Search

Chun-Ta Chiu,1 Hsiao-Han Tsai,2 Jing-Yuan Chen,1,3 Che-Ming Jack Hu,2 Hui-Wen Chen1,3 1Department of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan; 2Institute of Biomedical Sciences, Academia Sinica, Taipei, 115, Taiwan; 3Animal Resource Center, National Taiwan University, Taipei, 10617, TaiwanCorrespondence: Hui-Wen Chen, Department of Veterinary Medicine, National Taiwan University, 1 Sec 4 Roosevelt Road, Taipei, 10617, Taiwan, Tel +886 2 33669450, Email winnichen@ntu.edu.twIntroduction: The clinical success of mRNA vaccine during the COVID-19 pandemic has inspired emerging approaches to elevate mRNA vaccine immunogenicity. Among them, antigen fusion protein designs for improved immune cell targeting have been shown to augment humoral immunity against small antigen targets.Methods: This research demonstrates that SARS-CoV-2 receptor binding domain (RBD) fusion with a minimalistic peptide segment of complement component 3b (C3b, residues 727– 767) ligand can improve mRNA vaccine immunogenicity through antigen targeting to complement receptor 1 (CR1). We affirm vaccines’ antigenicity and targeting ability towards specific receptors through Western blot and immunofluorescence assay. Furthermore, mice immunization studies help the investigation of the antibody responses.Results: Using SARS-CoV-2 Omicron RBD antigen, we compare mRNA vaccine formulations expressing RBD fusion protein with mouse C3b peptide (RBD-mC3), RBD fusion protein with mouse Fc (RBD-Fc), and wild-type RBD. Our results confirm the proper antigenicity and normal functionality of RBD-mC3. Upon validating comparable antigen expression by the different vaccine formulations, receptor-targeting capability of the fusion antigens is further confirmed. In mouse immunization studies, we show that while both RBD-mC3 and RBD-Fc elevate vaccine immunogenicity, RBD-mC3 leads to more sustained RBD-specific titers over the RBD-Fc design, presumably due to reduced antigenic diversion by the minimalistic targeting ligand.Conclusion: The study demonstrates a novel C3b-based antigen design strategy for immune cell targeting and mRNA vaccine enhancement. Keywords: vaccinology, nanotechnology, complement component 3b, follicular dendritic cells, complement receptor 1, immune cell targeting

Ching-Yen Chen,1,2 Tze-Chun Tang,3 Tzu-Ting Chen,4 Ya Mei Bai,5,6 Huei-Huang Tsai,7 Hou-Liang Chen,7 Chun-Jen Huang,8,9 Chih-Ken Chen,1,2 Chun-Chih Chen,10 Mei-Chun Hsiao,11 Chia-Yih Liu,2,12 Hong-Shiow Yeh,13 Nan-Ying Chiu,10 Cheng-Chen Hsiao,14 Cheng-Sheng Chen,8,9 Tung-Ping Su5,15,16 1Department of Psychiatry, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan; 2School of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Dr Tang’s Psychiatric Clinic, Kaohsiung, Taiwan; 4Department of Psychiatry, National Taiwan University Hospital, Yunlin Branch Hospital, Yunlin, Taiwan; 5Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan; 6Department of Psychiatry, College of Medicine, National Yang-Ming University, Taipei, Taiwan; 7Tsao Tun Psychiatric Center, Ministry of Health and Welfare, Nantou, Taiwan; 8Department of Psychiatry, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 9Department of Psychiatry, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Department of Psychiatry, Changhua Christian Hospital Lukang Branch Hospital, Changhua, Taiwan; 11Yong Mei Psychiatric Clinic, Taoyuan City, Taiwan; 12Department of Psychiatry, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan; 13Department of Psychiatry, Mackay Memorial Hospital, Taipei, Taiwan; 14Cheng Chen Hsiao Clinic, Chiayi, Taiwan; 15Division of Psychiatry, Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan; 16Department of Psychiatry, Cheng Hsin General Hospital, Taipei, Taiwan Purpose: Paliperidone extended release (ER) is an oral psychotropic treatment formulated to release paliperidone at a controlled, gradually ascending rate. We evaluated the efficacy and safety of switching to paliperidone ER in Taiwanese patients with schizophrenia who were unresponsive or intolerant to previous antipsychotic therapy.Patients and methods: This was a 24-week, open-label, single-arm, multicenter, Phase IV trial. Based on consulting psychiatrists’ judgment, patients were deemed eligible for the switch to paliperidone ER; the switch was achieved by cross-tapering, using a recommended starting dose of 6 mg. Eligibility considerations included lack of efficacy, tolerability, and/or adherence to previous oral antipsychotic medication. Results: Of the 297 enrolled patients, 178 (59.5%) completed the study. The main reasons for discontinuation included insufficient efficacy (8.7%), patient decision (8.4%), and adverse events (AEs; 6.4%). Improvements in the: Positive and Negative Syndrome Scale total score and Clinical Global Impression-Severity score were observed only in patients treated at medical centers and not in those treated at psychiatric hospitals. The most common AEs were insomnia, headache, constipation, and extrapyramidal syndrome. One or more serious AEs were reported in 11 (3.7%) patients; none resulted in death. No significant changes in body weight, plasma glucose, or lipid levels were observed.Conclusion: Switching to paliperidone ER was effective and well tolerated for up to 24 weeks in patients with schizophrenia who were unresponsive or intolerant to previous antipsychotic therapy. The observed differences in treatment between psychiatric hospitals and medical centers with regard to dosage and titration of paliperidone ER warrant further investigation. Keywords: prospective, switch study, open-label, paliperidone extended release, schizophrenia, settings

Astrocytes, the most abundant cells in the central nervous system, promote synapse formation and help to refine neural connectivity. Although they are allocated to spatially distinct regional domains during development, it is unknown whether region-restric

1. Perindopril, a new ACE inhibitor, is a prodrug requiring conversion into its active form perindoprilat by hydrolysis in the liver. 2. The pharmacodynamics and pharmacokinetics of perindopril (8 mg oral) and perindoprilat (2 mg intravenously) were studied in a double-blind randomised crossover study in a group of patients with compensated biopsy-proven hepatic cirrhosis. 3. Blood pressure and heart rate responses were similar after the two routes of administration as were plasma renin activity and aldosterone levels following dosing. 4. The AUC of perindoprilat after oral administration of perindopril represented 46 +/- 4% of the total AUC of perindopril and its metabolite when expressed in molar terms. Comparison with the AUC of perindoprilat after its intravenous administration suggested that 30 +/- 6% of the oral dose of perindopril was converted to its active metabolite. 5. The findings are comparable with those in healthy subjects. It appears that the presence of relatively mild hepatic cirrhosis does not significantly alter the pharmacokinetics of perindopril. [ABSTRACT FROM AUTHOR]

Purpose of Review: Intracerebral hemorrhage (ICH) is a devastating stroke with limited medical treatments; thus, timely exploration of emerging therapeutic targets is essential. This review focuses on the latest strategies to mitigate secondary brain injury post-ICH other than targeting surgery or hemostasis, addressing a significant gap in clinical practice and highlighting potential improvements in patient outcomes., Recent Findings: Promising therapeutic targets to reduce secondary brain injury following ICH have recently been identified, including attenuation of iron toxicity and inhibition of ferroptosis, enhancement of endogenous resorption of hematoma, and modulation of perihematomal inflammatory responses and edema. Additionally, novel insights suggest the lymphatic system of the brain may potentially play a role in hematoma clearance and edema management. Various experimental and early-phase clinical trials have demonstrated these approaches may potentially offer clinical benefits, though most research remains in the preliminary stages., Summary: Continued research is essential to identify multifaceted treatment strategies for ICH. Clinical translation of these emerging targets could significantly enhance the efficacy of therapeutic interventions and potentially reduce secondary brain damage and improve neurological recovery. Future efforts should focus on large-scale clinical trials to validate these approaches, to pave the way for more effective treatment protocols for spontaneous ICH., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Blood-based biomarkers may offer a non-invasive approach to diagnose cerebral amyloid angiopathy (CAA), especially in early-stage. We evaluated the ability of plasma phosphorylated tau-217 (p-tau 217) to differentiate CAA from Alzheimer's disease (AD) and deep perforator arteriopathy (DPA)., Methods: Patients with AD (age 73.7 ± 8.1 years), probable CAA (74.8 ± 6.9 years), or DPA (66.1 ± 10.4 years) were enrolled from memory and stroke clinics at a medical center in Taiwan. All participants received amyloid and tau PET scans. Plasma biomarkers were measured via a SIMOA immunoassay platform. The diagnostic utility of p-tau 217 was assessed using ROC analyses and the Youden cutoff. Associations between plasma p-tau 217 and neuroimaging variables in CAA were explored., Results: Patients with CAA had lower plasma p-tau 217 (0.69 ± 0.76 vs. 1.28 ± 0.97 pg/mL, p < 0.001) and a lower p-tau 217/Aβ40 ratio (0.003 ± 0.002 vs. 0.006 ± 0.003, p < 0.001) than the AD group but higher levels than the DPA group (p-tau 217, 0.27 ± 0.13 pg/mL, p = 0.001; p-tau 217/Aβ40, 0.001 ± 0.0005, p < 0.001), although adjustment attenuated the difference in p-tau 217 between CAA and DPA. Plasma Aβ40, Aβ42, and Aβ40/Aβ42 were not significantly different between groups. Plasma p-tau 217 had moderate to good diagnostic utility to differentiate CAA vs. AD (sensitivity, 64.4%; specificity, 89.5%; AUC, 0.809) and CAA vs. DPA (sensitivity, 67.8%; specificity, 100%; AUC, 0.855). In CAA, p-tau 217 significantly correlated with the severity of CAA, amyloid PET signal intensity, and lobar microbleed count (p < 0.001)., Conclusions: Plasma p-tau 217 may represent a non-invasive biomarker for distinguishing cerebral amyloid angiopathy (CAA) from other conditions, including AD and DPA., (© 2025 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Human-induced pluripotent stem cell (hiPSC) technology has been applied in pathogenesis studies, drug screening, tissue engineering, and stem cell therapy, and patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs) have shown promise in disease modeling, including diabetic cardiomyopathy. High glucose (HG) treatment induces lipotoxicity in hiPSC-CMs, as evidenced by changes in cell size, beating rate, calcium handling, and lipid accumulation. Empagliflozin, an SGLT2 inhibitor, effectively mitigates the hypertrophic changes, abnormal calcium handling, and contractility impairment induced by HG. Glucose concentration influences SGLT2 expression in cardiomyocytes, highlighting its potential role in diabetic cardiomyopathy. These findings support the potential utility of hiPSC-CMs in studying diabetic cardiomyopathy and the efficacy of empagliflozin in ameliorating HG-induced cardiomyocyte dysfunction. Such research may advance developments in precision medicine and therapeutic interventions for patients with diabetic cardiomyopathy., Competing Interests: Declarations. Ethical Approval: The study received approval from the Institutional Review Board of Chang-Gung Memorial Hospital (approval number: #202101606B0). Consent to Participate: Peripheral blood mononuclear cells (PBMCs) were collected from four subjects after obtaining written informed consent: one healthy subject and three diabetic patients (one type 1 without as well as one type 1 and one type 2 with diabetic cardiomyopathy and heart failure with HFpEF). Consent to Publish: Not applicable. Competing Interests: All authors disclose any potential conflicts of interest and there are no competing interests at all., (© 2025. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Controlling hypertension has become an important issue in the elderly population in whom neurological comorbidities are highly prevalent. Most of the large-scale trials focusing on hypertension management in older populations have excluded patients with comorbid neurological disorders. However, this population requires special considerations, as the benefits of antihypertensive agents are mostly uncertain and there is a higher risk of adverse events. In this review article, we discuss current evidence regarding the management of elderly patients with hypertension and common neurological disorders, including stroke and neurodegenerative diseases. In elderly patient with a history of stroke, the blood pressure management strategy is generally similar to that for young patients, however the benefits of stroke prevention from blood pressure control are less significant. For patients with neurodegenerative disorders such as cognitive dysfunction and Parkinson's disease, achieving adequate blood pressure control may be beneficial in reducing cardiovascular risks, although the higher risk of adverse events from antihypertensive treatment may offset some of these benefits. Special considerations for factors such as orthostatic hypotension, risk of falls, polypharmacy, and significant drug-drug interactions are required but frequently neglected in clinical practice. More efforts are warranted to determine the optimal treatment strategy for elderly populations with neurological disorders., Competing Interests: Declarations of interest None., (Copyright © 2025 Formosan Medical Association. Published by Elsevier B.V. All rights reserved.)

Background: Multimodal treatment involving preoperative chemoradiotherapy (CRT) followed by surgery is the current standard of care for rectal cancer. Despite advancements, the risk of recurrence, metastasis, and decreased survival remains high. This study aims to evaluate potential biomarkers to stratify prognosis in patients with rectal cancer undergoing preoperative CRT and surgery., Methods: Through data mining of receptor-binding pathways in a published transcriptome for rectal cancer cases, ITLN1 was identified as the most relevant gene associated with poor response to chemoradiation (GO:0005102). Rectal cancer specimens (n = 343) collected between 1998 and 2017 were analyzed for ITLN1 expression using immunohistochemistry. The association between ITLN1 protein expression and clinicopathological features was assessed using Pearson's chi-square test. Survival outcomes based on ITLN1 expression were evaluated using the Kaplan-Meier method and compared with Log rank tests., Results: ITLN1 immunoreactivity was significantly elevated in rectal tumor tissues. High ITLN1 expression was strongly associated with adverse clinicopathological features, including advanced post-treatment tumor status (T3-4; p = 0.001), post-treatment nodal status (N1-2; p < 0.001), vascular invasion (p = 0.017), perineural invasion (p = 0.001), and a lower degree of tumor regression (p = 0.009). Uni- and multivariable analyses revealed that high ITLN1 expression correlated with poorer disease-specific survival, local recurrence-free survival, and distant metastasis-free survival compared to low ITLN1 expression., Conclusion: Elevated ITLN1 expression is significantly associated with aggressive tumor behavior and unfavorable survival outcomes in rectal cancer. These findings highlight ITLN1 as a potential prognostic biomarker and provide a foundation for future research into its role in rectal cancer progression and treatment response., Competing Interests: The authors report no conflicts of interest in this work., (© 2025 Chou et al.)

Background and Purpose: Although amyloid positron emission tomography (PET) might provide a molecular diagnosis for cerebral amyloid angiopathy (CAA), it does not have sufficient specificity for this condition relative to incipient Alzheimer's disease (AD). To identify a regional amyloid uptake pattern specific to CAA, we attempted to reduce this overlap by selecting "pure CAA" (i.e., fulfilling the criteria for probable CAA but without tau PET AD signature) and "pure AD" (i.e., positive amyloid PET and presence of tau PET AD signature, but without lobar hemorrhagic lesions). We hypothesized that occipital tracer uptake relative to the whole cortex (WC) would be higher in patients with pure CAA and may serve as a specific diagnostic marker., Methods: Patients who fulfilled these criteria were identified. In addition to the occipital region of interest (ROI), we assessed the frontal and posterior cingulate cortex (PCC) ROIs that are sensitive to AD. Amyloid PET uptake was expressed as the absolute standardized uptake value ratio (SUVR) and ROI/WC ratio. The diagnostic utility of amyloid PET was assessed using the Youden index cutoff., Results: Eighteen patients with AD and 42 patients with CAAs of comparable age were eligible. The occipital/WC was significantly higher in CAA than AD (1.02 [0.97-1.06] vs. 0.95 [0.87-1.01], P=0.001), with an area under curve of 0.762 (95% confidence interval [CI] 0.635-0.889) and a specificity of 72.2% (95% CI 46.5-90.3) at Youden cutoff (0.98). The occipital lobe, frontal lobe, PCC and WC SUVRs were significantly lower in CAA than in AD. The frontal/WC and PCC/WC ratios did not differ significantly between the groups., Conclusion: Using stringent patient selection to minimize between-condition overlap, this study demonstrated the specificity of higher relative occipital amyloid uptake in CAA than in AD.

Computed tomography (CT) of the chest is routinely performed as part of head and neck cancer (HNC) staging. Pulmonary nodules incidentally encountered present a clinical dilemma, as they may indicate early malignancy. Clinically indeterminant nodules are those that cannot be classed as definitively malignant or benign. This study aimed to assess the outcomes of pulmonary nodules detected on initial staging chest CT in a consecutive cohort of patients with oral and oropharyngeal squamous cell carcinoma (SCC). A retrospective cohort study of newly diagnosed oral or oropharyngeal SCC patients with pulmonary nodules identified on staging chest CT at a single institution was conducted. Pulmonary nodules were categorised as benign, indeterminant, or malignant. Indeterminant nodules underwent further investigations with either repeat imaging or needle biopsy to exclude malignancy. Descriptive and bivariate statistics were used to evaluate the association between pulmonary metastasis and patient demographics, disease characteristics, and nodular features. P values of ≤ 0.05 were considered statistically significant. Of 579 patients diagnosed with HNC who had undergone staging chest CT between 2010 and 2015, 154 had pulmonary nodules. Indeterminant pulmonary nodules at staging in 26 patients (16.9%) were later confirmed to be lung metastases. Pulmonary nodules of subsolid type found in patients with N2/N3 disease were significantly more likely to be metastatic. Isolated pulmonary nodules in the right lung were more likely to be benign. A HNC-specific protocol for the management of incidental pulmonary nodules should now be developed to guide the interval and duration of required clinical and radiological surveillance, taking into account the disease characteristics and nodular features., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved.)

Introduction: Neoadjuvant concurrent chemoradiotherapy (CCRT) is routinely used before surgery in patients with locally advanced rectal cancer to reduce tumor size and decrease the risk of local recurrence. However, the disease-specific survival has not improved in most cases due to distant metastases. In selected individuals exhibiting a clinical complete response, non-operative management may be allowed; however, those who presented no or little response tend to have an inferior prognosis. Consequently, refined molecular characterization could aid in predicting which patients would benefit from neoadjuvant chemoradiotherapy., Methods: The mRNA level (by transcriptomic profiling) and protein expression (by immunohistochemical staining) of C-X-C motif chemokine ligand 11 (CXCL11) were integrated to predict neoadjuvant chemoradiotherapy efficacy. For survival analysis, clinicopathological features and CXCL11 immunoreactivity that were statistically significant in univariate analysis were included in multivariate analysis using the Cox proportional hazards regression model., Results: We identified that the CXCL11 level exhibits the most significant downregulation among neoadjuvant chemoradiotherapy non-responders. Using tumor samples from our rectal cancer cohort (n = 343) with immunohistochemistry validation, we demonstrated that low CXCL11 immunoexpression shows significant correlations with advanced disease and positive lymph nodes both prior to and following CCRT (all p < 0.001), vascular and perineural invasion (p < 0.001 and p = 0.006), and poor response to CCRT (p < 0.001). Moreover, low CXCL11 immunoexpression was an independent adverse prognostic factor significantly associated with patient survival. Additionally, we further identified pyroptotic cell death as an unrevealed role of CXCL11 in rectal cancer through bioinformatic analysis., Conclusion: CXCL11 expression may serve as an early predictor of clinical outcomes and aid in therapeutic decision-making by identifying individuals likely to respond to neoadjuvant chemoradiotherapy in rectal cancer., Competing Interests: Declarations. Ethics approval and consent to participate: In general, all participants provided informed consent prior to the storage of their samples in the biobank. The Ethics Committee and Institutional Review Board of Chi Mei Medical Center (10302014) approved this study, including the use of deidentified tumor samples from the biobank. The study was conducted in accordance with the ethical principles of the Declaration of Helsinki and governmental regulations. Consent for publication: Not applicable. Conflict of interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024. The Author(s).)

Background: Breast cancer (BC) is the most common cancer in women and accounts for approximately 15% of all cancer deaths among women globally. The underlying mechanism of BC patients with small tumor size and developing distant metastasis (DM) remains elusive in clinical practices., Methods: We integrated the gene expression of BCs from ten RNAseq datasets from Gene Expression Omnibus (GEO) database to create a genetic prediction model for distant metastasis-free survival (DMFS) in BC patients with small tumor sizes (≤ 2 cm) using weighted gene co-expression network (WGCNA) analysis and LASSO cox regression., Results: ABHD11, DDX39A, G3BP2, GOLM1, IL1R1, MMP11, PIK3R1, SNRPB2, and VAV3 were hub metastatic genes identified by WGCNA and used to create a risk score using multivariable Cox regression. At the cut-point value of the median risk score, the high-risk score (≥ median risk score) group had a higher risk of DM than the low-risk score group in the training cohort [hazard ratio (HR) 4.51, p < 0.0001] and in the validation cohort (HR 5.48, p = 0.003). The nomogram prediction model of 3-, 5-, and 7-year DMFS shows good prediction results with C-indices of 0.72-0.76. The enriched pathways were immune regulation and cell-cell signaling. EGFR serves as the hub gene for the protein-protein interaction network of PIK3R1, IL1R1, MMP11, GOLM1, and VAV3., Conclusion: Prognostic gene signature was predictive of DMFS for BCs with small tumor sizes. The protein-protein interaction network of PIK3R1, IL1R1, MMP11, GOLM1, and VAV3 connected by EGFR merits further experiments for elucidating the underlying mechanisms., (© 2024. The Author(s).)

Purpose: The needs of head and neck cancer (HNC) carers tends to be poorly addressed as most support systems are directed towards patients. This systematic review synthesises the existing qualitative evidence from carers for adult HNC patients to explore their experiences and needs as a basis to inform the initial development of an item prompt list for HNC carers for use in routine clinical practice., Methods: Seven electronic databases were searched from their inception until November 2022, supplemented by citation chaining and snowballing. Primary qualitative or mixed-methods studies reporting the experiences of carers for HNC patients, elicited using interviews, were included. Screening and selection, data extraction and quality assessment (Critical Appraisal Skills Programme Checklist) were independently conducted by two researchers. Data were analysed using inductive thematic synthesis and confidence evaluated using GRADE CERQual., Results: Thirty studies met the inclusion criteria. Two overarching themes and nine subthemes emerged: (i) the experiences of loss associated with being a carer (loss of: role and everyday routine, certainty leading to emotional distress, security as fear of recurrence prevailed, finances, intimacy and togetherness, enjoyment from social activities); and (ii) factors promoting coping and adjustment to role of carer (information, supportive mechanisms, personal attributes)., Conclusion: New insight into the experiences of HNC carers provides the basis for item generation of a HNC carer prompt tool., Implications for Cancer Survivors: With such a range of potential unmet concerns, the development of a prompt list should help to elicit these and provide additional means to targeted support., (© 2024 The Author(s). Psycho‐Oncology published by John Wiley & Sons Ltd.)

Familial Hypercholesterolemia (FH) is an inherited disorder that significantly increases an individual's risk of developing premature cardiovascular disease (CVD). Early intervention involving lifestyle modification and medication is crucial in preventing CVD. Prior studies have shown that lipid-lowering therapy in children is safe and effective. Despite FH being a treatable and manageable condition, the condition is still underdiagnosed and undertreated. Universal lipid screening (ULS) in children has been recommended by some medical experts in the United States as a strategy to identify cases of FH and maximize the benefits of early invention. However, lipid screening is not routinely offered in pediatric clinics. This study aimed to explore parental experience with FH diagnosis in their children, identify key facilitators and barriers in children's diagnosis and care, and examine parental perspectives on ULS in children in the United States. A total of fourteen semi-structured interviews were conducted with participants recruited through the Family Heart Foundation. Thematic analysis identified three key themes: role of family history in facilitating child's FH diagnosis, barriers and challenges in post-diagnosis care, and attitudes towards ULS in children. All participants supported ULS in children and emphasized the value of early diagnosis and treatment for FH. However, a lack of guidance or referral after the child's diagnosis was a concern raised by many participants. This underscores the need for accessible and comprehensive care amid ongoing efforts to increase pediatric diagnosis of FH., (© 2024. The Author(s).)

Developing evidence-based parameters to enhance the reliability of face emotion recognition (FER) systems in detecting depression among the elderly is essential. This study aims to elucidate the relationship between the ratio of each emotion valence captured by the FER system and heart rate variability (HRV) while participants watch a video in relation to their depression scores. YOLO, an open-source data analysis toolkit, was used to extract three facial emotion valence features (neutral, positive, and negative) and determine the ratio of each emotion valence over time during video viewing. Additionally, HRV was assessed, and the Geriatric Depression Scale was administered to understand the correlation between FER parameters and depression scores.

Background: The volume of water that can be swallowed without risk of choking or aspiration is a common way to assess swallowing function in patients with dysphagia in institutional settings. However, no evidence-based study has established what volumes of water are safest and most effective for testing., Objective: A validated portable non-invasive device for swallowing and respiration (NIDSAR) was employed to determine safe swallowing volumes for nursing home residents with different levels of dysphagia., Methods: Participants (N = 94) were grouped by the absence or presence of a nasogastric (NG)-tube: those without an NG-tube (n = 60) and those with an NG-tube (n = 34).Swallowing 1 ml, 3 ml, and 5 ml of water was assessed with the Functional Oral Intake Scale (FOIS) and compared with measures with objective scores from the portable NIDSAR. In addition, swallowing measures were compared between groups, as well as relationships with participant-reported choking frequency., Results: Participants without an NG-tube had significant different scores for swallowing during the respiration phase and pharyngeal stage for both 3 ml (t = 3.894 to 4.277, p < .001) and 5 ml (t = 1.999 to 2.944, p < .05 to p < .01) compared with participants with an NG-tube., Discussion: Our research revealed that participants with frequent episodes of choking required more time to swallow 1 ml compared with 3 ml or 5 ml which might be a function of piecemeal swallowing., Conclusions: NIDSAR measures with 3 ml and 5 ml boluses of water are effective volumes for safely assessing swallowing ability of nursing home residents with dysphagia without risk of choking or aspiration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer after hepatocellular carcinoma. Through data mining of publicly available iCCA transcriptomic datasets from the Gene Expression Omnibus, we identified SFN as the most significantly up-regulated gene in iCCA compared to normal tissue, focusing on the Gene Ontology term "cell proliferation" (GO:0008283). SFN encodes the 14-3-3σ protein, also known as stratifin, which plays crucial roles in various cellular processes., Materials and Methods: Immunohistochemistry was used to assess stratifin expression in 182 patients with localized iCCAs undergoing surgical resection. Patients were divided into low and high expression groups, and the association between stratifin expression and clinicopathological features was analyzed. Univariate and multivariate survival analyses were performed to assess overall survival (OS), disease-specific survival (DSS), local recurrence-free survival (LRFS), and metastasis-free survival (MeFS)., Results: Elevated stratifin expression in iCCAs was significantly associated with the absence of hepatitis, positive surgical margins, advanced primary tumor stages, and higher histological grades (all p ≤ 0.011). Survival analyses demonstrated a significant negative association between stratifin expression and all prognostic indicators, including OS, DSS, LRFS, and MeFS (all p ≤ 0.0004). Multivariate analysis revealed that stratifin overexpression was significantly correlated with poorer outcomes in terms of DSS, LRFS, and MeFS (all p < 0.001)., Conclusions: These findings suggest that stratifin may play a crucial role in iCCA oncogenesis and tumor progression, serving as a potential novel prognostic biomarker., (Copyright © 2024 Asian Surgical Association and Taiwan Society of Coloproctology. Published by Elsevier B.V. All rights reserved.)

Background: Inguinal hernia repair (IHR) is a common surgical procedure worldwide. Although IHR can be performed by the minimally invasive method, which accelerates recovery, postoperative urinary retention (POUR) remains a common complication that significantly impacts patients. Thus, it is essential to identify the risk factors associated with POUR to diminish its negative impact., Methods: We conducted a single-center retrospective review of elective IHR from 2018 to 2021. POUR was defined as the postoperative use of straight catheter or placement of an indwelling catheter to relieve the symptoms. Adjusted multivariate regression analysis was performed to address the associations of clinicodemographic, surgical, and intraoperative factors with POUR., Results: A total of 946 subjects were included in the analysis after excluding cases of emergent surgery, recurrent hernia, or concomitant operations. The median age was 68.4 years, and 92.0% of the patients were male. Twenty-three (2.4%) patients developed POUR. In univariate analysis, POUR in comparison with non-POUR was significantly associated with increased age (72.2 versus 68.3 years, P = 0.012), a greater volume of intraoperative fluid administered (500 versus 400 ml, P = 0.040), and the diagnosis with benign prostate hypertrophy (34.8% versus 16.9%, P = 0.025). In the multivariate model, both increased age (odds ratio [OR] 1.04, 95% CI 1.01-1.08; P = 0.049) and a greater volume of intraoperative fluid administered (OR 1.12 per 100-mL increase, 95% CI 1.01-1.27; P = 0.047) were significantly associated with the occurrence of POUR., Conclusions: We found that increased age and a greater volume of intraoperative fluid administered were significantly associated with the occurrence of POUR. Limiting the administration of intraoperative fluid may prevent POUR. From the perspective of practical implications, specific guidelines or clinical pathways should be implemented for fluid management and patient assessment., (© 2024. The Author(s).)

Objective: Evaluating pain in individuals with dementia can be difficult when verbal communication is limited. Vocalization has emerged as a potential avenue for assessments of pain in nonverbal populations. This study aimed to evaluate if physiological assessments of vocalization were correlated with observational assessments of pain during routine blood tests for persons with dementia., Design: A cross-sectional descriptive study., Setting and Participants: Sixty older adults (aged ≥65 years old) with dementia requiring routine finger puncture and peripheral venipuncture for routine blood tests were recruited by purposive sampling from 3 long-term care facilities in Taiwan., Methods: Observational assessments were conducted with the Pain Assessment in Advanced Dementia (PAINAD) instrument; physiological biomarkers of vocalization were assessed with a noninvasive sensing device and microphone (NISDM). Assessments were conducted simultaneously in one session during situations of increasing pain levels: at rest, making a sound, finger puncture, and peripheral venipuncture. PAINAD scores were compared with signal recording measures from the NISDM. Analysis of variance and Pearson correlation coefficient assessed correlations between observational and physiological measures., Results: Most participants were female (63.3%); mean age was 81.27 years (SD = 9.69); Clinical Dementia Rating was 2.23 ± 0.70; and Mini-Mental State Examination was 7.07 ± 6.95. Signal recording measures using the NISDM during finger puncture and venipuncture were significantly greater compared with measures at rest and making sound, indicating higher signal levels were associated with pain. PAINAD scores were significantly correlated with physiological measures for vocalization variables of sound amplitude (r = 0.49, P < .001), shimmer (r = 0.63, P < .001), and inhalation-to-exhalation amplitude ratio (r = 0.48, P < .001)., Conclusions and Implications: Elevated vocalizations detected with the NISDM were correlated with increased pain scores on the PAINAD instrument. Physiological measures of pain using novel vocalization biomarkers have the potential to enhance the quality of care for individuals with dementia and limited communication abilities., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Sarcopenia, characterized by degenerative skeletal muscle loss, is increasingly linked to poor surgical outcomes. Glutamine, an immune-modulating formula, may stimulate muscle protein synthesis and inhibit degradation. We used the psoas major muscle area (PMMA) at the third lumbar vertebra, normalized for height (PMMA index), as a skeletal muscle indicator. This study investigates whether perioperative glutamine supplementation mitigates psoas muscle atrophy., Methods: We enrolled gastric adenocarcinoma (GA) patients undergoing gastrectomy. Computed tomography assessed the psoas muscle short axis. Muscle atrophy was estimated by changes between preoperative and three-month post-gastrectomy scans. Perioperative glutamine supplementation (PGS) comprised five-day parenteral plus one-month oral use. Propensity score matching minimized potential bias. A linear regression model predicted the association., Results: Of 516 patients analyzed (2016-2019), 100 (19.4%) received PGS. After propensity score matching, each group contained 97 cases. The PGS group showed a significantly higher median PMMA index change than the non-PGS group (0.3 vs. -0.3 cm 2 /m 2 , p = 0.004). Multivariate analysis revealed that PGS was significantly associated with increased PMMA index (coefficient = 0.60; 95% CI: 0.19-1.01; p = 0.005)., Conclusions: PGS may help restore psoas muscle atrophy in GA patients undergoing gastrectomy. The underlying mechanisms likely relate to glutamine's role in protein metabolism and immune function. Further studies are needed to elucidate these mechanisms fully.

Background: Asthma has been identified as different phenotypes due to various risk factors. Age differences may have potential effects on asthma phenotypes. Our study aimed to identify potential asthma phenotypes among adults divided by age as either younger or older than 65 years. We also compared differences in blood granulocyte patterns, occupational asthmagens, and asthma control-related outcomes among patient phenotype clusters., Methods: We recruited nonelderly (<65 years old) (n = 726) and elderly adults (≥65 years old) (n = 201) with mild-to-severe asthma. We conducted a factor analysis to select 17 variables. A two-step cluster analysis was used to classify subjects with asthma phenotypes, and a discriminant analysis was used to verify the classification of cluster results., Results: There were three clusters with different characteristics identified in both the nonelderly and elderly asthmatic adults. In the nonelderly patient group, cluster 2 (obese, neutrophilic phenotypes) had a 1.85-fold significantly increased risk of asthma exacerbations. Cluster 3 (early-onset, atopy, and smoker with an eosinophil-predominant pattern) had a 2.37-fold risk of asthma exacerbations and higher oral corticosteroid (OCS) use than cluster 1 (late-onset and LMW exposure with paucigranulocytic blood pattern). Among elderly patients, cluster 2 had poor lung function and more ex-smokers. Cluster 3 (early-onset, long asthma duration) had the lowest paucigranulocytic blood pattern percentages in the elderly group., Conclusions: The novelty of the clusters was found in age-dependent clusters. We identified three distinct phenotypes with heterogeneous characteristics, asthma exacerbations and medicine use in nonelderly and elderly asthmatic patients, respectively. Classification of age-stratified asthma phenotypes may lead to precise identification of patients, which provides personalized disease management., (Copyright © 2024 Japanese Society of Allergology. Published by Elsevier B.V. All rights reserved.)

Tau, a hallmark of Alzheimer's disease, is poorly characterized in cerebral amyloid angiopathy. We aimed to assess the clinico-radiological correlations between tau positron emission tomography scans and cerebral amyloid angiopathy. We assessed cerebral amyloid and hyperphosphorylated tau in patients with probable cerebral amyloid angiopathy ( n = 31) and hypertensive small vessel disease ( n = 27) using 11 C-Pittsburgh compound B and 18 F-T807 positron emission tomography. Multivariable regression models were employed to assess radio-clinical features related to cerebral tau pathology in cerebral amyloid angiopathy. Cerebral amyloid angiopathy exhibited a higher cerebral tau burden in the inferior temporal lobe [1.25 (1.17-1.42) versus 1.08 (1.05-1.22), P < 0.001] and all Braak stage regions of interest ( P < 0.05) than hypertensive small vessel disease, although the differences were attenuated after age adjustment. Cerebral tau pathology was significantly associated with cerebral amyloid angiopathy-related vascular markers, including cortical superficial siderosis ( β = 0.12, 95% confidence interval 0.04-0.21) and cerebral amyloid angiopathy score ( β = 0.12, 95% confidence interval 0.03-0.21) after adjustment for age, ApoE4 status and whole cortex amyloid load. Tau pathology correlated significantly with cognitive score (Spearman's ρ =-0.56, P = 0.001) and hippocampal volume (-0.49, P = 0.007), even after adjustment. In conclusion, tau pathology is more frequent in sporadic cerebral amyloid angiopathy than in hypertensive small vessel disease. Cerebral amyloid angiopathy-related vascular pathologies, especially cortical superficial siderosis, are potential markers of cerebral tau pathology suggestive of concomitant Alzheimer's disease., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Primary aldosteronism is associated with various types of cardiovascular and cerebrovascular damage independently of hypertension. Although chronic hypertension and related cerebral arteriosclerosis are the main risk factors for intracerebral hemorrhage, the effects of aldosteronism remain poorly understood. We enrolled 90 survivors of hypertensive intracerebral hemorrhage, 21 of them with aldosteronism and 69 with essential hypertension as controls in this study. Clinical parameters and neuroimaging markers of cerebral small vessel disease were recorded, and its correlations with aldosteronism were investigated. Our results showed that the aldosteronism group (55.2 ± 9.7 years, male 47.6%) had similar hypertension severity but exhibited a higher cerebral microbleed count (interquartile range) (8.5 [2.0‒25.8] vs 3 [1.0‒6.0], P = 0.005) and higher severity of dilated perivascular space in the basal ganglia (severe perivascular space [number >20], 52.4% vs. 24.6%, P = 0.029; large perivascular space [>3 mm], 52.4% vs. 20.3%, P = 0.010), compared to those with essential hypertension (53.8 ± 11.7 years, male 73.9%). In multivariate models, aldosteronism remained an independent predictor of a higher (>10) microbleed count (odds ratio = 8.60, P = 0.004), severe perivascular space (odds ratio = 4.00, P = 0.038); the aldosterone-to-renin ratio was associated with dilated perivascular space (P = 0.043) and large perivascular space (P = 0.008). In conclusions, survivors of intracerebral hemorrhage with aldosteronism showed a tendency towards more severe hypertensive arteriopathy than the essential hypertension counterparts independently of blood pressure; aldosteronism may contribute to dilated perivascular space around the deep perforating arteries. Aldosteronism is associated with more severe cerebral small vessel disease in hypertensive intracerebral hemorrhage., (© 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Lobar cerebral microbleeds are a characteristic neuroimaging finding in cerebral amyloid angiopathy (CAA) but can also be found in hypertensive arteriolosclerosis. We aimed to investigate whether CAA is more associated with intracortical lobar microbleeds than hypertensive arteriosclerosis. Ninety-one survivors of spontaneous intracerebral hemorrhage with at least one lobar microbleed were included and underwent brain MRI and amyloid PET. We categorized lobar microbleeds as intracortical, juxtacortical, or subcortical. We assessed the associations between the lobar microbleed categories and microangiopathy subtypes or cerebral amyloid load based on the Pittsburgh Compound-B PET standardized uptake value ratio (SUVR). Patients with CAA had a higher prevalence of intracortical lobar microbleeds (80.0% vs. 50.8%, P = 0.011) and lower prevalence of subcortical lobar microbleeds (13.3% vs. 60.1%, P < 0.001) than patients with hypertensive arteriolosclerosis. Strictly intracortical/juxtacortical lobar microbleeds were associated with CAA (OR 18.9 [1.9-191.4], P = 0.013), while the presence of subcortical lobar microbleeds was associated with hypertensive arteriolosclerosis (OR 10.9 [1.8-68.1], P = 0.010). Amyloid retention was higher in patients with strictly intracortical/juxtacortical CMBs than those without (SUVR = 1.15 [1.05-1.52] vs. 1.08 [1.02-1.19], P = 0.039). Amyloid retention positively correlated with the number of intracortical lobar microbleeds (P < 0.001) and negatively correlated with the number of subcortical lobar microbleeds (P = 0.018). CAA and cortical amyloid deposition are more strongly associated with strictly intracortical/juxtacortical microbleeds than subcortical lobar microbleeds. Categorization of lobar microbleeds based on anatomical location may help differentiate the underlying microangiopathy and potentially improve the accuracy of current neuroimaging criteria for cerebral small vessel disease., (© 2024. The Author(s).)

Background: In Taiwan, lung cancers occur predominantly in never-smokers, of whom nearly 60% have stage IV disease at diagnosis. We aimed to assess the efficacy of low-dose CT (LDCT) screening among never-smokers, who had other risk factors for lung cancer., Methods: The Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT) was a nationwide, multicentre, prospective cohort study done at 17 tertiary medical centres in Taiwan. Eligible individuals had negative chest radiography, were aged 55-75 years, had never smoked or had smoked fewer than 10 pack-years and stopped smoking for more than 15 years (self-report), and had one of the following risk factors: a family history of lung cancer; passive smoke exposure; a history of pulmonary tuberculosis or chronic obstructive pulmonary disorders; a cooking index of 110 or higher; or cooking without using ventilation. Eligible participants underwent LDCT at baseline, then annually for 2 years, and then every 2 years up to 6 years thereafter, with follow-up assessments at each LDCT scan (ie, total follow-up of 8 years). A positive scan was defined as a solid or part-solid nodule larger than 6 mm in mean diameter or a pure ground-glass nodule larger than 5 mm in mean diameter. Lung cancer was diagnosed through invasive procedures, such as image-guided aspiration or biopsy or surgery. Here, we report the results of 1-year follow-up after LDCT screening at baseline. The primary outcome was lung cancer detection rate. The p value for detection rates was estimated by the χ 2 test. Univariate and multivariable logistic regression analyses were used to assess the association between lung cancer incidence and each risk factor. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LDCT screening were also assessed. This study is registered with ClinicalTrials.gov, NCT02611570, and is ongoing., Findings: Between Dec 1, 2015, and July 31, 2019, 12 011 participants (8868 females) were enrolled, of whom 6009 had a family history of lung cancer. Among 12 011 LDCT scans done at baseline, 2094 (17·4%) were positive. Lung cancer was diagnosed in 318 (2·6%) of 12 011 participants (257 [2·1%] participants had invasive lung cancer and 61 [0·5%] had adenocarcinomas in situ). 317 of 318 participants had adenocarcinoma and 246 (77·4%) of 318 had stage I disease. The prevalence of invasive lung cancer was higher among participants with a family history of lung cancer (161 [2·7%] of 6009 participants) than in those without (96 [1·6%] of 6002 participants). In participants with a family history of lung cancer, the detection rate of invasive lung cancer increased significantly with age, whereas the detection rate of adenocarcinoma in situ remained stable. In multivariable analysis, female sex, a family history of lung cancer, and age older than 60 years were associated with an increased risk of lung cancer and invasive lung cancer; passive smoke exposure, cumulative exposure to cooking, cooking without ventilation, and a previous history of chronic lung diseases were not associated with lung cancer, even after stratification by family history of lung cancer. In participants with a family history of lung cancer, the higher the number of first-degree relatives affected, the higher the risk of lung cancer; participants whose mother or sibling had lung cancer were also at an increased risk. A positive LDCT scan had 92·1% sensitivity, 84·6% specificity, a PPV of 14·0%, and a NPV of 99·7% for lung cancer diagnosis., Interpretation: TALENT had a high invasive lung cancer detection rate at 1 year after baseline LDCT scan. Overdiagnosis could have occurred, especially in participants diagnosed with adenocarcinoma in situ. In individuals who do not smoke, our findings suggest that a family history of lung cancer among first-degree relatives significantly increases the risk of lung cancer as well as the rate of invasive lung cancer with increasing age. Further research on risk factors for lung cancer in this population is needed, particularly for those without a family history of lung cancer., Funding: Ministry of Health and Welfare of Taiwan., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: F-18-fluorothymidine (FLT) is a positron emission tomography (PET) tracer for imaging cell proliferation in vivo. We aimed to assess FLT uptake as a marker for cerebral cell proliferation in a rat model of ischemic stroke and patients with cerebral infarct, correlating with disease severity and outcomes., Methods: Cerebral FLT PET was performed in rats subjected to transient middle cerebral artery occlusion (MCAO) and patients with cerebral infarct. PET data were analyzed and expressed as average standardized uptake value ratios (SUVRs) using cerebellar cortex as reference. Infarct volume was analyzed by 2,3,5-triphenyltetrazolium chloride staining in rats and by magnetic resonance imaging in patients. Neurological function was assessed using modified Neurological Severity Score (mNSS) for rats and National Institutes of Health Stroke Scale (NIHSS) for patients., Results: Seven days post-MCAO, rats' FLT PET displayed higher SUVRs in the infarcted brain, declining gradually until Day 28. FLT-binding ratio (SUVR in the infarcted brain divided by that in contralateral side) correlated positively with stroke severity (p < 0.001), and to early mNSS decline in rats with mild to moderate stroke severity (p = 0.031). In 13 patients with cerebral infarct, FLT PET showed high SUVR in the infarcted regions. FLT-binding ratio correlated positively with infarct volume (p = 0.006). Age-adjusted initial NIHSS (p = 0.035) and early NIHSS decline (p = 0.076) showed significance or a trend toward positive correlation with the FLT-binding ratio., Interpretation: In vivo FLT PET detects poststroke cerebral cell proliferation, which is associated with stroke severity and/or outcomes in MCAO rats and patients with cerebral infarct., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background: Cigarette smoking and particulate matter (PM) with aerodynamic diameter < 2.5 μm (PM 2.5 ) are major preventable cardiovascular mortality and morbidity promoters. Their joint role in metabolic syndrome (MS) pathogenesis is unknown. We determined the risk of MS based on PM 2.5 and cigarette smoking in Taiwanese adults., Methods: The study included 126,366 Taiwanese between 30 and 70 years old with no personal history of cancer. The Taiwan Biobank (TWB) contained information on MS, cigarette smoking, and covariates, while the Environmental Protection Administration (EPA), Taiwan, contained the PM 2.5 information. Individuals were categorized as current, former, and nonsmokers. PM 2.5 levels were categorized into quartiles: PM 2.5  ≤ Q1, Q1 < PM 2.5  ≤ Q2, Q2 < PM 2.5  ≤ Q3, and PM 2.5  > Q3, corresponding to PM 2.5 ≤ 27.137, 27.137 < PM 2.5  ≤ 32.589, 32.589 < PM 2.5 ≤ 38.205, and PM 2.5  > 38.205 μg/m 3 ., Results: The prevalence of MS was significantly different according to PM 2.5 exposure ( p -value = 0.0280) and cigarette smoking ( p -value < 0.0001). Higher PM 2.5 levels were significantly associated with a higher risk of MS: odds ratio (OR); 95% confidence interval (CI) = 1.058; 1.014-1.104, 1.185; 1.134-1.238, and 1.149; 1.101-1.200 for 27.137 < PM 2.5  ≤ 32.589, 32.589 < PM 2.5 ≤ 38.205, and PM 2.5  > 38.205 μg/m 3 , respectively. The risk of MS was significantly higher among former and current smokers with OR; 95% CI = 1.062; 1.008-1.118 and 1.531; 1.450-1.616, respectively, and a dose-dependent p -value < 0.0001. The interaction between both exposures regarding MS was significant ( p -value = 0.0157). Stratification by cigarette smoking revealed a significant risk of MS due to PM 2.5 exposure among nonsmokers: OR (95% CI) = 1.074 (1.022-1.128), 1.226 (1.166-1.290), and 1.187 (1.129-1.247) for 27.137 < PM 2.5  ≤ 32.589, 32.589 < PM 2.5 ≤ 38.205, and PM 2.5  > 38.205 μg/m 3 , respectively. According to PM 2.5 quartiles, current smokers had a higher risk of MS, regardless of PM 2.5 levels (OR); 95% CI = 1.605; 1.444-1.785, 1.561; 1.409-1.728, 1.359; 1.211-1.524, and 1.585; 1.418-1.772 for PM 2.5 ≤ 27.137, 27.137 < PM 2.5  ≤ 32.589, 32.589 < PM 2.5 ≤ 38.205, and PM 2.5  > 38.205 μg/m 3 , respectively. After combining both exposures, the group, current smokers; PM 2.5  > 38.205 μg/m 3 had the highest odds (1.801; 95% CI =1.625-1.995)., Conclusion: PM 2.5 and cigarette smoking were independently and jointly associated with a higher risk of MS. Stratified analyses revealed that cigarette smoking might have a much higher effect on MS than PM 2.5 . Nonetheless, exposure to both PM 2.5 and cigarette smoking could compound the risk of MS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tsai, Tantoh, Lu, Chen and Liaw.)

Background: Concurrent chemoradiotherapy (CCRT) is suggested before resection surgery in the control of rectal cancer. Unfortunately, treatment outcomes are widely variable and highly patient-specific. Notably, rectal cancer patients with distant metastasis generally have a much lower survival rate. Accordingly, a better understanding of the genetic background of patient cohorts can aid in predicting CCRT efficacy and clinical outcomes for rectal cancer before distant metastasis., Methods: A published transcriptome dataset (GSE35452) (n=46) was utilized to distinguish prospective genes concerning the response to CCRT. We recruited 172 rectal cancer patients, and the samples were collected during surgical resection after CCRT. Immunohistochemical (IHC) staining was performed to evaluate the expression level of regenerating family member 3 alpha (REG3A). Pearson's chi-squared test appraised the relevance of REG3A protein expression to clinicopathological parameters. The Kaplan-Meier method was utilized to generate survival curves, and the log-rank test was performed to compare the survival distributions between two given groups., Results: Employing a transcriptome dataset (GSE35452) and focusing on the inflammatory response (GO: 0006954), we recognized that REG3A is the most significantly upregulated gene among CCRT nonresponders (log2 ratio=1.2472, p=0.0079). Following IHC validation, high immunoexpression of REG3A was considerably linked to advanced post-CCRT tumor status (p<0.001), post-CCRT lymph node metastasis (p=0.042), vascular invasion (p=0.028), and low-grade tumor regression (p=0.009). In the multivariate analysis, high immunoexpression of REG3A was independently correlated with poor disease-specific survival (DSS) (p=0.004) and metastasis-free survival (MeFS) (p=0.045). The results of the bioinformatic analysis also supported the idea that REG3A overexpression is implicated in rectal carcinogenesis., Conclusion: In the current study, we demonstrated that REG3A overexpression is correlated with poor CCRT effectiveness and inferior patient survival in rectal cancer. The predictive and prognostic utility of REG3A expression may direct patient stratification and decision-making more accurately for those patients., (©The Author(s) 2024. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Iron is critical during host-microorganism interactions 1-4 . Restriction of available iron by the host during infection is an important defence strategy, described as nutritional immunity 5 . However, this poses a conundrum for externally facing, absorptive tissues such as the gut epithelium or the plant root epidermis that generate environments that favour iron bioavailability. For example, plant roots acquire iron mostly from the soil and, when iron deficient, increase iron availability through mechanisms that include rhizosphere acidification and secretion of iron chelators 6-9 . Yet, the elevated iron bioavailability would also be beneficial for the growth of bacteria that threaten plant health. Here we report that microorganism-associated molecular patterns such as flagellin lead to suppression of root iron acquisition through a localized degradation of the systemic iron-deficiency signalling peptide Iron Man 1 (IMA1) in Arabidopsis thaliana. This response is also elicited when bacteria enter root tissues, but not when they dwell on the outer root surface. IMA1 itself has a role in modulating immunity in root and shoot, affecting the levels of root colonization and the resistance to a bacterial foliar pathogen. Our findings reveal an adaptive molecular mechanism of nutritional immunity that affects iron bioavailability and uptake, as well as immune responses., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Several early noncontrast CT (NCCT) signs of spontaneous intracerebral hemorrhage (ICH) can predict hematoma expansion (HE). However, the associations of underlying cerebral small vessel disease (SVD) on early NCCT signs and HE have been less explored., Methods: We conducted an analysis of all patients with spontaneous supratentorial ICH and received follow-up imaging between 2016 and 2020 at a stroke center. The early NCCT signs were categorized as shape or density signs. HE was defined as an increase in hematoma volume ≥6 mL or 33% from baseline. The severity of SVD was assessed by both a 3-point CT-based and a 4-point magnetic resonance imaging (MRI)-based SVD score. Regression models were used to examine the associations between SVD score and hematoma volume, NCCT signs, and HE., Results: A total of 328 patients (median age: 64 years; 38% female) were included. The median baseline ICH volume was 8.6 mL, with 38% of the patients had shape signs and 52% had density signs on the initial NCCT. Higher MRI-SVD scores were associated with smaller ICH volumes (p = 0.0006), fewer shape (p = 0.001), or density signs (p = 0.0003). Overall, 16% of patients experienced HE. A higher MRI-SVD score was inversely associated with HE (adjusted odds ratio 0.71, 95% CI: 0.53-0.96). Subgroup analysis revealed that this association was primarily observed in patients who were younger (&lt;65 years), male, had deep hemorrhage, or did not meet the criteria for cerebral amyloid angiopathy diagnosis., Conclusions: In patients with spontaneous ICH, a more severe SVD was associated with smaller hematoma volume, fewer NCCT signs, and a lower risk of HE. Further research is required to investigate why a higher burden of severely diseased cerebral small blood vessels is associated with less bleeding., (© 2023 S. Karger AG, Basel.)

Fibroblast growth factor 23 (FGF23) is a phosphate-regulating (Pi-regulating) hormone produced by bone. Hereditary hypophosphatemic disorders are associated with FGF23 excess, impaired skeletal growth, and osteomalacia. Blocking FGF23 became an effective therapeutic strategy in X-linked hypophosphatemia, but testing remains limited in autosomal recessive hypophosphatemic rickets (ARHR). This study investigates the effects of Pi repletion and bone-specific deletion of Fgf23 on bone and mineral metabolism in the dentin matrix protein 1-knockout (Dmp1KO) mouse model of ARHR. At 12 weeks, Dmp1KO mice showed increased serum FGF23 and parathyroid hormone levels, hypophosphatemia, impaired growth, rickets, and osteomalacia. Six weeks of dietary Pi supplementation exacerbated FGF23 production, hyperparathyroidism, renal Pi excretion, and osteomalacia. In contrast, osteocyte-specific deletion of Fgf23 resulted in a partial correction of FGF23 excess, which was sufficient to fully restore serum Pi levels but only partially corrected the bone phenotype. In vitro, we show that FGF23 directly impaired osteoprogenitors' differentiation and that DMP1 deficiency contributed to impaired mineralization independent of FGF23 or Pi levels. In conclusion, FGF23-induced hypophosphatemia is only partially responsible for the bone defects observed in Dmp1KO mice. Our data suggest that combined DMP1 repletion and FGF23 blockade could effectively correct ARHR-associated mineral and bone disorders.

Background: Family history of gout and sex are independently associated with gout. However, there is a paucity of research regarding the joint role of both factors in gout pathogenesis. Therefore, we assessed the independent and combined association of family history of gout and sex with gout., Methods: Our analysis included 132,311 Taiwan Biobank (TWB)-enrolled individuals comprising 21,159 gout cases and 111,152 controls. We subcategorized the family history of gout as (1) both siblings and parents had gout), (2) only parents had gout, and (3) only siblings had gout., Results: Generally, sex (men compared to women) and family history of gout were independently associated with a higher risk of gout. The odds ratio (OR); 95% confidence interval (CI) was 9.175; 8.801-9.566 for sex, and 2.306; 2.206-2.410 for family history. For the subcategories 'both siblings and had gout,' 'only parents had gout,' and 'only siblings had gout,' the odds ratios (ORs); 95% confidence intervals (CIs) were 4.944; 4.414-5.538, 2.041; 1.927-2.161, and 2.162; 2.012-2.323, respectively. The interaction between sex and family history was significant (p value = 0.0001). After stratification by sex, family history of gout remained significantly associated with a higher risk of gout in both sexes, even though the odds ratios were higher in men. For the subcategories 'both siblings and parents had gout,' 'only parent had gout,' and 'only siblings had gout,' the corresponding ORs; 95% CIs were 6.279; 5.243-7.520, 2.211; 2.062-2.371, and 2.148; 1.955-2.361 in men and 4.199; 3.566-4.945, 1.827; 1.640-2.035, and 2.093; 1.876-2.336 in women. After integrating sex and family history (reference: women with no family history), the highest risk of gout was observed in men who had at least one parent and sibling with a history of gout (OR; 95% CI 55.774; 46.360-67.101)., Conclusion: Sex and family history of gout were independently and interactively associated with gout. Sex-wise, men had a higher risk of gout than women. Family history was associated with a higher risk of gout in both sexes, but men had a higher risk. Notably, men having both siblings and parents with gout had the highest risk of gout., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Gene expression signatures provide valuable information to guide postoperative treatment in breast cancer (BC) patients. However, genetic tests are prohibitively expensive for the majority of BC patients. Immunohistochemical staining (IHC) subtype classification system has been widely used for treatment guideline and is affordable to most BC patients. We aimed to revise immunohistochemical staining (IHC) subtyping to better match gene expression-based Prediction Analysis of Microarray 50 (PAM50) subtyping. Real world data of 372 BC patients were recruited in the Tri-Service General Hospital between Jan 2019 and Dec 2021. Clinical pathological information, blood, twelve pathological tissue slide samples, and fresh surgical tumor specimens were collected to examine IHC and PAM50. Current IHC subtyping (cIHC) tends to misclassify PAM50-based luminal A (lum A) to luminal B (lum B) by 35.81%, PAM50-lum B to PAM50-lum A by 9.09%, PAM50-Her2-enriched to lum B by 61.11%, PAM50-based Her2-enriched to lum B by 61.11%, and PAM50-based basal-like to lum B by 33.33%. We used random forest to identify estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), and Ki-67 status as the best indicators for revised IHC subtyping (rIHC4) and revised the classification rules by stratified analysis and prediction efficacy. rIHC4 increased the concordance rate for PAM50 subtypes from 68.3% to 74.7%. Both sensitivity and precision increased in most rIHC4 subtypes. Sensitivity increased from 33.3% to 87.4% in the Her2-enriched subtype; precision increased more evidently in the basal-like and lum B subtypes, from 71.4% to 83.3% and 57% to 65.1%, respectively. Our rIHC4 subtyping improved consistency with the PAM50 subtype, which could improve clinical management of BC patients without increasing medical expense., Competing Interests: None., (AJCR Copyright © 2023.)

Background: Understanding the experience of eating for nursing home residents with dysphagia is essential for developing effective and holistic compensatory intervention programmes for older adults with dysphagia. However, there is a lack of studies on the experience of eating for older adults with dysphagia, especially for individuals in Asian cultures., Objectives: This study aimed to understand the experience of eating for older nursing home residents who have difficulty swallowing (dysphagia), which is often a problem for this population., Methods: This qualitative descriptive study recruited older nursing home residents with dysphagia from facilities in central Taiwan. Residents were recruited by purposive sampling. Data were collected through individual in-depth semistructured face-to-face interviews. Interviews were audio-recorded and transcribed interview data were analysed with content analysis., Results: A total of 20 residents participated in the study; the mean age was 78.7 years (standard deviation = 8.54 years); male and female residents were equally represented. The main core theme describing the experience of eating for nursing home residents with dysphagia was irregular coughing, which often occurred spontaneously. Three subthemes described how residents responded: making adjustments to eating and swallowing, receiving assistance from NH staff and fear of eating., Conclusions: Our findings can serve as an evidence-based reference for clinical care aimed at nursing home residents with dysphagia. Support programmes that provide safe swallowing skills and emotional support for managing dysphagia are recommended., Implications for Practice: Nursing home residents with dysphagia should receive interventions focussed on self-supporting care, training in swallowing skills and emotional support., (© 2023 John Wiley & Sons Ltd.)

Cholangiocarcinoma is a common malignancy with increasing incidence worldwide. Most patients are diagnosed at the advanced stage with poor survival rate. Laminin subunit γ2 (LAMC2) is a heparin binding-associated gene involved in tumorigenesis and has been implicated in the prognosis of various types of cancers. However, it is unclear whether expression of LAMC2 is associated with the clinical outcome of patients with cholangiocarcinoma. In the present study, the role and prognostic value of LAMC2 expression in patients with cholangiocarcinoma was investigated. Clinical information and pathological characteristics were analyzed and the association between LAMC2 expression and clinical characteristics, pathological findings and patient outcomes, including metastasis-free and disease-specific survival, were investigated. Data from 182 patients with cholangiocarcinoma were evaluated. High LAMC2 expression was associated with higher tumor stage (P < 0.001), large duct type (P=0.024) and poor histological grade (P = 0.002). Kaplan-Meier analysis showed high LAMC2 expression was associated with lower overall (P=0.003), disease-specific (P = 0.0025), local recurrence-free (P < 0.0001) and metastasis-free survival (P < 0.0001). Moreover, multivariate analysis demonstrated that increased LAMC2 expression was a significant predictive risk factor for overall [hazard ratio (HR) 1.713; P = 0.034], disease-specific (HR 2.011; P = 0.039), local recurrence-free (HR 2.721; P < 0.001) and metastasis-free survival (HR 3.117; P < 0.001). Gene enrichment analysis using Gene Ontology showed that terms associated with LAMC2 upregulation were 'regulation of platelet-derived growth factor receptor-βsignaling pathway' and 'platelet-derived growth factor receptor-β signaling pathway'. The present study indicated that LAMC2 was upregulated in cholangiocarcinoma tumor tissue and had an inverse association with overall, disease-specific, local recurrence-free and metastasis-free survival in patients with cholangiocarcinoma. These results suggested that LAMC2 may serve as a potential biomarker for cholangiocarcinoma., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Ong et al.)

Cartilage oligomeric matrix protein (COMP) interacts with various extracellular matrix proteins in tissues. Elevated COMP levels recently linked to worse overall survival in multiple cancer types. COMP's significance in intrahepatic cholangiocarcinoma (iCCA) remains uncertain. Here we report a retrospective study to explore COMP's impact on iCCA outcomes. We collected 182 patients' iCCA tumor tissues. COMP overexpression was associated with adverse factors like R1 resection (p = 0.008), advanced T stage (p < 0.001), large duct type (p = 0.004), and poorly differentiated histology (p = 0.002). COMP overexpression correlates with poorer DFS (HR, 3.651; p = 0.001), OS (HR, 1.827; p = 0.023), LRFS (HR, 4.077; p < 0.001), and MFS (HR, 3.718; p < 0.001). High COMP expression ties to worse overall survival (p = 0.0001), DSS (p < 0.0001), LRFS (p < 0.0001), and MFS (p < 0.0001). In conclusion, COMP overexpression links to poor prognosis and pathological features in iCCA, indicating its potential as a biomarker., (© 2023. Springer Nature Limited.)

Background: To investigate the association between cerebral amyloid deposition and long-term cognitive outcomes in patients with hemorrhagic small vessel disease (SVD) and survivors of intracerebral hemorrhage (ICH)., Methods: Patients experiencing an ICH without overt dementia were prospectively recruited (n = 68) for brain MRI and Pittsburgh compound B (PiB) positron emission tomography scans at baseline. Cognitive function was assessed using the mini-mental status examination (MMSE) and clinical dementia rating after an overall median follow-up of 3.8 years. A positive amyloid scan was defined as a global PiB standardized uptake value ratio >1.2. Associations between follow-up cognitive outcomes and neuroimaging markers were explored using multivariable Cox regression models., Results: PiB(+) patients were older (72.1 ± 7.8 vs. 59.9 ± 11.7, p = .002) and more frequently had cerebral amyloid angiopathy (CAA) (63.6% vs. 15.8%, p = .002) than PiB(-) patients. PiB(+) was associated with a higher risk of dementia conversion (32.9 vs. 4.0 per 100-person-years, hazard ratio [HR] = 15.7 [3.0-80.7], p = .001) and MMSE score decline (58.8 vs. 9.9 per 100-person-years, HR = 6.2 [1.9-20.0], p = .002). In the non-CAA subgroup (n = 52), PiB(+) remained an independent predictor of dementia conversion, p = .04). In the Cox models, PiB(+) was an independent predictor of dementia conversion (HR = 15.8 [2.6-95.4], p = .003) and MMSE score decline (HR = 5.7 [1.6-20.3], p = .008) after adjusting for confounders., Conclusions: Cerebral amyloid deposition potentially contributes to long-term cognitive decline in SVD-related ICH., (© 2023 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)