Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

Purpose: Current guidelines recommend vaccination at least 2 weeks before chemotherapy initiation to optimize the immune response despite limited evidence. Our previous study indicated no differences in short-term immune response for the 13-valent pneumococcal conjugate vaccine (PCV13) according to the vaccination timing. This study aims to investigate the long-term efficacy of PCV13 and clinical factors associated with the respective antibody response. Materials and Methods: Patients with gastric or colorectal cancer who received adjuvant chemotherapy were enrolled and divided into two groups: vaccinated 2 weeks before chemotherapy (arm A) and vaccinated concurrently with chemotherapy (arm B). Serum samples were collected before vaccination and in one month, 3 years, and 5 years. Immune responses were measured using enzyme-linked immunosorbent assay and multiplex opsonophagocytosis assay. Results: Including 63 patients, both groups showed an initial increase in the geometric mean titers of opsonophagocytic activity and the geometric mean concentrations of serotype-specific IgG levels after one month, followed by a decline at 3 and 5 years, particularly for serotypes 1, 14, 18C, and 19A. Despite the decline, global protection was maintained for 5 years, although global response decreased. The two arms did not show significant differences in immunogenicity nor in factors such as vaccination timing, age, cancer type, or chemotherapy regimen. Conclusion Vaccination timing is not a significant factor for the immunogenicity of PCV13 in cancer patients undergoing adjuvant chemotherapy. Global protection against pneumococcal infection was sustained for > 5 years, and global response remained in over half of patients.

Objective: Depression involves mood-related behavioral changes typically monitored through subjective reports, which are limited by recall bias and low temporal resolution. Digital mental health tools offer objective, continuous monitoring, but prior studies have focused on outpatients subject to environmental variability. In this preliminary feasibility study, we examined psychiatric inpatients in a controlled setting to assess associations between behavioral regularity and depression severity, highlighting the clinical potential of digital phenotyping. Methods: Thirty-five adults from a closed psychiatric ward were recruited, and data from 10 inpatients with ≥7 days of valid monitoring were analyzed. Depression severity was assessed weekly using the Hamilton Depression Rating Scale (HAMD) and Dysfunctional Self-focus Attributes Scale, yielding 18 samples. Hourly accelerometer and location data from wearable devices and ward sensors were processed to generate digital phenotypes—interdaily stability (IS), intradaily variability (IV), ratio of IS to IV (ISV), entropy (EN), and normalized entropy (NE)—segmented into daytime and nighttime. Linear mixed models assessed group differences, and correlation and multiple regression examined associations with depression. Results: Patients with asymptomatic/mild depression showed significantly higher IS_day and ISV_day, and lower EN_night, and NE_night (all p<0.05). These four features correlated with HAMD after false discovery rate (all p<0.05) correction. A regression model including IS_day and NE_night explained 60.6% of HAMD variance (p<0.05). Conclusion Digital monitoring provides an objective and continuous method to assess depression severity. By capturing macro- and micro-level movement regularity across day and night in an inpatient environment, this approach offers practical relevance for psychiatric care. However, results should be considered preliminary due to the limited sample size.

Purpose: Persistent postoperative stiffness is a common complication after arthroscopic rotator cuff repair (ARCR).We hypothesized that a subacromial steroid injection (SAI) may improve the early outcomes in patients with persistent stiffness without increasing steroid-associated complications. Therefore, we evaluated the effectiveness and safety of SAI in patients with persistent stiffness 3 months after ARCR. Methods: We retrospectively analyzed 300 ARCR cases performed between January 2012 and May 2014, in which repair integrity was confirmed at postoperative 3 months. Patients were divided into SAI and control groups. The SAI group received a single SAI (triamcinolone 40 mg and ropivacaine 52.5 mg) to address postoperative stiffness, with no additional SAI thereafter. The control group did not receive any injections until the final follow-up. Functional and radiological outcomes were compared between the two groups. Results: The mean follow-up period was 18.1±4.7 months (range, 12.1–37.2 months), with no difference between groups (p=0.731). At the time of injection, the range of motion was significantly lower in the SAI (all p＜0.001). However, functional outcomes were comparable between the two groups at 3 months after injection and the final follow-up (all p＞ 0.05). The healing failure rate at the final follow-up also did not differ between the SAI and control groups (14.9% vs. 13.2%, p=0.671). Conclusion This short-term follow-up study suggests that the administration of a single SAI to treat persistent stiffness at 3 months after ARCR may improve functional recovery without increasing the risk of healing failure.

Background: Immunocompromised patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection often have prolonged viral shedding, and some are clinically suspected of reinfection with different SARSCoV-2 variants. However, data on this issue are limited. This study investigated the SARS-CoV-2 variants in serially collected respiratory samples from immunocompromised patients with prolonged viral shedding for over 12 weeks or relapsed viral shedding after at least 2 weeks of viral clearance. Materials and Methods: From February 2022 to September 2023, we prospectively enrolled immunocompromised patients with coronavirus disease 2019 who had hematologic malignancies or had undergone transplantation and were admitted to a tertiary hospital. Weekly saliva or nasopharyngeal swabs were collected from enrolled patients for at least 12 weeks after diagnosis. Genomic RNA polymerase chain reaction (PCR) was performed on samples, and those testing positive underwent viral culture to isolate the live virus. Spike gene full sequencing via Sanger sequencing and real-time reverse transcription-PCR for detecting mutation genes were conducted to identify SARSCoV-2 variants. Results: Among 116 enrolled patients, 20 with prolonged or relapsed viral shedding were screened to identify the variants. Of these 20 patients, 7 (35%) exhibited evidence of re-infection; one of 8 patients with prolonged viral shedding and 6 of 12 with relapsed viral shedding were reinfected with SARS-CoV-2. Conclusion Our data suggest that approximately one-third of immunocompromised patients with persistent or relapsed viral shedding had reinfection with different variants of SARS-CoV-2.

Purpose: This study examined the status of arthroscopic shoulder surgery in ambulatory settings by analyzing a single institutional database. Materials and Methods: Three hundred and eight arthroscopic shoulder surgeries performed between June 2022 and March 2023 were reviewed retrospectively. Propensity score matching (1-to-2) was performed between the day surgery group and the inpatient group according to sex, age, tear size, and interscalene nerve block (ISNB). Finally, 59 patients in the day surgery group and 118 patients in the inpatient group were matched. The indications of the day surgery were pre-determined according to the American Society of Anesthesiologists classification I or II, and the patient's social, medical, and surgical factors were thoroughly analyzed to define the target group of the day surgery. Complications related to voiding difficulty were prevented by classifying the patients using the International Prostate Symptom Score (IPSS) before surgery, and preventive medications were prescribed in the higher-risk patients with an IPSS of more than 7. To reduce postoperative pain, ISNB and patient-controlled analgesia (PCA) were applied to all patients during the study period, while day surgery patients received an additional bolus injection (5 cc of 0.375% ropivacaine+5 cc of normal saline) before discharge instead of continuous ISNB PCA. This study compared the postoperative pain assessments at discharge and on postoperative days 1, 2, and 14, as well as the total volume of saline irrigation, surgical time, and complications between the day surgery and inpatient groups. Results: The visual analogue scale for pain (pVAS) at the time of surgery were comparable in the day surgery group (4.1±1.5) and inpatient surgery group (4.1±1.1), with no significant difference between them (p=0.35). Similarly, the postoperative pVAS at 1, 2, and 14 days postoperatively was similar in the two groups (all p>0.05). The surgical-related factors, such as the total volume of saline irrigation and surgical time, were similar in the two groups. Furthermore, there was no significant difference in postoperative complications between the two groups (all p>0.05). Conclusion These results show that arthroscopic shoulder surgery in ambulatory settings is a safe alternative to inpatient surgery.

Purpose: Persistent postoperative stiffness is a common complication after arthroscopic rotator cuff repair (ARCR).We hypothesized that a subacromial steroid injection (SAI) may improve the early outcomes in patients with persistent stiffness without increasing steroid-associated complications. Therefore, we evaluated the effectiveness and safety of SAI in patients with persistent stiffness 3 months after ARCR. Methods: We retrospectively analyzed 300 ARCR cases performed between January 2012 and May 2014, in which repair integrity was confirmed at postoperative 3 months. Patients were divided into SAI and control groups. The SAI group received a single SAI (triamcinolone 40 mg and ropivacaine 52.5 mg) to address postoperative stiffness, with no additional SAI thereafter. The control group did not receive any injections until the final follow-up. Functional and radiological outcomes were compared between the two groups. Results: The mean follow-up period was 18.1±4.7 months (range, 12.1–37.2 months), with no difference between groups (p=0.731). At the time of injection, the range of motion was significantly lower in the SAI (all p＜0.001). However, functional outcomes were comparable between the two groups at 3 months after injection and the final follow-up (all p＞ 0.05). The healing failure rate at the final follow-up also did not differ between the SAI and control groups (14.9% vs. 13.2%, p=0.671). Conclusion This short-term follow-up study suggests that the administration of a single SAI to treat persistent stiffness at 3 months after ARCR may improve functional recovery without increasing the risk of healing failure.

Background: Immunocompromised patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection often have prolonged viral shedding, and some are clinically suspected of reinfection with different SARSCoV-2 variants. However, data on this issue are limited. This study investigated the SARS-CoV-2 variants in serially collected respiratory samples from immunocompromised patients with prolonged viral shedding for over 12 weeks or relapsed viral shedding after at least 2 weeks of viral clearance. Materials and Methods: From February 2022 to September 2023, we prospectively enrolled immunocompromised patients with coronavirus disease 2019 who had hematologic malignancies or had undergone transplantation and were admitted to a tertiary hospital. Weekly saliva or nasopharyngeal swabs were collected from enrolled patients for at least 12 weeks after diagnosis. Genomic RNA polymerase chain reaction (PCR) was performed on samples, and those testing positive underwent viral culture to isolate the live virus. Spike gene full sequencing via Sanger sequencing and real-time reverse transcription-PCR for detecting mutation genes were conducted to identify SARSCoV-2 variants. Results: Among 116 enrolled patients, 20 with prolonged or relapsed viral shedding were screened to identify the variants. Of these 20 patients, 7 (35%) exhibited evidence of re-infection; one of 8 patients with prolonged viral shedding and 6 of 12 with relapsed viral shedding were reinfected with SARS-CoV-2. Conclusion Our data suggest that approximately one-third of immunocompromised patients with persistent or relapsed viral shedding had reinfection with different variants of SARS-CoV-2.

Purpose: This study examined the status of arthroscopic shoulder surgery in ambulatory settings by analyzing a single institutional database. Materials and Methods: Three hundred and eight arthroscopic shoulder surgeries performed between June 2022 and March 2023 were reviewed retrospectively. Propensity score matching (1-to-2) was performed between the day surgery group and the inpatient group according to sex, age, tear size, and interscalene nerve block (ISNB). Finally, 59 patients in the day surgery group and 118 patients in the inpatient group were matched. The indications of the day surgery were pre-determined according to the American Society of Anesthesiologists classification I or II, and the patient's social, medical, and surgical factors were thoroughly analyzed to define the target group of the day surgery. Complications related to voiding difficulty were prevented by classifying the patients using the International Prostate Symptom Score (IPSS) before surgery, and preventive medications were prescribed in the higher-risk patients with an IPSS of more than 7. To reduce postoperative pain, ISNB and patient-controlled analgesia (PCA) were applied to all patients during the study period, while day surgery patients received an additional bolus injection (5 cc of 0.375% ropivacaine+5 cc of normal saline) before discharge instead of continuous ISNB PCA. This study compared the postoperative pain assessments at discharge and on postoperative days 1, 2, and 14, as well as the total volume of saline irrigation, surgical time, and complications between the day surgery and inpatient groups. Results: The visual analogue scale for pain (pVAS) at the time of surgery were comparable in the day surgery group (4.1±1.5) and inpatient surgery group (4.1±1.1), with no significant difference between them (p=0.35). Similarly, the postoperative pVAS at 1, 2, and 14 days postoperatively was similar in the two groups (all p>0.05). The surgical-related factors, such as the total volume of saline irrigation and surgical time, were similar in the two groups. Furthermore, there was no significant difference in postoperative complications between the two groups (all p>0.05). Conclusion These results show that arthroscopic shoulder surgery in ambulatory settings is a safe alternative to inpatient surgery.

Purpose: Persistent postoperative stiffness is a common complication after arthroscopic rotator cuff repair (ARCR).We hypothesized that a subacromial steroid injection (SAI) may improve the early outcomes in patients with persistent stiffness without increasing steroid-associated complications. Therefore, we evaluated the effectiveness and safety of SAI in patients with persistent stiffness 3 months after ARCR. Methods: We retrospectively analyzed 300 ARCR cases performed between January 2012 and May 2014, in which repair integrity was confirmed at postoperative 3 months. Patients were divided into SAI and control groups. The SAI group received a single SAI (triamcinolone 40 mg and ropivacaine 52.5 mg) to address postoperative stiffness, with no additional SAI thereafter. The control group did not receive any injections until the final follow-up. Functional and radiological outcomes were compared between the two groups. Results: The mean follow-up period was 18.1±4.7 months (range, 12.1–37.2 months), with no difference between groups (p=0.731). At the time of injection, the range of motion was significantly lower in the SAI (all p＜0.001). However, functional outcomes were comparable between the two groups at 3 months after injection and the final follow-up (all p＞ 0.05). The healing failure rate at the final follow-up also did not differ between the SAI and control groups (14.9% vs. 13.2%, p=0.671). Conclusion This short-term follow-up study suggests that the administration of a single SAI to treat persistent stiffness at 3 months after ARCR may improve functional recovery without increasing the risk of healing failure.