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: The triggering receptor expressed on myeloid cells 2 (TREM2) creates an immunosuppressive environment, but the effects of anticancer treatment on TREM2 and the tumor microenvironment (TME) are not well established. This study investigates the impact of chemotherapy on TREM2-expressing macrophages within the lung adenocarcinoma TME. Materials and Methods: Using single-cell RNA sequencing datasets of paired normal-appearing lung tissue (NL) and tumor (Tu), human and mouse lung cancer tissue, and THP-1 cells, we observed the effects of anticancer drugs on them. Results: Myeloid cells (MY) were the second-most abundant non-epithelial component in the Tu, though less prevalent than in NL. Specific MY subclusters abundant in Tu showed overexpression of TREM2. In lung cancer-induced Kras-G12D mice, M2 proportion increased in Tu compared to NL; cisplatin increased TREM2+ M2 proportion in Tu. TREM2+ cells in Tu showed interactions with cell clusters showing characteristics of interstitial macrophage such as mo-lineage, mono-Mc, and CD163/LGMN cells via FN:CD44 and MIF:CD74+CXCR4, suggesting that they influence the recruitment of those cells to Tu and TME reshape. In M0-state THP-1 cells, cisplatin and osimertinib treatments induced polarization towards M1 and M2 states and increased TREM2 expression. Cisplatin promoted uptake of phosphatidylserine-coated latex beads by M0 cells, whereas osimertinib reduced uptake by polarized macrophages. These findings suggest anticancer treatments impact the lung immune microenvironment by altering the TREM2+ cells. Conclusion Given TREM2’s central inhibitory role in the tumor immune environment, effects of chemotherapeutic agents should be considered in developing TREM2-targeting therapies.

Purpose: The male predominance in the incidence of gastric cancer (GC) is established; however, sex differences in the prognosis of GC remain controversial. As such, this study analyzed the prognosis of patients with GC based on age and sex. Materials and Methods: Data from 14,739 patients diagnosed with GC at Seoul National University Bundang Hospital between 2003 and 2023 were analyzed. Baseline characteristics, histological types of GC, overall and GC-specific survival rates (age and stage stratification), and associated risk factors were analyzed. Results: Females were significantly younger (p < 0.001) and exhibited more gastric body cancers (p < 0.001) and tumors with diffuse-type or poorly differentiated histology (p < 0.001) than males. Females exhibited an advantage over males in terms of overall survival (p=0.004), but not in GC-specific survival. However, age stratification revealed significant sex differences, that females < 50 years of age exhibited survival disadvantages (p < 0.001); however, this trend was reversed with age, and females > 60 years exhibited survival advantages (p < 0.001) for both overall and GC-specific survival. This may be explained by the lower ratio of diffuse-type GC as females age. Furthermore, in the analysis according to stage, females with stage IV disease exhibited significant survival disadvantages, with significantly younger age and a higher proportion of diffuse-type GC which exhibits aggressive features, resulting in poorer survival than in males. Conclusion Age and stage stratification revealed significant differences in survival between the sexes, which can be helpful for public health strategies.

Subglottic stenosis (SGS) and tracheal stenosis (TS) are rare conditions that can cause significant breathing difficulties and, if not properly managed, may lead to life-threatening complications. Despite their clinical importance, debate continues regarding the optimal management of adult SGS and TS, and no comprehensive guidelines have been established to date. The Korean Bronchoesophagological Society appointed a task force to develop clinical practice guidelines with the goal of providing evidence-based recommendations for managing SGS and TS in adults. The task force conducted a systematic review of the relevant literature by searching PubMed, Embase, and the Cochrane Library using predefined search terms aligned with key clinical questions. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, which also informed the formulation and reporting of the recommendations. The strength of each recommendation reflects the guideline panel’s confidence that the benefits of an intervention outweigh its risks for eligible patients. After drafting the guidelines, feedback was obtained through Delphi questionnaires completed by members of the Korean Bronchoesophagological Society. Ultimately, the committee developed 17 evidence-based recommendations across four categories: initial evaluation, medical management, surgical treatment, and postoperative management and rehabilitation. These guidelines aim to support clinicians in delivering optimal care to adult patients with SGS and TS.

Alterations in gait patterns often indicate health status, and their analysis enables the diagnosis and assessment of various health conditions. This study aimed to develop a noncontact gait analysis system using red, green, and blue-depth (RGB-D) cameras and to evaluate its potential clinical applicability. A single case study was conducted to assess changes in the gait patterns of a patient with stroke before and after the application of an ankle-foot orthosis. Twenty walking trials were recorded to evaluate the key gait parameters. The custom RGB-D camera-based gait analysis system demonstrated the potential to rapidly quantify key gait parameters in the patient. Compared with normative data, it effectively identified characteristic stroke-related gait impairments such as shorter step lengths and slower gait speeds. However, the intraclass correlation coefficient analysis indicated low measurement reliability. Although the stance time and minimum knee angle on the left and right sides exceeded the standard error of measurement (SEM), no changes exceeded the minimal detectable change (MDC) criteria. Moreover, other gait parameters did not show significant changes beyond SEM or MDC, limiting the interpretability of the results. Therefore, further technological developments and data collection are required to improve test-retest reliability and sensitivity to change.

Objective: This study aimed to compare aneuploidy rates and clinical outcomes between trophectoderm biopsy at fresh blastocyst (biopsy-fresh) followed by vitrification and biopsy at vitrified-warmed blastocyst (biopsy-vitri) followed by next day transfer (without re-vitrification). Methods: This retrospective study included 844 patients undergoing 844 cycles conducted from August 2019 to December 2023. Preimplantation genetic testing for aneuploidy (PGT-A) was performed via trophectoderm biopsy using array comparative genomic hybridization or next-generation sequencing for comprehensive 24-chromosome screening. Patients were divided into two groups based on the blastocyst status at the time of biopsy: the biopsy-fresh group (531 patients) and the biopsy-vitri group (313 patients). Results: The clinical pregnancy rate was significantly higher in the biopsy-fresh group compared to the biopsy-vitri group (58.7% vs. 45.6%; odds ratio [OR], 1.695; 95% confidence interval [CI], 1.215 to 2.364; p=0.002). Furthermore, the biopsy-fresh group showed higher implantation rates (45.6% vs. 32.1%; OR, 1.767; 95% CI, 1.274 to 2.451; p=0.002), ongoing pregnancy or live birth rates per cycle (48.0% vs. 35.8%; OR, 1.652; 95% CI, 1.177 to 2.319; p=0.004), and rates of good-quality blastocysts (57.1% vs. 32.1%, p<0.001) compared with the biopsy-vitri group. Miscarriage rates did not differ significantly between the groups (18.2% vs. 21.4%; OR, 0.818; 95% CI, 0.457 to 1.465; p=0.501). Conclusion Biopsy at fresh blastocyst demonstrated superior clinical outcomes compared with biopsy at vitrified-warmed blastocyst, likely due to better embryo quality. Both biopsy at fresh blastocyst and vitrified-warmed blastocyst remain viable options for PGT-A, with biopsy at vitrified-warmed blastocyst serving as a practical alternative. Embryo quality and euploid status continue to be critical considerations for embryo transfer selection.

Hepatocellular carcinoma(HCC),which is essentially primary liver cancer,is closely related to CD8+T cell immune infiltration and immune suppression.We constructed a CD8+T cells related risk score model to pre-dict the prognosis of HCC patients and provided therapeutic guidance based on the risk score.Using integrated bulk RNA sequencing(RNA-seq)and single-cell RNA sequencing(scRNA-seq)datasets,we identified stable CD8+T cell signatures.Based on these signatures,a 3-gene risk score model,comprised of KLRB1,RGS2,and TN-FRSF1B was constructed.The risk score model was well validated through an independent external validation co-hort.We divided patients into high-risk and low-risk groups according to the risk score and compared the differ-ences in immune microenvironment between these two groups.Compared with low-risk patients,high-risk patients have higher M2-type macrophage content(P＜0.0001)and lower CD8+T cells infiltration(P＜0.0001).High-risk patients predict worse response to immunotherapy treatment than low-risk patients(P＜0.01).Drug sensitivity a-nalysis shows that PI3K-β inhibitor AZD6482 and TGFβRII inhibitor SB505124 may be suitable therapies for high-risk patients,while the IGF-1R inhibitor BMS-754807 or the novel pyrimidine-based anti-tumor metabolic drug Gemcitabine could be potential therapeutic choices for low-risk patients.Moreover,expression of these 3-gene mod-el was verified by immunohistochemistry.In summary,the establishment and validation of a CD8+T cell-derived risk model can more accurately predict the prognosis of HCC patients and guide the construction of personalized treatment plans.

Background: This study explores effective fixation methods for Pauwel type III femoral neck fractures by evaluating the biomechanical benefits of adding a screw to the Femoral Neck System (FNS). Methods: Computed tomography (CT) scans of an 82-year-old female patient with an intertrochanteric fracture were used to establish a finite element femur model with heterogeneous material properties. Finite element models of Pauwel type III fractures were created with and without an additional screw. The central and inferior trajectories of the FNS bolt were examined separately and combined with an additional screw for virtual fixation. Walking and stair-climbing loads were applied. Results: With the addition of a screw, both peak maximum and minimum principal strains consistently stayed comparable or decreased in models with both central and inferior bolt trajectories, while the volume of elements with principal strain exceeding 1% decreased by more than half. The peak von Mises stress observed in the implants ranged from 215.7 to 359.3 MPa, remaining below the titanium alloy's yield strength of 800 MPa. For normal walking, the addition of a screw to the central bolt trajectory model decreased the fracture gap by 50.6% and reduced sliding distance by 8.6%. For the inferior bolt trajectory, the gap was reduced by 57.9% and sliding distance by 25.0%.Under stair-climbing conditions, these improvements were also evident; the central trajectory model saw a halved fracture gap and a 7.9% decrease in sliding distance, while the inferior trajectory model experienced a 55.7% gap reduction and a 27.2% decrease in sliding distance. The additional screw increased the area ratio of the fracture site experiencing interfragmentary compression 34%–39%, while the additional screw alleviated peak interfragmentary compression by 12%–18% under both normal walking and stair-climbing conditions. Conclusions The addition of a screw reduced the fracture gap, sliding distance, and peak interfragmentary compression, while increasing the area ratio of interfragmentary compression under both walking and stair-climbing loads, regardless of the FNS bolt trajectory, suggesting a better mechanical environment for fracture healing.

Background: The removal of a well-fixed acetabular cup is a challenging, labor-intensive, and time-consuming step during revision hip arthroplasty. Although the advent of the manual osteotome, Explant, has simplified the procedure, it is still a stressful process as it dissipates the surgeon’s strength and time and risks an iatrogenic pelvic fracture. Recently, EZX, a powered tool for extraction of well-fixed acetabular cups with semicircular blade was invented. This study aimed to compare Explant and EZX in an experimental condition for their efficacy and safety. Methods: Cementless acetabular cups were press-fitted to 20 hemipelvic polyurethane models using foam adhesives. Ten cups were removed with each tool for comparison of the elapsed time, loads on the entire hemipelvis, periacetabular strain and temperature, volume of periacetabular bone removed, and diameter of the remaining acetabular rim. Strains and loads were quantitatively assessed using strain gauges and load cells for precise and reliable measurements. Results: The mean duration required to remove a well-fixed cup with EZX was 38.5 seconds (range, 25–55), whereas that with Explant was 543.7 seconds (range, 214–1,051) (p < 0.001). The load on the entire hemipelvis with EZX (mean, 9.1 kgf; range, 6.4–11.3) was 33% lower than that with Explant (mean, 13.6 kgf; range, 9.2–17.1) (p < 0.001). The periacetabular peak strains at the 3 positions with EZX were significantly lower than those with Explant (p < 0.001). The temperature during the removal did not differ significantly between the 2 tools. Although the mean volume of bone loss with Explant was 2.4 mL more than that with EZX (p < 0.001), the mean diameters of the remaining acetabular rim were not significantly different, measuring 54.1 mm with both tools. Conclusions The present experiment revealed that a well-fixed cup could be removed using a powered tool with less strength and time and less load on the entire pelvis. Although the powered tool removed a larger volume of bone, the diameters of the remaining acetabular rims were equivalent. This tool may help surgeons remove well-fixed cups in a short time and reduce the deforming load on the bone around the cup without increasing the size of the subsequent reconstruction cup.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.