Intrahepatic IgA complex induces polarization of cancer-associated fibroblasts to matrix phenotypes in the tumor microenvironment of HCC.

BACKGROUND AND AIMS: Cancer-associated fibroblasts (CAFs) play key roles in the tumor microenvironment. IgA contributes to inflammation and dismantling antitumor immunity in the human liver. In this study, we aimed to elucidate the effects of the IgA complex on CAFs in Pil Soo Sung the tumor microenvironment of HCC. APPROACH AND RESULTS: CAF dynamics in HCC tumor microenvironment were analyzed through single-cell RNA sequencing of HCC samples. CAFs isolated from 50 HCC samples were treated with mock or serum-derived IgA dimers in vitro. Progression-free survival of patients with advanced HCC treated with atezolizumab and bevacizumab was significantly longer in those with low serum IgA levels ( p <0.05). Single-cell analysis showed that subcluster proportions in the CAF-fibroblast activation protein-α matrix were significantly increased in patients with high serum IgA levels. Flow cytometry revealed a significant increase in the mean fluorescence intensity of fibroblast activation protein in the CD68 + cells from patients with high serum IgA levels ( p <0.001). We confirmed CD71 (IgA receptor) expression in CAFs, and IgA-treated CAFs exhibited higher programmed death-ligand 1 expression levels than those in mock-treated CAFs ( p <0.05). Coculture with CAFs attenuated the cytotoxic function of activated CD8 + T cells. Interestingly, activated CD8 + T cells cocultured with IgA-treated CAFs exhibited increased programmed death-1 expression levels than those cocultured with mock-treated CAFs ( p <0.05). CONCLUSIONS: Intrahepatic IgA induced polarization of HCC-CAFs into more malignant matrix phenotypes and attenuates cytotoxic T-cell function. Our study highlighted their potential roles in tumor progression and immune suppression.

Effects of sleep quality on diurnal variation of brain volume in older adults: A retrospective cross-sectional study.

AIM: Brain volume is influenced by several factors that can change throughout the day. In addition, most of these factors are influenced by sleep quality. This study investigated diurnal variation in brain volume and its relation to overnight sleep quality. METHODS: We enrolled 1,003 healthy Koreans without any psychiatric disorders aged 60 years or older. We assessed sleep quality and average wake time using the Pittsburgh Sleep Quality Index, and divided sleep quality into good, moderate, and poor groups. We estimated the whole and regional brain volumes from three-dimensional T1-weighted brain MRI scans. We divided the interval between average wake-up time and MRI acquisition time (INT) into tertile groups: short (INT1), medium (INT2), and long (INT3). RESULTS: Whole and regional brain volumes showed no significance with respect to INT. However, the `interaction between INT and sleep quality showed significance for whole brain, cerebral gray matter, and cerebrospinal fluid volumes (p < .05). The INT2 group showed significantly lower volumes of whole brain, whole gray matter, cerebral gray matter, cortical gray matter, subcortical gray matter, and cerebrospinal fluid than the INT1 and INT3 groups only in the individuals with good sleep quality. CONCLUSION: Human brain volume changes significantly within a day associated with overnight sleep in the individuals with good sleep quality.

The influence of n-3 polyunsaturated fatty acids on cognitive function in individuals without dementia: a systematic review and dose-response meta-analysis.

BACKGROUND: Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been suggested as a cognitive enhancing agent, though their effect is doubtful. We aimed to examine the effect of n-3 PUFA on the cognitive function of middle-aged or older adults without dementia. METHODS: We reviewed randomized controlled trials of individuals aged 40 years or older. We systematically searched PubMed/MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Library databases. We used the restricted cubic splines model for non-linear dose-response meta-analysis in terms of the standardized mean difference with 95% confidence intervals. RESULTS: The current meta-analysis on 24 studies (n 9660; follow-up 3 to 36 months) found that the beneficial effect on executive function demonstrates an upward trend within the initial 12 months of intervention. This effect is prominently observed with a daily intake surpassing 500 mg of n-3 PUFA and up to 420 mg of eicosapentaenoic acid (EPA). Furthermore, these trends exhibit heightened significance in regions where the levels of blood docosahexaenoic acid (DHA) + EPA are not very low. CONCLUSIONS: Supplementation of n-3 PUFA may confer potential benefits to executive function among the middle-aged and elderly demographic, particularly in individuals whose dietary DHA + EPA level is not substantially diminished.

Expansion of effector regulatory T cells in steroid responders of severe alcohol-associated hepatitis.

While steroid therapy is the preferred treatment for severe alcohol-associated hepatitis, the role of effector regulatory T (eTreg) cells and their association with steroid response and clinical outcomes in these patients remains to be elucidated. We prospectively enrolled 47 consecutive patients with alcohol-associated hepatitis, consisting of severe alcohol-associated hepatitis treated with steroids (n=18; steroid-treated group) and mild alcohol-associated hepatitis (n=29; nontreated group). After isolating peripheral blood mononuclear cells from the patients at enrollment and again 7 days later, the frequency of eTreg cells was examined using flow cytometry. Single-cell RNA sequencing analysis was conducted using paired peripheral blood mononuclear cells. In vitro experiments were also performed to assess phenotype changes and the suppressive function of Treg cells following steroid treatment. The steroid-treated group exhibited significantly higher Model for End-Stage Liver Disease scores than the nontreated group ( p < 0.01). Within the steroid-treated group, the proportion of eTreg cells significantly expanded in the steroid responders (n=13; p = 0.01). Furthermore, a significant positive correlation was observed between the decrease in the Model for End-Stage Liver Disease score and the increase in eTreg cells ( p < 0.05). Single-cell RNA sequencing using paired peripheral blood mononuclear cells (pre-steroid and post-steroid therapy) from a steroid responder revealed gene expression changes in T cells and monocytes, suggesting enhancement of Treg cell function. In vitro results showed an elevation in the proportion of eTreg cells after steroid therapy. In conclusion, our findings suggest that the efficacy of steroid therapy in patients with severe alcohol-associated hepatitis is mediated by an increase in the number of eTreg cells.

Differential HBV replicative markers and covalently closed circular DNA transcription in immune-active chronic hepatitis B with and without HBeAg.

BACKGROUND AND AIMS: Molecular processes driving immune-active chronic hepatitis B (CHB) with and without hepatitis B e antigen (HBeAg) remain incompletely understood. This study aimed to investigate expression profiles of serum and intrahepatic HBV markers and replicative activity of HBV in CHB patients with or without HBeAg. METHODS: This study recruited 111 untreated immune-active CHB (60 HBeAg-positive and 51 HBeAg-negative) patients and quantified intrahepatic covalently closed circular DNA (cccDNA), pre-genomic RNA (pgRNA), total HBV DNA (tDNA), and replicative intermediates as well as serum HBV markers (HBV DNA, hepatitis B surface antigen, hepatitis B core-related antigen). Correlations between HBV markers and clinico-virological factors influencing expression levels of HBV markers were analysed. RESULTS: Levels of all serum markers and intrahepatic cccDNA/tDNA as well as cccDNA transcriptional activity and virion productivity were significantly reduced in HBeAg-negative patients compared to those in HBeAg-positive patients. Additionally, correlations between intrahepatic cccDNA/pgRNA and serum markers were impaired in HBeAg-negative individuals. Aminotransferase levels were positively correlated with cccDNA transcriptional activity in HBeAg-positive patients, but not in HBeAg-negative patients. Notably, among HBeAg-positive patients, there was a progressive decline in pgRNA level, transcriptional activity, and serum HBV markers as liver fibrosis advanced, which was not observed in HBeAg-negative patients. CONCLUSIONS: HBeAg loss is correlated with diminished intrahepatic HBV reservoirs and cccDNA transcription, leading to decreased serum HBV marker levels. Circulating HBV markers are not reliable indicators of intrahepatic HBV replicative activity for HBeAg-negative patients. Our findings reveal distinct disease phenotypes between immune-active CHB with and without HBeAg, highlighting the need to establish optimal surrogate biomarkers that can accurately mirror intrahepatic viral activity to aid in decision-making for antiviral therapy for immune-active CHB.

Association of Depression With the Progression of Multimorbidity in Older Adults: A Population-Based Cohort Study.

BACKGROUND: The relationship between depression and the risk of multimorbidity progression has rarely been studied in older adults. This study was aimed to determine whether depression is associated with progression in the severity and complexity of multimorbidity, considering the influence of depression's severity and subtype. METHODS: As a part of the Korean Longitudinal Study on Cognitive Aging and Dementia, this population-based cohort study followed a random sample of community-dwelling Koreans aged 60 and older for 8 years at 2-year intervals starting in 2010. Participants included those who completed mood and multimorbidity assessments and did not exhibit complex multimorbidity at the study's outset. Depression was assessed using the Geriatric Depression Scale, while multimorbidity was evaluated using the Cumulative Illness Rating Scale. The study quantified multimorbidity complexity by counting affected body systems and measured multimorbidity severity by averaging scores across 14 body systems. FINDINGS: The 2,486 participants (age = 69.1 ± 6.5 years, 57.6% women) were followed for 5.9 ± 2.4 years. Linear mixed models revealed that participants with depression had a faster increase in multimorbidity complexity score (ß = .065, SE = 0.019, p = 0.001) than those without depression, but a comparable increase in multimorbidity severity score (ß = .001, SE = .009, p = 0.870) to those without depression. Cox proportional hazard models revealed that depression was associated with the risk of developing highly complex multimorbidity affecting five or more body systems, particularly in severe or anhedonic depression. INTERPRETATION: Depression was associated with the worsening of multimorbidity in Korean older adults, particularly when severe or anhedonic. Early screening and management of depression may help to reduce the burden of multimorbidity in older adults.

RECIST 1.1, mRECIST, and Choi criteria for evaluating treatment response and survival outcomes in hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab.

OBJECTIVES: We aimed to compare the early responder rates, defined as complete or partial responders, using response evaluation criteria in solid tumors (RECIST) 1.1, modified RECIST (mRECIST), and Choi criteria in advanced HCC patients treated with atezolizumab-bevacizumab (atezo-bev), and to correlate them with progression-free survival (PFS) and overall survival (OS). METHODS: This retrospective study included advanced HCC patients treated with ≥ 3 cycles of atezo-bev. Two reviewers assessed responses using RECIST 1.1, mRECIST, and Choi criteria at 1st follow-up imaging. Kaplan-Meier curves with log-rank tests evaluated and compared PFS and OS. Cox proportional hazard models identified survival outcome predictors. Kappa statistics assessed inter-reader agreement. RESULTS: We evaluated 77 patients (65 men; mean age, 62.8 ± 12.3 years). Choi's criteria revealed the highest early responders rate (53.2%), exceeding mRECIST (32.5-33.8%) and RECIST 1.1 (24.7-26.0%), with an excellent agreement in all criteria (κ, 0.85-0.95). Across criteria, a consistent number of patients progressed (23-26) and was associated with significantly poor OS (ps ≤ 0.049). Responders by any criteria showed longer PFS (ps ≤ 0.009), and 1-year OS (ps ≤ 0.01). Choi criteria linked to significantly better OS without landmark (p = 0.003), with 1-year OS rates at 76.9% for responders vs 38.1% for non-responders. Cox analysis identified responders by Choi criteria as a significant OS predictor. CONCLUSION: Choi criteria identified more early responders than RECIST 1.1 and mRECIST, significantly correlating with improved OS. Choi criteria could be considered as a formal response assessment criterion for the emerging atezo-bev systemic treatment. CLINICAL RELEVANCE STATEMENT: For atezo-bev treatment of advanced HCC, more comprehensive response criteria, such as Choi criteria, could be effective in identifying early responders and predicting survival outcomes along with RECIST 1.1 and mRECIST. KEY POINTS: Choi criteria identified a higher rate of early responders compared to mRECIST and RECIST1.1 following atezo-bev treatment. Responders by all criteria had longer PFS and 1-year OS, and only those by Choi criteria experienced longer OS without landmark time. Choi criteria, with RECIST 1.1 and mRECIST, is an effective response assessment tool for atezo-bev treatment.

Construction and validation of a brain magnetic resonance imaging template for normal older Koreans.

BACKGROUND: Spatial normalization to a standardized brain template is a crucial step in magnetic resonance imaging (MRI) studies. Brain templates made from sufficient sample size have low brain variability, improving the accuracy of spatial normalization. Using population-specific template improves accuracy of spatial normalization because brain morphology varies according to ethnicity and age. METHODS: We constructed a brain template of normal Korean elderly (KNE200) using MRI scans 100 male and 100 female aged over 60 years old with normal cognition. We compared the deformation after spatial normalization of the KNE200 template to that of the KNE96, constructed from 96 cognitively normal elderly Koreans and to that of the brain template (OCF), constructed from 434 non-demented older Caucasians to examine the effect of sample size and ethnicity on the accuracy of brain template, respectively. We spatially normalized the MRI scans of elderly Koreans and quantified the amount of deformations associated with spatial normalization using the magnitude of displacement and volumetric changes of voxels. RESULTS: The KNE200 yielded significantly less displacement and volumetric change in the parahippocampal gyrus, medial and posterior orbital gyrus, fusiform gyrus, gyrus rectus, cerebellum and vermis than the KNE96. The KNE200 also yielded much less displacement in the cerebellum, vermis, hippocampus, parahippocampal gyrus and thalamus and much less volumetric change in the cerebellum, vermis, hippocampus and parahippocampal gyrus than the OCF. CONCLUSION: KNE200 had the better accuracy than the KNE96 due to the larger sample size and was far accurate than the template constructed from elderly Caucasians in elderly Koreans.

Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patient with chronic hepatitis B.

BACKGROUND AND AIM: Our study evaluated the outcomes of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB). We assessed viral and biochemical responses as well as changes in the estimated glomerular filtration rate (eGFR) and bone mineral density (BMD). METHODS: This retrospective multicenter study included CHB patients who achieved virologic response (VR) (HBV DNA < 20 IU/mL) while on TDF and were subsequently switched to TAF between April 2018 and October 2021. RESULTS: This study included 309 patients with a median age of 59 years, and 42.1% were male. The mean duration of TDF and TAF administration were 54.0 and 37.5 months, respectively. All patients maintained VR after switching to TAF. Alanine aminotransferase (ALT) normalization rate significantly increased 6 months after switching (74.8%-83.5%; P = 0.008). Adjusted eGFR significantly improved at 6 months (+5.55 ± 10.52 mL/min/1.73 m2; P < 0.001) and 12 months (+6.02 ± 10.70 mL/min/1.73 m2; P < 0.001) after switching. In the subgroup of patients with renal impairment (eGFR < 60 mL/min/1.73 m2), significant improvement in renal function was observed at 6 months (+0.6 ± 10.5 mL/min/1.73 m2; P < 0.001) and 12 months (+1.0 ± 10.7 mL/min/1.73 m2; P < 0.001) after switching to TAF. In patients with osteoporosis (n = 182), switching to TAF resulted in significant improvement in spine and hip BMD at 12 months, with increases of 9.7% (95% CI: 7.0-12.5) and 9.4% (95% CI: 7.0-11.8), respectively. CONCLUSION: In this real-world study, switching to TAF was effective and safe in patients, with notable improvements in ALT levels, renal function, and BMD.

Lifestyle and incident dementia: A COSMIC individual participant data meta­analysis.

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

Features of colonic diverticulitis in children and adolescents: A multicenter study.

BACKGROUND: Colonic diverticulitis (CD), typically seen in the elderly of Western countries, is increasingly prevalent worldwide, yet data on CD in children and adolescents are scarce. This study explores the characteristics of CD in this younger demographic. METHODS: In a multicenter, retrospective review, 104 patients under 20 years diagnosed with CD at four Korean tertiary hospitals from June 2003 to December 2020 were analyzed. Abdominal CT scans were used for diagnosis, with the modified Hinchey classification assessing the severity of CD. RESULTS: CD was found in the cecum or ascending colon in 103 (99%) of cases. The mean patient age was 17.24 ±â€¯2.4 years, with males constituting 59.6% of cases. Solitary lesions were noted in 93 (89.4%) of patients. Severity was classified as modified Hinchey stage 0 in 58.7%, stage Ia in 29.8%, and stage Ib in 11.5%, with no cases of stage II or higher. Misdiagnosis as acute appendicitis occurred in six instances. IV antibiotics were administered to 68.3%, and oral antibiotics were sufficient for 24%. Surgical treatment was necessary for two patients. A 7.8% recurrence rate was noted among first-time CD patients, yet all cases were amenable to conservative management. CONCLUSION: While uncommon, CD in children and adolescents is a growing concern, with most cases presenting as solitary lesions in the cecum or ascending colon. The severity is typically less than that in adults, and conservative treatment is generally effective. These findings underscore the need for specific management guidelines for pediatric CD, advocating for non-surgical initial approaches.

Organocatalytic Asymmetric [4 + 2]-Cycloadditions of 2-Aminophenyl Enones with Isatin-Derived Ketimines: Diastereo- and Enantioselective Synthesis of Spirooxindole-Tetrahydroquinazolines.

A novel method for the enantioselective synthesis of spiro N,N-heterocyclic oxindoles has been developed, employing asymmetric [4 + 2]-cycloadditions of 2-aminophenyl enones with isatin-derived ketimines. This method employs an organocatalytic approach, utilizing a bifunctional squaramide-based catalyst. It enables the precise synthesis of chiral spirooxindole-tetrahydroquinazolines with intricate structures, featuring chiral quaternary centers. This process achieves remarkable results, including high yields and exceptional levels of enantioselectivity and diastereoselectivity (up to 96% yield, 95% ee, and >20:1 dr).

Organocatalytic Enantioselective Synthesis of Polycyclic Benzosultams from 2-Amino-ß-nitrostyrenes with Cyclic N-Sulfonyl Ketimines.

A highly efficient enantioselective [4 + 2] cycloaddition of 2-amino-ß-nitrostyrenes with cyclic N-sulfonyl ketimines has been developed. This reaction utilizes an organocatalytic approach, employing a multiple-hydrogen-bonding bifunctional squaramide-based catalyst. The process allows for the precise synthesis of chiral polycyclic benzosultams, showcasing intricate structures that incorporate chiral quaternary centers. Noteworthy outcomes of this method include high yields with excellent enantioselectivities and diastereoselectivities (up to 97% yield, 96% ee, and >20:1 dr).

Impaired Glymphatic Flow on Diffusion Tensor MRI as a Marker of Neurodegeneration in Alzheimer's Disease: Correlation with Gray Matter Volume Loss and Cognitive Decline Independent of Cerebral Amyloid Deposition.

Background: Impaired glymphatic flow on the Alzheimer's disease (AD) spectrum may be evaluated using diffusion tensor image analysis along the perivascular space (DTI-ALPS). Objective: We aimed to validate impaired glymphatic flow and explore its association with gray matter volume, cognitive status, and cerebral amyloid deposition on the AD spectrum. Methods: 80 participants (mean age, 76.9±8.5 years; 57 women) with AD (n = 65) and cognitively normal (CN) (n = 15) who underwent 3T brain MRI including DTI and/or amyloid PET were included. After adjusting for age, sex, apolipoprotein E status, and burden of white matter hyperintensities, the ALPS-index was compared according to the AD spectrum. The association between the ALPS-index and gray matter volume, cognitive status, and quantitative amyloid from PET was assessed. Results: The ALPS-index in the AD was significantly lower (mean, 1.476; 95% CI, 1.395-1.556) than in the CN (1.784;1.615-1.952; p = 0.026). Volumes of the entorhinal cortex, hippocampus, temporal pole, and primary motor cortex showed significant associations with the ALPS-index (all, p < 0.05). There was a positive correlation between the ALPS-index and MMSE score (partial r = 0.435; p < 0.001), but there was no significant correlation between the ALPS-index and amyloid SUVRs (all, p > 0.05). Conclusions: Decreased glymphatic flow measured by DTI-ALPS in AD may serve as a marker of neurodegeneration correlating with structural atrophy and cognitive decline.

Reliability and Validity of a Tablet-Based Neuropsychological Test (the Hellocog) for Screening Dementia.

OBJECTIVE: To address the gap in timely diagnosis of dementia due to limited screening tools, we investigated the validity and reliability of the Hellocog, computerized neuropsychological test based on tablets for screening dementia. The higher the probability score on the Hellocog, the higher the likelihood of dementia. METHODS: This study included 100 patients with dementia and 100 individuals with normal cognition who were aged 60 years or older and free of other major psychiatric, neurological, or medical conditions. They administered the Hellocog on a tablet under the supervision of a neuropsychologist. To determine test-retest reliability, 20 took the Hellocog again after 4 weeks. Diagnostic performance was assessed using the receiver operator characteristics (ROC) analysis. RESULTS: The Hellocog showed adequate internal consistency (Cronbach's alpha=0.69) and good test-retest reliability (intraclass correlation coefficient=0.86, p<0.001). Participants with dementia scored higher on the Hellocog than those with normal cognition (p<0.001), confirming its high criterion validity. Strong correlations with the Mini-Mental Status Examination (MMSE) score and the total score of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-TS) highlight the concurrent validity of the Hellocog. The area under the ROC curve for dementia of the Hellocog was excellent (0.971) and comparable to that of the MMSE and CERAD-TS. The sensitivity and specificity for dementia were 0.945 and 0.872%, respectively, which were slightly better than those of the MMSE and CERAD-TS. CONCLUSION: Hellocog stands out as a valid and reliable tool for self-administered dementia screening, with promise for improving early detection of dementia.

Wheat seedlings extract ameliorates sarcopenia in aged mice by regulating protein synthesis and degradation with anti-inflammatory and mitochondrial biogenesis effects.

BACKGROUND: Chronic inflammation, which becomes more prevalent during aging, contributes to sarcopenia by reducing muscle mass and strength. PURPOSE: Wheat seedlings extract (WSE) is known for its various physiological activities, including anti-inflammation and antioxidant effects. However, its efficacy against sarcopenia is not well documented. STUDY DESIGN: 8-week-old and 50-week-old C57BL/6 J mice were used as young control (YC group) and aged controls (AC group), respectively. Then, aged mice were randomly divided into 5 groups (WSE100mg/kg, WSE200mg/kg, WSE400mg/kg, and schizandrin as a positive control) and fed each experimental diet for 10 weeks. METHOD: We investigated the effects of WSE on muscle quality and protein homeostasis pathways based on improvements in mitochondrial function and chronic inflammation. We then used TNFα-treated C2C12 to investigate the effects of isoorientin (ISO) and isoschaftoside (ISS), the active substances of WSE, on the myogenic pathway. RESULTS: We administered WSE to aging mice and observed an increase in muscle mass, thickness, protein content, and strength in mice treated with WSE at a dose of 200 mg/kg or 400 mg/kg. Furthermore, the administration of WSE led to a reduction in inflammatory factors (TNFα, IL-1, and IL-6) and an increase in mitochondrial biogenesis (p-AMPK/SIRT3/PGC1α) in muscle. This effect was also observed in TNFα-induced muscle atrophy in C2C12 cells, and we additionally identified the upregulation of myogenic regulatory factors, including Myf5, Myf6, MyoD, and myogenin, by WSE, ISO, and ISS. CONCLUSION: These findings suggest that WSE could function as a dietary anti-inflammatory factor and mitochondrial activator, potentially exerting modulatory effects on the metabolism and mechanical properties of skeletal muscles in the aging population. Furthermore, Our results demonstrate the potential value of ISO and ISS as functional food ingredients for preventing muscle atrophy.

Role of Portosystemic Shunt and Portal Vein Stent in Managing Portal Hypertension Due to Hematological Diseases.

INTRODUCTION: Patients with hematological diseases experience complications related to portal hypertension, including life-threatening complications such as variceal bleeding. METHODS: We analyzed the prognosis of patients with hematological diseases and portal hypertension treated with transjugular intrahepatic portosystemic shunts (TIPS) or portal vein stents. We retrospectively assessed patients with hematological diseases and portal hypertension who had variceal bleeding. We evaluated the characteristics and prognosis of the enrolled patients. A total of 11 patients with hematological diseases who underwent TIPS, or portal vein stenting, were evaluated. RESULTS: The median follow-up period was 420 days. Of the 11 patients, eight showed resolution of portal hypertension and its complications following TIPS, or stent insertion. One patient experienced rebleeding due to incomplete resolution of portal hypertension, and two other patients also experienced rebleeding because they underwent TIPS closure or revision due to repetitive hepatic encephalopathy. CONCLUSION: Portosystemic shunt and stent installation are effective treatment options for portal hypertension due to hematological diseases.

White matter microstructural integrity as a key to effective propagation of gamma entrainment in humans.

Gamma entrainment through sensory stimulation has the potential to reduce the pathology of Alzheimer's disease in mouse models. However, clinical trials in Alzheimer's disease (AD) patients have yielded inconsistent results, necessitating further investigation. This single-center pre-post intervention study aims to explore the influence of white matter microstructural integrity on gamma rhythm propagation from the visual cortex to AD-affected regions in 31 cognitively normal volunteers aged ≥ 65. Gamma rhythm propagation induced by optimal FLS was measured. Diffusion tensor imaging was employed to assess the integrity of white matter tracts of interest. After excluding 5 participants with a deficit in steady-state visually evoked potentials, 26 participants were included in the final analysis. In the linear regression analyses, gamma entrainment was identified as a significant predictor of gamma propagation (p < 0.001). Furthermore, the study identified white matter microstructural integrity as a significant predictor of gamma propagation by flickering light stimulation (p < 0.05), which was specific to tracts that connect occipital and temporal or frontal regions. These findings indicate that, despite robust entrainment of gamma rhythms in the visual cortex, their propagation to other regions may be impaired if the microstructural integrity of the white matter tracts connecting the visual cortex to other areas is compromised. Consequently, our findings have expanded our understanding of the prerequisites for effective gamma entrainment and suggest that future clinical trials utilizing visual stimulation for gamma entrainment should consider white matter tract microstructural integrity for candidate selection and outcome analysis.

Exploration of neuroanatomical characteristics to differentiate prodromal Alzheimer's disease from cognitively unimpaired amyloid-positive individuals.

Differentiating clinical stages based solely on positive findings from amyloid PET is challenging. We aimed to investigate the neuroanatomical characteristics at the whole-brain level that differentiate prodromal Alzheimer's disease (AD) from cognitively unimpaired amyloid-positive individuals (CU A+) in relation to amyloid deposition and regional atrophy. We included 45 CU A+ participants and 135 participants with amyloid-positive prodromal AD matched 1:3 by age, sex, and education. All participants underwent 18F-florbetaben positron emission tomography and 3D structural T1-weighted magnetic resonance imaging. We compared the standardized uptake value ratios (SUVRs) and volumes in 80 regions of interest (ROIs) between CU A+ and prodromal AD groups using independent t-tests, and employed the least absolute selection and shrinkage operator (LASSO) logistic regression model to identify ROIs associated with prodromal AD in relation to amyloid deposition, regional atrophy, and their interaction. After applying False Discovery Rate correction at < 0.1, there were no differences in global and regional SUVR between CU A+ and prodromal AD groups. Regional volume differences between the two groups were observed in the amygdala, hippocampus, entorhinal cortex, insula, parahippocampal gyrus, and inferior temporal and parietal cortices. LASSO logistic regression model showed significant associations between prodromal AD and atrophy in the entorhinal cortex, inferior parietal cortex, both amygdalae, and left hippocampus. The mean SUVR in the right superior parietal cortex (beta coefficient = 0.0172) and its interaction with the regional volume (0.0672) were also selected in the LASSO model. The mean SUVR in the right superior parietal cortex was associated with an increased likelihood of prodromal AD (Odds ratio [OR] 1.602, p = 0.014), particularly in participants with lower regional volume (OR 3.389, p < 0.001). Only regional volume differences, not amyloid deposition, were observed between CU A+ and prodromal AD. The reduced volume in the superior parietal cortex may play a significant role in the progression to prodromal AD through its interaction with amyloid deposition in that region.

Optimal cut-offs of transient elastography and magnetic resonance elastography in diagnosing advanced liver fibrosis in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis.

Background/aims: Opinions differ regarding transient elastography and magnetic resonance elastography (TE/MRE) cut-offs for diagnosing advanced fibrosis (AF) in patients with non-alcoholic fatty liver disease (NAFLD). We investigated the diagnostic performance and optimal cut-off values of TE and MRE for diagnosing AF. Methods: Literature databases, including Medline, EMBASE, Cochrane Library, and KoreaMed, were used to identify relevant studies published up to June 13, 2023. We selected studies evaluating TE and MRE regarding the degree of liver fibrosis using liver biopsy as the reference. The sensitivity, specificity, and area under receiver operating characteristics curves (AUCs) of the pooled data for TE and MRE for each fibrosis stage and optimal cut-offs for AF were investigated. Results: A total of 19,199 patients from 63 studies using TE showed diagnostic AUC of 0.83(95% confidence interval: 0.80-0.86), 0.83(0.80-0.86), 0.87(0.84-0.90), and 0.94(0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages, respectively. Similarly, 1,484 patients from 14 studies using MRE showed diagnostic AUC of 0.89(0.86-0.92), 0.92(0.89-0.94), 0.89(0.86-0.92), and 0.94(0.91-0.96) for ≥F1, ≥F2, ≥F3, and F4 stages respectively. The diagnostic AUC for AF using TE was highest at 0.90 with a cut-off of 7.1-7.9 kPa, and that of MRE was highest at 0.94 with a cut-off of 3.62-3.8 kPa. Conclusions: TE(7.1-7.9 kPa) and MRE(3.62-3.8 kPa) with the suggested cut-offs showed favorable accuracy for diagnosing AF in patients with NAFLD. This result will serve as a basis for clinical guidelines for non-invasive tests and differential diagnosis of AF.