A Lignin Molecular Brace Controls Precision Processing of Cell Walls Critical for Surface Integrity in Arabidopsis.

The cell wall, a defining feature of plants, provides a rigid structure critical for bonding cells together. To overcome this physical constraint, plants must process cell wall linkages during growth and development. However, little is known about the mechanism guiding cell-cell detachment and cell wall remodeling. Here, we identify two neighboring cell types in Arabidopsis that coordinate their activities to control cell wall processing, thereby ensuring precise abscission to discard organs. One cell type produces a honeycomb structure of lignin, which acts as a mechanical "brace" to localize cell wall breakdown and spatially limit abscising cells. The second cell type undergoes transdifferentiation into epidermal cells, forming protective cuticle, demonstrating de novo specification of epidermal cells, previously thought to be restricted to embryogenesis. Loss of the lignin brace leads to inadequate cuticle formation, resulting in surface barrier defects and susceptible to infection. Together, we show how plants precisely accomplish abscission.

Gossypetin Prevents the Progression of Nonalcoholic Steatohepatitis by Regulating Oxidative Stress and AMP-Activated Protein Kinase.

Nonalcoholic steatohepatitis (NASH) is a severe liver metabolic disorder, however, there are still no effective and safe drugs for its treatment. Previous clinical trials used various therapeutic approaches to target individual pathologic mechanisms, but these approaches were unsuccessful because of the complex pathologic causes of NASH. Combinatory therapy in which two or more drugs are administered simultaneously to patients with NASH, however, carries the risk of side effects associated with each individual drug. To solve this problem, we identified gossypetin as an effective dual-targeting agent that activates AMP-activated protein kinase (AMPK) and decreases oxidative stress. Administration of gossypetin decreased hepatic steatosis, lobular inflammation and liver fibrosis in the liver tissue of mice with choline-deficient high-fat diet and methionine-choline deficient diet (MCD) diet-induced NASH. Gossypetin functioned directly as an antioxidant agent, decreasing hydrogen peroxide and palmitate-induced oxidative stress in the AML12 cells and liver tissue of MCD diet-fed mice without regulating the antioxidant response factors. In addition, gossypetin acted as a novel AMPK activator by binding to the allosteric drug and metabolite site, which stabilizes the activated structure of AMPK. Our findings demonstrate that gossypetin has the potential to serve as a novel therapeutic agent for nonalcoholic fatty liver disease /NASH. SIGNIFICANCE STATEMENT: This study demonstrates that gossypetin has preventive effect to progression of nonalcoholic steatohepatitis (NASH) as a novel AMP-activated protein kinase (AMPK) activator and antioxidants. Our findings indicate that simultaneous activation of AMPK and oxidative stress using gossypetin has the potential to serve as a novel therapeutic approach for nonalcoholic fatty liver disease /NASH patients.

Circadian rest-activity rhythm and longitudinal brain changes underlying late-life cognitive decline.

AIM: The neurobiological substrates underlying the relationship of circadian rest-activity rhythm (RAR) alteration with accelerated late-life cognitive decline are not clearly understood. In the present study, the longitudinal relationship of objectively measured circadian RAR with in vivo Alzheimer disease (AD) pathologies and cerebrovascular injury was investigated in older adults without dementia. METHODS: The present study included 129 participants without dementia who participated in the KBASE (Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease) cohort. All participants underwent actigraphy at baseline and two consecutive [11 C] Pittsburgh compound-B positron emission tomography (PET), [18 F] fluorodeoxyglucose-PET, magnetic resonance imaging, and Mini-Mental State Examination (MMSE) at baseline and at a 2-year follow-up assessment. The associations of circadian RAR with annualized change in neuroimaging measures including global amyloid-beta retention, AD-signature region cerebral glucose metabolism (AD-CM), and white matter hyperintensity volume were examined. RESULTS: Delayed acrophase at baseline was significantly associated with greater annualized decline of AD-CM over a 2-year period, but not with that of other neuroimaging measures. In contrast, other circadian RAR parameters at baseline had no association with annualized change of any neuroimaging measures. Annualized decline of AD-CM was also significantly positively associated with the annual change in MMSE scores. Furthermore, a mediation analysis showed that greater reduction in AD-CM mediated the effect of delayed acrophase at baseline on faster decline of MMSE score. CONCLUSION: The findings indicate that delayed acrophase in late life may cause or predict hypometabolism at AD-signature brain regions, which underlies cognitive decline in the near future.

Alterations of amygdala-prefrontal cortical coupling and attention deficit/hyperactivity disorder-like behaviors induced by neonatal habenula lesion: normalization by Ecklonia stolonifera extract and its active compound fucosterol.

Alterations of monoamine transmission in mesocorticolimbic regions have been suggested in the pathophysiology of attention deficit/hyperactivity disorder (ADHD). The habenula is an important brain area in regulation of monoamine transmission. In this study, we investigated behavioral and electrophysiological alterations induced by neonatal habenula lesion (NHL) in rats. In NHL rats, age-dependent behavioral alterations relevant to the ADHD symptoms, such as hyperlocomotion, impulsivity, and attention deficit, were observed. Local field potentials (LFPs) in mesocorticolimbic regions of anesthetized rats were examined with in vivo electrophysiological recordings. Abnormally enhanced synchronization of slow (delta) and fast (gamma) LFP oscillations between the amygdala (AMY) and prefrontal cortex (PFC) was found in juvenile, but not in adult, NHL rats. We further examined the effects of an extract and the active compound from the perennial large brown algae Ecklonia stolonifera (ES), which have previously been demonstrated to modulate monoamine transmission, on these NHL-induced alterations. One week of ES extract treatments normalized the NHL-induced behavioral alterations, whereas the active compound fucosterol improved attention deficit and impulsivity, but not hyperlocomotion, in NHL rats. Consistent with the behavioral effects, ES extract treatments also normalized augmented AMY-PFC coupling. These results suggest that altered limbic-cortical information processing may be involved in ADHD-like behavioral alterations induced by NHL, which could be ameliorated by the natural substance, such as ES that affects monoamine transmission.

Association of moderate alcohol intake with in vivo amyloid-beta deposition in human brain: A cross-sectional study.

BACKGROUND: An emerging body of literature has indicated that moderate alcohol intake may be protective against Alzheimer disease (AD) dementia. However, little information is available regarding whether moderate alcohol intake is related to reductions in amyloid-beta (Aß) deposition, or is protective via amyloid-independent mechanisms in the living human brain. Here we examined the associations of moderate alcohol intake with in vivo AD pathologies, including cerebral Aß deposition, neurodegeneration of AD-signature regions, and cerebral white matter hyperintensities (WMHs) in the living human brain. METHODS AND FINDINGS: The present study was part of the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE), an ongoing prospective cohort study that started in 2014. As of November 2016, 414 community-dwelling individuals with neither dementia nor alcohol-related disorders (280 cognitively normal [CN] individuals and 134 individuals with mild cognitive impairment [MCI]) between 56 and 90 years of age (mean age 70.9 years ± standard deviation 7.8; male, n [%] = 180 [43.5]) were recruited from 4 sites (i.e., 2 university hospitals and 2 public centers for dementia prevention and management) around Seoul, South Korea. All the participants underwent comprehensive clinical assessments comprising lifetime and current histories of alcohol intake and multimodal brain imaging, including [11C] Pittsburgh compound B positron emission tomography (PET), [18F] fluorodeoxyglucose (FDG) PET, and magnetic resonance imaging (MRI) scans. Lifetime and current alcohol intake were categorized as follows: no drinking, <1 standard drink (SD)/week, 1-13 SDs/week, and 14+ SDs/week. A moderate lifetime alcohol intake (1-13 SDs/week) was significantly associated with a lower Aß positivity rate compared to the no drinking group, even after controlling for potential confounders (odds ratio 0.341, 95% confidence interval 0.163-0.714, p = 0.004). In contrast, current alcohol intake was not associated with amyloid deposition. Additionally, alcohol intake was not related to neurodegeneration of AD-signature regions or cerebral WMH volume. The present study had some limitations in that it had a cross-sectional design and depended on retrospective recall for alcohol drinking history. CONCLUSIONS: In this study, we observed in middle- and old-aged individuals with neither dementia nor alcohol-related disorders that moderate lifetime alcohol intake was associated with lower cerebral Aß deposition compared to a lifetime history of not drinking. Moderate lifetime alcohol intake may have a beneficial influence on AD by reducing pathological amyloid deposition rather than amyloid-independent neurodegeneration or cerebrovascular injury.

Plasma tau/amyloid-ß1-42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer's disease.

One of the hallmarks of Alzheimer's disease is abnormal deposition of tau proteins in the brain. Although plasma tau has been proposed as a potential biomarker for Alzheimer's disease, a direct link to brain deposition of tau is limited. Here, we estimated the amount of in vivo tau deposition in the brain by PET imaging and measured plasma levels of total tau (t-tau), phosphorylated tau (p-tau, T181) and amyloid-ß1-42. We found significant correlations of plasma p-tau, t-tau, p-tau/amyloid-ß1-42, and t-tau/amyloid-ß1-42 with brain tau deposition in cross-sectional and longitudinal manners. In particular, t-tau/amyloid-ß1-42 in plasma was highly predictive of brain tau deposition, exhibiting 80% sensitivity and 91% specificity. Interestingly, the brain regions where plasma t-tau/amyloid-ß1-42 correlated with brain tau were similar to the typical deposition sites of neurofibrillary tangles in Alzheimer's disease. Furthermore, the longitudinal changes in cerebral amyloid deposition, brain glucose metabolism, and hippocampal volume change were also highly associated with plasma t-tau/amyloid-ß1-42. These results indicate that combination of plasma tau and amyloid-ß1-42 levels might be potential biomarkers for predicting brain tau pathology and neurodegeneration.

Neuroticism, conscientiousness, and in vivo Alzheimer pathologies measured by amyloid PET and MRI.

AIM: It has been suggested that personality traits, particularly neuroticism and conscientiousness, are risk factors for Alzheimer's disease (AD) and related cognitive decline. However, the underlying pathological links between personality traits and AD-related cognitive impairments remain unclear. Thus, the present study investigated associations of neuroticism and conscientiousness with in vivo cerebral amyloid-beta (Aß) burden, AD-signature regional neurodegeneration, and white matter hyperintensities (WMH) in non-demented middle- and old-aged adults. METHODS: A total of 397 non-demented participants underwent comprehensive clinical and neuropsychological assessments, 11 C-labeled Pittsburgh Compound B positron emission tomography, and magnetic resonance imaging. Additionally, the NEO Five-Factor Inventory was administered to both the participants and their informants to measure neuroticism and conscientiousness. RESULTS: Neither neuroticism nor conscientiousness was associated with cerebral Aß deposition or WMH. In contrast, higher neuroticism and lower conscientiousness, reported by informants in particular, were significantly associated with reduced AD-signature region cortical thickness. In regards to the direct and indirect effect of each personality on AD-signature region cortical thickness, only the direct effects were found, whereas indirect effects via Aß deposition or WMH were not. CONCLUSION: The present findings suggest that amyloid-independent regional neurodegeneration might underlie relations of neuroticism and conscientiousness with AD.

Early risk stratification for diffuse large B-cell lymphoma integrating interim Deauville score and International Prognostic Index.

The aim of this study was to evaluate the prognostic relevance of early risk stratification in diffuse large B-cell lymphoma (DLBCL) using interim Deauville score on positron emission tomography-computed tomography (PET-CT) scan and baseline International Prognostic Index (IPI). This retrospective study included 220 patients (median age, 64 years; men, 60%) diagnosed with DLBCL between 2007 and 2016 at our institution, treated with rituximab-based chemotherapy. Interim PET-CT was performed after three cycles of immuno-chemotherapy. Interim Deauville score was assessed as 4 or 5 in 49 patients (22.3%), and 94 patients (42.7%) had high-intermediate or high-risk IPI scores. In multivariate analysis, interim Deauville score (1-3 and 4-5) and baseline IPI (low/low-intermediate and high-intermediate/high) were independently associated with progression-free survival (for Deauville score, hazard ratio [HR], 1.00 vs. 2.96 [95% confidence interval (CI), 1.83-4.78], P < 0.001; for IPI, HR, 1.00 vs. 4.84 [95% CI, 2.84-8.24], P < 0.001). We stratified patients into three groups: low-risk (interim Deauville scores 1-3 and low/low-intermediate IPI), intermediate-risk (Deauville scores 1-3 with high-intermediate/high IPI or Deauville scores 4-5 with low/low-intermediate IPI), and high-risk (Deauville scores 4-5 and high-intermediate/high IPI). This early risk stratification showed a strong association with progression-free survival (HR, 1.00 vs. 3.98 [95% CI 2.10-7.54] vs. 13.97 [95% CI 7.02-27.83], P < 0.001). Early risk stratification using interim Deauville score and baseline IPI predicts the risk of disease progression or death in patients with DLBCL. Our results provide guidance with interim PET-driven treatment intensification strategies.

The effects of Engelhardtia chrysolepis Hance on long-term memory and potential dopamine involvement in mice.

Engelhardtia chrysolepis Hance (ECH) is a perennial plant used in traditional medicine. A major active ingredient of ECH is astilbin (ASB), which has recently been shown to have neuroprotective effects as well as to affect catecholamine neurotransmissions in brain areas such as the prefrontal cortex. In this study, we investigated the effects of ECH and ASB on long-term memory in mice using a battery of behavioral tests. Acute ECH treatments dose-dependently facilitated nonspatial, but not spatial, memory. ECH treatments also upregulated expression of tyrosine hydroxylase, the enzyme mediating catecholamine synthesis, in neuroblastoma cell culture. Acute ASB treatments similarly improved nonspatial memory, whereas chronic ASB treatments improved both nonspatial and spatial memory. In accordance with such behavioral effects, the increased ratio of tissue concentrations of dopamine metabolites over dopamine in striatal regions was observed in mice with chronic ASB treatments. These results suggest that ECH and its active ingredient ASB may facilitate long-term memory by modulating catecholamine transmission.

Brain Metabolites and Peripheral Biomarkers Associated with Neuroinflammation in Complex Regional Pain Syndrome Using [11C]-(R)-PK11195 Positron Emission Tomography and Magnetic Resonance Spectroscopy: A Pilot Study.

Ojjective: The aim of this study was to find peripheral biomarkers and central metabolites affecting neuroinflammation in complex regional pain syndrome (CRPS) patients using [11C]-(R)-PK11195 positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). Methods: Using MRS and PET, we measured associations between neurometabolites and neuroinflammation in 12 CRPS patients and 11 healthy controls. Also, we investigated various peripheral parameters that may affect neuroinflammation in CRPS. Results: We found positive correlations of Lipid (Lip)13a/total creatine (tCr) and Lip09/tCr with neuroinflammation, the distribution volume ratio (DVR) of [11C]-(R)-PK11195 in the right and left insula in CRPS patients. However, these correlations were not found in controls. High hemoglobin levels correlated with decreased neuroinflammation (the DVR of [11C]-(R)-PK11195) in the right thalamus and left insula in healthy controls. We found that high levels of glucose and pH correlated with increased neuroinflammation, but high levels of CO2, basophil, and creatinine were associated with decreased neuroinflammation in the left thalamus and the right and left insula in CRPS patients. Conclusions: This is the first report indicating that elevated neuroinflammation levels are associated primarily with lipids in the brain and pH, glucose, CO2, basophil, and creatinine in the peripheral parameters in CRPS patients. Our results suggest that characterizing the peripheral biomarkers and central metabolites affecting neuroinflammation is essential to understanding the pathophysiology of CRPS.

Successful re-administration of Pazopanib in a patient with metastatic renal cell carcinoma and a history of Pazopanib-induced nephrotic syndrome: a case report.

BACKGROUND: Drug-induced nephrotic syndrome (NS) can be resolved by eliminating the causative agents. However, patients with metastatic cancer have not been previously reported to achieve complete recovery from anticancer drug-induced NS after discontinuation of treatment, because many patients die of cancer progression before NS is restored. CASE PRESENTATION: A 67-year-old man presented with edema of both lower extremities. He received pazopanib therapy for recurrent metastatic renal cell carcinoma (mRCC) for 17 months. Laboratory examinations revealed 7484.58 mg/day of 24-h urine protein, 434 mg/dL of serum cholesterol, and 2.9 g/dL of serum albumin. He was diagnosed with NS, and pazopanib treatment was discontinued. Four months later, he completely recovered from NS. He was then treated with temsirolimus and nivolumab sequentially for > 26 months. Pazopanib was re-introduced following disease progression, and demonstrated antitumor effects for 7 months without NS recurrence. CONCLUSION: Pazopanib-induced NS can occur late in patients with mRCC, and its subsequent discontinuation can enable patients to completely recover from its adverse effects. Moreover, pazopanib treatment may be re-introduced without the recurrence of NS.

Aberrant interactions of peripheral measures and neurometabolites with lipids in complex regional pain syndrome using magnetic resonance spectroscopy: A pilot study.

Background The aim of this study was to assess peripheral measures and central metabolites associated with lipids using magnetic resonance spectroscopy. Results Twelve patients with complex regional pain syndrome (CRPS) and 11 healthy controls participated. Using magnetic resonance spectroscopy, we measured the levels of lipid 13a (Lip13a) and lipid 09 (Lip09) relative to total creatine (tCr) levels in the right and left thalamus. We found negative correlations of Lip13a/tCr in the right thalamus with red blood cells or neutrophils, but a positive correlation between Lip13a/tCr and lymphocytes in the controls. We found negative correlations between Lip09/tCr and peripheral pH or platelets in the controls. There were positive correlations between Lip09a/tCr and myo-inositol/tCr, between Lip13a/tCr and N-acetylaspartate (NAA)/tCr, and between Lip09/tCr and NAA/tCr in healthy controls. On the other hand, there were positive correlations between Lip13a/tCr and Lip09/tCr and urine pH in CRPS patients. There were significant correlations between Lip13a/tCr or Lip09/tCr and different peripheral measures depending on the side of the thalamus (right or left) in CRPS patients. Conclusion This is the first report indicating that abnormal interactions of Lip13a and Lip09 in the thalamus with peripheral measures and central metabolites may mediate the complex pathophysiological mechanisms underlying CRPS.

Benign metastasizing leiomyoma presenting as multiple cystic pulmonary nodules: a case report.

BACKGROUND: Benign metastatic leiomyoma (BML) is an extremely rare disease. Although uterine leiomyomas are benign histologically, they can metastasize to distant sites. While the incidence is very low, the lung is the organ most frequently affected by BML. Pulmonary BML usually presents as numerous well-defined nodules of various sizes, while the cavitary or cystic features in the nodules are rarely observed on radiologic images. CASE PRESENTATION: A 52-year-old woman complained of cough and dyspnea for one month. She had been previously diagnosed with uterine leiomyoma and had undergone total hysterectomy about 14 years prior. High-resolution computed tomography (CT) images showed that there were multiple cystic nodules of various sizes in both lungs. Pathologic examination revealed that the pulmonary nodule had complex branching glandular structures lined by a single layer of simple cuboidal to columnar epithelium that was surrounded by abundant spindle cells. Additional immunohistochemistry data suggested that pulmonary nodule diagnosis was BML-associated uterine leiomyoma. CONCLUSION: In this report, we introduce an interesting case of pulmonary BML that presented as a combination of various kinds of nodules including simple round nodules, simple cysts, and cysts with a solid portion, which are very rare radiologic features of BML in lung. In addition, when the patient is a woman of reproductive age, physicians should meticulously review the gynecological history and suspect BML when there are various cystic pulmonary lesions.

Long-Term Outcomes after Imatinib Mesylate Discontinuation in Chronic Myeloid Leukemia Patients with Undetectable Minimal Residual Disease.

BACKGROUND: Imatinib mesylate (IM) discontinuation is under active investigation in chronic myeloid leukemia-chronic phase (CML-CP) patients with undetectable minimal residual disease (UMRD). However, limited data exist on the long-term outcomes following IM discontinuation in patients treated with frontline IM therapy. METHODS: We consecutively enrolled patients with CML-CP who discontinued IM after achieving UMRD for ≥12 months between June 2009 and January 2013. RESULTS: Nineteen patients (8 male, 11 female) were included. After IM discontinuation, 14 patients (74%) lost UMRD after a median of 4.0 months. Of the 14 patients with molecular relapses, 12 (86%) relapsed within the first 9 months after IM discontinuation and 2 (14%) relapsed at 20.5 and 22.8 months, respectively. No molecular relapse was observed after 2 years of IM discontinuation. With a median follow-up of 58.1 months (range 23.0-66.5), the estimated UMRD persistence rate at 5 years was 23.7%. IM was readministered in all patients with molecular relapse, and 12 patients (86%) reachieved UMRD at a median of 5.3 months. A high-risk Sokal score, delayed UMRD achievement and short-term IM therapy were significantly associated with molecular relapse. CONCLUSION: These findings suggest that IM discontinuation in patients who achieved UMRD after frontline IM therapy resulted in favorable long-term outcomes in terms of safety and feasibility.

The association of cardiovascular risk factors with saturated fatty acids and fatty acid desaturase indices in erythrocyte in middle-aged Korean adults.

BACKGROUND: The quality of dietary fats is associated with risk of cardiovascular diseases (CVD). We aimed to investigate the association between fatty acids in erythrocyte membrane phospholipids and CVD risk factors in middle-aged Korean adults. METHODS: Fifty-five middle-aged adults who underwent health examinations were included in this retrospective and cross-sectional study. Anthropometry, serum lipids, clinical parameters, and erythrocyte membrane phospholipid fatty acid data were obtained from a registry. RESULTS: The proportion of C14:0 and C16:0 was greatly elevated in high quartile groups for triglyceride (TG) and systolic and diastolic blood pressure groups (SBP and DBP) (p = 0.042, p = 0.021, or p = 0.008 respectively) compared to low quartile groups. While C16:1n7 and/or C18:1n9 were positively associated with CVD risk factors, the delta 9 desaturase activity index (D9D) (C18:1n9/C18:0) was only significantly increased in high quartile groups for TG and blood pressures (p = 0.001, p = 0.002 or p = 0.003). Conversely, TG and blood pressures showed inverse relationships with C20:4n6 or D5D (C20:4n6/C20:3n6). C18:3n6 and/or D6D (C18:3n6/C18:2n6) were positively associated with insulin resistance and diabetic parameters. Particularly high D6D was detected in high quartile groups of FBS and insulin (p = 0.016 and p = 0.042). In linear regression analysis, D9D and/or C14:0 + C16:0 were significant contributors to serum TG and blood pressures. D6D was a contributing factor to FBS. CONCLUSIONS: The indices of D9D and D6D from erythrocyte membrane phospholipids and the proportion of saturated fatty acids were increased as the cardiovascular risk factors, including serum TG, blood pressures, and FBS increased their levels (IRB number C2014199 (1396)).

Risk stratification for early mortality in newly diagnosed acute promyelocytic leukemia: a multicenter, non-selected, retrospective cohort study.

Introduction: Despite the current effective treatments for acute promyelocytic leukemia (APL), early mortality (EM), defined as death within 30 days of presentation, is a major hurdle to long-term survival. Methods: We performed a multicenter retrospective study to evaluate the incidence and clinical characteristics of EM in patients with newly diagnosed APL and to develop a risk stratification model to predict EM. Results: We identified 313 eligible patients diagnosed between 2000 and 2021 from five academic hospitals. The median age was 50 years (range 19-94), and 250 (79.9%) patients were <65 years. Most patients (n=274, 87.5%) received their first dose of all-trans retinoic acid (ATRA) within 24 hours of presentation. EM occurred in 41 patients, with a cumulative incidence of 13.1%. The most common cause of EM was intracranial hemorrhage (n=22, 53.6%), and most EMs (31/41, 75.6%) occurred within the first seven days of APL presentation. In a multivariable analysis, we identified three independent factors predicting EM: age ≥65 years (HR, 2.56), white blood cell count ≥8.0 x 109/L (HR, 3.30), and ATRA administration >24 hours of presentation (HR, 2.95). Based on these factors, patients were stratified into three categories with a significantly increasing risk of EM: 4.1% for low risk (54.3%; no risk factors; HR 1), 18.5% for intermediate risk (34.5%; 1 factor; HR 4.81), and 40.5% for high risk (11.2%; 2-3 factors; HR 13.16). Discussion: The risk of EM is still not negligible in this era of ATRA-based therapies. Our risk model serves as a clinically useful tool to identify high-risk patients for EM who may be candidates for novel treatments and aggressive supportive strategies.

A multimodal machine learning model for predicting dementia conversion in Alzheimer's disease.

Alzheimer's disease (AD) accounts for 60-70% of the population with dementia. Mild cognitive impairment (MCI) is a diagnostic entity defined as an intermediate stage between subjective cognitive decline and dementia, and about 10-15% of people annually convert to AD. We aimed to investigate the most robust model and modality combination by combining multi-modality image features based on demographic characteristics in six machine learning models. A total of 196 subjects were enrolled from four hospitals and the Alzheimer's Disease Neuroimaging Initiative dataset. During the four-year follow-up period, 47 (24%) patients progressed from MCI to AD. Volumes of the regions of interest, white matter hyperintensity, and regional Standardized Uptake Value Ratio (SUVR) were analyzed using T1, T2-weighted-Fluid-Attenuated Inversion Recovery (T2-FLAIR) MRIs, and amyloid PET (αPET), along with automatically provided hippocampal occupancy scores (HOC) and Fazekas scales. As a result of testing the robustness of the model, the GBM model was the most stable, and in modality combination, model performance was further improved in the absence of T2-FLAIR image features. Our study predicts the probability of AD conversion in MCI patients, which is expected to be useful information for clinician's early diagnosis and treatment plan design.

Treatment Patterns and Prognosis of Palliative Chemotherapy Combined With Targeting Agents in Patients With Unresectable Metastatic Colorectal Cancer: CHOICE, A Multicenter Longitudinal Observational Study.

BACKGROUND/AIM: This study investigated the treatment patterns and prognosis of patients with metastatic or unresectable colorectal cancer (mCRC) treated with chemotherapy with targeting agents. PATIENTS AND METHODS: This longitudinal multicenter study included 963 patients with mCRC who were treated in Korea between 2016 and 2020. Treatment patterns and efficacy were compared according to the mutation status and clinical factors. RESULTS: As first-line therapy, most of the patients (83.5%) received FOLFOX plus bevacizumab (35.4%), followed by FOLFIRI plus bevacizumab (18.8%), FOLFIRI plus cetuximab (17.0%), and FOLFOX plus cetuximab (12.3%). Bevacizumab was the most frequent agent (78.8%) combined with chemotherapy in RAS-mutated CRC, while cetuximab (57.2%) in RAS wild-type CRC. Cetuximab was frequently combined with a doublet regimen in patients with left-sided CRC than in those with right-sided CRC (34.4% vs. 16%). As second-line therapy, most patients (63.4%) also received doublet regimens with bevacizumab, and FOLFIRI plus aflibercept was administered in 15.1%. The objective response rate with FOLFIRI plus cetuximab was significantly higher in patients with left-sided CRC than in those with right-sided CRC (59.2% vs. 30.8%, p=0.008) and marginally higher in patients with RAS wild-type CRC than in those with RAS-mutated CRC (55.6% vs. 0.0%, p=0.092). Progression-free survival (PFS) with FOLFOX plus bevacizumab was significantly shorter than that with FOLFIRI plus bevacizumab (p=0.030) in RAS-mutated CRC, whereas there were no significant differences between regimens in RAS wild-type CRC. CONCLUSION: In patients with unresectable metastatic colorectal cancer, doublet chemotherapy with targeting agents is the most common therapy and efficacy depends on the mutation status as well as clinical factors.