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Little is known about the ecology of insect species in the hyporheic zone of rivers, despite its importance in understanding how species survive in specialized habitats. We report on the life history and trophic characteristics of the hyporheic stonefly species Alloperla ishikariana Kohno, 1953 (Order: Plecoptera, Family: Chloroperlidae) in a gravel-bed river in northern Japan, using year-round sampling of both benthic and hyporheic larvae, as well as flying adults in the riparian zone. Adults emerged between May and August, and the larval cohort structure consisted of three sized groups with some sex dimorphism in their body size, with an average growth rate of 0.0043 mg/day. Diet analyses based on C and N stable isotope ratios indicated minimal ontogenetic diet shifts. In contrast, the temporal diet shift was more apparent with higher dependence on Oligochaeta in winter, with an increasing dependence on Chironomidae in spring and early summer. Other insect taxa, namely, Leuctridae and small-sized Lepidostoma, demonstrated a high to moderate affinity for the hyporheic zone. Alloperla ishikariana spent most of its larval stage in the hyporheic zone. With adults living from 7 to 10 days, A. ishikariana completes a life span of approximately 3 years with its larval stage in the dark. [ABSTRACT FROM AUTHOR]

Classical simultaneous confidence bands for survival functions (i.e., Hall–Wellner, equal precision, and empirical likelihood bands) are derived from transformations of the asymptotic Brownian nature of the Nelson–Aalen or Kaplan–Meier estimators. Due to the properties of Brownian motion, a theoretical derivation of the highest confidence density region cannot be obtained in closed form. Instead, we provide confidence bands derived from a related optimization problem with local time processes. These bands can be applied to the one-sample problem regarding both cumulative hazard and survival functions. In addition, we present a solution to the two-sample problem for testing differences in cumulative hazard functions. The finite sample performance of the proposed method is assessed by Monte Carlo simulation studies. The proposed bands are applied to clinical trial data to assess survival times for primary biliary cirrhosis patients treated with D-penicillamine. [ABSTRACT FROM AUTHOR]

Physiological constraints can limit thermal niche breadth in organisms, particularly for small-bodied ectotherms. Daily temperature fluctuations often surpass annual (seasonal) temperature variation in the tropics, suggesting diel temperature cycles could drive thermal specialization by individuals that are active at different times of the day. We used foraging workers of the Neotropical ant Ectatomma ruidum to assess whether diurnally and nocturnally active workers differed in thermal tolerance. We compared critical thermal maxima (CT) of nocturnal and diurnal foraging workers to explore thermal niche specialization over the diel cycle. We predicted that diurnally active workers would have higher CT because they occupy a warmer thermal niche. As predicted, diurnal foragers exhibited significantly higher CT (mean 1.1 °C difference) than nocturnal foragers. Diurnal and nocturnal foragers were similar in body size, and there was no relationship between worker size and CT. We discuss possible mechanisms for this pattern, and the implications of within- versus between-colony differences in CT. [ABSTRACT FROM AUTHOR]

We have studied the in vitro transfection of a plasmid DNA with thelacZgene to HeLa-S3 cells and hemolysis in a red blood cell (RBC) suspension under pulsed ultrasound with duty cycles?of 10, 20 and 30% using a digital sonifier at a frequency of 20 kHz and an intensity of 6.2 W/cm2 on the surface of a horn tip. Cultured HeLa-S3 cells in suspension were exposed to pulsed ultrasound for an apparent exposure timet' from 0 to 60 s. HeLa-S3 viability decreased as a single exponential function of the total exposure timet=?t' with a common time constantt=3.8 s for three duty cycles. Transfection was evaluated by counting the number of ß-galactosidase(ß-Gal)-positive cells relative to the total number of cells. Pulsed ultrasound provided an enhanced transfer of the ß-Gal plasmid to HeLa-S3 cells, 3.4-fold as compared with that in the case of the control. The optimal transfection efficiencies were 0.75, 0.80 and 0.74% neart=twith?=10, 20 and 30%, respectively. The number ratio of ß-Gal-positive cells to the surviving cells after exposure increased witht' according to a modified logistic equation. The degree of hemolysis also increased exponentially witht' at a time constantt'=t0/?for the RBC suspension in physiological saline at a hematocrit concentration of 0.5% witht0=0.9 s. Thus the total exposure time for the optimal transfection efficiency wast, that is, nearly four times oft0. Hemolysis in the RBC suspension may be a useful model for determining optimal transfection by pulsed ultrasound of various duty cycles. [ABSTRACT FROM AUTHOR]

Background: The prevalence of Helicobacter pylori infection in Crohn's disease (CD) patients was investigated to determine whether the presence and severity of gastroduodenal lesions were related to H. pylori infection.Methods: Infection rates were compared between CD group (n = 90) and the control group (n = 525). Correlations between endoscopically detected lesions and H. pylori positive rates were investigated. The relationship between drug therapy and the prevalence of H. pylori infection was also analyzed.Results: H. pylori-positive rate of the 90 CD patients attending our clinic was 16.7%, significantly lower than the rate in healthy controls (40.2%) (P = 0.0001). The involvement of H. pylori infection in the gastroduodenal lesions of CD patients was also examined. The prevalence of gastroduodenal lesions in all CD patients was high, 92.2%. The lesions observed included ulcers, erosion, and "bamboo joint-like lesions" of the stomach, and ulcers, erosion, stenosis, and elevated lesions of the duodenum. None of these lesions were found to be related to H. pylori infection. However, H. pylori infection was found to exacerbate gastric ulcers (P = 0.036). The analysis of a possible relationship between a history of drug therapy and the low prevalence of H. pylori infection in CD patients showed that the prevalence of H. pylori infection was significantly lower in patients who had received antibiotics for 2 weeks or more (P = 0.002).Conclusions: The results suggest that H. pylori infection is essentially unrelated to the gastroduodenal lesions observed in CD. It seems likely, however, that H. pylori infection may exacerbate gastric ulcers and that H. pylori can be eradicated by prolonged use of antibiotics. [ABSTRACT FROM AUTHOR]

To clarify the relation between neuronal protection against ischaemia and calcium/calmodulin-dependent protein kinase II (CaM kinase II) activity, we investigated temporal alterations of the kinase activity in the hippocampus after transient forebrain ischaemia under neuroprotective conditions, employing the gerbil bilateral carotid artery occlusion model. The hippocampal CA1 neuronal density at 2 hours after 5 minutes of forebrain ischaemia was 214.7±25.8 /mm (mean±S.D.), and did not differ from the control significantly; however, it decreased to 11.7±4.2 /mm at 7 days after the ischaemia. The neuronal density at 7 days after the ischaemia was 185.1±18.5 under the hypothermic conditions, 128.7±19.6 with the brief ischaemic pretreatment, 65.0±13.4 with administration of MK-801, and 20.5±4.2 with the repetitive hyperthermic pretreatment, respectively. The Ca2+/calmodulin-dependent activity of CaM kinase II in the hippocampal cytosolic fraction was decreased to 47.5% of the control value at 2 hours after the ischaemia, when CA1 neuronal death was not observed. In contrast, the activity was 98.8% of the control under the hypothermic conditions, 91.4% with the brief ischaemic pretreatment, 71.2% with administration of MK-801, and 47.9% with the repetitive hyperthermic pretreatment, respectively. These results indicated that the preservation of the Ca2+/calmodulin-dependent activity of cytosolic CaM kinase II after ischaemia parallelled the neuroprotective effect in the gerbil hippocampus. Thus, it is suggested that the preservation of the activity may be involved in the mechanism of neuronal protection against ischaemia. [ABSTRACT FROM AUTHOR]

The mechanism of the adhesion of the suspension particles on the wall surface of the glass container is discussed. Two types of mechanism are found; 1) simple adhesion where no mutual affinity or interaction exists between the particle and the wall, 2) adhesion with affinity. In the case of the simple adhesion, the suspension particle is pressed against the wall and trapped by a thin medium film, whose pressure increases with decreasing of the medium film thickness. Important in this process is the liquid film formation on the wall. Under the pressure, the particle superdissolves into the thin liquid film at the contacting point, and the excess particle component produced deposits on both surfaces of the wall and the particle, where no direct pressure works upon. The adhesion strength increases as time goes by, since the deposition grows according to time, as long as the medium film presents and the pressure works on the particle. Adhesion due to deposition is not so popular as that due to affinity, but it is considered as an important basic form of the adhesion. For the affinity adhesion, the commonest affinity is a hydrophobic bonding effect, which may be explained by van der Waals coefficient and by determination of sliding angle of the suspension particle in the dispersion medium. Electrostatic affinity is less popular than affinity by hydrophobic bonding, but adsorption of the medium component onto the particle or the wall sometimes causes the adhesion due to this. Zeta potential of chloramphenicol crystals and glass powder was measured and its influence on the adhesion was discussed in connection with adsorption of benzethonium chloride. It was found that the adhesion strength of this type does not increase with lapse of time. [ABSTRACT FROM AUTHOR]

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Concise synthesis of eight-membered lactones, a kind of medium-sized heterocycles widespread in many bioactive natural products, is highly significant. However, it still remains a challenge due to unfavorable entropic factor and transannular interaction. Herein, we disclose an enantioselective synthesis of eight-membered lactones through a Pd-catalyzed asymmetric (6 +2) dipolar annulation of vinyl oxetanes and α-diazo ketones (20 examples, up to 93% yield and 95:5 er). This reaction features simple operation, mild conditions and good enantiocontrol, especially the challenging chiral all-carbon quaternary stereocenter. A newly developed chiral hybrid P,S ligand and the in-situ photo-generation of ketene dipolarophiles are crucial to this success. [ABSTRACT FROM AUTHOR]

Improving the quality of ulcer healing (QOUH) is one of the valid methods of prevention of relapse of gastric ulcers. We investigated the effect of lafutidine on the QOUH of gastric ulcer compared with famotidine in a randomized, multi-centre controlled trial. Consecutive 80 patients with a gastric ulcer were randomly assigned to receive twice daily either lafutidine (10 mg) or famotidine (20 mg) for 12 weeks. Esophagogastroduodenoscopy was performed to examine the ulcer healing rate and rate of fl at type ulcer scars using dye-contrast. The gastric ulcer healing rate was 92.1% in the lafutidine group (35/38) and 94.7% in the famotidine group (36/38). The rate of flat-type ulcer scars was significantly higher in the lafutidine group (68.4%, 26/38) than in the famotidine group (42.1%, 16/38) (P = 0.021). In conclusion, the present study demonstrated that lafutidine, as compared to famotidine, yields a signifi cantly superior QOUH in patients with gastric ulcers in the clinical setting. [ABSTRACT FROM AUTHOR]

In patients with severe hypertension, chronic heart failure or a history of stroke, the lower limit of autoregulation of cerebral blood flow (CBF) is shifted to higher levels of blood pressure (BP) than those observed in healthy subjects. The aim of pharmacotherapy for hypertensive patients with an impaired autoregulation of CBF should be to reduce BP while preserving an appropriate CBF. In the present study, 16 hypertensive patients who had had an episode of stroke more than 4 weeks previously were administered the angiotensin II (AT1) receptor antagonist losartan at daily doses of 25-100?mg for 4 weeks. Systolic and diastolic blood pressures were recorded for 24?h using an ambulatory BP monitoring system. CBF in both hemispheres of the cerebrum and cerebellum was quantified using single photon emission tomography with N-isopropyl-p-[123I]iodoamphetamine. At baseline, CBF was 29.7±6.7?ml/min/100?g in the cerebrum and 31.5±7.5?ml/min/100?g in the cerebellum. At the end of treatment, BP was lower, while CBF increased by 7.7%in the cerebrum, and remained at the baseline level in the cerebellum. Thus, CBF was preserved despite the reduction in BP. We consider the use of losartan is advantageous for hypertensive patients with a history of stroke in whom autoregulation of CBF is potentially impaired.Journal of Human Hypertension (2004) 18, 693-699. doi:10.1038/sj.jhh.1001735 Published online 6 May 2004 [ABSTRACT FROM AUTHOR]

Background: Crohn's colitis, frequently accompanied by stenosis or narrowing, can be difficult to assess through conventional methods. We evaluated the usefulness of virtual computed tomographic colonography (CTC) for the detection of colonic lesions due to Crohn's disease.Methods: Forty-two lesions in 33 patients with Crohn's disease were examined by CTC and barium enema (BE). Twenty-two patients also were examined by colonoscopy (CS). The visualization ability of CTC was compared with those of the other two methods.Results: In the visualization of elevated lesions, there was no significant difference between CTC and BE (18 of 20, p = 0.487) or between CTC and CS (15 of 16, p = 0.99); however, ulcerative lesions were less often visualized by CTC. However, CTC enabled identification of serious lesions in the colon proximal to the stenosis in nine patients and was superior to BE and CS in terms of its ability to visualize the proximal site of the stenosis (p = 0.003).Conclusion: CTC is clinically useful for the evaluation of Crohn's colitis, especially those with stenotic lesions. [ABSTRACT FROM AUTHOR]

We investigated treatment-induced changes in venous return from the small bowel and small bowel intestinal mucosal injury induced by the treatment of esophageal varices in patients with portal hypertension. A total of 14 patients (age 59.8+/-9.5 years, five women and 9 men) who received prophylactic treatment of esophageal varices between December 1998 and March 1999 were investigated. Diamine oxidase (DAO) activity was measured before and after treatment. Changes in blood flow of the portal and superior mesenteric veins were investigated by Doppler ultrasonography in six patients. A significant decrease in DAO activity was observed three days after treatment (11.5+/-1.6 units/liter prior to treatment versus 8.6+/-1.6 units/liter three days after treatment; P < 0.001). Decreases in superior mesenteric and portal venous flow velocity were observed in four and three patients, respectively. In two patients with an increase in the cross-sectional area of the superior mesenteric vein with delayed venous return, a marked decrease in DAO activity was observed three days after treatment. In patients with portal hypertension, rapid reduction of pooling of portal flow caused by the treatment of esophageal varices can induce transient congestion of the mesenteric venous system which can produce some small bowel mucosal injury. [ABSTRACT FROM AUTHOR]

The role of network metrics in exploring brain networks of mental illness is crucial. This study focuses on quantifying a node controllability index (CA-scores) and developing a novel framework for studying the dysfunction of attention deficit hyperactivity disorder (ADHD) brains. By analyzing fMRI data from 143 healthy controls and 102 ADHD patients, the controllability metric reveals distinct differences in nodes (brain regions) and subsystems (functional modules). There are significantly atypical CA-scores in the Rolandic operculum, superior medial orbitofrontal cortex, insula, posterior cingulate gyrus, supramarginal gyrus, angular gyrus, precuneus, heschl gyrus, and superior temporal gyrus of ADHD patients. A comparison with measures of connection strength, eigenvector centrality, and topology entropy suggests that the controllability index may be more effective in identifying abnormal regions in ADHD brains. Furthermore, our controllability index could be extended to investigate functional networks associated with other psychiatric disorders. [ABSTRACT FROM AUTHOR]

Activating antibody-dependent cellular cytotoxicity (ADCC) by targeting claudin-18 isoform 2 (CLDN18.2) using zolbetuximab, a monoclonal antibody against CLDN18.2, has been considered a promising novel therapeutic strategy for gastric cancer (GC). However, the impact of CLDN18.2 expression on natural killer (NK) cells and monocytes/macrophages—crucial effector cells of ADCC—in GC has not been fully investigated. In the present study, we assessed the impact of CLDN18.2 expression on clinical outcomes, molecular features, and the frequencies of tumor-infiltrating NK cells and macrophages, as well as peripheral blood NK cells and monocytes, in GC by analyzing our own GC cohorts. The expression of CLDN18.2 did not significantly impact clinical outcomes of GC patients, while it was significantly and positively associated with Epstein–Barr virus (EBV) status and PD-L1 expression. The frequencies of tumor-infiltrating NK cells and macrophages, as well as peripheral blood NK cells and monocytes, were comparable between CLDN18.2-positive and CLDN18.2-negative GCs. Importantly, both CLDN18.2 expression and the number of tumor-infiltrating NK cells were significantly higher in EBV-associated GC compared to other molecular subtypes. Our findings support the effectiveness of zolbetuximab in CLDN18.2-positive GC, and offer a novel insight into the treatment of this cancer type, highlighting its potential effectiveness for CLDN18.2-positive/EBV-associated GC. [ABSTRACT FROM AUTHOR]

Multiple myeloma management requires a balance between maximizing survival, minimizing adverse events to therapy, and monitoring disease progression. While previous work has proposed data-driven models for individual tasks, these approaches fail to provide a holistic view of a patient's disease state, limiting their utility to assist physician decision-making. To address this limitation, we developed a transformer-based machine learning model that jointly (1) predicts progression-free survival (PFS), overall survival (OS), and adverse events (AE), (2) forecasts key disease biomarkers, and (3) assesses the effect of different treatment strategies, e.g., ixazomib, lenalidomide, dexamethasone (IRd) vs lenalidomide, dexamethasone (Rd). Using TOURMALINE trial data, we trained and internally validated our model on newly diagnosed myeloma patients (N = 703) and externally validated it on relapsed and refractory myeloma patients (N = 720). Our model achieved superior performance to a risk model based on the multiple myeloma international staging system (ISS) (p < 0.001, Bonferroni corrected) and comparable performance to survival models trained separately on each task, but unable to forecast biomarkers. Our approach outperformed state-of-the-art deep learning models, tailored towards forecasting, on predicting key disease biomarkers (p < 0.001, Bonferroni corrected). Finally, leveraging our model's capacity to estimate individual-level treatment effects, we found that patients with IgA kappa myeloma appear to benefit the most from IRd. Our study suggests that a holistic assessment of a patient's myeloma course is possible, potentially serving as the foundation for a personalized decision support system. [ABSTRACT FROM AUTHOR]

Whole genome duplication is frequently observed in cancer, and its prevalence in our prior analysis of end-stage, homologous recombination deficient high grade serous ovarian cancer (almost 80% of samples) supports the notion that whole genome duplication provides a fitness advantage under the selection pressure of therapy. Here, we therefore aim to identify potential therapeutic vulnerabilities in primary high grade serous ovarian cancer with whole genome duplication by assessing differentially expressed genes and pathways in 79 samples. We observe that MHC-II expression is lowest in tumors which have acquired whole genome duplication early in tumor evolution, and further demonstrate that reduced MHC-II expression occurs in subsets of tumor cells rather than in canonical antigen-presenting cells. Early whole genome duplication is also associated with worse patient survival outcomes. Our results suggest an association between the timing of whole genome duplication, MHC-II expression and clinical outcome in high grade serous ovarian cancer that warrants further investigation for therapeutic targeting. There is high prevalence of whole genome duplication (WGD) in high grade serous ovarian cancer. Here, the authors compare tumours with and without WGD and find that those that acquired WGD early during tumour evolution are associated with worse survival and have the lowest expression of MHC-II. [ABSTRACT FROM AUTHOR]

Boron neutron capture therapy (BNCT) is a unique radiotherapy of selectively eradicating tumor cells using boron compounds (e.g., 4-borono-l-phenylalanine [BPA]) that are heterogeneously taken up at the cellular level. Such heterogenicity potentially reduces the curative efficiency. However, the effects of temporospatial heterogenicity on cell killing remain unclear. With the technical combination of radiation track detector and biophysical simulations, this study revealed the cell cycle-dependent heterogenicity of BPA uptake and subsequent biological effects of BNCT on HeLa cells expressing fluorescent ubiquitination-based cell cycle indicators, as well as the modification effects of polyvinyl alcohol (PVA). The results showed that the BPA concentration in the S/G2/M phase was higher than that in the G1/S phase and that PVA enhances the biological effects both by improving the uptake and by canceling the heterogenicity. These findings might contribute to a maximization of therapeutic efficacy when BNCT is combined with PVA and/or cell cycle-specific anticancer agents. [ABSTRACT FROM AUTHOR]

Background: Telmisartan, a potent angiotensin II type-1 receptor blocker as well as partial PPAR–gamma agonist, has emerged as a versatile therapeutic agent with diverse pharmacological actions beyond its primary indication for essential hypertension. This review explores the complex mechanisms of action of telmisartan and clarifies its effectiveness in an inflammation, cancer, metabolic, and CNS disorders. Main body: Telmisartan inhibits many biochemical processes involved in the control of the cardiovascular system, such as vascular smooth muscle contraction, aldosterone production, and sympathetic tone modulation, by specifically targeting the angiotensin II type-1 receptor. Its distinct partial agonist action toward peroxisome proliferator-activated receptor gamma also imparts anti-inflammatory, antiproliferative, and antioxidant activities, making it a viable treatment for various diabetic patients who have atherosclerosis and myocardial infarction. Conclusion: Telmisartan's diverse pharmacological actions, encompassing anti-inflammatory, neuroprotective, nephroprotective, anticancer, and anti-anxiety properties, position it as a promising treatment option for a broad spectrum of medical conditions. [ABSTRACT FROM AUTHOR]

Recognizing the pivotal role of circadian rhythm in the human aging process and its scalability through wearables, we introduce CosinorAge, a digital biomarker of aging developed from wearable-derived circadian rhythmicity from 80,000 midlife and older adults in the UK and US. A one-year increase in CosinorAge corresponded to 8–12% higher all-cause and cause-specific mortality risks and 3–14% increased prospective incidences of age-related diseases. CosinorAge also captured a non-linear decline in resilience and physical functioning, evidenced by an 8–33% reduction in self-rated health and a 3–23% decline in health-related quality of life score, adjusting for covariates and multiple testing. The associations were robust in sensitivity analyses and external validation using an independent cohort from a disparate geographical region using a different wearable device. Moreover, we illustrated a heterogeneous impact of circadian parameters associated with biological aging, with young (<45 years) and fast agers experiencing a substantially delayed acrophase with a 25-minute difference in peak timing compared to slow agers, diminishing to a 7-minute difference in older adults (>65 years). We demonstrated a significant enhancement in the predictive performance when integrating circadian rhythmicity in the estimation of biological aging over physical activity. Our findings underscore CosinorAge's potential as a scalable, economic, and digital solution for promoting healthy longevity, elucidating the critical and multifaceted circadian rhythmicity in aging processes. Consequently, our research contributes to advancing preventive measures in digital medicine. [ABSTRACT FROM AUTHOR]

Background: Japanese traditional (Kampo) medicines containing ephedra may be used to treat colds during pregnancy. There are reports that ephedrine, a component of ephedra, has a risk of teratogenicity; however, the evidence remains equivocal. Objective: This study aimed to evaluate the risk of major congenital malformations (MCMs) associated with exposure to Kampo medicines containing ephedra during the first trimester of pregnancy using the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). Methods: To 23,730 mother–infant pairs who participated in the TMM BirThree Cohort Study from July 2013 to March 2017, questionnaires in early and middle pregnancy were distributed approximately at weeks 12 and 26 of pregnancy, respectively. Infants' risk of MCMs in women who used Kampo medicines containing ephedra or acetaminophen during the first trimester was assessed, and the odds ratios (ORs) were estimated with unadjusted and adjusted analyses. Results: Among 20,879 women, acetaminophen and Kampo medicines containing ephedra were used in 665 (3.19%) and 376 (1.80%) women, respectively, in the first trimester. Among the infants born to the mothers who used acetaminophen or Kampo medicine containing ephedra during the first trimester, 11 (1.65%) and 8 (2.13%), respectively, had overall MCMs. OR of overall MCMs was higher in women who used Kampo medicines containing ephedra than in those who used acetaminophen in the first trimester (adjusted OR, 1.45; 95% confidence interval (CIs), 0.57–3.71); however, the difference was not statistically significant. Conclusions: In this study, there was no statistically significant association between the use of Kampo medicines containing ephedra during the first trimester of pregnancy and the risk of MCMs. Although some point estimates of ORs exceeded 1.00, the absolute magnitude of any increased risks would be low. [ABSTRACT FROM AUTHOR]

A patient with primary non-Hodgkin's (B-cell type) lymphoma of the kidney developed hypercalcemia at the terminal stage of the disease. Although the plasma parathyroid hormone level was low, urinary cyclic AMP excretion was elevated. Serum osteocalcin (BGP) was suppressed and the plasma level of 1,25(OH)2D was within the normal range. Serum concentrations of PTH-related protein (PTHrP)-like immunoreactivity (PRP-LI) were elevated, and the tissue concentration of PRP-LI in the postmortem lymph node showed high level along with elevated serum PRP-LI, furthermore the production of PTHrP by the tumor was demonstrated by immunohistochemistry and Northern blotting analysis. These findings indicate that the hypercalcemia of the patient was caused by the PTHrP-producing B-cell lymphoma. Hypercalcemia was restored to normocalcemia by bisphosphonate treatment. Our case will add further information on humoral hypercalcemia in B-cell lymphoma, which rarely has been demonstrated to produce PTHrP. [ABSTRACT FROM AUTHOR]

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After tunnel excavation and unloading, the stress state of the rock mass is redistributed, resulting in varying radial stresses at different radial depths in the rock mass. Rock mechanics tests showed that the confining pressure, especially for soft rock, had a substantial impact on the mechanical properties of the rock which at various radial depths varied with the confining pressure. Therefore, the Mohr-coulomb strength criterion was used in this study to elastic-plastic analysis of deeply buried tunnels that took into account the coupling impact of strain-softening and confining pressure using the finite difference method. Then, regardless of whether the confining pressure is taken into account, the rock mass's plastic zone radius and deformation value were compared, which were considerably impacted by confining pressure: the effect is more pronounced when the rock strength is lower and the initial geostress is higher. The rock mass's strain-softening behaviors and its confining pressure effect should be highlighted while soft rock tunnel support structures were designed with the condition of high initial geostress in order to prevent the rock mass's distinct deformation of the rock mass caused by the calculation results distortion or even serious consequences like large deformation, damage or failure. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the utility of deep learning (DL) automated segmentation-based MRI radiomic features and clinical-radiological characteristics in predicting early recurrence after curative resection of single hepatocellular carcinoma (HCC). Methods: This single-center, retrospective study included consecutive patients with surgically proven HCC who underwent contrast-enhanced MRI before curative hepatectomy from December 2009 to December 2021. Using 3D U-net-based DL algorithms, automated segmentation of the liver and HCC was performed on six MRI sequences. Radiomic features were extracted from the tumor, tumor border extensions (5 mm, 10 mm, and 20 mm), and the liver. A hybrid model incorporating the optimal radiomic signature and preoperative clinical-radiological characteristics was constructed via Cox regression analyses for early recurrence. Model discrimination was characterized with C-index and time-dependent area under the receiver operating curve (tdAUC) and compared with the widely-adopted BCLC and CNLC staging systems. Results: Four hundred and thirty-four patients (median age, 52.0 years; 376 men) were included. Among all radiomic signatures, HCC with5 mmtumorborderextensionandliver showed the optimal predictive performance (training set C-index, 0.696). By incorporating this radiomic signature, rim arterial phase hyperenhancement (APHE), and incomplete tumor "capsule," a hybrid model demonstrated a validation set C-index of 0.706 and superior 2-year tdAUC (0.743) than both the BCLC (0.550; p < 0.001) and CNLC (0.635; p = 0.032) systems. This model stratified patients into two prognostically distinct risk strata (both datasets p < 0.001). Conclusion: A preoperative imaging model incorporating the DL automated segmentation-based radiomic signature with rim APHE and incomplete tumor "capsule" accurately predicted early postsurgical recurrence of a single HCC. Critical relevance statement: The DL automated segmentation-based MRI radiomic model with rim APHE and incomplete tumor "capsule" hold the potential to facilitate individualized risk estimation of postsurgical early recurrence in a single HCC. Key Points: A hybrid model integrating MRI radiomic signature was constructed for early recurrence prediction of HCC. The hybrid model demonstrated superior 2-year AUC than the BCLC and CNLC systems. The model categorized the low-risk HCC group carried longer RFS. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is recognized an independent risk factor for chronic kidney disease (CKD). The precise contribution and differential response to treatment strategies to reduce kidney dysfunction, depending on whether obesity is present alongside T2DM or not, remain to be fully clarified. Our objective was to improve our understanding of how obesity contributes to kidney function in patients with T2DM and coronary heart disease (CHD), who are highly predisposed to CKD, to assign the most effective dietary approach to preserve kidney function. Methods: 1002 patients with CHD and estimated glomerular filtration rate (eGFR)≥30 ml/min/1.73m2, were randomized to consume a Mediterranean diet (35% fat, 22% MUFA, < 50% carbohydrates) or a low-fat diet (28% fat, 12% MUFA, > 55% carbohydrates). Patients were classified into four groups according to the presence of T2DM and/or obesity at baseline: Non-Obesity/Non-T2DM, Obesity/Non-T2DM, Non-Obesity/T2DM and Obesity/T2DM. We evaluated kidney function using serum creatinine-based estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR) before and after 5-years of dietary intervention. Results: Patients with Obesity/T2DM had the lowest baseline eGFR and the highest baseline uACR compared to non-diabetics (p < 0.05). After dietary intervention, the Mediterranean diet induced a lower eGFR decline in patients with Obesity/T2DM, compared to a low-fat diet but not in the other groups (p = 0.014). The Mediterranean diet, but not the low-fat diet, also reduced uACR only in patients with Obesity/T2DM (p = 0.024). Conclusions: Obesity provided an additive effect to T2DM resulting in a more pronounced decline in kidney function compared to T2DM alone when compared to non-diabetics. In patients with concomitant presence of T2DM and obesity, with more metabolic complications, consumption of a Mediterranean diet seemed more beneficial than a low-fat diet in terms of preserving kidney function. These findings provide valuable insights for tailoring personalized lifestyle modifications in secondary prevention of cardiovascular disease. Trial registration: URL, http://www.cordioprev.es/index.php/en. Clinicaltrials.gov number, NCT00924937 [ABSTRACT FROM AUTHOR]

Engineering rockmass classifications are an integral part of design, support and excavation procedures of tunnels, mines, and other underground structures. These classifications are directly linked to ground reaction and support requirements. Various classification systems are in practice and are still evolving. As different classifications serve different purposes, it is imperative to establish inter-correlatability between them. The rating systems and engineering judgements influence the assignment of ratings owing to cognition. To understand the existing correlation between different classification systems, the existing correlations were evaluated with the help of data of 34 locations along a 618-m-long railway tunnel in the Garhwal Himalaya of India and new correlations were developed between different rock classifications. The analysis indicates that certain correlations, such as RMR-Q, RMR-RMi, RMi-Q, and RSR-Q, are comparable to the previously established relationships, while others, such as RSR-RMR, RCR-Qn, and GSI-RMR, show weak correlations. These deviations in published correlations may be due to individual parameters of estimation or measurement errors. Further, incompatible classification systems exhibited low correlations. Thus, the study highlights a need to revisit existing correlations, particularly for rockmass conditions that are extremely complex, and the predictability of existing correlations exhibit high variations. In addition to augmenting the existing database, new correlations for metamorphic rocks in the Himalayan region have been developed and presented that can serve as a guide for future rock engineering projects in such formations and aid in developing appropriate excavation and rock support methodologies. [ABSTRACT FROM AUTHOR]

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Immune checkpoint blockade (ICB) has improved outcome for patients with metastatic melanoma but not all benefit from treatment. Several immune- and tumor intrinsic features are associated with clinical response at baseline. However, we need to further understand the molecular changes occurring during development of ICB resistance. Here, we collect biopsies from a cohort of 44 patients with melanoma after progression on anti-CTLA4 or anti-PD1 monotherapy. Genetic alterations of antigen presentation and interferon gamma signaling pathways are observed in approximately 25% of ICB resistant cases. Anti-CTLA4 resistant lesions have a sustained immune response, including immune-regulatory features, as suggested by multiplex spatial and T cell receptor (TCR) clonality analyses. One anti-PD1 resistant lesion harbors a distinct immune cell niche, however, anti-PD1 resistant tumors are generally immune poor with non-expanded TCR clones. Such immune poor microenvironments are associated with melanoma cells having a de-differentiated phenotype lacking expression of MHC-I molecules. In addition, anti-PD1 resistant tumors have reduced fractions of PD1+ CD8+ T cells as compared to ICB naïve metastases. Collectively, these data show the complexity of ICB resistance and highlight differences between anti-CTLA4 and anti-PD1 resistance that may underlie differential clinical outcomes of therapy sequence and combination. A large fraction of patients with melanoma still does not benefit from immune checkpoint blockade, associated with both primary and acquired resistance. Here the authors report genetic and immunological patterns of resistance in patients with melanoma after progression on anti-CTLA4 or anti-PD1 monotherapy. [ABSTRACT FROM AUTHOR]

Carbaporphyrin dimers, investigated for their distinctive electronic structures and exceptional properties, have predominantly consisted of systems containing identical subunits. This study addresses the associated knowledge gap by focusing on asymmetric carbaporphyrin dimers with Janus-like characteristics. The synthesis of a Janus-type carbaporphyrin pseudo-dimer 5 is presented. It displays antiaromatic characteristics on the fused side and nonaromatic behavior on the unfused side. A newly synthesized tetraphenylene (TPE) linked bis-dibenzihomoporphyrin 8 and a previously reported dibenzo[g,p]chrysene (DBC) linked bis-dicarbacorrole 9 were prepared as controls. Comprehensive analyses, including 1H NMR spectral studies, single crystal X-ray diffraction analyses, and DFT calculations, validate the mixed character of 5. A further feature of the Janus pseudo-dimer 5 is that it may be transformed into a heterometallic complex, with one side coordinating a Cu(III) center and the other stabilizing a BODIPY complex. This disparate regiochemical reactivity underscores the potential of carbaporphyrin dimers as versatile frameworks, with electronic features and site-specific coordination chemistry controlled through asymmetry. These findings position carbaporphyrin dimers as promising candidates for advances in electronic structure studies, coordination chemistry, materials science, and beyond. Carbaporphyrin dimers, known for their interesting photophysical properties and application in metal-organic chemistry, generally contain two identical subunits. Here, the authors highlight the benefits that can accrue from breaking the inherent symmetry of carbaporphyrin dimers and details a new approach to creating heterobimetallic complexes. [ABSTRACT FROM AUTHOR]

Survival analysis is a family of statistical methods for analyzing event occurrence times. We adopt a mixed-integer optimization approach to estimation of sparse Cox proportional hazards (PH) models for survival analysis. Specifically, we propose a high-performance cutting-plane algorithm based on a reformulation of our sparse estimation problem into a bilevel optimization problem. This algorithm solves the upper-level problem using cutting planes that are generated from the dual lower-level problem to approximate an upper-level nonlinear objective function. To solve the dual lower-level problem efficiently, we devise a quadratic approximation of the Fenchel conjugate of the loss function. We also develop a computationally efficient least-squares method for adjusting quadratic approximations to fit each dataset. Computational results demonstrate that our method outperforms regularized estimation methods in terms of accuracy for both prediction and subset selection especially for low-dimensional datasets. Moreover, our quadratic approximation of the Fenchel conjugate function accelerates the cutting-plane algorithm and maintains high generalization performance of sparse Cox PH models. [ABSTRACT FROM AUTHOR]

Prolonged polishing deteriorates the shape accuracy of an optical element and reduces production efficiency simultaneously. In order to reduce the amount of polishing and polishing time, even obtain polish-free fine surfaces, a cerium oxide (CeO2) slurry-enhanced grinding (SEG) is investigated. However, the lack of in-depth mechanism explanation limits the optimization and application of SEG. In this research, a novel theoretical model was established to predict the surface roughness of the workpiece processed by CeO2 SEG. The modeling considered the effects of the protrusion height of active grains in the grinding wheel and the sizes and mass fractions of CeO2 particles in the grinding zone on undeformed chip thickness (UCT). Then, the mechanism of CeO2 SEG was investigated through the nanoindentation method. Indentation hardness and energy spectrum of the surface were estimated to verify the softened layer. The results showed that the model of surface roughness was well consistent with the experiment. CeO2 particle size significantly influenced the surface roughness than the mass fraction. The load-bearing effect of larger CeO2 particle size reduced the protruding height of the grinding wheel grains and reduced the UCT to a greater extent in the grinding process. The chemical reaction between CeO2 slurry and BK7 glass results in a softening layer which enhances the critical load and critical depth of the ductile–brittle transition of grinding. Finally, the optimized parameters were used for CeO2 SEG of ellipsoid BK7 optics and obtained the high surface quality. [ABSTRACT FROM AUTHOR]

Predicting clinical responses to tumor immunotherapy is essential to reduce side effects and the potential for sustained clinical responses. Nevertheless, preselecting patients who are likely to respond to such treatments remains highly challenging. Here, we explored the potential of microRNAs (miRNAs) as predictors of immune checkpoint blockade responses using a machine learning approach. First, we constructed random forest models to predict the response to tumor ICB therapy using miRNA expression profiles across 19 cancer types. The contribution of individual miRNAs to each prediction process was determined by employing SHapley Additive exPlanations (SHAP) for model interpretation. Remarkably, the predictive performance achieved by using a small number of miRNAs with high feature importance was similar to that achieved by using the entire miRNA set. Additionally, the genes targeted by these miRNAs were closely associated with tumor- and immune-related pathways. In conclusion, this study demonstrates the potential of miRNA expression data for assessing tumor immunotherapy responses. Furthermore, we confirmed the potential of informative miRNAs as biomarkers for the prediction of immunotherapy response, which will advance our understanding of tumor immunotherapy mechanisms. [ABSTRACT FROM AUTHOR]

Background: Inflammatory myofibroblastic tumor (IMT) of the stomach is an uncommon mesenchymal neoplasm. We present a case of gastric submucosal tumor (SMT) where the final diagnosis was IMT. Case presentation: A 69-year-old man presented with a 24-mm SMT on the posterior wall of the middle third of the stomach that was detected by screening upper gastrointestinal endoscopy. Abdominal contrast-enhanced computed tomography showed that the tumor was well-enhanced. Although endoscopic ultrasonography-guided biopsy was performed, the histological diagnosis was not confirmed preoperatively. Since the tumor was clinically suspected to be a gastrointestinal stromal tumor, we performed gastric wedge resection by laparoscopic–endoscopic cooperative surgery. Pathologically, proliferative spindle cells with a positive reaction for smooth muscle actin, negativity for c-kit, desmin, s-100, CD34, STAT-6, β-catenin and anaplastic lymphoma kinase 1 were identified. Hence, the tumor was finally diagnosed as an IMT originating from the stomach. Conclusions: When an SMT of the stomach is identified, the possibility of gastric IMT should be considered. [ABSTRACT FROM AUTHOR]

Belt electrode-skeletal muscle electrical stimulation (B-SES) involves the use of belt-shaped electrodes to contract multiple muscle groups simultaneously. Twitch contractions have been demonstrated to protect against denervation-induced muscle atrophy in rats, possibly through mitochondrial biosynthesis. This study examined whether inducing tetanus contractions with B-SES suppresses muscle atrophy and identified the underlying molecular mechanisms. We evaluated the effects of acute (60 Hz, 5 min) and chronic (60 Hz, 5 min, every alternate day for one week) B-SES on the tibialis anterior (TA) and gastrocnemius (GAS) muscles in Sprague–Dawley rats using belt electrodes attached to both ankle joints. After acute stimulation, a significant decrease in the glycogen content was observed in the left and right TA and GAS, suggesting that B-SES causes simultaneous contractions in multiple muscle groups. B-SES enhanced p70S6K phosphorylation, an indicator of the mechanistic target of rapamycin complex 1 activity. During chronic stimulations, rats were divided into control (CONT), denervation-induced atrophy (DEN), and DEN + electrically stimulated with B-SES (DEN + ES) groups. After seven days of treatment, the wet weight (n = 8–11 for each group) and muscle fiber cross-sectional area (CSA, n = 6 for each group) of the TA and GAS muscles were reduced in the DEN and DEN + ES groups compared with that in the CON group. The DEN + ES group showed significantly higher muscle weight and CSA than those in the DEN group. Although RNA-seq and pathway analysis suggested that mitochondrial biogenesis is a critical event in this phenomenon, mitochondrial content showed no difference. In contrast, ribosomal RNA 28S and 18S (n = 6) levels in the DEN + ES group were higher than those in the DEN group, even though RNA-seq showed that the ribosome biogenesis pathway was reduced by electrical stimulation. The mRNA levels of the muscle proteolytic molecules atrogin-1 and MuRF1 were significantly higher in DEN than those in CONT. However, they were more suppressed in DEN + ES than those in DEN. In conclusion, tetanic electrical stimulation of both ankles using belt electrodes effectively reduced denervation-induced atrophy in multiple muscle groups. Furthermore, ribosomal biosynthesis plays a vital role in this phenomenon. [ABSTRACT FROM AUTHOR]

The intricate crosstalk of various cell death forms was recently implicated in cancers, laying a foundation for exploring the association between cell death and cancers. Recent evidence has demonstrated that biological networks outperform snapshot gene expression profiles at discovering promising biomarkers or heterogenous molecular subtypes across different cancer types. In order to investigate the behavioral patterns of cell death-related interaction perturbation in colorectal cancer (CRC), this study constructed the interaction-perturbation network with 11 cell death pathways and delineated four cell death network (CDN) derived heterogeneous subtypes (CDN1-4) with distinct molecular characteristics and clinical outcomes. Specifically, we identified a subtype (CDN4) endowed with high autophagy activity and the worst prognosis. Furthermore, AOC3 was identified as a potential autophagy-related biomarker, which demonstrated exceptional predictive performance for CDN4 and significant prognostic value. Overall, this study sheds light on the complex interplay of various cell death forms and reveals an autophagy-related gene AOC3 as a critical prognostic marker in CRC. In colorectal cancer, four cell death subtypes (CDN1-4) are identified, each with distinct traits and prognoses. [ABSTRACT FROM AUTHOR]

The timing and fitness effect of somatic copy number alterations (SCNA) in cancer evolution remains poorly understood. Here we present a framework to determine the timing of a clonal SCNA that encompasses multiple gains. This involves calculating the proportion of time from its last gain to the onset of population expansion (lead time) as well as the proportion of time prior to its first gain (initiation time). Our method capitalizes on the observation that a genomic segment, while in a specific copy number (CN) state, accumulates point mutations proportionally to its CN. Analyzing 184 whole genome sequenced samples from 75 patients across five tumor types, we commonly observe late gains following early initiating events, occurring just before the clonal expansion relevant to the sampling. These include gains acquired after genome doubling in more than 60% of cases. Notably, mathematical modeling suggests that late clonal gains may contain final-expansion drivers. Lastly, SCNAs bolster mutational diversification between subpopulations, exacerbating the circle of proliferation and increasing heterogeneity. [ABSTRACT FROM AUTHOR]

Benzoxazole is an attractive scaffold in medicinal chemistry due to its diverse biological applications. From 2016 to 2023, a plethora of benzoxazole derivatives have been synthesized and evaluated for their pharmacological activities but a review on this topic was found lacking. This review thus aims to fill the gap and discusses the pharmacological activities of the synthesized derivatives, emphasizing their interactions with key biological targets implicated in diseases such as cancer, diabetes, pain, inflammation, and cardiovascular disorders. Relevant works were selected mainly from databases such as PubMed and Google Scholar to offer a comprehensive overview of derivatives with promising bioactivities. The limitations pertinent to some derivatives, such as poor in vitro or in vivo activities, were highlighted, while their prospects in drug discovery was discussed. [ABSTRACT FROM AUTHOR]

Introduction: The majority of patients in the intensive care unit (ICU) are at risk for at least one electrolyte abnormality and critically ill patients are the most vulnerable population to the effects of suboptimal electrolyte levels. These patients have unique characteristics impacting implications of the electrolyte disturbances and management. Areas Covered: In the ICU, magnesium, potassium, calcium, phosphorous, and sodium are the most commonly encountered electrolytes that can be abnormal in the critically ill. Critical illness both is affected by and affects disturbances of these electrolytes which can result in more severe illness, longer duration of mechanical ventilation, increased dialysis support, longer length of stay, and increased mortality. Often, patients have multiple imbalances that require correction. Removal or mitigation of the cause should be undertaken whenever possible and should be concurrent with any therapeutic management used to correct the electrolyte imbalance. Selection of medication to correct electrolyte imbalances should be undertaken according to available evidence and drug-specific characteristics that impact medication delivery in the critically ill. Electrolyte disturbances, measurements, and corrections are ubiquitous in the ICU. Published literature on the management of electrolytes in the critically ill is limited. Management should consider factors unique to the critically ill when selecting optimal treatment approach and it is essential to individualize treatment to a patient's unique needs and adapt management to the patient's chancing clinical situation. [ABSTRACT FROM AUTHOR]

Anticoagulation therapy has undergone significant evolution, marked by the emergence of direct oral anticoagulants with distinct advantages. Despite these advancements, challenges persist in managing residual thrombotic and bleeding risks, particularly among vulnerable populations. The pursuit of alternative drugs has honed in on factor XI/XIa inhibitors. This comprehensive review delves into several key aspects regarding this new target: (i) the role of factor XI in the coagulation cascade; (ii) the genetic evidence and pathophysiologic rationale supporting factor XI inhibition as a therapeutic target; (iii) an exploration of the various types of factor XI/XIa inhibitors currently under investigation; (iv) potential applications of these medications, spanning thromboprophylaxis after orthopedic surgery, stroke prevention in atrial fibrillation, secondary prevention after acute coronary syndrome, non-cardioembolic stroke, thromboprophylaxis after foreign material implantation, end-stage renal disease, and patients with cancer; and (v) an overview of ongoing studies, recent findings, and the future trajectory of research into these drugs. [ABSTRACT FROM AUTHOR]

Background: Lung congestion is frequent in heart failure (HF) and is associated with symptoms and poor prognosis. Lung ultrasound (LUS) identification of B-lines may help refining congestion assessment on top of usual care. Three small trials comparing LUS-guided therapy to usual care in HF suggested that LUS-guided therapy could reduce urgent HF visits. However, to our knowledge, the usefulness of LUS in influencing loop diuretic dose adjustment in ambulatory chronic HF has not been studied. Aims: To study whether to show or not LUS results to the HF assistant physician would change loop diuretic adjustments in "stable" chronic ambulatory HF patients. Methods: Prospective randomised single-blinded trial comparing two strategies: (1) open 8-zone LUS with B-line results available to clinicians, or (2) blind LUS. The primary outcome was change in loop diuretic dose (up- or down-titration). Results: A total of 139 patients entered the trial, 70 were randomised to blind LUS and 69 to open LUS. The median (percentile25-75) age was 72 (63–82) years, 82 (62%) were men, and the median LVEF was 39 (31–51) %. Randomisation groups were well balanced. Furosemide dose changes (up- and down-titration) were more frequent among patients in whom LUS results were open to the assistant physician: 13 (18.6%) in blind LUS vs. 22 (31.9%) in open LUS, OR 2.55, 95%CI 1.07–6.06. Furosemide dose changes (up- and down-titration) were more frequent and correlated significantly with the number of B-lines when LUS results were open (Rho = 0.30, P = 0.014), but not when LUS results were blinded (Rho = 0.19, P = 0.13). Compared to blind LUS, when LUS results were open, clinicians were more likely to up-titrate furosemide dose if the result "presence of pulmonary congestion" was identified and more likely to decrease furosemide dose in the case of an "absence of pulmonary congestion" result. The risk of HF events or cardiovascular death did not differ by randomisation group: 8 (11.4%) in blind LUS vs. 8 (11.6%) in open LUS. Conclusions: Showing the results of LUS B-lines to assistant physicians allowed more frequent loop diuretic changes (both up- and down-titration), which suggests that LUS may be used to tailor diuretic therapy to each patient congestion status. [ABSTRACT FROM AUTHOR]

The clinical implications of extrachromosomal DNA (ecDNA) in cancer therapy remain largely elusive. Here, we present a comprehensive analysis of ecDNA amplification spectra and their association with clinical and molecular features in multiple cohorts comprising over 13,000 pan-cancer patients. Using our developed computational framework, GCAP, and validating it with multifaceted approaches, we reveal a consistent pan-cancer pattern of mutual exclusivity between ecDNA amplification and microsatellite instability (MSI). In addition, we establish the role of ecDNA amplification as a risk factor and refine genomic subtypes in a cohort from 1015 colorectal cancer patients. Importantly, our investigation incorporates data from four clinical trials focused on anti-PD-1 immunotherapy, demonstrating the pivotal role of ecDNA amplification as a biomarker for guiding checkpoint blockade immunotherapy in gastrointestinal cancer. This finding represents clinical evidence linking ecDNA amplification to the effectiveness of immunotherapeutic interventions. Overall, our study provides a proof-of-concept of identifying ecDNA amplification from cancer whole-exome sequencing (WES) data, highlighting the potential of ecDNA amplification as a valuable biomarker for facilitating personalized cancer treatment. 'Extrachromosomal DNA has been previously linked to tumour progression and heterogeneity, but its potential as a cancer biomarker has not been fully explored. Here, the authors develop a computational framework to refine genomic subtypes and predict response to immunotherapy in gastrointestinal cancer. [ABSTRACT FROM AUTHOR]

The aim of the current study is to test how psychological distress mediates the associations between neighborhood social cohesion (NSC) and cognitive performance including episodic memory, semantic verbal fluency, fluid reasoning, and numeracy in older adults. Nine multiple regressions were used to analyze the associations between NSC and cognitive performance, NSC and psychological distress, and psychological distress and cognitive performance respectively based on data from 4922 older adults with a mean age of 66.51 (S.D. = 8.27) years old and 47.01% males from Understanding Society: the UK Household Longitudinal Study (UKHLS). Moreover, a mediation analysis was conducted by the mediation toolbox on MATLAB 2018a (https://github.com/canlab/MediationToolbox). The current study found that NSC is positively related to all cognitive measures but negatively related to psychological distress, whereas psychological distress is negatively associated with all cognitive performance. Moreover, there was a complete mediation effect of psychological distress on the positive association between NSC and semantic verbal fluency and the association between NSC and fluid reasoning. However, NSC only partially mediated the positive associations between NSC and episodic memory and numeracy respectively. From a policy standpoint, findings from the current study contribute evidence that reinforces the need for program designers and policymakers to join the WHO's global efforts to build age-friendly communities, which promotes NSC, then leads to reduced psychological distress, and thus better cognitive functions among the elderly. Preserving cognitive functions may in turn reduce health care burdens. [ABSTRACT FROM AUTHOR]