibited a higher risk of incident AF (adjusted hazard ratio, 1.85; 95% confidence interval, 1.19-2.87). Old age, female sex, lower educational level, smoking, cardiovascular diseases (hypertension, diabetes mellitus, and coronary artery disease), and inflammation were associated with 'poor' SRH. Along with SRH, age, male sex, urban residence, hypertension, and myocardial infarction were also associated with a higher risk of incidental AF. The combined model, which included conventional risk factors and SRH, demonstrated a marginally improved performance in predicting incident AF (concordance index: 0.704 vs. 0.714, P = 0.058). Poor SRH is independently associated with the development of AF in Korean adults. However, it plays a limited role in AF surveillance when combined with conventional AF risk factors., (© 2024. The Author(s).)

This study aimed to investigate the relationship between perceived stress and life satisfaction under the influence of mobile phone addiction and sport commitment. Participants were recruited from eight universities located in six Chinese cities, naming Chongqing, Maoming, Nanjing, Suzhou, Shijiazhuang, and Zhengzhou. The sample consisted of 575 participants enrolled in Chinese universities, with 309 (53.7%) being female students. The mediation model was tested under the structural equation modeling framework using Mplus. Results showed that (1) perceived stress had a direct and negative impact on life satisfaction, and it also had indirect effects through the two mediators; (2) perceived stress positively predicted mobile phone addiction, which, in turn, negatively impacted life satisfaction; (3) perceived stress negatively predicted sport commitment, which, in turn, positively impacted life satisfaction. By emphasizing the mediating roles of mobile phone addiction and sport commitment, our findings highlight the importance of addressing these factors in interventions aimed at encouraging college students' well-being. Implications for intervention design to promoter health among university students should take into account the mediating roles of mobile phone addiction and sport commitment., (© 2024. The Author(s).)

Urate-lowering treatment (ULT) to target with xanthine oxidase inhibitors (XOIs) paradoxically causes early increase in gouty arthritis flares. Because delayed reduction in flare burden is mechanistically unclear, we tested for ULT inflammation responsiveness markers. Unbiased proteomics analyzed blood samples (baseline, 48 weeks ULT) in two, independent ULT out trial cohorts (n = 19, n = 30). STRING-db and multivariate analyses supplemented determinations of altered proteins via Wilcoxon matched pairs signed rank testing in XOI ULT responders. Mechanistic studies characterized proteomes of cultured XOI-treated murine bone marrow macrophages (BMDMs). At 48 weeks ULT, serum urate normalized in all gout patients, and flares declined in association with significantly altered proteins (p < 0.05) in clustering and proteome networks in sera and peripheral blood mononuclear cells. Sera demonstrated altered complement activation and regulatory gene ontology biologic processes. In both cohorts, a treatment-emergent serum interactome included key gouty inflammation mediators (C5, IL-1B, CXCL8, IL6). Last, febuxostat treatment decreased complement activation biologic process proteins in cultured BMDMs. Reduced gout flares are linked with a XOI treatment-emergent serum protein interactome that includes inflammation regulators, associated with altered complement activation and regulatory biologic processes. Serum and leukocyte proteomics could help identify when gouty inflammatory processes begin to subside in response to ULT.Trial Registration: ClinicalTrials.gov Identifier NCT02579096, posted October 19, 2015., (© 2024. The Author(s).)

This large community-based cohort study investigates the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), specifically Liraglutide and Semaglutide, on the risk of developing psychiatric conditions such as depression, anxiety, and suicidal behaviors in patients with obesity. Utilizing post-marketing data, this research compares patients prescribed GLP-1 RAs (cases) with those not taking these medications (controls). The analysis spanned data from January 1, 2015, to December 31, 2023. To minimize selection bias, we employed 1:1 propensity score matching to account for demographic factors such as age, sex, race, and comorbidities. After matching, the study included 162,253 case and control patients. This study showed a significant association between GLP-1 RA treatment and an 98% increased risk of any psychiatric disorders. Notably, patients on GLP-1 RAs exhibited a 195% higher risk of major depression, a 108% increased risk for anxiety, and a 106% elevated risk for suicidal behavior. These findings underscore the critical need for physicians to thoroughly assess patient history before prescribing GLP-1 RAs and highlight the urgent requirement for further prospective clinical trials to fully understand the implications of GLP-1 RA use on mental health in the obese patient population., (© 2024. The Author(s).)

Older age (≥ 65 years) is associated with impaired responses to influenza vaccination, leading to the preferential recommendation of MF59-adjuvanted (MF59Flu) or high-dose (HDFlu) influenza vaccines for this age group in the United States. Herein, we characterized transcriptomic profiles of CD4 + T cells isolated from 234 recipients (≥ 65 years) of either MF59Flu or HDFlu vaccine, prior to vaccination and 28 days thereafter. We identified 412 and 645 differentially expressed genes (DEGs) in CD4 + T cells of older adults after receiving MF59Flu and HDFlu, respectively. DEGs in CD4 + T cells of MF59Flu recipients were enriched in 14 KEGG pathways, all of which were downregulated. DEGs in CD4 + T cells of HDFlu recipients were enriched in 11 upregulated pathways and 20 downregulated pathways. CD4 + T cells in both vaccine groups shared 50 upregulated genes and 75 downregulated genes, all of which were enriched in 7 KEGG pathways. The remaining 287 and 520 DEGs were specifically associated with MF59Flu and HDFlu, respectively. Unexpectedly, none of these DEGs was significantly correlated with influenza A/H3N2-specific HAI titers, suggesting these DEGs at the individual level may have a limited role in protection against influenza. Our findings emphasize the need for further investigation into other factors influencing immunity against influenza in older adults., (© 2024. The Author(s).)

Emergency computed tomography (CT) often does not allow for comprehensive coronary artery assessment. However, CT may reveal pathological myocardial hypoperfusion suggestive of acute myocardial infarction (AMI), especially in patients presenting with a different diagnostic hypothesis. CT hypoperfusion is known to be associated with myocardial infarction, however the diagnostic value of CT hypoperfusion for the detection of AMI is still not well evaluated. This was a single-centre retrospective study including patients who underwent invasive coronary angiography (ICA) due to suspected AMI based on incidental perfusion defects upon emergency CT imaging between 2018 and 2023. A total of 22 patients (mean age 66.3 ± 10.8 years, 11 female) were included in this analysis. The diagnosis of AMI was established in all cases leading to ICA. Culprit coronary artery lesions with an indication of percutaneous coronary intervention were detected in all patients who underwent ICA. Spearmann correlation for hypoperfused segments on CT imaging and the corresponding vascular territory upon ICA was significantly substantial (ρ = 0.73, p = < 0.001). The higher the number of affected myocardial segments, the faster ICA was initiated. Mean time between the suspicion of AMI on CT imaging and ICA was 196 (29-4044) minutes. Myocardial hypoperfusion on emergency CT imaging should be considered as AMI until proven otherwise, independent of the clinical scenario leading to performance of CT imaging and whether imaging was performed for the exclusion of non-cardiac pathologies. Early initiation of further diagnostic workup may potentially avoid delays to invasive treatment and reduce the CT-to-catheter-time. Our study explicitly underlines that myocardial hypoperfusion upon contrast enhanced CT imaging needs to be considered as sign of acute myocardial infarction and indicates targeted clinical workup to rule out this diagnosis and to shorten the timeframe from imaging diagnosis to interventional treatment., (© 2024. The Author(s).)

Recent information regarding the characteristics of people living with human immunodeficiency virus (HIV) (PLWH) is lacking. Therefore, we examined the incidence of HIV infection and epidemiologic characteristics of PLWH in South Korea using recent National Health Insurance Service database data. The HIV infection rate was 4.13 per 100,000 in 2017, 4.19 per 100,000 in 2018, 6.61 per 100,000 in 2019, 5.98 per 100,000 in 2020, 8.81 per 100,000 in 2021, and 4.14 per 100,000 in 2022. In 2016, the mean age of PLWH was 45.7 years (SD: 13.8 years), and it gradually increased to 49.0 years (standard deviation: 13.7 years) in 2022 over 7 years in South Korea. The proportion of male individuals among PLWH was 90.7% (19,970/22,026) in 2016, and it gradually increased to 92.3% (22,943/24,857) in 2022 over 7 years in South Korea. The proportion of anti-retroviral therapy (ART) users among PLWH in South Korea was 92.6% (20,388/22,026) in 2016, and it gradually increased to 97.9% (24,328/24,857) in 2022 over 7 years. In this population-based cohort analysis, we presented the HIV infection incidence and epidemiologic features of PLWH in South Korea. This study's results may influence future infection prevention strategies and policies for PLWH., (© 2024. The Author(s).)

Tandem autologous stem cell transplantation can improve the prognosis of patients with multiple myeloma. However, the precise role of tandem transplantation remains debatable. We evaluated the clinical benefits of tandem transplantation retrospectively. Of the 655 included patients, 117 underwent tandem transplantation; the remaining were assigned to the control group. After a single transplantation, the tandem group achieved a complete remission (CR) rate of 24.8%, which increased to 46.2% after a second transplantation. The tandem group had a significantly longer median PFS than the control group in patients with International Staging System (ISS) III and high-risk cytogenetics (23.1 vs. 14.7 months, p = 0.007 for ISS III; 21.7 vs. 13.2 months, p = 0.042 for high-risk cytogenetics). The tandem group exhibited significantly superior PFS to the control group (20.3 vs. 12.6 months, p = 0.003) among patients who failed to achieve CR after a single transplantation. Tandem transplantation was associated with significantly improved PFS after adjusting for maintenance therapy in patients with ISS III, those with high-risk cytogenetics, and those who did not achieve CR after a single transplantation. Following propensity score matching, the tandem group exhibited significantly longer PFS than the control group (30.3 vs. 13.5 months, p = 0.028). Tandem transplantation should be considered in high-risk patients., (© 2024. The Author(s).)

Drug-coated balloons (DCB) are increasingly utilized in percutaneous coronary intervention (PCI), but their effectiveness in coronary artery disease (CAD) needs further exploration. This study investigates the efficacy and safety of a DCB-based strategy for de novo left anterior descending artery (LAD) disease. Patients with de novo LAD lesions treated with DCB alone or combined with drug-eluting stents (DES) and were retrospectively enrolled from 2010 to 2023 (n = 268). The comparator group consisted of patients treated with second-generation DES from a Korean multicenter registry (n = 4,147). The primary endpoint was three-year major adverse cardiovascular events (MACE), including cardiac death, myocardial infarction, target vessel revascularization, target lesion thrombosis, and major bleeding. In the DCB-based group (n = 268), 218 (81.3%) received DCB-only, while 50 (18.7%) underwent a hybrid approach. After propensity score-matching of 243 paired subjects, baseline characteristics were balanced. The DCB-based PCI reduced overall stent burden by 86.7% and significantly lowered the risk of MACE at three years compared to DES-only PCI (4.5% vs. 7.6%, HR 0.50, 95% CI 0.28-0.90; p = 0.020). The most significant reduction was in major bleeding. The DCB-based approach offers an alternative to DES-only strategy for LAD PCI by reducing three-year MACE risk, supporting its use in treating de novo CAD., (© 2024. The Author(s).)

Recent studies indicate a potential link between oral health and cognitive function; however, long-term associations remain unclear. This study aimed to identify oral health factors that predict changes in cognitive function among older adults over time. The study included 583 independent older adults (201 male, 382 female) with a mean age of 72.7 years. Cognitive function was assessed using Mini-Mental State Examination (MMSE) at baseline and follow-up over two years, with relative change in MMSE (rMMSE) calculated. Baseline oral health variables included number of remaining teeth, masticatory performance, occlusal force, oral diadochokinesis and tongue pressure. Physical performance and confounding factors were also considered. The relationship between rMMSE and the variables was analyzed using Pearson's correlation, Mann-Whitney U test, and multiple linear regression analysis. Cognitive function declined in 196 subjects, with rMMSE significantly correlated with oral diadochokinesis. Regression analysis revealed significant associations between cognitive changes and oral diadochokinesis (p = 0.020) and knee extension strength as a physical performance (p = 0.047). Our findings suggest that cognitive decline may be indicated by declines in both physical and oral motor performance. Incorporating oral diadochokinesis testing into health screenings could aid early detection of cognitive decline, improving outcomes and reducing healthcare burdens., (© 2024. The Author(s).)

Extracellular vesicle-derived DNA (evDNA) encapsulates the complete genome and mutational status of cells; however, whether cancer cell-derived evDNA mirrors the epigenetic features of parental genomic DNA remains uncertain. This study aimed to assess and compare the DNA methylation patterns of evDNA from cancer cell lines and primary cancer tissues with those of the nuclear genomic DNA. We isolated evDNA secreted by two cancer cell lines (HCT116 and MDA-MB-231) from various subcellular compartments, including the nucleus and cytoplasm. Additionally, we obtained evDNA and nuclear DNA (nDNA) from the primary cancer tissues of colon cancer patients. We conducted a comprehensive genome-wide DNA methylation analysis using the Infinium Methylation EPIC BeadChip, examining > 850,000 CpG sites. Remarkable similarities were observed between evDNA and nDNA methylation patterns in cancer cell lines and patients. This concordance extended to clinical cancer tissue samples, showcasing the potential utility of evDNA methylation patterns in deducing cellular origin within heterogeneous populations through methylation-based deconvolution. The observed concordance underscores the potential of evDNA as a noninvasive surrogate marker for discerning tissue origin, particularly in cancer tissues, offering a promising future for cancer diagnostics. This finding enhances our understanding of cellular origins and would help develop innovative diagnostic and therapeutic strategies for cancer., (© 2024. The Author(s).)

Postnatal kidney growth is substantial and involves expansion in kidney tubules without growth of new nephrons, which are the functional units of the kidney. Proliferation and differentiation pathways underpinning nephron elongation are not well defined. To address this, we performed sequential characterization of mouse kidney transcriptomics at the single cell level. Single nuclear RNA sequencing (snRNA-seq) was performed on kidney tissue from male and female mice at 1, 2, 4 and 12 weeks of age using the 10x Chromium platform. Unbiased clustering was performed on 68,775 nuclei from 16 animals. 31 discrete cellular clusters were seen, which were identified through comparison of their gene expression profiles to canonical markers of kidney cell populations. High levels of proliferation were evident at early time points in some cell types, especially tubular cells, but not in other cell types, for example podocytes. Proliferation was especially evident in Proximal Tubular Cells (PTCs) which are the most abundant cell type in the adult kidney. Uniquely when compared to other kidney cell types, PTCs demonstrated sex-specific expression profiles at late, but not early, time points. Mapping of PTC differentiation pathways using techniques including trajectory and RNA Velocity analyses delineated increasing PTC specialization and sex-specific phenotype specification. Our single-cell transcriptomics data characterise cellular states observed during kidney growth. We have identified PTC differentiation pathways that lead to sex-specific tubular cell phenotypes. Tubular proliferative responses are of central importance in postnatal kidney growth and have also been linked to kidney recovery versus fibrosis following injury. Our unbiased and comprehensive dataset of tubular cell development can be used to identify candidate pathways for therapeutic targeting., (© 2024. The Author(s).)

Upper gastrointestinal (UGI) symptoms are among the common complaints among patients visiting health facilities. Because of the scarcity of gastrointestinal endoscopy services and gastroenterologists, the pattern of common upper gastrointestinal diseases has not been well studied in the study setting. This study aimed to determine the pattern of upper gastrointestinal diseases among patients undergoing esophagogastroduodenoscopy (EGD). An institution-based cross-sectional study was conducted at three hospitals in Asella town, southeast Ethiopia. A total of 279 study subjects were included in the study. Three-fourths (74%) of the study participants had abnormal endoscopic findings. The clinical indications for endoscopic examination were dyspepsia (32.6%), peptic ulcer disease (PUD) (27.2%), suspicion of gastric cancer (13.3%), and suspicion of esophageal cancer (11.5%). The abnormal endoscopic findings were esophageal cancer (10.4%), gastric cancer (10%), duodenal ulcer (DU) (9.3%), and gastritis (8.6%). The abnormal biopsy findings were esophageal cancer (7.5%), gastric adenocarcinoma (6.4%), and gastritis (3.9%). Dyspepsia, peptic ulcer disease, and suspicion of UGI malignancies were the most common clinical indications for endoscopic examination, while esophageal cancer and gastric cancer were the most common abnormal endoscopic findings. The most common abnormal biopsy results were esophageal squamous cell carcinoma and gastric adenocarcinoma. It is advised to have a high index of suspicion for esophageal cancer and gastric cancer for patients who present with alarming upper gastrointestinal symptoms in the study setting., (© 2024. The Author(s).)

Few studies have explored the association between residential noise exposure and burnout. In this study, we investigated the association between residential noise exposure and burnout prevalence among 5416 health-care workers in Taiwan from 2012 to 2017. Burnout was evaluated using the Mandarin version of the Copenhagen Burnout Inventory by considering both continuous and binary measures. We applied ordinary Kriging models to calculate the annual average residential noise exposure at an individual level. Multivariable linear regression models and logistic regression models were employed. Restricted cubic splines were used to explore dose-response relationships. The median age of the health-care workers was 31.5 years. In the multivariable linear regression models, exposure to residential noise (per 1 dBA) was associated with increases in personal burnout and work-related burnout scores by 1.59 ± 0.25 and 1.38 ± 0.20, respectively. In the multivariable logistic regression models, the adjusted odds ratios were 1.24 (95% confidence interval [CI]: 1.16, 1.32) for personal burnout and 1.19 (95% CI: 1.13, 1.26) for work-related burnout per 1-dBA increase in residential noise exposure. Linear dose-response associations of burnout with residential noise level were detected. Our findings suggest that exposure to residential noise may increase the risk of burnout among health-care workers., (© 2024. The Author(s).)

Patients with traumatic brain injury (TBI) frequently exhibit concomitant immunosuppression. In this study, we evaluated the predictive values of soluble programmed death-1 (sPD-1) and soluble programmed death ligand-1 (sPD-L1) in patients with severe TBI. Peripheral blood sPD-1 and sPD-L1 levels were measured within 48 h of patient admission. A total of 20 healthy volunteers and 82 patients were enrolled in this study. The levels of sPD-1 and sPD-L1 were upregulated in patients with severe TBI (P < 0.001). They were significantly increased in the post-TBI severe pneumonia group and among non-survivors (P < 0.001). The area under the curves (AUCs) for sPD-1 and sPD-L1 levels to predict severe pneumonia were 0.714 and 0.696, respectively, and the AUCs to predict mortality were 0.758 and 0.735. The levels of sPD-1 and sPD-L1 are correlated with the GCS scores at admission, APACHE II scores, length of MV, and time elapsed to mortality. The levels of sPD-1 and sPD-L1 emerged as independent predictive factors for severe pneumonia and mortality. This study demonstrates that upregulation of sPD-1 and sPD-L1 in severe TBI patients is significantly associated with severe pneumonia and mortality, suggesting their potential as predictive biomarkers for these outcomes., (© 2024. The Author(s).)

Proteinuria selectivity index (PSI) is a potential tool for histological classification and prediction of treatment response in nephrotic syndrome, but evidence is insufficient. Clinical relevance of fractional excretion of sodium (FENa) in nephrotic syndrome remains largely unexplored. This multicenter retrospective study included patients with nephrotic syndrome who underwent kidney biopsy between January 2012 and June 2022. Optimal cutoffs for predicting complete remission based on PSI and FENa were determined using receiver operating characteristic curves. Patients were divided into two groups using these cutoffs and followed until complete remission. Of the 611 patients included, 177 had minimal change disease (MCD), 52 had focal segmental glomerulosclerosis (FSGS), and 149 had membranous nephropathy (MN). Median (interquartile range) PSI were 0.14 (0.09-0.19) for MCD, 0.33 (0.23-0.40) for FSGS, and 0.20 (0.14-0.30) for MN. FENa were 0.24 (0.09-0.68), 1.03 (0.50-2.14), and 0.78 (0.41-1.28). Patients with low PSI and FENa had a higher incidence of complete remission. Cox regression analyses demonstrated that both parameters were associated with achieving complete remission (HR 2.73 [95% CI 1.97-3.81] and HR 1.93 [95% CI 1.46-2.55], respectively). PSI and FENa may be useful for histological classification and predicting remission in nephrotic syndrome., (© 2024. The Author(s).)

The communication between intestinal Glucagon like peptide 1 (GLP-1)-producing cells and the peripheral nervous system has garnered renewed interest considering the availability of anti-obesity and anti-diabetic approaches targeting GLP-1 signaling. While it is well-established that intestinal GLP-1 cells can exert influence through paracrine mechanisms, recent evidence suggests the possible existence of synaptic-like connections between GLP-1 cells and peripheral neurons, including those of the vagus nerve. In this study, using a reporter Phox2b-Cre-Tomato mouse model and super-resolution confocal microscopy, we demonstrated that vagal axons made apparent contacts with less than 0.5% of GLP-1 cells. Moreover, immunohistochemistry combined with super-resolution confocal microscopy revealed abundant post-synaptic density 95 (PSD-95) immunoreactivity within the enteric plexus of the lower intestines of C57/BL6 mice, with virtually none in its mucosa. Lastly, utilizing RNAScope in situ hybridization in the lower intestines of mice, we observed that GLP-1 cells expressed generic markers of secretory cells such as Snap25 and Nefm, but neither synaptic markers such as Syn1 and Nrxn2, nor glutamatergic markers such as Slc17a7. Through theoretical considerations and a critical review of the literature, we concluded that intestinal GLP-1 cells primarily communicate with vagal neurons through paracrine mechanisms, rather than synaptic-like contacts., (© 2024. The Author(s).)

Anecdotal evidence from preliminary observations has noted multiple instances where osteoporosis is present in elderly patients before the clinical detection of bowel disease, even in the absence of overt gastrointestinal symptoms. However, any potential association between these conditions remains to be further investigated. This computed tomography (CT) study investigates whether patients with gastrointestinal (GI) perforation have lower bone mineral density (BMD) than age and sex matched controls. BMD was measured by drawing 3D regions of interest in the bone marrow of the L1-L3 vertebral bodies on CT scans of each of 37 GI perforations and matched controls. Spectrometric calibration of Hounsfield units to the mineral scale was performed with density measurements in the paravertebral muscles (erector spinae) and subcutaneous adipose tissue. The mean BMD of patients with GI perforation (135.9 ± 24.3 mg/ml) was significantly lower than that of controls (96.9 ± 27.5 mg/ml, p < 0.05). The calculated T-and Z-scores of bone mineral density were also significantly different between the two groups (p < 0.05 for each) and were - 2.9 (± 0.90) and - 0.8 (± 0.91) in patients with GI perforation and - 1.6 (± 0.83) and 0 (± 0.96) in the control group, respectively. The results imply that patients with gastrointestinal (GI) perforation have lower bone mineral density (BMD) than age-and sex-matched controls, posing the question whether the screening and aggressive management of osteoporosis is high-risk populations for gastrointestinal perforation can prevent gastrointestinal complications in targeted populations., (© 2024. The Author(s).)

The spatial resolution in magnetic resonance imaging is mainly limited by low SNR, which is commonly addressed by long measurement times or dedicated hardware. In single digit micron resolutions, diffusion becomes a further limiting factor since depending on the gradient strength, the diffusion length of particles may approach the target resolutions. Spatial resolution improvement has been addressed by microscopy inserts comprising dedicated gradient systems and RF-coils, usually designed for NMR spectrometers that are often equipped with a deuterium lock for field drift compensations. The presented microscopy insert has been designed to provide single-digit micron resolutions on horizontal preclinical imaging systems utilizing their full imaging and user interface capabilities. The incorporated gradient provides an efficiency of 0.135 T/(m∙A) which in combination with the system's gradient amplifiers yields a maximum of 27 T/m. With the additional low noise amplifier added to the RF-path a three-fold SNR improvement could be achieved for small samples. Furthermore, a modified constant time imaging sequence was introduced to improve the capability of the setup for ultra-high-resolution imaging demonstrated on zebrafish embryos at different development stages with (9 μm)³ resolution., (© 2024. The Author(s).)

Predicting major adverse cardiovascular events (MACE) is crucial due to its high readmission rate and severe sequelae. Current risk scoring model of MACE are based on a few features of a patient status at a single time point. We developed a self-attention-based model to predict MACE within 3 years from time series data utilizing numerous features in electronic medical records (EMRs). In addition, we demonstrated transfer learning for hospitals with insufficient data through code mapping and feature selection by the calculated importance using Xgboost. We established operational definitions and categories for diagnoses, medications, and laboratory tests to streamline scattered codes, enhancing clinical interpretability across hospitals. This resulted in reduced feature size and improved data quality for transfer learning. The pre-trained model demonstrated an increase in AUROC after transfer learning, from 0.564 to 0.821. Furthermore, to validate the effectiveness of the predicted scores, we analyzed the data using traditional survival analysis, which confirmed an elevated hazard ratio for a group with high scores., (© 2024. The Author(s).)

Minimal change disease (MCD) is a common cause of nephrotic syndrome. Due to its rapid progression, early detection is essential; however, definitive diagnosis requires invasive kidney biopsy. This study aims to develop non-invasive predictive models for diagnosing MCD by machine learning. We retrospectively collected data on demographic characteristics, blood tests, and urine tests from patients with nephrotic syndrome who underwent kidney biopsy. We applied four machine learning algorithms-TabPFN, LightGBM, Random Forest, and Artificial Neural Network-and logistic regression. We compared their performance using stratified 5-repeated 5-fold cross-validation for the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). Variable importance was evaluated using the SHapley Additive exPlanations (SHAP) method. A total of 248 patients were included, with 82 cases (33%) were diagnosed with MCD. TabPFN demonstrated the best performance with an AUROC of 0.915 (95% CI 0.896-0.932) and an AUPRC of 0.840 (95% CI 0.807-0.872). The SHAP methods identified C3, total cholesterol, and urine red blood cells as key predictors for TabPFN, consistent with previous reports. Machine learning models could be valuable non-invasive diagnostic tools for MCD., (© 2024. The Author(s).)

"Long COVID", which describes a diverse set of symptoms or conditions that persist or develop after four weeks from the onset of initial SARS-CoV-2 infection has been introduced. However, the true prevalence varies worldwide. This study aimed to determine the point prevalence and clinical characteristics of long COVID at three and six months after acute COVID-19 infection in Thailand. Methods All adult patients who were diagnosed with COVID-19 by positive nasopharyngeal RT-PCR for SARS-CoV-2 at Thammasat University Hospital between October and December 2021 were recruited and followed for long COVID symptoms by telephone interviews at 3 and 6 months after an acute infection. Among 1,400 eligible COVID-19 cases, interviews were complete for 1,129 and 932 individuals at 3 and 6 months, respectively. Of those, 431 and 314 reported at least one symptom consistent with long COVID. The point prevalence was 38.2% (95% confidence interval: 35.3-41.1%) and 33.7% (95% confidence interval: 30.7-36.7%) respectively. Female gender, disease severity, and symptomatic acute infection were identified as independent risk factors. Conclusion Based on the reported symptoms, long COVID is commonly observed either at 3 or 6 months in our study., (© 2024. The Author(s).)

Several studies have investigated whether sarcopenia is associated with diabetic microvascular complications, but very few have examined associations between sarcopenia and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM). Therefore, we investigated associations of muscle strength (handgrip strength [HGS]) and mass (appendicular skeletal muscle mass index [ASMI]) and CAN in patients with T2DM. We enrolled 342 patients in this retrospective, cross-sectional study. Cardiovascular reflex tests were used to assess CAN according to Ewing's protocol. Relative HGS was determined after normalizing absolute HGS to body weight (HGS/body weight [kg]). We defined low HGS and low ASMI according to a consensus report of the Asian Group for Sarcopenia. Logistic regression analyses were carried out to assess the associations between relative HGS or ASMI quartiles and the presence of CAN in patients with T2DM. The prevalence rates of CAN, low HGS, and low ASMI in the study subjects were 34.8%, 17.3%, and 18.7%, respectively. Low HGS was significantly more prevalent in patients with CAN than those without CAN (23.5% vs. 13.9%, p = 0.025). The CAN scores were significantly and negatively correlated with relative HGS but not with ASMI. Relative HGS was negative correlated with age, glycated hemoglobin, fasting plasma glucose, hsCRP, body mass index, and HOMA-IR and positively correlated with ASMI. The prevalence of CAN gradually increased with decreasing quartile of relative HGS (28.4% in Q4, 31.8% in Q3, 34.2% in Q2, and 45.3% in Q1, p = 0.02 for trend). Multivariable-adjusted prevalence ratios (PRs) for CAN, determined by comparing the first, second, and third quartiles with the fourth quartile of relative HGS, were 4.4 with a 95% confidence interval (95% CI) of [1.1 to 17.3]), 2.3 (95% CI [0.8 to 6.9]), and 1.2 (95% CI [0.4 to 3.7]), respectively. The prevalence of CAN and the PRs (95% [CI]) for CAN based on ASMI were not statistically significant. Our findings suggest that low muscle strength rather than low muscle mass was significantly associated with the presence of CAN. Therefore, HGS testing could help identify patients who would benefit from screening for earlier diagnosis of CAN., (© 2024. The Author(s).)

Stomach adenocarcinoma (STAD) is a prevalent malignancy that is highly aggressive and heterogeneous. Intratumor heterogeneity (ITH) showed strong link to tumor progression and metastasis. High ITH may promote tumor evolution. An ITH-related signature (IRS) was created using as integrative technique including 10 machine learning methods based on TCGA, GSE15459, GSE26253, GSE62254 and GSE84437 datasets. The relevance of IRS in predicting the advantages of immunotherapy was assessed using a number of prediction scores and three immunotherapy datasets (GSE78220, IMvigor210 and GSE91061). Vitro experiments were performed to verify the biological functions of AKR1B1. The RSF + Enet (alpha = 0.1) projected model was proposed as the ideal IRS because it had the highest average C-index. The IRS demonstrated a strong performance in serving as an independent risk factor for the clinical outcome of STAD patients. It performed exceptionally well in predicting the overall survival rate of STAD patients, as seen by the TCGA cohort's AUC of 1-, 3-, and 5-year ROC curves, which were 0.689, 0.683, and 0.669, respectively. A low IRS score demonstrated a superior response to immunotherapy, as seen by a lower TIDE score, lower immune escape score, greater TMB score, higher PD1&CTLA4 immunophenoscore, higher response rate, and improved prognosis. Common chemotherapeutic and targeted treatment regimens had lower IC50 values in the group with higher IRS scores. Vitro experiment showed that AKR1B1 was upregulated in STAD and knockdown of AKR1B1 obviously suppressed tumor cell proliferation and migration. The present investigation produced the best IRS for STAD, which may be applied to prognostication, risk stratification, and therapy planning for STAD patients., (© 2024. The Author(s).)

Electrical cardioversion (ECV) a widely utilized intervention for persistent atrial fibrillation (AF) aimed at restoring sinus rhythm. However, ECV can be ineffective, raising questions about subsequent treatment options. This study aimed to compare the outcomes of non-ablation therapy versus ablation therapy following unsuccessful ECV. A total of 125 consecutive patients with persistent AF who underwent unsuccessful ECV between November 2017 and August 2023 was included in this retrospective analysis. Of these, 51.2% received only medical therapy (non-ablation therapy group, n = 64), while 48.8% underwent AF ablation (ablation therapy group, n = 61). Various ablation methods were employed, including catheter and thoracoscopic ablation. Ablation therapy was associated with significantly better AF-free survival compared to non-ablation therapy [hazard ratio (HR), 0.37; 95% confidence interval (CI) 0.22-0.61; p < 0.01]. There was no difference of AF-free survival between catheter ablation and thoracoscopic ablation groups (HR 0.79, 95% CI 0.34-1.83; p = 0.58). AF duration > 5 year (HR 1.51; 95% CI 0.930-2.437; p = 0.10), BMI ≤ 25 kg/m 2 (HR 1.61; 95% CI 1.004-2.581; p = 0.05) and diabetes (HR 2.38; 95% CI 0.902-6.266; p = 0.08) were considerable as predictor of AF recurrence. Ablation therapy following unsuccessful ECV was associated with maintaining sinus rhythm, regardless of the specific ablation method utilized., (© 2024. The Author(s).)

We assessed the effect of continuity of care (COC) on the frequency of hospitalization for Ambulatory care-sensitive conditions (ACSCs) to estimate the impact of COC and hearing disability relative to the controls. This retrospective cohort study used claim data of Korean National Health Insurance Service - National Sample Cohort 2.0 DB. We used propensity score matching to determine a control group for the hearing disability group by age, sex, and the Charlson Comorbidity Index. The hearing-impaired group included 720 participants, and the non-disabled control group, consisting of individuals without any form of disability, had 1,423 individuals. We used the frequency of hospitalization for ACSCs during one-year follow-up as the dependent variable for Poisson regression. We measured COC with the Bice-Boxerman Continuity of Care Index (COCI); higher COCI values represent better continuity of care, with COCI values ranging from 0 to 1. Poisson regression showed that disability status modifies the effect of COCI on the incidence of hospitalization. COCI = 1 reduced hospitalizations in people with hearing disabilities (adjusted Incidence Rate Ratio [aIRR]: 0.30, 95% CI: 0.20-0.44) but was not statistically significant for controls. In the COCI = 1 group, the effect of disability was not significant(aIRR: 1.10, 95% CI: 0.83-1.44). Compared to people without disabilities, enhanced COC for people with hearing disabilities was more effective in preventing hospitalizations for ACSCs., (© 2024. The Author(s).)

The prevalence of osteoporosis has drastically increased recently. It is not only the most frequent but is also a major global public health problem due to its high morbidity. There are many risk factors associated with osteoporosis were identified. However, most studies have used the traditional multiple linear regression (MLR) to explore their relationships. Recently, machine learning (Mach-L) has become a new modality for data analysis because it enables machine to learn from past data or experiences without being explicitly programmed and could capture nonlinear relationships better. These methods have the potential to outperform conventional MLR in disease prediction. In the present study, we enrolled a Chinese post-menopause cohort followed up for 4 years. The difference of T-score (δ-T score) was the dependent variable. Information such as demographic, biochemistry and life styles were the independent variables. Our goals were: (1) Compare the prediction accuracy between Mach-L and traditional MLR for δ-T score. (2) Rank the importance of risk factors (independent variables) for prediction of δ T-score. Totally, there were 1698 postmenopausal women were enrolled from MJ Health Database. Four different Mach-L methods namely, Random forest (RF), eXtreme Gradient Boosting (XGBoost), Naïve Bayes (NB), and stochastic gradient boosting (SGB), to construct predictive models for predicting δ-BMD after four years follow-up. The dataset was then randomly divided into an 80% training dataset for model building and a 20% testing dataset for model testing. A 10-fold cross-validation technique for hyperparameter tuning was used. The model with the lowest root mean square error for the validation dataset was viewed as the best model for each ML method. The averaged metrics of the RF, SGB, NB, and XGBoost models were used to compare the model performance of the benchmark MLR model that used the same training and testing dataset as the Mach-L methods. We defined that the priority demonstrated in each model ranked 1 as the most critical risk factor and 22 as the last selected risk factor. For Pearson correlation, age, education, BMI, HDL-C, and TSH were positively and plasma calcium level, and baseline T-score were negatively correlated with δ-T score. All four Mach-L methods yielded lower prediction errors than the MLR method and were all convincing Mach-L models. From our results, it could be noted that education level is the most important factor for δ-T Score, followed by DBP, smoking, SBP, UA, age, and LDL-C. All four Mach-L outperformed traditional MLR. By using Mach-L, the most important six risk factors were selected which are, from the most important to the least: DBP, SBP, UA, education level, TG and sleeping hour. δ T score was positively related to SBP, education level, UA and TG and negatively related to DBP and sleeping hour in postmenopausal Chinese women., (© 2024. The Author(s).)

Cyclophilin A (CypA) is a novel renal inflammation biomarker, with levels altered in various diseases, particularly in patients with diabetes mellitus (DM) and kidney damage. This study aimed to investigate the correlation between urinary cyclophilin A (uCypA) and chronic kidney disease (CKD) conditions with and without type 2 diabetes mellitus (T2DM) using an in-house enzyme-linked immunoassay (ELISA) method. A uCypA strip-test prototype was also developed. An indirect ELISA was performed to determine the uCypA levels. A 0.48 µg/mL uCypA cutoff differentiated healthy patients from those with early-stage CKD (stages I and II). The uCypA levels were significantly increased in patients with progression of renal deterioration, especially in the T2DM with late-stage CKD group, compared to the control group. Fasting blood sugar (FBS), estimated glomerular filtration rate (eGFR), albumin/creatinine ratio, and metformin use were associated with uCypA levels. Multinomial logistic regression analysis revealed an association between uCypA levels and T2DM diagnosed for over five years and early-stage CKD. This finding shows that uCypA could be used as a biomarker for distinguishing early-stage CKD as well as T2DM complications, which is beneficial for patients to be aware of their health status and change their behavior to slow kidney deterioration., (© 2024. The Author(s).)

Corneal ulcers, whether melting or indolent, are common in humans and companion animals. Treatment involves local administration of antibiotic eye drops and corneal healing drugs. Compared to traditional treatments for ulcerative keratitis, herbal medicines offer unique advantages, such as potent anti-inflammatory effects and inhibition of proinflammatory cytokines. Curcumin, extracted from the Curcuma Longa plant, possesses extensive pharmacological properties, such as anti-inflammatory, anti-cancer, and antioxidant properties, and is used in various medicines. In this study, we developed a novel ophthalmic drop hydrogel using a formulation of Curcumin NPs encapsulated with β-cyclodextrin and hyaluronic acid, to accelerate corneal healing and improve the quality of healed structures. The formation of Curcumin NPs into Hyaluronic acid-based hydrogels was characterized by zeta, FTIR, and scanning electron microscope (SEM) analyses. A total of 25 healthy male New Zealand Albino rabbits were experimentally induced with ulcerative keratitis and treated individually with topical medication. Rabbits were divided into five groups. Fluorescein dye staining, corneal clarity score, Schirmer tear test, proinflammatory cytokine measurement, and pathologic factors assessments were used to evaluate the optimised Curcumin NPs with β-cyclodextrin in Hyaluronic acid hydrogel. Our results demonstrated that the optimized Curcumin NPs with β-cyclodextrin in hyaluronic acid hydrogel significantly reduced the frequency of medication administration compared to conventional therapies, enhancing the quality of healed structures and effectively treating ulcerative keratitis. All findings in this study provide new insight into designing and fabricating novel ophthalmic medicine for ulcerative keratitis for topical usage., (© 2024. The Author(s).)

SHP-1, a nonreceptor protein tyrosine phosphatase encoded by ptpn6, has been regarded as a regulatory protein of hematopoietic cell biology for years. However, there is now increasing evidence to support its role in tumors. Thus, the role of ptpn6 for prognosis and immune regulation across 33 tumors was investigated, aiming to explore its functional heterogeneity and clinical significance in pan-cancer. Differential expression of ptpn6 was found between cancer and adjacent normal tissues, and its expression was significantly correlated with the prognosis of tumor patients. In most cancers, ptpn6 expression was significantly associated with immune infiltration. This was further confirmed by ptpn6-related genes/proteins enrichment analysis. Additionally, genetic alterations in ptpn6 was observed in most cancers. As for epigenetic changes, it's phosphorylation levels significantly altered in 6 tumors, while methylation levels significantly altered in 12 tumors. Notably, the methylation levels of ptpn6 were significantly decreased in 11 tumors, accompanied by its increased expression in 8 of them, suggesting that the hypomethylation may be related to its increased expression. Our results show that ptpn6 plays a specific role in tumor immunity and exerts a pleiotropic effect in a variety of tumors. It can serve as a prognostic factor for some cancers. Especially in LGG, KIRC, UCS and TGCT, the increased expression of ptpn6 is associated with poor prognosis and high immune infiltration. This aids in understanding the role of ptpn6 in tumor biology, and can provide insight into presenting a potential biomarker for poor prognosis and immune infiltration in cancers., (© 2024. The Author(s).)

Peak oxygen pulse (O 2 P peak ) is an important index of cardiorespiratory fitness (CRF). The FRIEND database is a global source of reference values for CRF. However, no reference equation is tailored for endurance athletes (EA) to predict O 2 P peak . Here, we adjusted the well-established FRIEND equation for O 2 P peak to the characteristics of the EA population. 32 (34.0%) female EA and 62 (66.0%) male well-trained EA underwent maximal cardiopulmonary exercise test on a treadmill. V̇O 2max was 4.5 ± 0.5 L min -1 in males and 3.1 ± 0.4 L min -1 in females. O 2 P peak was 23.6 ± 2.8 mL beat -1 and 16.4 ± 2.0 mL beat -1 for males and females, respectively. Firstly, we externally validated the original FRIEND equation. Secondly, using multiple linear regression, we adjusted the FRIEND equation for O 2 P peak to the population of EA. The original FRIEND equation underestimated O 2 P peak for 2.9 ± 2.9 mL beat -1 (P < .001) in males and 2.2 ± 2.1 mL beat -1 (P < .001) in females. The updated equation was 1.36 + 1.07 (23.2 · 0.09 · age - 6.6 [if female]). The new equation explained 62% of the variance and significantly predicted O 2 P peak (R 2  = 0.62, β = 0.78, P < .001). The error of the EA-adjusted model was 0.1 ± 2.9 mL beat -1 (P = .82) and 0.2 ± 2.1 mL beat -1 (P = .65) for males and females respectively. Recalibration of the original FRIEND equation significantly enhances its accuracy among EA. The error of the EA-adjusted model was negligible. A new recalibrated equation should be used to predict O 2 P peak in the population of EA., (© 2024. The Author(s).)

Surgical occlusion of the left atrial appendage (LAA) during cardiac surgery in patients with atrial fibrillation (AF) is known to reduce thromboembolism. However, data on the clinical significance of LAA occlusion (LAAO) in patients with mitral regurgitation (MR) are lacking. A total of 237 AF patients with chronic severe MR who underwent mitral valve (MV) surgery were retrospectively analyzed. Patients were divided into two groups according to concomitant LAAO or LAA preservation. The primary outcome was a composite of all-cause death and thromboembolic events (ischemic stroke or systemic embolism). The LAA was surgically occluded in 98 (41%) patients and preserved in 139 (59%) patients. During the follow-up period (median, 37 months), 29 primary outcomes occurred. In the Kaplan-Meyer analysis, the LAA preservation group showed a greater cumulative incidence of the primary outcome (P = 0.002) and thromboembolic events (P = 0.003) than the LAAO group. In the univariate Cox regression analysis, coronary artery disease, CHA 2 DS 2 -VASc score, a cauliflower-shaped LAA, Maze, and no LAAO were significantly associated with the primary outcome. In the multivariate Cox regression analysis, concomitant LAAO was significantly linked to the primary outcome (hazard ratio [HR]: 0.30, 95% confidence interval [CI]: 0.10-0.91, P = 0.033) and thromboembolic events (HR: 0.19, 95% CI: 0.04-0.87, P = 0.032). These benefits from LAAO were consistent, even after propensity score-matched analysis. For patients undergoing surgery for chronic MR who also have AF, concomitant surgical LAAO is associated with favorable clinical outcome., (© 2024. The Author(s).)

Despite advancements in diagnostic modalities, delineating the etiology of fever of unknown origin (FUO) remains a significant challenge for clinicians. Notably, cases with hematological malignancies often have a poor prognosis due to delayed diagnosis. This study investigated the potential of readily obtainable laboratory markers to differentiate hematological causes from other etiologies during the early stages of FUO. A retrospective analysis was conducted on the medical records of 100 patients who fulfilled the modified FUO criteria between January 2010 and April 2023. Hematological etiologies were identified in 26 of the 100 patients. Peripheral blood neutrophil, lymphocyte, platelet counts, and the systemic immune inflammation (SII) index, were significantly lower in the hematological group compared to the non-hematological group. Conversely, serum ferritin levels were demonstrably higher in the hematological group. ROC analysis identified a neutrophil-to-ferritin ratio (NFR) cutoff value of < 8.53 as optimal for predicting hematological etiology. Subsequent multivariate analysis demonstrated that the NFR was the sole independent predictor of hematological etiology (p = 0.013).This study proposes a novel approach for early diagnosis of a potentially life-threatening subset of FUO patients. The NFR presents as an inexpensive and readily available marker for predicting hematological etiology in FUO cases., (© 2024. The Author(s).)

Early peritoneal dialysis (PD)-related infection is a severe complication. This study investigated the relationship between patient-doctor contact (PDC) duration and early PD-related infection. In the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS) Korea, incident dialysis patients receiving PD were divided into two groups based on PDC duration (< 15 min versus ≥ 15 min), which was defined as the duration a nephrologist typically spends with a patient receiving PD during each visit according to the facility practice pattern. Early risks of PD-related infections, such as peritonitis and catheter-related infection (onset within 3 and 12 months of PD), were compared to the PDC duration using Cox regression. The study included 276 patients (184 [66.7%] in the shorter PDC group [< 15 min] and 92 [33.3%] in the longer PDC group [≥ 15 min]). The average age did not differ between the groups. The incidences of 3- and 12-month PD-related infections were significantly lower in the longer PDC group than in the shorter PDC group (3 months: 1.1% versus 9.8%, P = 0.007; 12 months: 9.8% versus 23.4%, P = 0.007). Longer PDC was independently associated with a lower risk of PD-related infections at 3 and 12 months (3 months: adjusted hazard ratio [aHR], 0.11; 95% confidence interval [CI], 0.02-0.85, P = 0.034; 12 months: aHR, 0.43; 95% CI 0.19-0.99, P = 0.048). Overall, a longer PDC duration was associated with a significantly lower risk of early PD-related infection., (© 2024. The Author(s).)

Effective antihypertensive therapy is essential for achieving optimal blood pressure (BP) control and reducing cardiovascular events. This double-blind, multicenter, randomized trial aimed to compare the antihypertensive efficacy and safety of a combination of amlodipine (AML) and candesartan cilexetil (CC) versus AML monotherapy in patients with essential hypertension (HTN). After a 4-week run-in period with AML 5 mg, patients whose HTN remained uncontrolled (diastolic BP [DBP]) ≥ 90 mmHg and < 120 mmHg) were randomized to receive either AML + CC or AML alone for 8 weeks. Efficacy was assessed by measuring changes in DBP and systolic BP (SBP). The primary safety measure was the incidence of adverse events (AEs). A total of 174 participants were included in the efficacy analysis. After 8 weeks, DBP decreased by -9.92 ± 0.86 mmHg in the AML + CC arm and - 2.08 ± 0.86 mmHg in the AML arm (p < 0.0001). SBP decreased by -14.27 ± 1.39 mmHg in the AML + CC arm versus - 2.77 ± 1.39 mmHg in the AML arm (p < 0.0001). AEs occurred in 11.24% of the AML + CC group and 5.62% of the AML group (p = 0.1773). AML + CC combination therapy demonstrated superior efficacy with good tolerance, making it a promising option for patients with inadequately controlled hypertension on amlodipine alone., (© 2024. The Author(s).)

Radiofrequency ablation is a promising technique for arrhythmia treatment in horses. Due to the thicker myocardial wall and higher blood flow in horses, it is unknown if conventional radiofrequency settings used in human medicine can be extrapolated to horses. The study aim is to describe the effect of ablation settings on lesion dimensions in equine myocardium. To study species dependent effects, results were compared to swine myocardium. Right ventricular and right and left atrial equine myocardium and right ventricular swine myocardium were suspended in a bath with circulating isotonic saline at 37 °C. The ablation catheter delivered radiofrequency energy at different-power-duration combinations with a contact force of 20 g. Lesion depth and width were measured and lesion volume was calculated. Higher power or longer duration of radiofrequency energy delivery increased lesion size significantly in the equine atrial myocardium and in equine and swine ventricular myocardium (P < 0.001). Mean lesion depth in equine atrial myocardium ranged from 2.9 to 5.5 mm with a diameter ranging from 6.9 to 10.1 mm. Lesion diameter was significantly larger in equine tissue compared to swine tissue (P = 0.020). Obtained data in combination with estimated wall thickness can improve lesion transmurality which might reduce arrhythmia recurrence. Optimal ablation settings may differ between species., (© 2024. The Author(s).)

Primary cultures of proximal tubule cells are widely used to model the behavior of kidney epithelial cells in vitro. However, de-differentiation of primary cells upon culture has been observed and appreciated for decades, yet the mechanisms driving this phenomenon remain poorly understood. This confounds the interpretation of experiments using primary kidney epithelial cells and prevents their use to engineer functional kidney tissue ex vivo. In this report, we measure the dynamics of cell-state transformations in early primary culture of mouse proximal tubules to identify key pathways and processes that correlate with and may drive de-differentiation. Our data show that the loss of proximal-tubule-specific genes is rapid, uniform, and sustained even after confluent, polarized epithelial monolayers develop. This de-differentiation occurs uniformly across many common culture condition variations. Changes in early culture were strongly associated with the loss of HNF4A. Exogenous re-expression of HNF4A can promote expression of a subset of proximal tubule genes in a de-differentiated proximal tubule cell line. Using genetically labeled proximal tubule cells, we show that selective pressures very early in culture influence which cells grow to confluence. Together, these data indicate that the loss of in vivo function in proximal tubule cultures occurs very early and suggest that the sustained loss of HNF4A is a key regulatory event mediating this change., (© 2024. The Author(s).)

We aimed to compare the associations of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) with coronary artery calcification (CAC). Patients who simultaneously underwent ultrasonography to diagnose hepatic steatosis and cardiac computed tomography to detect CAC were included. The presence and severity of CAC were defined with CAC-score thresholds of > 0 and > 300, respectively, and patients were divided into the following groups: no MASLD or MAFLD (reference), MASLD-only, MAFLD-only, and overlapping groups. Overall, 1,060/2,773 (38.2%) patients had CAC, of which 196 (18.5%) had severe CAC. The MASLD and MAFLD prevalence rates were 32.6% and 45.2%, respectively, with an overlap of 30.7%. In an ASCVD risk score-adjusted model, both MASLD (adjusted odd ratios [aOR], 1.21; 95% confidence interval [CI], 1.02-1.44; p = 0.033) and MAFLD (aOR 1.20; 95% CI 1.01-1.42, p = 0.034) were associated with CAC, whereas only MASLD (aOR 1.38; 95% CI 1.01-1.89, p = 0.041) was associated with severe CAC. Compared to the reference group, the overlapping group showed an association with CAC (aOR 1.22; 95% CI 1.01-1.47; p = 0.038); however, the MASLD and MAFLD subgroups did not differ in their association with CAC. MASLD may predict a higher risk of ASCVD more effectively than MAFLD., (© 2024. The Author(s).)