Abstract Background Integrating behavioural assessments with blood-based biomarkers (BBM) could improve diagnostic accuracy for Mild Cognitive Impairment (MCI) linked to early-stage neurodegenerative disease (NDD). This study investigates the potential of combining neuropsychiatric symptoms (NPS) with BBM to enhance the differentiation between older adults with MCI and those with Normal Cognition (NC) in a multi-ethnic Southeast Asian cohort. Methods This cross-sectional study analyzed baseline data from the Biomarkers and Cognition Study, Singapore(BIOCIS). Data from 678 participants (mean[SD]age 59.16[11.02]years, 39.50% males) with NC and MCI were included. Behavioral symptoms were assessed using the Mild Behavioral Impairment Checklist (MBI-C) and Depression, Anxiety, and Stress Scales (DASS). Blood samples were analyzed for amyloid-beta (Aβ40, Aβ42), phosphorylated Tau (p-tau181), neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). Regression models adjusted for age, education, gender, cognitive status (CS) and APOE-ε4 status were used. Discriminative power was evaluated using the area under the curve (AUC) to assess the combined predictive accuracy of behavioral and biological markers for CS, i.e., MCI status over CN. Results The study included MBI-C scores (total, interest, mood, control) and BBM levels (Aβ40, NfL, GFAP) were significantly higher in MCI group, compared to CN group. Elevated GFAP (OR:3.636, 95% CI:1.959, 6.751, p<0.001) and higher MBI-C-Mood scores (OR:2.614, 95% CI:1.538, 4.441, p<0.001) significantly increased the likelihood of MCI. The combined model, integrating NPS and BBM markers, showed strong discriminative ability for MCI (AUC = 0.786), with 64.7% sensitivity and 84.9% specificity at a threshold of 0.616, compared to NPS markers (AUC: 0.593) or BBM (AUC: 0.697) alone. Conclusions and Relevance The combined use of BBM and NPS achieved optimal accuracy in distinguishing MCI from NC, with strong associations between GFAP, MBI-C Mood scores, and CS. These findings underscore neuroinflammation and mood disturbances as critical factors in early NDD, supporting the importance of dual-dimension screening strategies. Integrating NPS and BBM represents a novel and effective diagnostic approach for detection of MCI due to AD or other dementias. The integrated framework, leveraging both pathophysiological and neuropsychiatric markers, facilitates earlier diagnosis, potentially improving clinical decision-making and enabling targeted disease-modifying therapies for individuals with neurodegenerative disorders.
Stomatin‑like protein 2 (SLP‑2) is associated with poor prognosis in several types of cancer, including pancreatic cancer (PC); however, the molecular mechanism of its involvement remains elusive. The present study aimed to elucidate the role of this protein in the development of PC. Human PC cell lines AsPC‑1 and PANC‑1 were transfected by a vector expressing SLP‑2 shRNA. Analyses of cell proliferation, migration, invasion, chemosensitivity, and glucose uptake were conducted, while a mouse xenograft model was used to evaluate the functional role of SLP‑2 in PC. Immunohistochemical analysis was retrospectively performed on human tissue samples to compare expression between the primary site (n=279) and the liver metastatic site (n=22). Furthermore, microarray analysis was conducted to identify the genes correlated with SLP‑2. In vitro analysis demonstrated that cells in which SLP‑2 was suppressed exhibited reduced cell motility and glucose uptake, while in vivo analysis revealed a marked decrease in the number of liver metastases. Immunohistochemistry revealed that SLP‑2 was increased in liver metastatic sites. Microarray analysis indicated that this protein regulated the expression of glutamine‑fructose‑6‑phosphate transaminase 2 (GFPT2), a rate‑limiting enzyme of the hexosamine biosynthesis pathway. SLP‑2 contributed to the malignant character of PC by inducing liver metastasis. Cell motility and glucose uptake may be induced via the hexosamine biosynthesis pathway through the expression of GFPT2. The present study revealed a new mechanism of liver metastasis and indicated that SLP‑2 and its downstream pathway could provide novel therapeutic targets for PC.
Abstract Developing versatile ionoelastomers, the alternatives to hydrogels and ionogels, will boost the advancement of high‐performance ionotronic devices. However, meeting the requirements of bio‐derivation, high toughness, high stretchability, autonomous self‐healing ability, high ionic conductivity, reprocessing, and favorable recyclability in a single ionoelastomer remains a challenging endeavor. Herein, a dynamic covalent and supramolecular design, lipoic acid (LA)‐based dynamic covalent ionoelastomer (DCIE), is proposed via melt building covalent adaptive networks with hierarchically dynamic bonding (CAN‐HDB), wherein lithium bonds aid in the dissociation of ions and the integration of dynamic disulfide metathesis, lithium bonds, and binary hydrogen bonds enhances the mechanical performances, self‐healing capability, reprocessing, and recyclability. Therefore, the trade‐off among mechanical versatility, ionic conductivity, self‐healing capability, reprocessing, and recyclability is successfully handled. The obtained DCIE demonstrates remarkable stretchability (1011.7%), high toughness (3877 kJ m −3 ), high ionic conductivity (3.94 × 10 −4 S m −1 ), outstanding self‐healing capability, reprocessing for 3D printing, and desirable recyclability. Significantly, the selective ion transport endows the DCIE with multisensory feature capable of generating continuous electrical signals for high‐quality sensations towards temperature, humidity, and strain. Coupled with the straightforward methodology, abundant availability of LA and HPC, as well as multifunction, the DCIEs present new concept of advanced ionic conductors for developing soft ionotronics.
Abstract Background and purpose A new noninvasive biomarker is being sought to predict the prognosis of patients with pancreatic cancer. Red-cell volume distribution width (RDW), a descriptive parameter for erythrocyte variation, has been shown to have prognostic value for some tumor types. Our purpose was to assess the RDW value to predict the prognosis of patients with pancreatic cancer. Methods The subjects of this retrospective study were 792 patients who underwent radical surgery for pancreatic cancer, divided into high-RDW and low-RDW groups based on receiver operating characteristic (ROC) curve analysis (15.6%). The controlling nutritional status (CONUT) score was used to assess preoperative nutritional status. Statistical analysis was conducted to investigate the differences between the high and low RDW groups, and to explore the possibility of the RDW being used as prognostic predictor for patients with pancreatic cancer. Results The immune-nutritional status was worse in the high-RDW group than in the low-RDW group. The high-RDW group patients also had a poorer prognosis. Risk factor analysis showed that the RDW could be an independent risk factor for pancreatic cancer. Conclusions The RDW is associated with immune-nutritional status in pancreatic cancer patients and can be used as an independent prognostic factor for their postoperative survival.
Pancreatic head ductal adenocarcinoma (PHDAC) patients with the same tumor-node-metastasis (TNM) stage may share different outcomes after pancreaticoduodenectomy (PD). Therefore, a novel method to identify patients with poor prognosis after PD is urgently needed. We aimed to develop a nomogram to estimate survival in PHDAC after PD.To estimate survival after PD, a nomogram was developed using the Tongji Pancreatic cancer cohort comprising 355 PHDAC patients who underwent PD. The nomogram was validated under the same conditions in another cohort (N = 161) from the National Taiwan University Hospital. Prognostic factors were assessed using LASSO and multivariate Cox regression models. The nomogram was internally validated using bootstrap resampling and then externally validated. Performance was assessed using concordance index (c-index) and calibration curve. Clinical utility was evaluated using decision curve analysis (DCA), X-tile program, and Kaplan-Meier curve in both training and validation cohorts.Overall, the median follow-up duration was 32.17 months, with 199 deaths (64.82%) in the training cohort. Variables included in the nomogram were age, preoperative CA 19-9 levels, adjuvant chemotherapy, Tongji classification, T stage, N stage, and differentiation degree. Harrell's c-indices in the internal and external validation cohorts were 0.79 (95% confidence interval [CI], 0.76-0.82) and 0.83 (95% CI, 0.78-0.87), respectively, which were higher than those in other staging systems. DCA showed better clinical utility.The nomogram was better than TNM stage and Tongji classification in predicting PHDAC patients' prognosis and may improve prognosis-based selection of patients who would benefit from PD.
The incidence of postoperative morbidity after pancreaticoduodenectomy (PD) is high; however, whether fluid management after surgery affects postoperative morbidity is unclear. This study aimed to determine whether fluid balance in patients undergoing PD is associated with postoperative complications and mortality.Data from a computer-based database of patients who underwent PD between 2016 and 2019 were retrospectively analyzed. Patients were stratified into four quartiles according to their fluid balance at 0-24, 24-48, 48-72, and 72-96 h after surgery. The predefined primary outcome measures were morbidity and mortality rates.A total of 301 patients were included. The morbidity and mortality rates in the cohort were 56.5% and 3.7%, respectively. The most common complications after PD were postoperative pancreatic fistula (31.9%) and delayed gastric emptying (31.6%). Patients with a higher fluid balance in the 0-24-, 24-48-, and 48-72-h postoperative periods had a higher morbidity rate and longer hospital stay than those with a lower fluid balance (all P < 0.05). Patients with a fluid balance of 4212 mL during the postoperative 0-72 h were most likely to develop complications (P < 0.001). The area under the receiver operating characteristic curve was 0.71 (0.65-0.77), with a sensitivity of 58.24% and a specificity of 77.10%.Higher postoperative fluid balance seems to be associated with increased morbidity after PD compared to lower fluid balance. Surgeons should pay close attention to the occurrence of complications in patients with a high fluid balance.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)
'/%3e%3cuse xlink:href='%23a' transform='translate(288.889 -214.211)'/%3e%3cuse xlink:href='%23a' transform='translate(108 342.749)'/%3e%3cuse xlink:href='%23a' transform='translate(469.189 342.749)'/%3e%3c/svg%3e)