Efficacy and safety of adjunctive perampanel treatment in pediatric patients with epilepsy aged 4-12 years: a real-world study.

OBJECTIVE: To determine the efficacy and safety of perampanel (PER) as an adjunctive therapy in children aged 4-12 years with epilepsy. METHODS: We performed a non-randomized, open-label, placebo-uncontrolled, real-world self-controlled study that included 216 young children (aged 4-12 years) with epilepsy who received PER as adjunctive therapy at the children's hospital affiliated with Chongqing Medical University from July 4, 2020, to September 20, 2023. RESULTS: (1) The efficacy rates of adjunctive PER therapy at 3, 6, 9, and 12 months were 62.8%, 67.8%, 65.3%, and 61.2%, respectively. PER showed efficacy in alleviating focal seizures, generalized tonic-clonic seizures, myoclonic seizures, and absence seizures. The efficacy rates for variants of self-limited epilepsy with centrotemporal spikes (SeLECTS) and Lennox-Gastaut syndrome (LGS) were 89.5% and 66.7%, respectively. (2) Focal non-motor onset seizures with or without impaired awareness, focal to bilateral tonic-clonic seizures (FBTCS), LGS, variants of SeLECTS, the number of concomitant antiseizure medications (ASMs), a family history of epilepsy, and focal lesions on cranial magnetic resonance imaging were independent factors affecting efficacy. The order of PER addition did not affect efficacy. The retention rates at 3, 6, 9, and 12 months were 90.7%, 84.7%, 74.7%, 64.9%, respectively. (3) Adverse reactions occurred in 45 patients (45/216, 20.8%), with irritability/aggressive behavior (18/216, 8.3%) and somnolence (14/216, 6.5%) being the most common. Twelve patients (12/216, 5.6%) withdrew from the study because of adverse reactions. CONCLUSION: In young Chinese children with epilepsy, PER is effective, safe, and well-tolerated as an adjunctive therapy, making it a viable option for use with broad-spectrum ASMs.

Treg Immunomodulation Contributes to the Anti-atherosclerotic Effects of Huxin Formula in ApoE-/- Mice.

OBJECTIVE: To explore the effects of Huxin formula (HXF) in curtailing atherosclerosis and its underlying mechanism. METHODS: According to random number table method, 24 specific pathogen free male ApoE-/- mice were randomly divided into model group, HXF low-dose (HXF-L) group (8.4 g/kg daily), HXF high-dose (HXF-H) group (16.8 g/kg daily), and pravastatin (8 mg/kg daily) group in Experiment I (n=6 per group). C57BL/6J mice served as the control group (n=6). ApoE-/- mice in HXF-L, HXF-H, pravastatin groups were fed a Western diet and administered continuously by gavage for 12 weeks, while C57BL/6J mice in the control group were fed conventional lab mouse chow for 12 weeks. Further, Tregs were depleted by weekly intraperitoneal injection of purified anti-mouse CD25 antibody (PC61, 250 µg per mouse) for 4 weeks in Experiment II (n=6 per group). Oil Red O and Masson staining were used to evaluate the plaque area and aortic root fibrosis. The CD4+CD25+Foxp3+Treg counts in the lymph nodes and spleen cells were detected using flow cytometric analysis. The transforming growth factor-ß1 (TGF-ß1), interleukin (IL)-10, and IL-6 serum levels were examined by MILLIPLEX® MAP technology. Quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot were utilized to assess the expression of TGF-ß mRNA and protein in the aorta. The expression of CD4+T lymphocytes, macrophages and smooth muscle cells in the aortic root were detected by immunofluorescence staining. RESULTS: HXF reduced plaque area in ApoE-/- mice (P<0.01). HXF increased the Treg counts in the lymph nodes and spleen cells (P<0.05 or P<0.01). Moreover, HXF alleviated inflammatory response via elevating IL-10 and TGF-ß 1 serum levels (P<0.05), while decreasing the IL-6 serum levels in ApoE-/- mice (P>0.05). Also, HXF upregulated the expression of TGF-ß mRNA and protein in the aorta (P<0.05). Additionally, HXF attenuated CD4+T lymphocytes, macrophages and smooth muscle cells in aortic root plaque (P<0.01). Furthermore, the depletion of Tregs with CD25 antibody (PC61) curtailed the reduction in plaque area and aortic root fibrosis by HXF (P<0.01). CONCLUSION: HXF relieved atherosclerosis, probably by restraining inflammatory response, reducing inflammatory cell infiltration and attenuating aortic root fibrosis by increasing Treg counts.

Screening parameters for diagnosing primary aldosteronism in patients with moderate to severe obstructive sleep apnea hypopnea syndrome and resistant hypertension.

Background: Patients with obstructive sleep apnea hypopnea syndrome (OSAHS) combined with resistant hypertension (RH) have a high risk of developing primary aldosteronism (PA). This study investigated the aldosterone-renin ratio (ARR), plasma aldosterone concentration (PAC), and plasma renin activity (PRA) to determine the optimal cutoff values for PA diagnosis in patients with OSAHS combined with RH. Methods: Patients diagnosed with moderate and severe OSAHS combined with RH were recruited from the inpatient clinic of the Department of Endocrinology at Ji'an Central Hospital between October 2020 and April 2023. The included patients were divided into PA and no-PA groups. Diagnostic accuracy measures were calculated for each group, and receiver operating characteristic (ROC) curves were generated. Results: A total of 241 patients were included, of which 103 had positive ARR screening results in the diagnostic accuracy analysis and 66 were diagnosed with PA. PAC and ARR showed moderate predictive capacity for PA, with area under the curve (AUC) values of 0.66 [95% confidence interval (CI): 0.55-0.77] and 0.72 (95% CI: 0.63-0.82), respectively, while PRA exhibited a limited predictive capacity (AUC = 0.51, 95% CI: 0.40-0.63). Using 45 as the optimal cutoff value for ARR, the sensitivity was 86% and the specificity was 52%. The optimal cutoff value for PAC was 17, with a sensitivity of 78% and a specificity of 55%. Notably, in patients with severe OSAHS, ARR at screening demonstrated significant predictive value for PA, with an AUC of 0.84 (95% CI: 0.72-0.96), a sensitivity of 85%, and a specificity of 76%. Conversely, in patients with moderate OSAHS, only ARR demonstrated significant predictive value for PA diagnosis, while PAC did not demonstrate notable diagnostic value. Conclusion: ARR and PAC are initial screening tools for PA, facilitating early detection, particularly in low-resource settings. In patients with OSAHS and RH, the ARR and PAC thresholds for PA diagnosis may require more stringent adjustment.

Deciphering antifungal and antibiofilm mechanisms of isobavachalcone against Cryptococcus neoformans through RNA-seq and functional analyses.

Cryptococcus neoformans has been designated as critical fungal pathogens by the World Health Organization, mainly due to limited treatment options and the prevalence of antifungal resistance. Consequently, the utilization of novel antifungal agents is crucial for the effective treatment of C. neoformans infections. This study exposed that the minimum inhibitory concentration (MIC) of isobavachalcone (IBC) against C. neoformans H99 was 8 µg/mL, and IBC dispersed 48-h mature biofilms by affecting cell viability at 16 µg/mL. The antifungal efficacy of IBC was further validated through microscopic observations using specific dyes and in vitro assays, which confirmed the disruption of cell wall/membrane integrity. RNA-Seq analysis was employed to decipher the effect of IBC on the C. neoformans H99 transcriptomic profiles. Real-time quantitative reverse transcription PCR (RT-qPCR) analysis was performed to validate the transcriptomic data and identify the differentially expressed genes. The results showed that IBC exhibited various mechanisms to impede the growth, biofilm formation, and virulence of C. neoformans H99 by modulating multiple dysregulated pathways related to cell wall/membrane, drug resistance, apoptosis, and mitochondrial homeostasis. The transcriptomic findings were corroborated by the antioxidant analyses, antifungal drug sensitivity, molecular docking, capsule, and melanin assays. In vivo antifungal activity analysis demonstrated that IBC extended the lifespan of C. neoformans-infected Caenorhabditis elegans. Overall, the current study unveiled that IBC targeted multiple pathways simultaneously to inhibit growth significantly, biofilm formation, and virulence, as well as to disperse mature biofilms of C. neoformans H99 and induce cell death.

CT-Based Radiomics Analysis of Different Machine Learning Models for Discriminating the Risk Stratification of Pheochromocytoma and Paraganglioma: A Multicenter Study.

RATIONALE AND OBJECTIVES: Using different machine learning models CT-based radiomics to integrate clinical radiological features to discriminating the risk stratification of pheochromocytoma/paragangliomas (PPGLs). MATERIALS AND METHODS: The present study included 201 patients with PPGLs from three hospitals (training set: n = 125; external validation set: n = 45; external test set: n = 31). Patients were divided into low-risk and high-risk groups using a staging system for adrenal pheochromocytoma and paraganglioma (GAPP). We extracted and selected CT radiomics features, and built radiomics models using support vector machines (SVM), k-nearest neighbors, random forests, and multilayer perceptrons. Using receiver operating characteristic curve analysis to select the optimal radiomics model, a combined model was built using the output of the optimal radiomics model and clinical radiological features, and its accuracy and clinical applicability were evaluated using calibration curves and clinical decision curve analysis (DCA). RESULTS: Finally, 13 radiomics features were selected to construct machine learning models. In the radiomics model, the SVM model demonstrated higher accuracy and stability, with an AUC value of 0.915 in the training set, 0.846 in external validation set, and 0.857 in external test set. Combining the outputs of SVM models with two clinical radiological features, a combined model constructed has demonstrated optimal risk stratification ability for PPGLs with an AUC of 0.926 for the training set, 0.883 for the external validation set, and 0.899 for the external test set. The calibration curve and DCA show good calibration accuracy and clinical effectiveness for the combined model. CONCLUSION: Combined model that integrates radiomics and clinical radiological features can discriminate the risk stratification of PPGLs.

High preseason temperature variability drives convergence of xylem phenology in the Northern Hemisphere conifers.

Wood growth is key to understanding the feedback of forest ecosystems to the ongoing climate warming. An increase in spatial synchrony (i.e., coincident changes in distant populations) of spring phenology is one of the most prominent climate responses of forest trees. However, whether temperature variability contributes to an increase in the spatial synchrony of spring phenology and its underlying mechanisms remains largely unknown. Here, we analyzed an extensive dataset of xylem phenology observations of 20 conifer species from 75 sites over the Northern Hemisphere. Along the gradient of increase in temperature variability in the 75 sites, we observed a convergence in the onset of cell enlargement roughly toward the 5th of June, with a convergence in the onset of cell wall thickening toward the summer solstice. The increase in rainfall since the 5th of June is favorable for cell division and expansion, and as the most hours of sunlight are received around the summer solstice, it allows the optimization of carbon assimilation for cell wall thickening. Hence, the convergences can be considered as the result of matching xylem phenological activities to favorable conditions in regions with high temperature variability. Yet, forest trees relying on such consistent seasonal cues for xylem growth could constrain their ability to respond to climate warming, with consequences for the potential growing season length and, ultimately, forest productivity and survival in the future.

Performance of the 2019 ACR/EULAR Classification Criteria for IgG4-Related Disease in a Large Chinese Cohort.

OBJECTIVE: The purpose of this research was to ascertain the effectiveness of the newly established criteria for classifying IgG4-related disease (IgG4-RD), as applied to a large Chinese cohort in real-world clinical settings. METHODS: Patient data were procured from the digital health records of 4 prominent academic hospitals. The criterion standard for identifying IgG4-RD patients was from a seasoned rheumatologist. The control group consisted of individuals with other ailments such as cancer, other forms of pancreatitis, infectious diseases, and illnesses that mimic IgG4-RD. RESULTS: A total of 605 IgG4-RD patients and 760 mimickers were available for analysis. The 2019 EULAR/ACR criteria have a sensitivity of 69.1% and a specificity of 90.9% in this large Chinese cohort. IgG4-RD had a greater proportion of males (55.89% vs 36.25%, p < 0.001), an older average age at diagnosis (54.91 ± 13.44 vs 48.91 ± 15.71, p < 0.001), more pancreatic (29.59% vs 6.12%, p < 0.001) and salivary gland (63.30% vs 27.50%, p < 0.001) involvement, and a larger number of organ involvement (3.431 ± 2.054 vs 2.062 ± 1.748, p < 0.001) compared with mimickers. CONCLUSIONS: The 2019 EULAR/ACR criteria are effective in classifying IgG4-RD in Chinese patients, demonstrating high specificity and moderate sensitivity.

Implementation and effectiveness of a nurse navigation programme based on noddings' care theory in first-year undergraduate nursing students for professional identity and career planning: A quasi-experimental study.

AIMS: Development and evaluation of the effectiveness of a Nurse Navigation programme based on Noddings' Care theory on two dependent variables which were professional identity and career planning among first-year undergraduate nursing students. BACKGROUND: First-year undergraduate nursing students generally have a low sense of professional identity and career planning, resulting in a loss of nursing power after graduation. Implemention of a Nurse Navigation program based on Noddings' Care theory may be potentially useful in cultivating their professional identity and career planning. DESIGN: A quasi-experimental study. METHODS: A convenience sample of 122 first-year undergraduate nursing students from two medical universities was recruited between September 2021 and June 2022. Students in the experimental group (n = 63) participated in the Nurse Navigation programme based on Noddings' Care theory, which contained four core components, spreading over 50 lessons. Those in the control group (n = 59) underwent a traditional training programme with five components across 44 lessons. The two groups were compared in terms of their level of professional identity by Professional identity questionnaire for nurse students (PIQNS) and career planning by Career planning questionnaire (CPQ) after the training using the t-test. RESULTS: The mean score of professional identity in the experimental group increased significantly from 51.02 ± 8.46 at baseline to 58.02 ± 8.81 after the intervention (p < 0.001), with a large effect size (Cohen's d=0.810). Also, this post-intervention score was statistically significantly higher than that (52.86 ± 9.27) in the control group (p = 0.002), with a medium effect size (Cohen's d=0.571). The mean score of career planning in the experimental group increased significantly from 81.76 ± 9.86 at baseline to 94.52 ± 10.81 after the intervention (p < 0.001), with a large effect size (Cohen's d = 1.233). Also, this post-intervention score was statistically significantly higher than that (88.25 ± 9.30) in the control group (p < 0.001), with a medium effect size (Cohen's d=0.623). CONCLUSIONS: The Nurse Navigation programme based on Noddings' Care theory showed effectiveness in enhancing professional identity and career planning among first-year undergraduate nursing students in China. Further rigorous studies are needed to examine its effectiveness and long-term impacts on these students.

[Distribution Characteristics and Risk Assessment of Tetracycline Antibiotics (TCs) in Soil-Vegetable System with Soil Fertilized with Animal Manure].

The effects of antibiotic contamination on vegetable safety and the ecological risks of soil after returning livestock and poultry manure to the land require sufficient future attention. Tetracycline antibiotics (TCs) are often detected at high concentrations in livestock manure and vegetable production soils. Recently, pot experiments and field investigation methods have often been used to understand the effects of TCs contamination on the vegetable safety and ecological risks of soil, whereas field experiments are employed less frequently. This study investigated the distribution characteristics of TCs in the soil-vegetable system following manure application using a combination of pot and field experiments. The human health risks of the edible parts of Chinese flowing cabbage were assessed using the health risk quotient method based on the acceptable daily intake (ADI-HQ), and the ecological risks of TCs-contaminated soils were evaluated using the risk quotient method associated with the species sensitivity distribution model (SSD-RQ). The results showed that oxytetracycline (OTC) was the major type of TCs in Chinese flowering cabbage based on both the pot and field experiments. The maximum contents (dry weight) of OTC in the aboveground parts of the Chinese flowering cabbage for the pot and field experiments were 29.25 µg·kg-1 and 45.03 µg·kg-1, respectively, whereas those of their underground parts were 87.32 µg·kg-1 and 135.44 µg·kg-1, respectively. Meanwhile, higher contents of TCs were detected in Chinese flowering cabbage collected from the field experiment than those from the pot experiment. OTC was also the major type of TCs in soil from both the pot and field experiments, with their contents up to 604.30 µg·kg-1 and 1013.68 µg·kg-1, respectively. Higher residual contents of three TCs were detected in soils collected from the field experiment than those from the pot experiment. Under the experimental conditions, with the except that OTC in Chinese flowering cabbage from the field experiment would pose medium health risks (HQ>0.1) to children, the contents of three TCs in other treated Chinese flowering cabbage would pose low health risks (HQ ≤ 0.1) to adults and children. In the pot experiments, three TCs present in Chinese flowering cabbage would pose low health risks (HQ ≤ 0.1) to adults and children. Additionally, the TCs in soils with manure application from the pot and field experiments may have posed both moderate or high levels of ecological risks (HQ>0.1 or HQ>1). Therefore, the effects of antibiotic contamination on vegetable safety and their potential ecological risks on soil following manure fertilization need to be given special attention.

Use of extracorporeal membrane oxygenation during resection of recurrent laryngeal papillomatosis: A case report.

RATIONALE: Recurrent laryngeal papillomatosis (RLP) is a common benign tumor in the larynx of children, which is characterized by high recurrence rate and rapid growth, leading to clinical symptoms such as hoarseness and difficulty breathing. Low-temperature plasma radiofrequency ablation (RFA) is the main treatment, but ventilation problems are often encountered during surgery. PATIENT CONCERNS: We report a case of a 2-year-old child with RLP who underwent low-temperature plasma RFA with the assistance of a laryngoscope. However, the surgery had to be temporarily stopped due to ventilation difficulties and difficulty in maintaining blood oxygen saturation during the procedure. DIAGNOSIS: The child was diagnosed with RLP. INTERVENTIONS: The child underwent low-temperature plasma RFA supported by laryngoscopy assisted by ECMO. OUTCOMES: Despite ventilation problems during surgery, the use of ECMO support helped maintain good oxygen saturation in the child and provided a clear surgical field, enabling the tumor to be quickly and cleanly removed. Therefore, the use of ECMO provided critical support during the surgery. LESSONS: This case highlights the importance of airway management during laryngeal papillomatosis surgery. A thorough airway assessment should be performed before anesthesia, and early use of ECMO can reduce harm to the child and ensure the child's safety.

In Situ Activation of the Receptor Aggregation for Cell Apoptosis by an AI-Au Intelligent Nanomachine via Tumor Extracellular Acidity.

Polyvalent ligand-induced cell receptor aggregation is closely related to cell behavior regulation. At present, most of the means to induce receptor aggregation rely on external stimuli such as light, heat, and magnetic fields, which may cause side effects to normal cells. How to achieve receptor aggregation on the cancer cell surface to achieve cell apoptosis selectively is still a challenge. Therefore, by taking advantage of the unique property of cancer cells' slightly acidic microenvironment, an easy-to-use apoptosis-inducing mode for the in situ activation of cell surface nucleolin clustering has been developed, which not only opened a new channel for nucleolin receptor aggregation to regulate cell function and further development but also avoided damage to normal cells, providing a new strategy for tumor treatment. Dual functional ssDNA (AS1411 aptamer and pH-responsive I-strand sequence) was modified on the surface of gold nanoparticles (AuNPs) to fabricate AI-Au intelligent nanomachines. Then, the specific binding on cancer cells and aggregation of the nucleolin receptors can be achieved via the formation of an i-Motif structure among adjacent AuNPs under the acidic microenvironment. The result showed that AI-Au nanomachines mediated nucleolin cross-linking on the cell surface, resulting in a cytotoxic effect of approximately 60%. Experiments such as calcein-AM/PI staining, nuclear dye staining, and flow cytometry demonstrated that cell apoptosis became more evident with the increase of acidity under the cell surface microenvironment. Immunofluorescence imaging further confirmed the Cyt-c/caspase-3 apoptosis pathway induced by AI-Au nanomachines. The proposed strategy used for specific cancer cell apoptosis by the in situ activation of tumor cell membrane receptor aggregation is inexpensive and simple to use, which not only provides a new means of nucleolin receptor aggregation for regulating cell function but also offers a new strategy for tumor treatment with reduced side effect to normal cells. This work is significant for comprehending the ligand-induced receptor aggregation process and can lead to the development of a promising anticancer drug.

Radiomics Based on DCE-MRI for Predicting Response to Neoadjuvant Therapy in Breast Cancer.

RATIONALE AND OBJECTIVES: To compare the value of radiomics and diameter% based on pre- and early-treatment dynamic enhanced MR (DCE-MRI) of the breast in predicting response to neoadjuvant therapy (NAT) in breast cancer and to construct a tool for early noninvasive prediction of NAT outcomes. MATERIALS AND METHODS: Retrospective analysis of clinical and imaging data of 142 patients with primary invasive breast cancer who underwent DCE-MRI before and after two cycles of NAT at our institution. Enroled patients were randomly assigned in a 7:3 ratio to the training group and the test group. Patients were divided into pathological complete response (pCR) and non-pathological complete response groups based on surgical pathology findings after NAT. The maximum diameter relative regression values (Diameter%) before and after treatment were calculated and the conventional imaging Diameter% model was constructed. Based on pre- and early-NAT DCE-MRI, the optimal features of pre-NAT, early-NAT, and delta radiomics were screened using redundancy analysis, least absolute shrinkage, and selection operator methods to construct the corresponding radiomics model and calculate the Radscores. Indicators that were statistically significant in the univariate analysis of clinical data were further screened by stepwise regression and combined with Radscores to construct the fusion model. All models were evaluated and compared. RESULTS: In the test set, the area under the curve (AUC) of the delta radiomics model (0.87) was higher than that of the pre-NAT, early-NAT radiomics models (0.57, 0.78) and the Diameter% model (0.83). The fusion model had the best efficacy in predicting pCR after NAT, with AUCs of 0.91 in the training and test sets. And its nomogram plot showed that Radscore of early-NAT radiomics had the greatest weight. In the test set, the fusion model and Delta radiomics model improved the efficacy of predicting pCR by 35.56% and 14.19%, respectively, compared to the Diameter% model (P = 0 and .039). Clinical decision curves showed the highest overall clinical benefit for the fusion model. CONCLUSION: Radiomics, especially delta and early-NAT radiomics, may be potential biomarkers for early noninvasive prediction of NAT outcomes. And a fusion model constructed from meaningful clinicopathological indicators combined with radiomics can effectively predict NAT response.

Factors associated with spontaneous miscarriage risk in IUI treatment: A retrospectively cohort of 31,933 cycles.

To determine the factors associated with intrauterine insemination (IUI) miscarriages and reduce the IUI miscarriage rate, a retrospective study was performed by reviewing 31,933 IUI cycles from 2006 to 2018. The overall there were 14.50% clinical pregnancies, and 16.74% miscarriages. Logistic regression revealed the following three predictive variables: females aged ≥ 35 years (odds ratio [OR] = 2.131; p < 0.001), spontaneous miscarriage history (OR = 1.513; p = 0.005), and ovarian stimulation schemes such as clomiphene citrate (CC) (OR = 1.459; p = 0.003). The natural cycle led to a lower miscarriage rate for patients without spontaneous miscarriage history both for those over 35 years old (OR = 0.402; p = 0.034) and for those under 35 years old (OR = 0.806; p = 0.017). Gonadotropin (Gn) showed the lowest miscarriage rate for patients without abortion history, though no significant differences were found. Patients under 35 with a history of miscarriage were protected from miscarriage by using CC and Gn together (OR = 0.516; p = 0.032). No significant differences were found between various ovarian protocols when patients with abortion history were aged ≥ 35 years (p = 0.606). CC + Gn showed the lowest miscarriage rate. In conclusion, the natural cycle could be suggested for infertility couples to minimize abortion risk. When ovarian induction is required, CC + Gn had the lowest miscarriage rate for women with a history of spontaneous miscarriage while Gn is more successful for individuals without such a history.

A longer wood growing season does not lead to higher carbon sequestration.

A reliable assessment of forest carbon sequestration depends on our understanding of wood ecophysiology. Within a forest, trees exhibit different timings and rates of growth during wood formation. However, their relationships with wood anatomical traits remain partially unresolved. This study evaluated the intra-annual individual variability in growth traits in balsam fir [Abies balsamea (L.) Mill.]. We collected wood microcores weekly from April to October 2018 from 27 individuals in Quebec (Canada) and prepared anatomical sections to assess wood formation dynamics and their relationships with the anatomical traits of the wood cells. Xylem developed in a time window ranging from 44 to 118 days, producing between 8 and 79 cells. Trees with larger cell production experienced a longer growing season, with an earlier onset and later ending of wood formation. On average, each additional xylem cell lengthened the growing season by 1 day. Earlywood production explained 95% of the variability in xylem production. More productive individuals generated a higher proportion of earlywood and cells with larger sizes. Trees with a longer growing season produced more cells but not more biomass in the wood. Lengthening the growing season driven by climate change may not lead to enhanced carbon sequestration from wood production.

Glutamate dehydrogenase hyperinsulinism: mechanisms, diagnosis, and treatment.

Congenital hyperinsulinism (CHI) is a genetically heterogeneous disease, in which intractable, persistent hypoglycemia is induced by excessive insulin secretion and increased serum insulin concentration. To date,15 genes have been found to be associated with the pathogenesis of CHI. Glutamate dehydrogenase hyperinsulinism (GDH-HI) is the second most common type of CHI and is caused by mutations in the glutamate dehydrogenase 1 gene. The objective of this review is to summarize the genetic mechanisms, diagnosis and treatment progress of GDH-HI. Early diagnosis and treatment are extremely important to prevent long-term neurological complications in children with GDH-HI.

A deep residual attention-based U-Net with a biplane joint method for liver segmentation from CT scans.

Liver tumours are diseases with high morbidity and high deterioration probabilities, and accurate liver area segmentation from computed tomography (CT) scans is a prerequisite for quick tumour diagnosis. While 2D network segmentation methods can perform segmentation with lower device performance requirements, they often discard the rich 3D spatial information contained in CT scans, limiting their segmentation accuracy. Hence, a deep residual attention-based U-shaped network (DRAUNet) with a biplane joint method for liver segmentation is proposed in this paper, where the biplane joint method introduces coronal CT slices to assist the transverse slices with segmentation, incorporating more 3D spatial information into the segmentation results to improve the segmentation performance of the network. Additionally, a novel deep residual block (DR block) and dual-effect attention module (DAM) are introduced in DRAUNet, where the DR block has deeper layers and two shortcut paths. The DAM efficiently combines the correlations of feature channels and the spatial locations of feature maps. The DRAUNet with the biplane joint method is tested on three datasets, Liver Tumour Segmentation (LiTS), 3D Image Reconstruction for Comparison of Algorithms Database (3DIRCADb), and Segmentation of the Liver Competition 2007 (Sliver07), and it achieves 97.3%, 97.4%, and 96.9% Dice similarity coefficients (DSCs) for liver segmentation, respectively, outperforming most state-of-the-art networks; this strongly demonstrates the segmentation performance of DRAUNet and the ability of the biplane joint method to obtain 3D spatial information from 3D images.

LOX-1 Regulation in Anti-atherosclerosis of Active Compounds of Herbal Medicine: Current Knowledge and the New Insight.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) have recently been identified to be closely related to the occurrence and development of atherosclerosis (AS). A growing body of evidence has suggested Chinese medicine takes unique advantages in preventing and treating AS. In this review, the related research progress of AS and LOX-1 has been summarized. And the anti-AS effects of 10 active components of herbal medicine through LOX-1 regulation have been further reviewed. As a potential biomarker and target for intervention in AS, LOX-1 targeted therapy might provide a promising and novel approach to atherosclerotic prevention and treatment.

A critical thermal transition driving spring phenology of Northern Hemisphere conifers.

Despite growing interest in predicting plant phenological shifts, advanced spring phenology by global climate change remains debated. Evidence documenting either small or large advancement of spring phenology to rising temperature over the spatio-temporal scales implies a potential existence of a thermal threshold in the responses of forests to global warming. We collected a unique data set of xylem cell-wall-thickening onset dates in 20 coniferous species covering a broad mean annual temperature (MAT) gradient (-3.05 to 22.9°C) across the Northern Hemisphere (latitudes 23°-66° N). Along the MAT gradient, we identified a threshold temperature (using segmented regression) of 4.9 ± 1.1°C, above which the response of xylem phenology to rising temperatures significantly decline. This threshold separates the Northern Hemisphere conifers into cold and warm thermal niches, with MAT and spring forcing being the primary drivers for the onset dates (estimated by linear and Bayesian mixed-effect models), respectively. The identified thermal threshold should be integrated into the Earth-System-Models for a better understanding of spring phenology in response to global warming and an improved prediction of global climate-carbon feedbacks.

Radiomics Based on Dynamic Contrast-Enhanced MRI to Early Predict Pathologic Complete Response in Breast Cancer Patients Treated with Neoadjuvant Therapy.

RATIONALE AND OBJECTIVES: To investigate the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-based radiomics at baseline and after two cycles of neoadjuvant therapy (NAT) and associated longitudinal changes for early prediction of the NAT response in patients with breast cancer. MATERIALS AND METHODS: One hundred seventeen patients with breast cancer who underwent DCE-MRI before NAT and after two cycles of NAT from April 2019 to November 2021 were enrolled retrospectively. Patients were randomly divided into a training set (n = 81) and a test set (n = 36) at a ratio of 7:3. Clinical-pathological data and the relative tumor maximum diameter regression value (diameter%) were also collected. A total of 851 radiomic features were extracted from the phase with the most pronounced tumor enhancement on DCE-MRI T1 imaging acquired both pre- and post-treatment. Delta and delta% radiomics features were also calculated. The Least Absolute Shrinkage and Selection Operator (LASSO) method was applied to select features, and a logistic regression model was used to calculate pre-NAT, early-NAT, delta, and delta% radscores and then select among four radscores to build a Fusion radiomics model. The final clinical-radiomics model was constructed by combining fusion radscores and clinical-pathological variables. The discrimination and clinical utility of the models were further evaluated and compared. RESULTS: The area under the curve (AUC) values of the fusion radiomics model based on pre-NAT, Delta, and Delta% radscores were 0.868 of 0.825. The clinical-radiomics model integrating Fusion radscores and clinical-pathological variables achieved AUC values of 0.920 of 0.884, which were higher than those of the clinical model constructed by AUC values (0.858/0.831), although no significant improvement was observed in the test set (Delong test, p = 0.196). Decision curve analysis (DCA) showed that the clinical-radiomics model demonstrated more clinical utility than the clinical model. CONCLUSION: DCE-MRI-based radiomics features may have potential for pathological complete response (pCR) prediction in the early phase of NAT. By combining radiomics features and clinical-pathological characteristics, higher diagnostic performance can be achieved.