Networks in the human brain are extremely complex and sophisticated. The abstract model of the human brain has been used in software development, specifically in artificial intelligence. Despite the ...remarkable outcomes achieved using artificial intelligence, the approach consumes a huge amount of computational resources. A possible solution to this issue is the development of processing circuits that physically resemble an artificial brain, which can offer low-energy loss and high-speed processing. This study demonstrated the synaptic functions of conductive polymer wires linking arbitrary electrodes in solution. By controlling the conductance of the wires, synaptic functions such as long-term potentiation and short-term plasticity were achieved, which are similar to the manner in which a synapse changes the strength of its connections. This novel organic artificial synapse can be used to construct information-processing circuits by wiring from scratch and learning efficiently in response to external stimuli.
Hemimetabolous insects, such as the two-spotted cricket Gryllus bimaculatus, can recover lost tissues, in contrast to the limited regenerative abilities of human tissues. Following cricket leg ...amputation, the wound surface is covered by the wound epidermis, and plasmatocytes, which are insect macrophages, accumulate in the wound region. Here, we studied the function of Toll-related molecules identified by comparative RNA sequencing during leg regeneration. Of the 11 Toll genes in the Gryllus genome, expression of Toll2-1, Toll2-2 and Toll2-5 was upregulated during regeneration. RNA interference (RNAi) of Toll, Toll2-1, Toll2-2, Toll2-3 or Toll2-4 produced regeneration defects in more than 50% of crickets. RNAi of Toll2-2 led to a decrease in the ratio of S- and M-phase cells, reduced expression of JAK/STAT signalling genes, and reduced accumulation of plasmatocytes in the blastema. Depletion of plasmatocytes in crickets using clodronate also produced regeneration defects, as well as fewer proliferating cells in the regenerating legs. Plasmatocyte depletion also downregulated the expression of Toll and JAK/STAT signalling genes in the regenerating legs. These results suggest that Spz-Toll-related signalling in plasmatocytes promotes leg regeneration through blastema cell proliferation by regulating the Upd-JAK/STAT signalling pathway.
Recently, patients with out-of-hospital cardiac arrest (OHCA) refractory to conventional resuscitation have started undergoing extracorporeal cardiopulmonary resuscitation (ECPR). However, the ...mortality rate of these patients remains high. This study aimed to clarify whether a center ECPR volume was associated with the survival rates of adult patients with OHCA resuscitated using ECPR. This was a secondary analysis of a retrospective multicenter registry study, the SAVE-J II study, involving 36 participating institutions in Japan. Centers were divided into three groups according to the tertiles of the annual average number of patients undergoing ECPR: high-volume (≥ 21 sessions per year), medium-volume (11-20 sessions per year), or low-volume (< 11 sessions per year). The primary outcome was survival rate at the time of discharge. Patient characteristics and outcomes were compared among the three groups. Moreover, a multivariable-adjusted logistic regression model was applied to study the impact of center ECPR volume. A total of 1740 patients were included in this study. The center ECPR volume was strongly associated with survival rate at the time of discharge; furthermore, survival rate was best in high-volume compared with medium- and low-volume centers (33.4%, 24.1%, and 26.8%, respectively; P = 0.001). After adjusting for patient characteristics, undergoing ECPR at high-volume centers was associated with an increased likelihood of survival compared to middle- (adjusted odds ratio 0.657; P = 0.003) and low-volume centers (adjusted odds ratio 0.983; P = 0.006). The annual number of ECPR sessions was associated with favorable survival rates and lower complication rates of the ECPR procedure.Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000041577 (unique identifier: UMIN000036490).
Foxp3-expressing CD25
CD4
regulatory T cells (Tregs) are abundant in tumor tissues. Here, hypothesizing that tumor Tregs would clonally expand after they are activated by tumor-associated antigens to ...suppress antitumor immune responses, we performed single-cell analysis on tumor Tregs to characterize them by T cell receptor clonotype and gene-expression profiles. We found that multiclonal Tregs present in tumor tissues predominantly expressed the chemokine receptor CCR8. In mice and humans, CCR8
Tregs constituted 30 to 80% of tumor Tregs in various cancers and less than 10% of Tregs in other tissues, whereas most tumor-infiltrating conventional T cells (Tconvs) were CCR8
CCR8
tumor Tregs were highly differentiated and functionally stable. Administration of cell-depleting anti-CCR8 monoclonal antibodies (mAbs) indeed selectively eliminated multiclonal tumor Tregs, leading to cure of established tumors in mice. The treatment resulted in the expansion of CD8
effector Tconvs, including tumor antigen-specific ones, that were more activated and less exhausted than those induced by PD-1 immune checkpoint blockade. Anti-CCR8 mAb treatment also evoked strong secondary immune responses against the same tumor cell line inoculated several months after tumor eradication, indicating that elimination of tumor-reactive multiclonal Tregs was sufficient to induce memory-type tumor-specific effector Tconvs. Despite induction of such potent tumor immunity, anti-CCR8 mAb treatment elicited minimal autoimmunity in mice, contrasting with systemic Treg depletion, which eradicated tumors but induced severe autoimmune disease. Thus, specific removal of clonally expanding Tregs in tumor tissues for a limited period by cell-depleting anti-CCR8 mAb treatment can generate potent tumor immunity with long-lasting memory and without deleterious autoimmunity.
Abstract Objective The objective of this study was to provide a convenient preoperative prediction of the risk of early postoperative mortality. Materials and methods This retrospective study ...included patients who underwent surgery for spinal metastasis at our hospital between 2009 and 2021. Preoperative blood test data of all patients were collected, and the survival time was calculated by dividing the blood data. A multivariate analysis was conducted using a Cox proportional hazards model to identify prognostic factors. Results The study population included 83 patients (average: 64.5 years), 22 of whom died within 3 months. The most common lesion was the thoracic spine, and incomplete paralysis was observed in 57 patients. The surgical methods included posterior implant fixation (n = 17), posterior decompression (n = 31), and posterior decompression with fixation (n = 35). In the univariate analysis, the presence of abnormal values was significantly associated with postoperative survival in six preoperative blood collection items (hemoglobin, C-reactive protein, albumin, white blood cell, gamma-glutamyl transpeptidase, and lactate dehydrogenase). In a multivariate analysis, four test items (hemoglobin, C-reactive protein, white blood cell, and lactate dehydrogenase) were identified as independent prognostic factors. Comparing cases with ≥3 abnormal values among the above four items (high-risk group; n = 23) and those with ≤2 (low-risk group; n = 60), there was a significant difference in survival time. In addition, it was possible to predict cases of early death within 3 months after surgery with 73% sensitivity and 89% specificity. Conclusions The study showed that four preoperative blood test abnormalities (hemoglobin, C-reactive protein white blood cell, and lactate dehydrogenase) indicated the possibility of early death within 3 months after surgery.
The transradial approach using a Simmons-shaped catheter has been increasingly used for diagnostic cerebral angiography and neurointervention. In the transradial approach for neurointervention, the ...right radial artery is mainly used. However, in interventional cardiology, there are apparent clinical benefits with the left transradial approach for right-handed patients. To our knowledge, no studies have reported on neurointervention with the routine use of the left transradial approach. We therefore devised a novel technique for cases with an unachievable form of the Simmons shape using the standard technique, which we named the “interchange technique.” The purpose of this study was to evaluate the technical feasibility of the left transradial neurointervention.
This study is a retrospective review of our prospective database of consecutive patients who underwent a left transradial neurointervention, using a 6-French Simmons guiding sheath, performed from January through April 2021. The outcome variables studied were successful catheterization and procedure-related complications.
Twenty-one patients underwent a left transradial neurointervention including cerebral aneurysm coiling, carotid artery stenting, and meningioma embolization. The Simmons shape could not be formed with the standard technique for 3 patients, for whom we successfully formed the Simmons shape with our new interchange technique. The procedure was completely achieved in all 21 patients. No patients required crossover to the right radial or femoral arteries, and there were no radial artery spasms or occlusions or any procedural complications.
The left transradial approach for neurointervention is a technically feasible, safe, and effective alternative while providing more comfort to right-handed patients.
The success of antithrombotic therapies is assessed based on thrombotic and bleeding events. Simultaneously assessing both kinds of events might be challenging, and recurrent bleeding events are ...often ignored. We tried to confirm the effects of kidney function on outcome events in patients undergoing antithrombotic therapy.
As a post hoc subgroup analysis of the Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial, a randomized clinical trial with a median follow-up of 36 months, patients were divided into high and low estimated glomerular filtration rate (eGFR) groups with a cutoff value of 50 mL/min. The cumulative incidence of bleeding and crude incidence of recurrent bleeding per 100 patient-years were calculated. We used the Cox regression model with multiple failure time data for recurrent bleeding events.
Among 2092 patients, 1386 (66.3%) showed high eGFR. The cumulative bleeding events per 100 patients at 1 year were 5.4 and 6.2 in the high and low eGFR groups, respectively. The difference continued to increase over time. The hazard ratio for time to the first bleeding event in the high eGFR group was 0.875 (95% confidence interval 0.701-1.090, p = .234) and that for the first composite event was 0.723 (95% confidence interval 0.603-0.867, p < .000). The recurrent bleeding events per 100 person-years were 11.3 and 15.3 in the high and low eGFR groups, respectively, with a rate ratio of 0.738 (95% confidence interval 0.615-0.886, p = .001). During the observation period, the risk of bleeding changed with time. It peaked soon after the study enrollment in both groups. It decreased continuously in the high eGFR group but remained high in the low eGFR group.
We reaffirmed that kidney function affects bleeding events in patients on antithrombotic therapy, considering recurrent events. Patients should have detailed discussions with physicians regarding the possible bleeding events when continuing antithrombotic therapy, especially in patients with decreased kidney function.
UMIN Clinical Trials Registry, UMIN000016612 . ClinicalTrials.gov, NCT02642419 . Registered on 21 October 2015.
The corrosion degradation of the steel sheet pile material accelerates in recent years. The extremely accelerated corrosion induces the thickness loss and decreases the mechanical characteristics. It ...is essential to evaluate the corroded situations for the design and maintenance of the infrastructures. In this study, the spatial characteristics of the corrosion loss in service steel sheet pile canals were evaluated by the geostatistics with the variogram and kriging. In experimental procedures, steel sheet pile thicknesses were measured in service drainage canals. The thickness sampling was conducted in the air, tidal, water, sludge and soil zones. In analytical procedures, the variogram analysis is conducted for modeling of the spatial structures of the corrosion loss distribution. The ordinary kriging based on the theoretical variogram interpolates the no-sampling area. As a result, the thickness profile shows the largest corrosion loss in the tidal zone. The kriging interpolation shows the acceleration of the corrosion in the flanges of the tidal zone.
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