Background: Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023. Results: Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038). Conclusion Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.

Background: Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023. Results: Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038). Conclusion Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.

Background: Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023. Results: Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038). Conclusion Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.

Objectives: The association between statin use and depression is well studied, but the studies on the association of statin use and bipolar disorders are limited. Thus, we aimed to investigate the effects of taking statin on risk of bipolar disorder using national claims data of South Korea. Methods: A total of 5713871 subjects who did not take statin and were not diagnosed with bipolar disorder before the health examination were included. Among eligible subjects, 315537 subjects started taking statin within 1 year after taking the health examination and 5398334 subjects did not. After 9 years of follow-up, the incidence of bipolar disorder was determined for each group. Results: Compared to subjects who were not exposed to statin, subjects who were exposed to statin showed a greater incidence of bipolar disorder and an increased risk of bipolar disorder (hazard ratio [HR]: 1.66; 95% confidence interval [CI]: 1.58 to 1.75), and after adjusting for age, sex, low income, regular exercise, smoking, drinking, diabetes mellitus, hypertension, body mass index, cholesterol and depression (adjusted HR: 1.32; 95% CI: 1.24 to 1.40). Conclusions This result showed an increased risk of bipolar disorder after taking statin, but the underlying biological mechanism needs further investigations. This study has clinical implications for patients taking statins, which require early assessment and response in addition to drug treatment and lifestyle modification, considering the possibility that unhealthy lifestyle habits may appear as part of the mood symptoms of bipolar disorder.

Objective: Previous studies have investigated obesity and appetite changes in patients with depression, which consisted of a small age range of adults and used body mass index rather than abdominal obesity. The objective of this study is to examine the relationship between abdominal obesity and the risk of depression by sex and age groups. Methods: This study utilized the National Health Insurance Sharing Service (NHISS) database of South Korea, which includes those over 20 years old and who had undergone a health examination in 2009 and their claims data between 2009 and 2018. The diagnosis of depressive episodes was based on the International Statistical Classification of Disease and Related Health Problems 10th revision. Abdominal obesity was measured by waist circumference (WC) and was divided into six levels (cm). Cox proportional-hazard regression analyses were conducted to examine the relationship between abdominal obesity and the risk of depression by sex and age groups. Results: Among 9,041,751 participants, 1,376,279 were diagnosed with depression. Those with higher WC (90 cm or higher for males, 85 cm or higher for females) showed an increased risk for depression in both sexes (hazard ratio [HR]=1.09, 95% confidence interval [CI]: 1.07–1.11 for males, HR=1.03, 95% CI: 1.02–1.05 for females). Underweight males (WC<80 cm) also showed an increased risk for depression (HR=1.05, 95% CI: 1.04–1.05). Conclusion It has been found that higher WC was associated with increased risks of depression in both sexes. Although underweight males showed an elevated risk of depression, a healthy weight is associated with fewer depression symptoms.

Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.

Objectives: The association between statin use and depression is well studied, but the studies on the association of statin use and bipolar disorders are limited. Thus, we aimed to investigate the effects of taking statin on risk of bipolar disorder using national claims data of South Korea. Methods: A total of 5713871 subjects who did not take statin and were not diagnosed with bipolar disorder before the health examination were included. Among eligible subjects, 315537 subjects started taking statin within 1 year after taking the health examination and 5398334 subjects did not. After 9 years of follow-up, the incidence of bipolar disorder was determined for each group. Results: Compared to subjects who were not exposed to statin, subjects who were exposed to statin showed a greater incidence of bipolar disorder and an increased risk of bipolar disorder (hazard ratio [HR]: 1.66; 95% confidence interval [CI]: 1.58 to 1.75), and after adjusting for age, sex, low income, regular exercise, smoking, drinking, diabetes mellitus, hypertension, body mass index, cholesterol and depression (adjusted HR: 1.32; 95% CI: 1.24 to 1.40). Conclusions This result showed an increased risk of bipolar disorder after taking statin, but the underlying biological mechanism needs further investigations. This study has clinical implications for patients taking statins, which require early assessment and response in addition to drug treatment and lifestyle modification, considering the possibility that unhealthy lifestyle habits may appear as part of the mood symptoms of bipolar disorder.

Objective: Previous studies have investigated obesity and appetite changes in patients with depression, which consisted of a small age range of adults and used body mass index rather than abdominal obesity. The objective of this study is to examine the relationship between abdominal obesity and the risk of depression by sex and age groups. Methods: This study utilized the National Health Insurance Sharing Service (NHISS) database of South Korea, which includes those over 20 years old and who had undergone a health examination in 2009 and their claims data between 2009 and 2018. The diagnosis of depressive episodes was based on the International Statistical Classification of Disease and Related Health Problems 10th revision. Abdominal obesity was measured by waist circumference (WC) and was divided into six levels (cm). Cox proportional-hazard regression analyses were conducted to examine the relationship between abdominal obesity and the risk of depression by sex and age groups. Results: Among 9,041,751 participants, 1,376,279 were diagnosed with depression. Those with higher WC (90 cm or higher for males, 85 cm or higher for females) showed an increased risk for depression in both sexes (hazard ratio [HR]=1.09, 95% confidence interval [CI]: 1.07–1.11 for males, HR=1.03, 95% CI: 1.02–1.05 for females). Underweight males (WC<80 cm) also showed an increased risk for depression (HR=1.05, 95% CI: 1.04–1.05). Conclusion It has been found that higher WC was associated with increased risks of depression in both sexes. Although underweight males showed an elevated risk of depression, a healthy weight is associated with fewer depression symptoms.

Nanobodies derived from camelids and sharks offer unique advantages in therapeutic applications due to their ability to bind to epitopes that were previously inaccessible. Traditional methods of nanobody development face challenges such as ethical concerns and antigen toxicity. Our study presents a synthetic, phagedisplayed nanobody library using trinucleotide-directed mutagenesis technology, which allows precise amino acid composition in complementarity-determining regions (CDRs), with a focus on CDR3 diversity. This approach avoids common problems such as frameshift mutations and stop codon insertions associated with other synthetic antibody library construction methods. By analyzing FDA-approved nanobodies and Protein Data Bank sequences, we designed sub-libraries with different CDR3 lengths and introduced amino acid substitutions to improve solubility. The validation of our library through the successful isolation of nanobodies against targets such as PD-1, ATXN1 and STAT3 demonstrates a versatile and ethical platform for the development of high specificity and affinity nanobodies and represents a significant advance in biotechnology.

Background: The effects of psychotic disorders on cardiometabolic diseases and premature death need to be determined in Asian populations. Methods: In this population-based matched cohort study, the Korean National Health Insurance Service database (2002 to 2018) was used. The risk of type 2 diabetes mellitus (T2DM), acute myocardial infarction (AMI), ischemic stroke, composite of all cardiometabolic diseases, and all-cause death during follow-up was compared between individuals with psychotic disorders treated with antipsychotics (n=48,162) and 1:1 matched controls without psychiatric disorders among adults without cardiometabolic diseases before or within 3 months after baseline. Results: In this cohort, 53,683 composite cases of all cardiometabolic diseases (during median 7.38 years), 899 AMI, and 1,216 ischemic stroke cases (during median 14.14 years), 7,686 T2DM cases (during median 13.26 years), and 7,092 deaths (during median 14.23 years) occurred. The risk of all outcomes was higher in subjects with psychotic disorders than matched controls (adjusted hazard ratios [95% confidence intervals]: 1.522 [1.446 to 1.602] for T2DM; 1.455 [1.251 to 1.693] for AMI; 1.568 [1.373 to 1.790] for ischemic stroke; 1.595 [1.565 to 1.626] for composite of all cardiometabolic diseases; and 2.747 [2.599 to 2.904] for all-cause mortality) during follow-up. Similar patterns of associations were maintained in subgroup analyses but more prominent in younger individuals (P for interaction <0.0001) when categorized as those aged 18–39, 40–64, or ≥65 years. Conclusion Patients with psychotic disorders treated with antipsychotics were associated with increased risk of premature allcause mortality and cardiometabolic outcomes in an Asian population. This relationship was more pronounced in younger individuals, especially aged 18 to 39 years.