Affective computing for human-machine interaction via a bionic organic memristor exhibiting selective in situ activation.

Affective computing, representing the forefront of human-machine interaction, is confronted with the pressing challenges of the execution speed and power consumption brought by the transmission of massive data. Herein, we introduce a bionic organic memristor inspired by the ligand-gated ion channels (LGICs) to facilitate near-sensor affective computing based on electroencephalography (EEG). It is constructed from a coordination polymer comprising Co ions and benzothiadiazole (Co-BTA), featuring multiple switching sites for redox reactions. Through advanced characterizations and theoretical calculations, we demonstrate that when subjected to a bias voltage, only the site where Co ions bind with N atoms from four BTA molecules becomes activated, while others remain inert. This remarkable phenomenon resembles the selective in situ activation of LGICs on the postsynaptic membrane for neural signal regulation. Consequently, the bionic organic memristor network exhibits outstanding reliability (200 000 cycles), exceptional integration level (210 pixels), ultra-low energy consumption (4.05 pJ), and fast switching speed (94 ns). Moreover, the built near-sensor system based on it achieves emotion recognition with an accuracy exceeding 95%. This research substantively adds to the ambition of realizing empathetic interaction and presents an appealing bionic approach for the development of novel electronic devices.

Adherence to a planetary health diet, genetic susceptibility, and incident cardiovascular disease: a prospective cohort study from the UK Biobank.

BACKGROUND: The influence of adherence to a planetary health diet (PHD) proposed by the EAT-Lancet Commission on cardiovascular disease (CVD) is inconclusive. Besides, whether genetic susceptibility to CVD can modify the association of PHD with CVD remains unknown. OBJECTIVE: We aimed to investigate the association between adherence to PHD and CVD, and to evaluate the interaction between PHD and genetic predisposition to CVD. METHODS: This study included 114,165 participants who completed at least two 24-hour dietary recalls and were initially free of cardiovascular disease from the UK biobank. PHD score was calculated to assess adherence to PHD. Genetic risk was evaluated using the polygenic risk score. Incidence of total CVD, ischemic heart disease (IHD), atrial fibrillation (AF), heart failure (HF), and stroke were identified via electronic health records. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 9.9 years, 10,071 (8.8%) incident CVD cases were documented. Compared to participants with the lowest adherence to PHD, HRs (95% CIs) for total CVD, IHD, AF, HF, and stroke among those with the highest adherence were 0.79 (0.74, 0.84), 0.73 (0.67, 0.79), 0.90 (0.82, 0.99), 0.69 (0.59, 0.82), and 0.88 (0.75, 1.04), respectively. No significant interaction between genetic risk of CVD and PHD was observed. Participants with high genetic risk and low PHD score, as compared with those with low genetic risk and high PHD score, had a 48% (95% CI, 40%, 56%) higher risk of CVD. The population-attributable risk (95% CI) of CVD for poor adherence to PHD ranged from 8.79% (5.36%, 12.51%) to 14.00% (9.00%, 18.88%). CONCLUSIONS: These findings suggest that higher adherence to PHD was associated with lower risks of total CVD, IHD, AF, and HF in populations across all genetic risk categories.

A novel fast robust optimization algorithm for intensity-modulated proton therapy with minimum monitor unit constraint.

BACKGROUND: Intensity-modulated proton therapy (IMPT) optimizes spot intensities and position, providing better conformability. However, the successful application of IMPT is dependent upon addressing the challenges posed by range and setup uncertainties. In order to address the uncertainties in IMPT, robust optimization is essential. PURPOSE: This study aims to develop a novel fast algorithm for robust optimization of IMPT with minimum monitor unit (MU) constraint. METHODS AND MATERIALS: The study formulates a robust optimization problem and proposes a novel, fast algorithm based on the alternating direction method of multipliers (ADMM) framework. This algorithm enables distributed computation and parallel processing. Ten clinical cases were used as test scenarios to evaluate the performance of the proposed approach. The robust optimization method (RBO-NEW) was compared with plans that only consider nominal optimization using CTV (NMO-CTV) without handling uncertainties and PTV (NMO-PTV) to handle the uncertainties, as well as with conventional robust-optimized plans (RBO-CONV). Dosimetric metrics, including D95, homogeneity index, and Dmean, were used to evaluate the dose distribution quality. The area under the root-mean-square dose (RMSD)-volume histogram curves (AUC) and dose-volume histogram (DVH) bands were used to evaluate the robustness of the treatment plan. Optimization time cost was also assessed to measure computational efficiency. RESULTS: The results demonstrated that the RBO plans exhibited better plan quality and robustness than the NMO plans, with RBO-NEW showing superior computational efficiency and plan quality compared to RBO-CONV. Specifically, statistical analysis results indicated that RBO-NEW was able to reduce the computational time from 389.70 ± 207.40 $389.70\pm 207.40$ to 228.60 ± 123.67 $228.60\pm 123.67$ s ( p < 0.01 $p<0.01$ ) and reduce the mean organ-at-risk (OAR) dose from 9.38 ± 12.80 $9.38\pm 12.80$ % of the prescription dose to 9.07 ± 12.39 $9.07\pm 12.39$ % of the prescription dose ( p < 0.05 $p<0.05$ ) compared to RBO-CONV. CONCLUSION: This study introduces a novel fast robust optimization algorithm for IMPT treatment planning with minimum MU constraint. Such an algorithm is not only able to enhance the plan's robustness and computational efficiency without compromising OAR sparing but also able to improve treatment plan quality and reliability.

Learning Molecular Representation in a Cell.

Predicting drug efficacy and safety in vivo requires information on biological responses (e.g., cell morphology and gene expression) to small molecule perturbations. However, current molecular representation learning methods do not provide a comprehensive view of cell states under these perturbations and struggle to remove noise, hindering model generalization. We introduce the Information Alignment (InfoAlign) approach to learn molecular representations through the information bottleneck method in cells. We integrate molecules and cellular response data as nodes into a context graph, connecting them with weighted edges based on chemical, biological, and computational criteria. For each molecule in a training batch, InfoAlign optimizes the encoder's latent representation with a minimality objective to discard redundant structural information. A sufficiency objective decodes the representation to align with different feature spaces from the molecule's neighborhood in the context graph. We demonstrate that the proposed sufficiency objective for alignment is tighter than existing encoder-based contrastive methods. Empirically, we validate representations from InfoAlign in two downstream tasks: molecular property prediction against up to 19 baseline methods across four datasets, plus zero-shot molecule-morphology matching.

Disorder of consciousness related pattern could distinguish minimally conscious state from unresponsive wakefulness syndrome: A F-18-FDG-PET study.

BACKGROUND: Accurate evaluation of level of disorder of consciousness (DOC) is clinically challenging. OBJECTIVE: This study aimed to establish a distinctive DOC-related pattern (DOCRP) for assessing disease severity and distinguishing unresponsive wakefulness syndrome (UWS) from minimally conscious state (MCS). METHODS: Fifteen patients with DOC and eighteen health subjects with F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET) were enrolled in this study. All patients were assessed by Coma Recovery Scale-Revised (CRS-R) and all individuals were randomly divided into two cohorts (Cohort A and B). DOCRP was identified in Cohort A and subsequently validated in Cohort B and A+B. We also assessed the discriminatory power of DOCRP between MCS and UWS. RESULTS: The DOCRP was characterized bilaterally by relatively decreased metabolism in the medial and lateral frontal lobes, parieto-temporal lobes, cingulate gyrus and caudate, associated with relatively increased metabolism in the cerebellum and brainstem. DOCRP expression exhibited high accuracy in differentiating DOC patients from controls (P<0.0001, AUC=1.000), and furthermore could effectively distinguish MCS from UWS (P=0.037, AUC=0.821, sensitivity: 85.7 %, specificity: 75.0 %). Particularly in the subgroup of DOC patients survived global hypoxic-ischemic brain injury, DOCRP expression exhibited even better discriminatory power between MCS and UWS (P=0.046, AUC=1.000). CONCLUSIONS: DOCRP might serve as an objective biomarker in distinguishing between UWS and MCS, especially in patients survived global hypoxic-ischemic brain injury. TRIAL REGISTRATION NUMBER: ChiCTR2300073717 (Chinese clinical trial registry site, http://www.chictr.org).

Different antithrombotic strategies after coronary artery bypass grafting to prevent adverse events: a retrospective analysis.

OBJECTIVE: Coronary artery bypass grafting (CABG) is associated with antithrombotic therapy in terms of postoperative adverse events; however, it is still unknown whether the early use of such drugs after CABG is safe and effective. In this study, we aim to evaluate the relationship between different postoperative antithrombotic strategies and in-hospital adverse events in patients undergoing isolated coronary artery bypass grafting surgery. METHODS: This was a single-center, retrospective cohort analysis of patients undergoing isolated CABG due to coronary artery disease (CAD) between 2001 and 2012. Data were extracted from the Medical Information Mart for Intensive Care III database. The patients involved were divided into the ASA (aspirin 81 mg per day only) or DAPT (aspirin plus clopidogrel 75 mg per day) group according to the antiplatelet strategy. Patients were also stratified into subgroups based on the type of anticoagulation. The in-hospital risk of bleeding and adverse events was investigated and compared between groups. Propensity score matching (PSM) was performed to reduce the potential effects of a selection bias. RESULTS: A total of 3274 patients were included in this study, with 2358 in the ASA group and 889 in the DAPT group. Following the PSM, no significant difference was seen in the risk of major bleeding between the two groups according to the PLATO, TIMI or GUSTO criteria. There was no difference in the postoperative mortality. In subgroup analysis, patients given anticoagulant therapy had an increased incidence of bleeding-related events. Multivariable analysis revealed that postoperative anticoagulant therapy and the early use of heparin, but not DAPT, were independent predictors of bleeding-related events. CONCLUSIONS: Postoperative DAPT was not associated with an increased occurrence of bleeding-related events in patients undergoing isolated CABG and appears to be a safe antiplatelet therapy. The addition of anticoagulants to antiplatelet therapy increased the risk of bleeding and should be considered cautiously in clinical practice.

Association of life's essential 8 with risk of recurrent cardiovascular events among patients with coronary heart disease.

AIMS: To examine the association of Life's Essential 8 (LE8) with the risk of recurrent cardiovascular events among patients with CHD. METHODS: This prospective cohort study included 11,997 patients with CHD from the UK Biobank. The LE8 score was generated using five lifestyle factors (diet, body mass index, physical activity, smoking, and sleep) and three biological factors (blood lipids, blood glucose, and blood pressure). LE8 score ranged from 0 to 100 and was categorized into quartiles. Cox proportional hazards regression models were applied to estimate the hazard ratio (HR) and 95% CI (confidence interval). RESULTS: During a median follow up of 12.5 years, we documented 3366 recurrent cardiovascular events, 1068 myocardial infarction, 1829 heart failure events, 703 strokes, and 934 cardiovascular deaths. The multivariable-adjusted HR (95% CI) for the highest versus the lowest quartile of LE8 score was 0.57 (0.50, 0.65) for recurrent cardiovascular events, 0.66 (0.52, 0.83) for myocardial infarction, 0.54 (0.45, 0.67) for heart failure, 0.50 (0.36, 0.68) for stroke, and 0.46 (0.37, 0.56) for cardiovascular death. Furthermore, the population attributable fraction of the lowest to the highest quartile of LE8 score were ranged from 16.2% to 32.5% for the various cardiovascular outcomes. In addition, biomarkers including renal function and inflammation collectively explained 47.6%-87.7% of the associations between the lifestyle factors and recurrent cardiovascular events. CONCLUSIONS: Better cardiovascular health as measured by LE8 was associated with significantly lower risk of recurrent cardiovascular events among patients with CHD. Clinicians should prioritize educating patients with CHD on the importance of optimal cardiovascular health for secondary prevention. In addition, our findings indicated significant mediation effect of biomarkers involving of glycemic control, renal function, liver function, lipid profile, and systemic inflammation on the associations between overall lifestyle factors and recurrent cardiovascular events.

Identification of a gene expression signature of vascular invasion and recurrence in stage I lung adenocarcinoma via bulk and spatial transcriptomics.

Microscopic vascular invasion (VI) is predictive of recurrence and benefit from lobectomy in stage I lung adenocarcinoma (LUAD) but is difficult to assess in resection specimens and cannot be accurately predicted prior to surgery. Thus, new biomarkers are needed to identify this aggressive subset of stage I LUAD tumors. To assess molecular and microenvironment features associated with angioinvasive LUAD we profiled 162 resected stage I tumors with and without VI by RNA-seq and explored spatial patterns of gene expression in a subset of 15 samples by high-resolution spatial transcriptomics (stRNA-seq). Despite the small size of invaded blood vessels, we identified a gene expression signature of VI from the bulk RNA-seq discovery cohort (n=103) and found that it was associated with VI foci, desmoplastic stroma, and high-grade patterns in our stRNA-seq data. We observed a stronger association with high-grade patterns from VI+ compared with VI- tumors. Using the discovery cohort, we developed a transcriptomic predictor of VI, that in an independent validation cohort (n=60) was associated with VI (AUROC=0.86; p=5.42×10-6) and predictive of recurrence-free survival (HR=1.98; p=0.024), even in VI- LUAD (HR=2.76; p=0.003). To determine our VI predictor's robustness to intra-tumor heterogeneity we used RNA-seq data from multi-region sampling of stage I LUAD cases in TRACERx, where the predictor scores showed high correlation (R=0.87, p<2.2×10-16) between two randomly sampled regions of the same tumor. Our study suggests that VI-associated gene expression changes are detectable beyond the site of intravasation and can be used to predict the presence of VI. This may enable the prediction of angioinvasive LUAD from biopsy specimens, allowing for more tailored medical and surgical management of stage I LUAD.

Intraoperative urinary tract resection and construction in CRS + HIPEC procedures: a single center retrospective analysis.

INTRODUCTION: The safety and efficacy of CRS + HIPEC combined with urinary tract resection and reconstruction are controversial. This study aims to summarize the clinicopathological features and to evaluate the safety and survival prognosis of CRS + HIPEC combined with urinary tract resection and reconstruction. METHODS: The patients who underwent urinary tract resection and reconstruction as part of CRS surgery were retrospectively selected from our disease-specific database for analysis. The clinicopathological characteristics, treatment-related variables, perioperative adverse events (AEs), and survival outcomes were studied using a descriptive approach and the K-M analysis with log-rank comparison. RESULTS: Forty-nine patients were enrolled. Perioperative serious AEs (SAEs) were observed in 11 patients (22.4%), with urinary SAEs occurring in 3 patients (6.1%). Additionally, there were 23 cases (46.8%) involving urinary adverse events (UAEs). The median overall survival (OS) in the entire cohort was 59.2 (95%CI: 42.1-76.4) months. The median OS of the UAE group and No-UAE group were 59.2 months (95%CI not reached), and 50.5 (95%CI: 11.5 to 89.6) months, respectively, with no significant difference (P = 0.475). Furthermore, there were no significant differences in OS based on the grade of UAEs or the number of UAEs (P = 0.562 and P = 0.622, respectively). CONCLUSION: The combination of CRS + HIPEC with urinary tract resection and reconstruction is associated with a high incidence of Grade I-II UAEs, which do not have an impact on OS. The safety profile of this combined technique is acceptable. However, this is a retrospective single-center single-arm analysis, with limitations of generalizability and potential selection bias. The findings need high-level validation.

Association between weight-adjusted waist index and kidney stones: a propensity score matching study.

Objective: This study aimed to investigate the association between weight-adjusted waist index (WWI), a novel adiposity index, and kidney stone (KS). Methods: Data were obtained from the National Health and Nutrition Examination Survey 2007-2018. According to the history of KS, participants were divided into the non-stone group and the stone group. Weighted multivariable logistic regression analyses were used to evaluate the correlation between WWI and KS in unadjusted, partially adjusted, and all-adjusted models. A restricted cubic spline (RCS) analysis assessed the association between continuous WWI and KS risk and obtained the risk function inflection point. Then, subgroup analysis based on the risk function inflection point was conducted to dissect the association in specific subgroups. In addition, the above analyst methods were repeatedly performed in populations after propensity score matching (PSM). The receiver operating characteristic (ROC) curve was applied to compare the ability to predict KS occurrence among WWI, visceral adiposity index (VAI), and body mass index (BMI). Results: Weighted multivariable logistic regression analyses found a positive association between continuous WWI and KS risk in the all-adjusted model [odds ratio (OR) = 1.03; 95% confidence interval (CI), 1.02-1.04; P < 0.001]. In further analysis, the Q4 WWI group was linked to the highest KS risk when compared to the Q1-Q3 group (OR = 1.06; 95% CI, 1.05-1.08, P < 0.001). RCS analysis found a linear significant correlation between continuous WWI and KS risk, and the risk function inflection point is 11.08 cm/√kg. Subgroup analysis confirmed that WWI was associated with KS risk in different groups. After PSM, increased WWI was still related to a high risk of KS. Moreover, the ROC curve demonstrated that WWI has a higher predictive ability of KS occurrence than VAI and BMI (area under curve, 0.612 vs. 0.581 vs. 0.569). Conclusion: In the US adult population, elevated WWI value was associated with an increased risk of KS. Furthermore, WWI was a better predictor of KS occurrence than VAI and BMI.

Serum 25-hydroxyvitamin D concentrations, vitamin D receptor polymorphisms, and risk of infections among individuals with type 2 diabetes: a prospective cohort study.

BACKGROUND: Evidence on the association between serum 25-hydroxyvitamin D [25(OH)D] and infections among patients with type 2 diabetes (T2D), a group susceptible to vitamin D deficiency and infections, is limited. OBJECTIVES: We aimed to examine this association in individuals with T2D, and to evaluate whether genetic variants in vitamin D receptor (VDR) would modify this association. METHODS: This study included 19,851 participants with T2D from UK Biobank. Infections were identified by linkage to hospital inpatient and death registers. Negative binomial regression models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs), with adjustment of potential confounders. RESULTS: In patients with T2D, the incidence rate of infections was 29.3/1000 person-years. Compared to those with 25(OH)D of 50.0-74.9 nmol/L, the multivariable-adjusted IRRs and 95% CIs of total infections, pneumonia, gastrointestinal infections and sepsis were 1.44 (1.31, 1.59), 1.49 (1.27, 1.75), 1.47 (1.22, 1.78), and 1.41 (1.14, 1.73), respectively, in patients with 25(OH)D <25.0 nmol/L. Nonlinear inverse associations between 25(OH)D concentrations and the risks of total infections (P-overall <0.001; P-nonlinear = 0.002) and gastrointestinal infections (P-overall <0.001; P-nonlinear = 0.040) were observed, with a threshold effect at ∼50.0 nmol/L. The vitamin D-infection association was not modified by genetic variants in VDR (all P-interaction >0.050). CONCLUSIONS: In patients with T2D, lower serum 25(OH)D concentration (<50 nmol/L) was associated with higher risks of infections, regardless of genetic variants in VDR. Notably, nonlinear inverse associations between 25(OH)D concentrations and the risks of infections were found, with a threshold effect at ∼50.0 nmol/L. These findings highlighted the importance of maintaining adequate vitamin D in reducing the risk of infections in patients with T2D.

Proteomic Analysis of Differences in the Freezability of Porcine Sperm Identifies α-Amylase As a Key Protein.

To investigate the mechanisms underlying the differences in the freezability of boar semen, Yorkshire boars with freezing-tolerant semen (YT, n = 3), Yorkshire boars with freezing-sensitive semen (YS, n = 3), Landrace boars with freezing-tolerant semen (LT, n = 3), and Landrace boars with freezing-sensitive semen (LS, n = 3) were selected for this study. Their sperm was subjected to protein extraction, followed by data-independent acquisition proteomics and functional bioinformatics analysis. A total of 3042 proteins were identified, of which 2810 were quantified. Some key KEGG pathways were enriched, such as starch and sucrose metabolism, carbohydrate digestion and absorption, mineral absorption, the HIF-1 signaling pathway, and the necroptosis pathways. Through PRM verification, we found that several proteins, such as α-amylase and epididymal sperm-binding protein 1, can be used as molecular markers of the freezing resistance of boar semen. Furthermore, we found that the addition of α-amylase to cryoprotective extender could significantly improve the post-thaw motility and quality of boar semen. In summary, this study revealed some molecular markers and potential molecular pathways contributing to the high or low freezability of boar sperm, identifying α-amylase as a key protein. This study is valuable for optimizing boar semen cryopreservation technology.

Diagnostic value of galectin-3, fractalkine, IL-6, miR-21 and cardiac troponin I in human ischemic cardiomyopathy.

OBJECTIVE: The primary objective of this study was to assess the diagnostic potential of galectin-3 (Gal-3), fractalkine (FKN), interleukin (IL)-6, microRNA(miR)-21, and cardiac troponin I (cTnI) in patients with ischemic cardiomyopathy (ICM). METHOD: A total of 78 ICM patients (Case group) and 80 healthy volunteers (Control group) admitted to our hospital for treatment or physical examination from Aug. 2018 to Feb. 2020 were included in the current study. The serum concentration of Gal-3, FKN, IL-6, miR-21, and plasma expression of cTnI of both groups were determined. The severity of ICM was classified using New York Heart Association (NYHA) scale. RESULTS: When compared with the control group, the case group had a significantly high blood concentration of Gal-3, FKN, IL-6, miR-21, and cTnI (P < 0.001). NYHA class II patients had lower blood levels of Gal-3, FKN, IL-6, miR-21, and cTnI than that in patients of NYHA class III and IV without statistical significance (P > 0.05). However, statistical significance could be achieved when comparing the above-analyzed markers in patients classified between class III and IV. Correlation analysis also revealed that serum levels of Gal-3, FKN, IL-6, miR-21, and cTnI were positively correlated with NYHA classification (R = 0.564, 0.621, 0.792, 0.981, P < 0.05). CONCLUSION: Our study revealed that up-regulated serum Gal-3, FKN, IL-6, miR-21, and cTnI levels were closely related to the progression of ICM. This association implies that these biomarkers have diagnostic potential, offering a promising avenue for early detection and monitoring of ICM progression.

Feasibility and safety of cryoballoon ablation for atrial fibrillation and closing patent foramen ovale without implantation：A pilot study.

BACKGROUND: Patent foramen ovale (PFO) affects 20%-34% of adults and is associated with strokes and other disorders. The conventional treatment of PFO-related strokes is a closure procedure. The metal device is associated with some adverse events. OBJECTIVE: Our aim was to investigate the efficacy and safety of PFO closure using cryoablation without implantation in patients with atrial fibrillation (AF) who underwent pulmonary vein isolation (PVI). METHODS: We divided the 22 patients with both PFO and AF who underwent PVI via cryoablation into 2 groups: standard PVI + atrial septum (AS) cryoablation group (group 1, n = 11) and standard PVI group (group 2, n = 11). The guidewire accesses the left atrium through the PFO without AS puncture during the procedure. Standard PVI via cryoablation was performed. The cryoballoon was retracted to the right atrium and inflated against the AS post-PVI. Patients in group 1 had cryoablation for 120-150 seconds, whereas patients in group 2 received sham ablation. The co-primary end points were the PFO closure rate and a composite of AF recurrence and stroke/transient ischemic attack (TIA) events. RESULTS: There were no differences in procedure-related adverse events between the 2 groups. Neither group had an ischemic stroke report at 1-year follow-up. The PFO closure rate at 6 months in group 1 was significantly higher than that in group 2 (7 [63.6%] vs 1 [9.1%]; P = .002). AF recurrence after ablation was comparable in both groups at 3 months (3 [27.3%] vs 1 [9.1%]; P = .269), 6 months (0 vs 0), and 12 months (2 [18.2%%] vs 1 [9.1%]; P = .534) of follow-up. CONCLUSION: Cryoablation is a safe and effective approach to close PFO in patients with AF undergoing PVI in a single procedure.

Rapidly responsive and highly selective NIR fluorescent probe for detecting hydrogen sulfide in food samples and living cells.

Hydrogen sulfide (H2S) is a pungent gas that is one of the key mediators of signal transduction in biological systems, and its presence is related to the freshness of some protein foods. Using phenothiazine derivatives as fluorophores and 2, 4-dinitrobenzene sulfonate (DNBS) fragments as reaction groups, a near-infrared (NIR) probe WX-HS for H2S identification was designed. With the addition of H2S, WX-HS appeared a strong fluorescence signal at 660 nm with short reaction time (90 s) and high sensitivity, and fluorescence state change from non-fluorescent to orange-red. In addition, WX-HS could effectively detect H2S produced during food oxidation. Based on its low cytotoxicity, the WX-HS probe further enabled the detection and imaging of H2S in A549 cells.

Effects of axial loading and positions on lumbar spinal stenosis: an MRI study using a new axial loading device.

OBJECTIVE: A new axial loading device was used to investigate the effects of axial loading and positions on lumbar structure and lumbar spinal stenosis. METHODS: A total of 40 patients sequentially underwent 4 examinations: (1) the psoas-relaxed position MRI, (2) the extended position MRI, (3) the psoas-relaxed position axial loading MRI, (4) the extended position axial loading MRI. The dural sac cross-sectional area, sagittal vertebral canal diameter, disc height and ligamentum flavum thickness of L3-4, L4-5, L5-S1 and lumbar lordosis angle were measured and compared. A new device with pneumatic shoulder-hip compression mode was used for axial loading. RESULTS: In the absence of axial loading, there was a significant reduction in dural sac cross-sectional area with extension only seen at the L3-4 (p = 0.033) relative to the dural sac area in the psoas-relaxed position. However, with axial loading, there was a significant reduction in dural sac cross-sectional area at all levels in both psoas-relaxed (L3-4, p = 0.041; L5-S1, p = 0.005; L4-5, p = 0.002) and extension (p < 0.001) positions. The sagittal vertebral canal diameter and disc height were significantly reduced at all lumbar levels with axial loading and extension (p < 0.001); however, in psoas-relaxed position, the sagittal vertebral canal diameter was only reduced with axial loading at L3-4 (p = 0.018) and L4-5 (p = 0.011), and the disc height was reduced with axial-loading at all levels (L3-4, p = 0.027; L5-S1, p = 0.001; L4-5, p < 0.001). The ligamentum flavum thickness and lumbar lordosis in extension position had a statistically significant increase compared to psoas-relaxed position with or without axial loading (p < 0.001). CONCLUSION: Both axial loading and extension of lumbar may exacerbate lumbar spinal stenosis. Axial loading in extension position could maximally aggravate lumbar spinal stenosis, but may cause some patients intolerable. For those patients, axial loading MRI in psoas-relaxed position may be a good choice.

Chromium Catalyzed Asymmetric Reformatsky Reaction.

This study describes an unprecedented chromium-catalyzed asymmetric Reformatsky reaction, enabling the synthesis of chiral ß-hydroxy carbonyl compounds from α-chlorinated or α-brominated esters and amides. By employing a chiral chromium/diarylamine bis(oxazoline) catalyst, we achieved relatively broad functional group tolerance. Distinct from known reports, the protocol operates under both classical and photoredox conditions, facilitated by the in-situ formation of a nucleophilic chiral chromium intermediate through a radical-polar crossover mechanism. Preliminary mechanistic insights, supported by DFT calculations, identify the nucleophilic aldehyde addition as the key stereo-determining step. This approach not only overcomes the limitations of existing Reformatsky reactions but also provides a versatile strategy for accessing complex chiral molecules.

Ileocecal valve-preservation ileocecostomy (IVPI) in infants with extremely short distal ileum after primary stoma.

PURPOSE: Preserving the ileocecal valve (ICV) has shown significant benefits. We present our experience with 18 infants who underwent ileocecal valve-preservation ileocecostomy (IVPI) with an extremely short distal ileum after primary ileostomy. METHODS: A retrospective analysis was conducted on IVPI cases between 2014 and 2020. Medical records were reviewed, including birth weight, age, primary diseases, length of ileus stump, surgical time and procedure, time to enteral feeding, postoperative hospital stay, and complications. RESULTS: Eighteen patients (male: female = 12:6, median birth weight 1305 (750-4000) g, median gestational age 29 + 5 (27 + 6-39 + 6) weeks) were included in the analysis. Causes of surgery included necrotizing enterocolitis (13), ileocecal intestinal atresia (1), ileum volvulus (2), meconium peritonitis (1), and secondary intestinal fistula (1). The median corrected age of ileostomy closure was 3.2 months (2.0-8.0 months). The distance from the distal ileal stoma to the ICV ranged from 0.5 to 2 cm. The median length of the residual bowel was 90 cm (50-130 cm). ICV-plasty was performed in 3 cases due to secondary ICV occlusion or stenosis. All patients resumed feeding within 6 to 11 days after surgery. The postoperative hospital stay ranged from 12 to 108 days (median: 16.5 days). Complications included incisional infections in 2 cases, anastomotic stricture and adhesive ileus in 1 case, nosocomial sepsis and septic shock in 1 case. All children showed normal growth and development during a 6-65 month follow-up. CONCLUSIONS: IVPI is safe and feasible for infants with an extremely short distal ileal stump. ICV-plasty could be applicable for cases with ileocecal occlusion/stenosis.

Dissection of molecular mechanisms of liver injury induced by microcystin-leucine arginine via single-cell RNA-sequencing.

The occurrence of poisoning incidents caused by cyanobacterial blooms has aroused wide public concern. Microcystin-leucine arginine (MC-LR) is a well-established toxin produced by cyanobacterial blooms, which is widely distributed in eutrophic waters. MC-LR is not only hazardous to the water environment but also exerts multiple toxic effects including liver toxicity in both humans and animals. However, the underlying mechanisms of MC-LR-induced liver toxicity are unclear. Herein, we used advanced single-cell RNA sequencing technology to characterize MC-LR-induced liver injury in mice. We established the first single-cell atlas of mouse livers in response to MC-LR. Our results showed that the differentially expressed genes and pathways in diverse cell types of liver tissues of mice treated with MC-LR are highly heterogeneous. Deep analysis showed that MC-LR induced an increase in a subpopulation of hepatocytes that highly express Gstm3, which potentially contributed to hepatocyte apoptosis in response to MC-LR. Moreover, MC-LR increased the proportion and multiple subtypes of Kupffer cells with M1 phenotypes and highly expressed proinflammatory genes. Furthermore, the MC-LR increased several subtypes of CD8+ T cells with highly expressed multiple cytokines and chemokines. Overall, apart from directly inducing hepatocytes apoptosis, MC-LR activated proinflammatory Kupffer cell and CD8+ T cells, and their interaction may constitute a hostile microenvironment that contributes to liver injury. Our findings not only present novel insight into underlying molecular mechanisms but also provide a valuable resource and foundation for additional discovery of MC-LR-induced liver toxicity.

Determinants of successful ictal SPECT injection in phase 1 epilepsy presurgical evaluation: Findings from the pediatric epilepsy research consortium surgery database project.

OBJECTIVES: The main goal of presurgical evaluation in drug-resistant focal epilepsy is to identify a seizure onset zone (SOZ). Of the noninvasive, yet resource-intensive tests available, ictal single-photon emission computed tomography (SPECT) aids SOZ localization by measuring focal increases in blood flow within the SOZ via intravenous peri-ictal radionuclide administration. Recent studies indicate that geographic and center-specific factors impact utilization of these diagnostic procedures. Our study analyzed successful ictal SPECT acquisition (defined as peri-ictal injection during inpatient admission) using surgery-related data from the Pediatric Epilepsy Research Consortium (PERC) surgery database. We hypothesized that a high seizure burden, longer duration of video EEG monitoring (VEEG), and more center-specific hours of SPECT availability would increase the likelihood of successful ictal SPECT. METHODS: We identified study participants (≤18 years of age) who underwent SPECT as part of their phase 1 VEEG from January 2018 to June 2022. We assessed association between ictal SPECT outcomes (success vs. failure) and variables including patient demographics, epilepsy history, and center-specific SPECT practices. RESULTS: Phase 1 VEEG monitoring with ictal SPECT injection was planned in 297 participants and successful in 255 participants (85.86%). On multivariable analysis, the likelihood of a successful SPECT injection was higher in patients of non-Hispanic ethnicity (p = 0.040), shorter duration VEEG (p = 0.004), and higher hours of available SPECT services (p < 0.001). Higher seizure frequency (p = 0.033) was significant only in bivariate analysis. Patients treated at centers with more operational hours were more likely to experience pre-admission protocols prior to VEEG (p = 0.002). SIGNIFICANCE: There is inter-center variability in protocols and SPECT acquisition capabilities. Shorter duration of EEG monitoring, non-Hispanic ethnicity (when on private insurance), extended operational hours of nuclear medicine as noted on multivariate analysis and higher seizure frequency in bivariate analysis are strongly associated with successful ictal SPECT injection. PLAIN LANGUAGE SUMMARY: In pediatric patients with drug-resistant epilepsy, single-photon emission computed tomography (SPECT) scans can be helpful in localizing seizure onset zone. However, due to many logistical challenges described below, which include not only the half-life of the technetium isotope used to inject intravenously during a seizure (called the ictal SPECT scan) but also available nuclear scanner time in addition to the unpredictability of seizures, obtaining an ictal SPECT during a planned elective inpatient hospital stay is not guaranteed. Thus, as healthcare costs increase, planning a prolonged hospital stay during which an ictal SPECT scan is not feasible is not optimal. We leveraged our prospective surgery database to look at center-specific factors and patient-specific factors associated with an ictal SPECT injection in the first, pediatric-focussed, large-scale, multicenter, prospective, SPECT feasibility study. We found that longer availability of the scanner is the most important center-specific factor in assuring ictal SPECT injection. Although seizure frequency is an important patient-specific factor on bivariate analysis, this factor lost statistical significance when other factors like patient insurance status and video EEG duration were also considered in our multivariable logistical model.