Trajectories of pain and their associations with long-term cognitive decline in older adults: evidence from two longitudinal cohorts.

BACKGROUND: Pain is a dynamic experience that varies over time, but it remains unknown whether trajectories of pain are associated with subsequent cognitive decline. The purpose of this study was to identify distinct trajectories of pain presence and activity-limiting pain and investigate their longitudinal associations with the rate of subsequent cognitive decline in older adults. METHODS: A total of 5685 participants from the English Longitudinal Study of Ageing (ELSA) and 7619 participants from the Health and Retirement Study (HRS) were included. Pain presence trajectories were identified over eight years in the ELSA and 10 years in the HRS, while trajectories of activity-limiting pain were identified over 10 years in the HRS. We utilised linear mixed-effects models to investigate the long-term relationship between pain trajectories and the rate of cognitive decline across various domains, including memory, orientation, executive function and global cognition. RESULTS: Three pain presence trajectories were identified. Moderate-increasing and high-stable groups exhibited steeper declines in global cognition than the low-stable group. Furthermore, individuals in the moderate-increasing group experienced a more rapid decline in executive function, while the high-stable group showed a faster decline in orientation function. Two trajectories of activity-limiting pain were identified, with the moderate-increasing group experiencing a faster decline in orientation function and global cognition. CONCLUSIONS: The trajectories of both pain presence and activity-limiting pain are linked to the rate of subsequent cognitive decline among older people. Interventions for specific pain trajectories might help to delay the decline rate of cognition in specific domains.

Association between pain interference and motoric cognitive risk syndrome in older adults: a population-based cohort study.

OBJECTIVES: Motoric cognitive risk syndrome (MCR) is a pre-dementia condition characterized by subjective complaints in cognition and slow gait. Pain interference has previously been linked with cognitive deterioration; however, its specific relationship with MCR remains unclear. We aimed to examine how pain interference is associated with concurrent and incident MCR. METHODS: This study included older adults aged ≥ 65 years without dementia from the Health and Retirement Study. We combined participants with MCR information in 2006 and 2008 as baseline, and the participants were followed up 4 and 8 years later. The states of pain interference were divided into 3 categories: interfering pain, non-interfering pain, and no pain. Logistic regression analysis was done at baseline to examine the associations between pain interference and concurrent MCR. During the 8-year follow-up, Cox regression analysis was done to investigate the associations between pain interference and incident MCR. RESULTS: The study included 7120 older adults (74.6 ± 6.7 years; 56.8% females) at baseline. The baseline prevalence of MCR was 5.7%. Individuals with interfering pain had a significantly increased risk of MCR (OR = 1.51, 95% CI = 1.17-1.95; p = 0.001). The longitudinal analysis included 4605 participants, and there were 284 (6.2%) MCR cases on follow-up. Participants with interfering pain at baseline had a higher risk for MCR at 8 years of follow-up (HR = 2.02, 95% CI = 1.52-2.69; p < 0.001). CONCLUSIONS: Older adults with interfering pain had a higher risk for MCR versus those with non-interfering pain or without pain. Timely and adequate management of interfering pain may contribute to the prevention and treatment of MCR and its associated adverse outcomes.

Effects of combined morbid insomnia and sleep apnea on long-term cardiovascular risk and all-cause mortality in elderly patients: a prospective cohort study.

PURPOSE: It is reported that insomnia and obstructive sleep apnea (OSA) increase the incidence of adverse cardiovascular events. The aim of this study was to analyze the risk of cardiovascular disease and mortality in elderly patients with comorbid insomnia and obstructive sleep apnea (COMISA). METHODS: We included 868 elderly patients with OSA who underwent sleep monitoring at a multicenter sleep room from January 2015 to October 2017. We collected demographic data, clinical features, medical history, sleep parameters, and laboratory findings. Cox proportional hazards analysis was used to identify the relationship between COMISA and adverse cardiovascular events and all-cause mortality. RESULTS: There were 181 elderly patients with COMISA. The median follow-up was 43 months, during which we observed major adverse cardiac events (MACE) in 90 patients. The Kaplan-Meier survival curve indicated a significant relationship between COMISA and MACE (Plog Rank < 0.001). Multivariate Cox regression analysis showed that COMISA increased the incidence of MACE (HR = 2.328, 95% CI: 1.349-4.018, P = 0.002), hospitalization for unstable angina (HR = 2.915, 95% CI: 1.397-6.081, P = 0.004), and the combination of all events (HR = 2.301, 95% CI: 1.393-3.803, P = 0.001). However, there were no significant differences in cardiovascular death, all-cause mortality, myocardial infarction, or hospitalized heart failure in patients with COMISA (P > 0.05). Subgroup analyses showed that among COMISA patients, male sex (HR = 2.800, 95% CI: 1.458-5.377, P = 0.002), age < 70 years (HR = 4.050, 95% CI: 2.022-8.115, P < 0.001), and overweight and obesity (HR = 2.482, 95% CI: 1.383-4.453, P = 0.002) were associated with a higher risk of MACE. CONCLUSIONS: Our results showed that COMISA increased the risk of MACE, unstable angina, and the compound occurrence of all events. Male, overweight or obese COMISA patients under 70 years of age have an increased risk of MACE.

The impact of ankle-foot orthoses on mobility of dual-task walking in stroke patients? A cross-sectional two-factor factorial design clinical trial.

ABSTRACTTo assess the impact of ankle-foot orthoses (AFOs) on mobility and gait during dual-task walking in post-stroke survivors. In this cross-sectional, factorial design trial, stroke survivors performed four randomized tasks: (1) dual-task walking with AFOs, (2) single-task walking with AFOs, (3) dual-task walking without AFOs, and (4) single-task walking without AFOs. Primary outcome was the Timed Up and Go (TUG) test, with secondary outcomes including gait metrics, Tinetti scores, and auditory N-back tests. In the results, 48 subjects (38 males and 10 females; 19-65 years) completed the trial. Patients had a greater TUG score with AFOs compared with non-AFOs conditions (95% CI: 7.22-14.41, P < 0.001) in single-task and dual-task conditions. Secondary outcomes showed marked enhancement with AFOs during dual-task walking, with significant interaction effects in gait metrics, balance, and cognitive function (P < 0.05). Although not statistically significant, dual-task effects of TUG and walking speed were more pronounced during dual-task walking. In conclusion, AFOs enhance mobility and gait during both single and dual-task walking in post-stroke survivors.

Pial arteriovenous fistula resembling the vein of Galen aneurysmal malformation, treated with staged endovascular embolization: a case report.

A 41-month-old boy was presented to our hospital because of an intracranial mass suspected of cerebrovascular malformation. He was admitted and received cerebral angiography. The angiography result confirmed the intracranial mass was the dilated vein of Galen resulting from a pial arteriovenous fistula, which quite resembling the vein of Galen aneurysmal malformation. Considering one-time embolization of the fistula may greatly change the distribution of intracranial blood flow, we decided to perform staged embolization. In the first stage, we partially embolized the fistula, resulting in a sharp decrease in blood flow to the lesion. The second intervention was performed one month later, and completely embolized the fistula. The boy recoverd well and returned to normal childhood without any neurological deficits. Follow-up MR images obtained at 10 months after the last procedure showing total obliteration of the pAVF, gradually shrinking of the varix, and remodeling of the vein of Galen.

ipa1 improves rice drought tolerance at seedling stage mainly through activating abscisic acid pathway.

KEY MESSAGE: ipa1 enhances rice drought tolerance mainly through activating the ABA pathway. It endows rice seedlings with a more developed root system, smaller leaf stomata aperture, and enhanced carbon metabolism. Drought is a major abiotic stress to crop production. IPA1 (IDEAL PLANT ARCHITECTURE 1)/OsSPL14 encodes a transcription factor and has been reported to function in both rice ideal plant architecture and biotic resistance. Here, with a pair of IPA1 and ipa1-NILs (Near Iso-genic Lines), we found that ipa1 could significantly improve rice drought tolerance at seedling stage. The ipa1 plants had a better-developed root system and smaller leaf stomatal aperture. Analysis of carbon-nitrogen metabolism-associated enzyme activity, gene expression, and metabolic profile indicated that ipa1 could tip the carbon-nitrogen metabolism balance towards an increased carbon metabolism pattern. In both the control and PEG-treated conditions, ABA content in the ipa1 seedlings was significantly higher than that in the IPA1 seedlings. Expression of the ABA biosynthesis genes was detected to be up-regulated, whereas the expression of ABA catabolism genes was down-regulated in the ipa1 seedlings. In addition, based on yeast one-hybrid assay and dual-luciferase assay, IPA1 was found to directly activate the promoter activity of OsHOX12, a transcription factor promoting ABA biosynthesis, and OsNAC52, a positive regulator of the ABA pathway. The expression of OsHOX12 and OsNAC52 was significantly up-regulated in the ipa1 plants. Combined with the previous studies, our results suggested that ipa1 could improve rice seedling drought tolerance mainly through activating the ABA pathway and that regulation of the ipa1-mediated ABA pathway will be an important strategy for improving drought resistance of rice.

Quadriceps strength is negatively associated with knee joint structural abnormalities-data from osteoarthritis initiative.

OBJECTIVE: The aim of this study was to explore the longitudinal associations between baseline quadriceps strength and knee joint structural abnormalities in knee osteoarthritis (KOA). METHODS: This study is a longitudinally observational study based on Osteoarthritis Initiative (OAI) cohort, including men and women aged 45-79. Quadriceps strength was measured by isometric knee extension testing at baseline. Knee joint structural abnormalities, including cartilage damage, bone marrow lesions (BMLs), effusion-synovitis and Hoffa-synovitis, were evaluated by Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) at baseline and 1-year follow-up. Generalized estimating equations were employed to examine the associations between quadriceps strength and knee structural abnormalities. All analyses were stratified by sex. RESULTS: One thousand three hundred thirty-eight participants (523 men and 815 women) with a mean age of 61.8 years and a mean BMI of 29.4 kg/m2 were included in this study. For men, no significantly longitudinal association of quadriceps strength with structural abnormalities was detected. In contrast, quadriceps strength was significantly and negatively associated with changes in cartilage damage and BMLs in lateral patellofemoral joint (PFJ) (cartilage damage: OR: 0.91, 95% CI 0.84 to 0.99, P = 0.023; BMLs: OR: 0.85, 95% CI 0.74 to 0.96, P = 0.011) and effusion-synovitis (OR = 0.88, 95% CI 0.78 to 0.99, P = 0.045) among females longitudinally. Higher quadriceps strength was significantly associated with less progression of lateral PFJ cartilage damage, BMLs and effusion-synovitis in females. CONCLUSIONS: Higher quadriceps strength was associated with changes in cartilage damage and BMLs within the lateral PFJ and effusion-synovitis among females, suggesting the potential protective role of quadriceps strength on joint structures in women.

[Design and Verification of Human Metabolic Measurement System Based on STM32].

A high-precision human metabolic measurement system is designed. The system uses STM32F103 as the main control chip to acquire oxygen, carbon dioxide and flow signals to calculate four quantitative indicators: oxygen consumption(VO2), carbon dioxide production(VCO2), respiratory entropy(RQ) and resting energy metabolism(REE), and finally uses an upper computer to display the calculation results.In this paper, the signal acquisition circuit design was carried out for the oxygen sensor, carbon dioxide sensor and flow sensor, and the validity of the device was verified with the American machine MGCDiagnositcs using Bland-Altman analysis method, and the results showed that the four parameters of VO2,VCO2, RQ and REE of both devices fell in the agreement interval of more than 95%. The device thus provides accurate metabolic measurements and offers an effective tool for the field of general health and clinical nutrition support in China.

IPA1 Negatively Regulates Early Rice Seedling Development by Interfering with Starch Metabolism via the GA and WRKY Pathways.

Ideal Plant Architecture 1 (IPA1) encodes SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 14 (SPL14) with a pleiotropic effect on regulating rice development and biotic stress responses. To investigate the role of IPA1 in early seedling development, we developed a pair of IPA1/ipal-NILs and found that seed germination and early seedling growth were retarded in the ipa1-NIL. Analysis of the soluble sugar content, activity of amylase, and expression of the α-amylase genes revealed that the starch metabolism was weakened in the ipa1-NIL germinating seeds. Additionally, the content of bioactive gibberellin (GA) was significantly lower than that in the IPA1-NIL seeds at 48 h of imbibition. Meanwhile, the expression of GA synthesis-related gene OsGA20ox1 was downregulated, whereas the expression of GA inactivation-related genes was upregulated in ipa1-NIL seeds. In addition, the expression of OsWRKY51 and OsWRKY71 was significantly upregulated in ipa1-NIL seeds. Using transient dual-luciferase and yeast one-hybrid assays, IPA1 was found to directly activate the expression of OsWRKY51 and OsWRKY71, which would interfere with the binding affinity of GA-induced transcription factor OsGAMYB to inhibit the expression of α-amylase genes. In summary, our results suggest that IPA1 negatively regulates seed germination and early seedling growth by interfering with starch metabolism via the GA and WRKY pathways.

Characterization of Nitrate-Dependent As(III)-Oxidizing Communities in Arsenic-Contaminated Soil and Investigation of Their Metabolic Potentials by the Combination of DNA-Stable Isotope Probing and Metagenomics.

Arsenite (As(III)) oxidation has important environmental implications by decreasing both the mobility and toxicity of As in the environment. Microbe-mediated nitrate-dependent As(III) oxidation (NDAO) may be an important process for As(III) oxidation in anoxic environments. Our current knowledge of nitrate-dependent As(III)-oxidizing bacteria (NDAB), however, is largely based on isolates, and thus, the diversity of NDAB may be underestimated. In this study, DNA-stable isotope probing (SIP) with 13C-labeled NaHCO3 as the sole carbon source, amplicon sequencing, and shotgun metagenomics were combined to identify NDAB and investigate their NDAO metabolism. As(III) oxidation was observed in the treatment amended with nitrate, while no obvious As(III) oxidation was observed without nitrate addition. The increase in the gene copies of aioA in the nitrate-amended treatment suggested that As(III) oxidation was mediated by microorganisms containing the aioA genes. Furthermore, diverse putative NDAB were identified in the As-contaminated soil cultures, such as Azoarcus, Rhodanobacter, Pseudomonas, and Burkholderiales-related bacteria. Metagenomic analysis further indicated that most of these putative NDAB contained genes for As(III) oxidation and nitrate reduction, confirming their roles in NDAO. The identification of novel putative NDAB expands current knowledge regarding the diversity of NDAB. The current study also suggests the proof of concept of using DNA-SIP to identify the slow-growing NDAB.

A Novel Endovascular Technique for Recanalization of Carotid Artery Chronic Total Occlusion: Staged Carotid Angioplasty and Stenting.

AIM: Symptomatic carotid artery chronic total occlusion (SCACTO) can lead to neurocognitive function decline and carries a high risk or recurrent stroke. The treatment option is limited, endovascular intervention may be an alternative treatment but still controversial. To our knowledge, the staged carotid angioplasty and stenting (SCAS) did not previously reported. The purpose of this study was to report our experiences in this novel technique. METHODS: In 2017-2018, we attempted the staged carotid angioplasty and stenting (SCAS) approach in 13 patients who received SCACTO treatment. The SCAS approach involves two stages of intervention. The first stage involves initial recanalization and initial small-sized balloon angioplasty. The second stage, which is performed 4-6 weeks later, involves angioplasty and carotid stent placement. RESULTS: The success rate of SCAS was 76.9%. At the second stage, the lumen remained patent in all the patients. The mean spontaneous increase in lumen diameter after 4-6 weeks was 51.7%. The median length of the stent was 4.0 cm, and the median number of stents used was 1. One patient had a complication of dissection, with a complication rate of 7.6%. CONCLUSIONS: SCAS is a novel technique in the endovascular treatment of SCACTO. It is a feasible and safe approach that could reduce the complication rate and number of carotid stents needed.

[Design and Verification of a COPD Screening Equipment Based on Dual-differential Pressure Throttling Technique].

This study was to design a chronic obstructive pulmonary disease (COPD) screening equipment, based on the dual-differential pressure throttling technique. The technique combined a wide range, but low-resolution ratio sensor and a narrow range, but high-resolution ratio one. It can accurately detect the indexes of forced vital capacity (FVC), forced expiratory volume in one second (FEV1), one second rate(FEV1/FVC (%)), and achieve them in a low-cost way. The new designed machine will be compared with a British machine, named ML-3500. The correlations of FVC and FEV1 between new machine and ML-3500 were 0.998 and 0.999, respectively. The P values of paired t test of these two indexes were over 0.05. Bland-Altman analysis of FVC, FEV1 and FEV1/FVC (%) showed that more than 90% of the scatter points of the three parameters fell within the consistency interval. This machine can be used to accurately screen COPD and its low-cost would be advantage to promote in large population.

A Combination of Stable Isotope Probing, Illumina Sequencing, and Co-occurrence Network to Investigate Thermophilic Acetate- and Lactate-Utilizing Bacteria.

Anaerobic digestion is a complicated microbiological process that involves a wide diversity of microorganisms. Acetate is one of the most important intermediates, and interactions between acetate-oxidizing bacteria and archaea could play an important role in the formation of methane in anoxic environments. Anaerobic digestion at thermophilic temperatures is known to increase methane production, but the effects on the microbial community are largely unknown. In the current study, stable isotope probing was used to characterize acetate- and lactate-oxidizing bacteria in thermophilic anaerobic digestion. In microcosms fed 13C-acetate, bacteria related to members of Clostridium, Hydrogenophaga, Fervidobacterium, Spirochaeta, Limnohabitans, and Rhodococcus demonstrated elevated abundances of 13C-DNA fractions, suggesting their activities in acetate oxidation. In the treatments fed 13C-lactate, Anaeromyxobacter, Desulfobulbus, Syntrophus, Cystobacterineae, and Azospira were found to be the potential thermophilic lactate utilizers. PICRUSt predicted that enzymes related to nitrate and nitrite reduction would be enriched in 13C-DNA fractions, suggesting that the acetate and lactate oxidation may be coupled with nitrate and/or nitrite reduction. Co-occurrence network analysis indicated bacterial taxa not enriched in 13C-DNA fractions that may also play a critical role in thermophilic anaerobic digestion.

An Acute Ischemic Stroke Resulting from Aortic Dissection.

A 39-year-old man with syncope and persistent dizziness was sent to stroke emergency. Patient's diffusion magnetic resonance imaging of brain showed acute ischemia in right cerebella and right occipital lobe, thus intravenous recombinant tissue plasminogen activator was given to him. However, the patient behaved rather restless with repeated complaint of back and thoracic pain. Further thorax computed tomography angiography confirmed that the underlying cause turned out to be aortic dissection.

[Mechanical thrombectomy with the Solitaire AB device in acute ischemic stroke of posterior circulation: a series of 17 cases].

OBJECTIVE: To evaluate the efficacy and safety of mechanical thrombectomy with the Solitaire AB device in recanalization of patients with acute ischemic stroke of posterior circulation. METHODS: The clinical data of 17 consecutive patients with acute ischemic stroke of posterior circulation, treated with the Solitaire AB device from August 2011 to August 2015 in Department of Neurosurgery, the Military General Hospital of Beijing People's Liberation Army, were extracted and then retrospectively analyzed. There were 12 male and 5 female patients with a median age of 60 years (ranging from 44 to 75 years). Among them, 8 cases occluded in basilar artery, 4 cases occluded in vertebral artery and 5 cases occluded in vertebral plus basilar artery. Recanalization rate as well as complications after treatment were analysized. Also, neurological functions of the patients before and after treatment, measured by National Institute of Health stroke scale (NIHSS) score, were compared via t test and the clinical outcomes were assessed by modified Rankin score (mRS) at 90 days after treatment. RESULTS: Fifteen patients resulted in successfully recanalization, and 2 cases failed both of whose onset to sheath time were above 7.5 hours. The NIHSS score at 7 days was 11±10, which was significantly decreased compared to the admission NIHSS score 17±5 (t=2.949, P=0.009). No symptomatic intracranial hemorrhage case was found after thrombectomy. At 90 days, one patient died(mRS 6), one patient seriously disabled (mRS 5), two patients moderately seriously disabled (mRS 4), four patients resulted in moderate outcome (mRS 3) and the other 9 patients achieved good outcome (mRS 0 to 2). The dead and seriously disabled cases were both due to failure in recanalization. Two moderately seriously disabled cases were probably attributed to their severe admission condition (NIHSS >20) and prolonged time (onset to sheath time >6 hours). CONCLUSION: Mechanical thrombectomy with the Solitaire AB device contributes to a high rate of recanalization with a low probability of complication and improves functional outcome in patients with acute ischemic stroke of posterior circulation.

Ultra-early versus delayed coil treatment for ruptured poor-grade aneurysm.

INTRODUCTION: The timing of definitive aneurysm treatment (coiling or clipping) in poor-grade (Hunt-Hess IV or V) subarachnoid haemorrhage (SAH) patients has been a controversial topic. The purpose of this retrospective study was to analyse whether ultra-early coiling of ruptured intracranial aneurysms improves the clinical outcomes of poor-grade SAH patients. METHODS: The records of patients with aneurysmal SAH who were treated with endovascular coiling were retrieved. The patients were classified into two groups: group A (patients coiled within 24 h of SAH) and group B (patients coiled ≥ 24 h after SAH). For each group, the patient demographics, Fisher grade, aneurysm characteristics and clinical outcomes were recorded. Outcomes were measured at 6 months using the modified Rankin Scale (mRS). RESULTS: Thirty-one patients were coiled within 24 h of SAH (group A), and fourteen patients were coiled ≥24 h after SAH (group B). Groups A and B had similar clinical and angiographic characteristics. The clinical outcomes showed that a total of 58.1% of the patients (18 of 31) in group A were independent (mRS 0-2) compared with 21.4% of the patients (3 of 14) in group B (P = .028). Univariate analysis demonstrated that ultra-early coiling (P = .028) proved to be an independent predictor of better clinical outcomes (mRS 0-2). CONCLUSIONS: Ultra-early (<24 h after SAH) coiling of ruptured aneurysms was associated with improved clinical outcomes compared to coiling at ≥24 h in poor-grade SAH patients. Larger, prospective studies are required to adequately assess the outcome differences between these two groups.

[Comparative Study on the Three Algorithms of T-wave End Detection: Wavelet Method, Cumulative Points Area Method and Trapezium Area Method].

In order to find the most suitable algorithm of T-wave end point detection for clinical detection, we tested three methods, which are not just dependent on the threshold value of T-wave end point detection, i. e. wavelet method, cumulative point area method and trapezium area method, in PhysioNet QT database (20 records with 3 569 beats each). We analyzed and compared their detection performance. First, we used the wavelet method to locate the QRS complex and T-wave. Then we divided the T-wave into four morphologies, and we used the three algorithms mentioned above to detect T-wave end point. Finally, we proposed an adaptive selection T-wave end point detection algorithm based on T-wave morphology and tested it with experiments. The results showed that this adaptive selection method had better detection performance than that of the single T-wave end point detection algorithm. The sensitivity, positive predictive value and the average time errors were 98.93%, 99.11% and (--2.33 ± 19.70) ms, respectively. Consequently, it can be concluded that the adaptive selection algorithm based on T-wave morphology improves the efficiency of T-wave end point detection.

Locoregional interventional therapy for hepatocellular carcinoma: radiologic and clinical factors predictive of untreatable progression and time to untreatable progression.

Objective: In this retrospective cohort study, independent risk factors that influence untreatable progression (UP) and time to UP (TTUP) in patients with hepatocellular carcinoma (HCC) after locoregional interventional therapy were examined. The effects of initial response and best response on UP occurrence and TTUP after locoregional interventional therapy were evaluated. Methods: Data were collected from HCC patients who were initially treated with the drug-eluting beads-transcatheter arterial chemoembolization (DEB-TACE) procedure at our hospital from January 2017 to December 2022. Modified response evaluation criteria in solid tumors (m-RECIST) was used to evaluate the radiologic response of tumors. Logistic regression analysis was used to analyze the risk factors for UP in patients, and Cox regression analysis was used to discover independent variables that influenced TTUP. Results: A total of 93 patients who initially underwent the DEB-TACE procedure were included. Subsequent to initial treatment, 50 patients continued with DEB-TACE treatment, while 43 received DEB-TACE and sequential thermal ablation treatment. The probability of developing UP was 82.8% (n = 77). Furthermore, 49 (52.7%) patients achieved an initial response, and 70 (75.3%) achieved the best response. Multivariate logistic regression analysis confirmed three independent risk factors of UP, namely, age (odds ratio [OR]: 0.950, p = 0.044); initial response (OR: 0.177, p = 0.020); and treatment regimen (OR: 7.133, p = 0.007). Multivariate Cox regression found that total bilirubin (hazard ratio [HR]: 1.029, p = 0.002), tumor distribution (HR: 1.752, p = 0.034), Subjective Angiographic Chemoembolization Endpoint (SACE) classification (HR: 0.668, p = 0.043), number of tumors (HR: 1.130, p = 0.004), initial response (HR: 0.539, p = 0.019), and treatment regimen (HR: 4.615, p < 0.001) were independent variables that influenced TTUP. Conclusions: Age, initial response, and treatment regimen significantly affected the occurrence of UP in HCC patients. Initial response, SACE classification, treatment regimen, total bilirubin, number of tumors, and tumor distribution were significantly correlated with TTUP. The initial response following locoregional interventional therapy had greater effects on UP occurrence and TTUP than the best response.

Prediction of initial objective response to drug-eluting beads transcatheter arterial chemoembolization for hepatocellular carcinoma using CT radiomics-based machine learning model.

Objective: A prognostic model utilizing CT radiomics, radiological, and clinical features was developed and validated in this study to predict an objective response to initial transcatheter arterial chemoembolization with drug-eluting beads (DEB-TACE) for hepatocellular carcinoma (HCC). Methods: Between January 2017 and December 2022, the baseline clinical characteristics and preoperative and postoperative follow-up imaging data of 108 HCC patients who underwent the first time treatment of DEB-TACE were analyzed retrospectively. The training group (n = 86) and the validation group (n = 22) were randomly assigned in an 8:2 ratio. By logistic regression in machine learning, radiomics, and clinical-radiological models were constructed separately. Finally, the integrated model construction involved the integration of both radiomics and clinical-radiological signatures. The study compared the integrated model with radiomics and clinical-radiological models using calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Results: The objective response rate observed in a group of 108 HCC patients who received initial DEB-TACE treatment was found to be 51.9%. Among the three models, the integrated model exhibited superior predictive accuracy in both the training and validation groups. The training group resulted in an area under the curve (AUC) of 0.860, along with sensitivity and specificity values of 0.650 and 0.913, respectively. Based on the findings from the validation group, the AUC was estimated to be 0.927. Additionally, it was found that values of sensitivity and specificity were 0.875 and 0.833, respectively. In the validation group, the AUC of the integrated model showed a significant improvement when contrasted to the clinical-radiological model (p = 0.042). Nevertheless, no significant distinction was observed in the AUC when comparing the integrated model with the radiomics model (p = 0.734). The DCA suggested that the integrated model demonstrates advantageous clinical utility. Conclusion: The integrated model, which combines the CT radiomics signature and the clinical-radiological signature, exhibited higher predictive efficacy than either the radiomics or clinical-radiological models alone. This suggests that during the prediction of the objective responsiveness of HCC patients to the first DEB-TACE treatment, the integrated model yields superior outcomes.

A Membrane Lipid Signature Unravels the Dynamic Landscape of Group 1 ILCs.

In an era where the established lines between cell identities are blurred by intra-lineage plasticity, distinguishing between stable and transitional states becomes imperative. This challenge is particularly pronounced within the Group 1 ILC lineage, where the similarity and plasticity between NK cells and ILC1s obscure their classification and the assignment of their unique contributions to immune regulation. This study exploits the unique property of Asialo-GM1 (AsGM1)-a membrane lipid associated with cytotoxic attributes absent in ILC1s-as a definitive criterion to distinguish between these cells. By prioritizing cytotoxic potential as the cardinal differentiator, our strategic use of the AsGM1 signature achieved precise delineation of NK cells and ILC1s across tissues, validated by RNA-seq analysis. This capability extends beyond steady-state classifications, adeptly capturing the binary classification of NK cells and ILC1s during acute liver injury. By leveraging two established models of NK-to-ILC1 plasticity driven by TGFß and Toxoplasma gondii , we demonstrate the stability of the AsGM1 signature, which sharply contrasts with the loss of Eomes. This signature identified a spectrum of known and novel NK cell derivatives-ILC1-like entities that bridge traditional binary classifications in aging and infection. The early detection of the AsGM1 signature at the immature NK (iNK) stage, preceding Eomes, and its stability, unaffected by transcriptional reprogramming that typically alters Eomes, position AsGM1 as a unique, site-agnostic marker for fate mapping NK-to-ILC1 plasticity. This provides a powerful tool to explore the expanding heterogeneity within the Group 1 ILC landscape, effectively transcending the ambiguity inherent to the NK-to-ILC1 continuum.