Notes

Discerning Functionality associated with Co2 Nanorings via Uneven Intramicellar Phase-Transition-Induced Tip-to-Tip Set up.
Whole abdominal organ segmentation is important in diagnosing abdomen lesions, radiotherapy, and follow-up. However, oncologists' delineating all abdominal organs from 3D volumes is time-consuming and very expensive. Deep learning-based medical image segmentation has shown the potential to reduce manual delineation efforts, but it still requires a large-scale fine annotated dataset for training, and there is a lack of large-scale datasets covering the whole abdomen region with accurate and detailed annotations for the whole abdominal organ segmentation. In this work, we establish a new large-scale Whole abdominal ORgan Dataset (WORD) for algorithm research and clinical application development. This dataset contains 150 abdominal CT volumes (30495 slices). Each volume has 16 organs with fine pixel-level annotations and scribble-based sparse annotations, which may be the largest dataset with whole abdominal organ annotation. Several state-of-the-art segmentation methods are evaluated on this dataset. And we also invited three experienced oncologists to revise the model predictions to measure the gap between the deep learning method and oncologists. Afterwards, we investigate the inference-efficient learning on the WORD, as the high-resolution image requires large GPU memory and a long inference time in the test stage. We further evaluate the scribble-based annotation-efficient learning on this dataset, as the pixel-wise manual annotation is time-consuming and expensive. The work provided a new benchmark for the abdominal multi-organ segmentation task, and these experiments can serve as the baseline for future research and clinical application development.Designing of multiple-target directed ligands (MTDLs) has emerged as an attractive strategy for Alzheimer's disease (AD). Fusing the benzylpiperidine motif from AChE inhibitor donepezil and the 1,2,4-oxadiazole core from the Nrf2 activator 25 that was previously reported, we designed and synthesized a series of multifunctional anti-AD hybrids. The optimal hybrid 15a exhibited excellent AChE inhibitory (eeAChE IC50 = 0.07 ± 0.01 μM; hAChE IC50 = 0.38 ± 0.04 μM) and significant Nrf2 inductivity. It upregulated the protein and transcription level of Nrf2 and its downstream proteins HO-1, NQO1, and GCLM and promoted Nrf2 translocation from cytoplasm into nuclei. Additionally, 15a exhibited important neuroprotective function in protecting the cells from being damaged by H2O2 and Aβ1-42 aggregation and exerted antioxidant stress and anti-inflammatory activities in reducing the production of ROS and pro-inflammatory cytokines. Moreover, 15a effectively shortened the latency time and escape distance to the target, increased the arrival times, and simplified the tracks in Morris water maze test induced by scopolamine and Aβ1-42. At the same time, it significantly reduced the levels of proinflammatory factors in the mice model brains. These effects of 15a in improving cognition and alleviating inflammation were even better than the combination of AChE inhibitor and Nrf2 activator, suggesting a remarkable benefit for AD treatment. 15a could serve as a novel hit compound with Nrf2 inductive activity and AChE inhibitory activity for further research.The epigenetic regulator lysine specific demethylase 1 (LSD1), a MYCN cofactor, cooperatively silences MYCN suppressor genes. Furthermore, LSD1 has been correlated with adverse effects in neuroblastic tumors by propagating an undifferentiated, malignant phenotype. We observed that high LSD1 mRNA expression in MYCN-expressing neuroblastoma (NB) correlated with poor prognosis, implicating LSD1 as an oncogenic accomplice in high-grade NB. Thus, LSD1 inhibition is a potential strategy for targeting treatment-resistant MYCN-expressing NB. Tranylcypromine-based covalent LSD1 inhibitors have demonstrated anti-tumor activity but are associated with undesirable off-target effects, such that only 2 non-covalent LSD1 inhibitors are in clinical trials. We now report 3 novel scaffolds for reversible LSD1 inhibition 2-(arylsulfonamido)benzoic acid, N-(2-(1H-tetrazol-5-yl)phenyl)benzenesulfonamide and 2-(arylcarboxamido)benzoic acid analogues. The most active of these analogues, compound 48, exhibited potent and selective mixed reversible inhibition of LSD1 (IC50 = 0.58 μM) and significantly increased global H3K4me2 in NB cells. In addition, combination treatment with 48 and bortezomib in NB cells results in a synergistic effect.Pathogenic species of Borrelia are etiological agents of tick-borne relapsing fever (TBRF). Most species of TBRF Borrelia are transmitted by argasid ticks, and persistent colonization of the salivary glands is vital for spirochete transmission. This is due to the fast-feeding dynamics of the vector. However, the molecular mechanisms leading to vector colonization by the spirochete and their transmission to the vertebrate host remain vague. Previous work in Borrelia hermsii identified the arthropod associated lipoprotein (Alp) as being produced by spirochetes colonizing tick salivary glands. Upon transmission to mice, alp expression was down-regulated and the protein was undetectable in B. hermsii infecting mouse blood. Furthermore, Alp has homologs in multiple TBRF Borrelia species including Borrelia turicatae, Borrelia duttonii, and Borrelia recurrentis. To further evaluate the role of Alp in tick colonization and transmission, the gene was deleted in B. turicatae and the mutant's phenotype was evaluated. Our findings indicate that Alp is dispensable for colonization of the tick salivary glands and for the establishment of infection in laboratory mice.Hydrated electron (eaq-) based photochemical processes have emerged as a promising technology for contaminant removal in water due to the mild operating conditions. This review aims to provide a comprehensive and up-to-date summary on eaq- based photochemical processes for the decomposition of various oxidative contaminants. Specifically, the characteristics of different photo-reductive systems are first elaborated, including the environment required to generate sufficient eaq-, the advantages and disadvantages of each system, and the comparison of the degradation efficiency of contaminants induced by eaq-. In addition, the identification methods of eaq- (e.g., laser flash photolysis, scavenging studies, chemical probes and electron spin resonance techniques) are summarized, and the influences of operating conditions (e.g., solution pH, dissolved oxygen, source chemical concentration and UV type) on the performance of contaminants are also discussed. Considering the complexity of contaminated water, particular attention is paid to the influence of water matrix (e.g., coexisting anions, alkalinity and humic acid). Moreover, the degradation regularities of various contaminants (e.g., perfluorinated compounds, disinfection by-products and nitrate) by eaq- are summarized. We finally put forward several research prospects for the decomposition of contaminants by eaq- based photochemical processes to promote their practical application in water treatment.
We tried to differentiate childhood absence epilepsy (CAE) from juvenile absence epilepsy (JAE) based on their clinical characteristics. We planned to identify a cutoff point for the age at onset of seizures between CAE and JAE that is able to reliably predict the presence of generalized tonic-clonic seizures (GTCS) (that has important implications for treatment strategy and outcome prediction).

This was a retrospective database study. All patients with an electro-clinical diagnosis of CAE or JAE were studied at the outpatient epilepsy clinic at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2022. The receiver operating characteristic (ROC) curve was used for the statistical analysis to predict a cutoff point for the age at onset of seizures between the syndromes.

One hundred and ninety-six patients were studied. Generalized tonic-clonic seizure was reported by 134 patients (68.4%). The ROC curve of the age at seizure onset was an acceptable indicator to anticipate GTCS; the best cutoff point was at 9.65 years; 87 patients (44.4%) had CAE and 109 people (55.6%) had JAE. The odds ratio of the presence of GTCS in JAE compared with CAE was 3.6.

Syndrome diagnosis of CAE vs. JAE has important practical implications. The age at onset of seizures serves as a reliable and meaningful variable to differentiate CAE from JAE.
Syndrome diagnosis of CAE vs. JAE has important practical implications. The age at onset of seizures serves as a reliable and meaningful variable to differentiate CAE from JAE.
To report the efficacy and tolerability of brivaracetam (BRV) in add-on therapy in pediatric patients with severe drug-resistant epilepsy. Prognostic factors of clinical outcome were also analyzed.

This Italian multicenter retrospective observational study was conducted on 45 pediatric patients with severe drug-resistant epilepsy, treated with BRV for at least 1 month and with a follow-up >6 months. Demographic, clinical, and treatment variables were assessed at T0 (baseline, BRV introduction) and T1 (6 months after BRV introduction). The response was defined as ≥50% seizure frequency reduction; responders and non-responders were then compared to assess potential prognostic factors.

Forty-five patients (M=28, mean age 12.4+/-4.4 years) were enrolled (focal epilepsy=14; generalized epilepsy=2; epileptic encephalopathy=29). At T1, 19/45 patients (42.2%) were responders (≥50% seizure frequency reduction), with 4 patients (8.9%) achieving a≥75% seizure reduction and 2 patients (4.4%) becoming seizure free. Epilepsy onset at >12 months of age (p=0.001), disease duration ≤6 years (p=0.036), and lower seizure frequency at baseline (p=0.008) were the prognostic factors significantly associated with a better prognosis. No significant difference emerged for demographics, epilepsy types/etiology, intellectual disability, or therapy variables. At T1, 21 patients (46.6%) discontinued BRV, mainly due to lack of efficacy (13 subjects; 28.9%) and adverse events in 8 patients (17.8%).

Brivaracetam was an effective and tolerated treatment in pediatric patients with severe drug-resistant epilepsy, especially when the seizure onset was at >12 months of age, the epilepsy duration ≤6 years, and the seizure frequency before BRV treatment was low. selleck compound Further and controlled studies are needed.
12 months of age, the epilepsy duration ≤6 years, and the seizure frequency before BRV treatment was low. Further and controlled studies are needed.Diet is a health foundation that supports breastfeeding and enables lactating women's recovery. This study aimed to develop 3 valid diet adherence indices by clinimetric contrast with different parameters. We hypothesize that the 3 diet adherence-based indices are positively correlated with diet quality and milk biomarkers and directly related to calcium, fiber, and energy intake. A cross-sectional study recorded food frequency, anthropometric and dietary measures, and milk analysis to estimate correlations, sensitivity, and specificity (n = 284). Three reliable indices agreed by >75% with food frequency macronutritional (MDI), phytochemical (PDI), and energetic (EDI), which correlated positively to the Fat Quality Index and Minimum Dietary Diversity for Women. MDI and EDI correlated negatively to the Healthy Plant-Based Diet Index (H-PBDI), whereas PDI correlated positively. MDI correlated positively to the protein-to-carbohydrate ratio, whereas EDI correlated negatively. Inadequate intakes of calcium, fiber, and energy were indicated by MDI less then 19, PDI less then 19, and EDI ≥19, respectively, in a sensitive and specific manner.
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