Evaluation of automatic cochlear dimension measurement using ALPACA: a comparative study.

BACKGROUND: Cochlear dimension measurements are critical in diagnosing and managing congenital sensorineural hearing loss. OBJECTIVES: To evaluate the feasibility and reliability of an automated landmark approach for measuring cochlear dimensions (A-, B- and H-values). MATERIAL AND METHODS: Cochlear parameters from 100 patients were measured by MPR, manual three-dimensional and ALPACA. We assessed intra- and inter-observer reliability as well as inter-method reliability. Statistical analyses were conducted to detect differences between the right and left ears, as well as to assess the relevance of the values obtained using ALPACA. RESULTS: All A-, B-, and H-values measured by the various methods showed a high intra-observer reliability with intra-class correlation coefficients (ICC) ranging from 0.70 to 0.99, and values gained by ALPACA reaching the highest ICC. Inter-method reliability was at a good level with ICC ranging from 0.51 to 0.86. There were no significant differences between the right and left ears' measured values. Obvious positive correlations existed among cochlear dimensions measured by ALPACA. CONCLUSIONS AND SIGNIFICANCE: The ALPACA method can be used to measure cochlear dimensions. Values obtained by the method demonstrate high reliability and consistency with a significant reduction in intra-observer variability compared to results from conventional MPR and manual 3D measurements.

Interpretable semi-supervised clustering enables universal detection and intensity assessment of diverse aviation hazardous winds.

The identification of aviation hazardous winds is crucial and challenging in air traffic management for assuring flight safety, particularly during the take-off and landing phases. Existing criteria are typically tailored for special wind types, and whether there exists a universal feature that can effectively detect diverse types of hazardous winds from radar/lidar observations remains as an open question. Here we propose an interpretable semi-supervised clustering paradigm to solve this problem, where the prior knowledge and probabilistic models of winds are integrated to overcome the bottleneck of scarce labels (pilot reports). Based on this paradigm, a set of high-dimensional hazard features is constructed to effectively identify the occurrence of diverse hazardous winds and assess the intensity metrics. Verification of the paradigm across various scenarios has highlighted its high adaptability to diverse input data and good generalizability to diverse geographical and climate zones.

Effectiveness and mechanisms of mesenchymal stem cell therapy in preclinical animal models of hepatic fibrosis: a systematic review and meta-analysis.

Background: Liver damage due to long-term viral infection, alcohol consumption, autoimmune decline, and other factors could lead to the gradual development of liver fibrosis. Unfortunately, until now, there has been no effective treatment for liver fibrosis. Mesenchymal stem cells, as a promising new therapy for liver fibrosis, can slow the progression of fibrosis by migrating to the site of liver injury and by altering the microenvironment of the fibrotic area. Aim: By including all relevant studies to date to comprehensively assess the efficacy of mesenchymal stem cells for the treatment of hepatic fibrosis and to explore considerations for clinical translation and therapeutic mechanisms. Methods: Data sources included PubMed, Web of Science, Embase, and Cochrane Library, and were constructed until October 2023. Data for each study outcome indicator were extracted for comprehensive analysis. Results: The overall meta-analysis showed that mesenchymal stem cells significantly improved liver function. Moreover, it inhibited the expression level of transforming growth factor-ß [SMD = 4.21, 95% CI (3.02,5.40)], which in turn silenced hepatic stellate cells and significantly reduced the area of liver fibrosis [SMD = 3.61, 95% CI (1.41,5.81)]. Conclusion: Several outcome indicators suggest that mesenchymal stem cells therapy is relatively reliable in the treatment of liver fibrosis. The therapeutic effect is cell dose-dependent over a range of doses, but not more effective at higher doses. Bone-marrow derived mesenchymal stem cells were more effective in treating liver fibrosis than mesenchymal stem cells from other sources. Systematic Review Registration: Identifier CRD42022354768.

Photoinduced Palladium-Catalyzed Radical Germylative Arylation of Alkenes with Chlorogermanes.

We describe a visible light-induced palladium-catalyzed radical germylative arylation of alkenes with easily accessible chlorogermanes. This protocol provides expedient access to germanium-substituted indolin-2-ones in good to excellent yields under mild reaction conditions. The key step for this strategy lies in the reductive activation of germanium-chloride bonds with an excited palladium complex under visible light irradiation. The involvement of germanium radicals was evidenced by electron paramagnetic resonance spectroscopy experiments.

Single and combined strategies for mesenchymal stem cell exosomes alleviate liver fibrosis: a systematic review and meta-analysis of preclinical animal models.

Background: The efficacy of mesenchymal stem cells (MSCs) in treating liver fibrosis has been supported by various clinical studies. However, stem cell transplantation is limited in clinical application due to its low survival rate, low liver implantation rate, and possible carcinogenicity. Recently, there has been increasing interest in the use of MSC-exos due to their widespread availability, low immunogenicity, and non-carcinogenic properties. Numerous studies have demonstrated the potential of MSC-exos in treating liver fibrosis and preventing progression to end-stage liver disease. Objective: This study aimed to systematically investigate the efficacy of MSC-exos single administration in the treatment of hepatic fibrosis and the combined advantages of MSC-exos in combination with drug therapy (MSC-exos-drugs). Methods: Data sources included PubMed, Web of Science, Embase, and the Cochrane Library, which were built up to January 2024. The population, intervention, comparison, outcomes, and study design (PICOS) principle was used to screen the literature, and the quality of the literature was evaluated to assess the risk of bias. Finally, the data from each study's outcome indicators were extracted for a combined analysis. Results: After screening, a total of 18 papers (19 studies) were included, of which 12 involved MSC-exos single administration for the treatment of liver fibrosis and 6 involved MSC-exos-drugs for the treatment of liver fibrosis. Pooled analysis revealed that MSC-exos significantly improved liver function, promoted the repair of damaged liver tissue, and slowed the progression of hepatic fibrosis and that MSC-exos-drugs were more efficacious than MSC-exos single administration. Subgroup analyses revealed that the use of AD-MSC-exos resulted in more consistent and significant efficacy when MSC-exos was used to treat hepatic fibrosis. For MSC-exos-drugs, a more stable end result is obtained by kit extraction. Similarly, infusion through the abdominal cavity is more effective. Conclusion: The results suggest that MSC-exos can effectively treat liver fibrosis and that MSC-exos-drugs are more effective than MSC-exos single administration. Although the results of the subgroup analyses provide recommendations for clinical treatment, a large number of high-quality experimental validations are still needed. Systematic Review Registration: CRD42024516199.

Comparison of machine learning and conventional statistical modeling for predicting readmission following acute heart failure hospitalization.

INTRODUCTION: Developing accurate models for predicting the risk of 30-day readmission is a major healthcare interest. Evidence suggests that models developed using machine learning (ML) may have better discrimination than conventional statistical models (CSM), but the calibration of such models is unclear. OBJECTIVES: To compare models developed using ML with those developed using CSM to predict 30-day readmission for cardiovascular and noncardiovascular causes in HF patients. METHODS: We retrospectively enrolled 10,919 patients with HF (> 18 years) discharged alive from a hospital or emergency department (2004-2007) in Ontario, Canada. The study sample was randomly divided into training and validation sets in a 2:1 ratio. CSMs to predict 30-day readmission were developed using Fine-Gray subdistribution hazards regression (treating death as a competing risk), and the ML algorithm employed random survival forests for competing risks (RSF-CR). Models were evaluated in the validation set using both discrimination and calibration metrics. RESULTS: In the validation sample of 3602 patients, RSF-CR (c-statistic=0.620) showed similar discrimination to the Fine-Gray competing risk model (c-statistic=0.621) for 30-day cardiovascular readmission. In contrast, for 30-day noncardiovascular readmission, the Fine-Gray model (c-statistic=0.641) slightly outperformed the RSF-CR model (c-statistic=0.632). For both outcomes, The Fine-Gray model displayed better calibration than RSF-CR using calibration plots of observed vs predicted risks across the deciles of predicted risk. CONCLUSIONS: Fine-Gray models had similar discrimination but superior calibration to the RSF-CR model, highlighting the importance of reporting calibration metrics for ML-based prediction models. The discrimination was modest in all readmission prediction models regardless of the methods used.

Engineering oncogenic hotspot mutations on SF3B1 via CRISPR-directed PRECIS mutagenesis.

SF3B1 is the most recurrently mutated RNA splicing gene in cancer; However, the study of its pathogenic role has been hindered by a lack of disease-relevant cell line models. Here, we compared four genome engineering platforms to establish SF3B1 mutant cell lines: CRISPR-Cas9 editing, AAV HDR editing, base editing (ABEmax, ABE8e), and prime editing (PE2, PE3, PE5Max). We showed that prime editing via PE5max achieved the most efficient SF3B1 K700E editing across a wide range of cell lines. We further refined our approach by coupling prime editing with a fluorescent reporter that leverages a SF3B1 mutation-responsive synthetic intron to mark successfully edited cells. By applying this approach, called prime editing coupled intron-assisted selection (PRECIS), we introduced the K700E hotspot mutation into two chronic lymphocytic leukemia (CLL) cell lines, HG-3 and MEC-1. We demonstrated that our PRECIS-engineered cells faithfully recapitulate known mutant SF3B1 phenotypes including altered splicing, copy number variations, and cell growth defect. Moreover, we uncovered that SF3B1 mutation can cause the loss of Y chromosome in CLL. Our results showcase PRECIS as an efficient and generalizable method for engineering genetically faithful SF3B1 mutant models. Our approach provides new insights on the role of SF3B1 mutation in cancer and enables the generation of SF3B1 mutant cell lines in relevant cellular context.

MGA deletion leads to Richter's transformation by modulating mitochondrial OXPHOS.

Richter's transformation (RT) is a progression of chronic lymphocytic leukemia (CLL) to aggressive lymphoma. MGA (Max gene associated), a functional MYC suppressor, is mutated at 3% in CLL and 36% in RT. However, genetic models and molecular mechanisms of MGA deletion that drive CLL to RT remain elusive. We established an RT mouse model by knockout of Mga in the Sf3b1/Mdr CLL model using CRISPR-Cas9 to determine the role of Mga in RT. Murine RT cells exhibited mitochondrial aberrations with elevated oxidative phosphorylation (OXPHOS). Through RNA sequencing and functional characterization, we identified Nme1 (nucleoside diphosphate kinase) as an Mga target, which drives RT by modulating OXPHOS. Given that NME1 is also a known MYC target without targetable compounds, we found that concurrent inhibition of MYC and electron transport chain complex II substantially prolongs the survival of RT mice in vivo. Our results suggest that the Mga-Nme1 axis drives murine CLL-to-RT transition via modulating OXPHOS, highlighting a potential therapeutic avenue for RT.

Comparative study of different dosages of grain-sized moxibustion on uterine artery blood flow in patients with cold and dampness primary dysmenorrhea. / ä¸åŒå‰‚é‡éº¦ç²’ç¸å¯¹å¯’æ¹¿å‡æ»žåž‹åŽŸå‘æ€§ç—›ç»æ‚£è€ å­å®«åŠ¨è„‰è¡€æµå½±å“çš„æ¯”è¾ƒç ”ç©¶.

OBJECTIVES: To observe the differences in the effects of different dosages of grain-sized moxibustion on uterine artery blood flow in patients with cold and dampness primary dysmenorrhea (PD). METHODS: A total of 60 patients with PD were randomly divided into 3 groups with 20 cases in each group. Acupoints Sanyinjiao (SP6), Diji (SP8) and Xuehai (SP10) were selected in all the 3 groups, and different dosages of grain-sized moxibustion were used (3 moxa cones, 6 moxa cones, 9 moxa cones) respectively. Treatment started 7 days before menstruation for 3 times, lasting for a total of 3 menstrual cycles. The values of uterine artery blood flow parameters including pulsatility index (PI), resistance index (RI), and systolic/diastolic ratio (S/D) were recorded before and after treatment. The visual analog scale (VAS) score and cox menstrual symptom scale (CMSS) score (including severity ［CMSS-S］ and time of duration ［CMSS-T］) were evaluated before treatment, at the end of each menstrual cycle, and one menstrual cycle after treatment. RESULTS: The values of uterine artery blood flow parameters (PI, RI, S/D) after treatment in the 9 moxa cones group were lower than those before treatment, as well as lower than those in the 3 and 6 moxa cones groups after treatment (P<0.05). The VAS scores of the 3 moxa cones group were lower than those before treatment in the first and second cycle (P<0.05). The VAS scores of the 6 and 9 moxa cones groups were lower than those before treatment at each observation point (P<0.05), and were lower than those of the 3 moxa cones group in the third cycle of treatment and follow-up period (P<0.05). And the VAS score of the 9 moxa cones group was lower than that of the 6 moxa cones group during the follow-up period (P<0.05). Compared with the scores before treatment, the CMSS-T scores at each observation point after treatment were lower in the 9 moxa cones group (P<0.05)；the CMSS-T scores in the second and third cycle after treatment, and follow-up period were lower in the 6 moxa cones group (P<0.05), with the CMSS-S scores in the second and third cycle after treatment, and follow-up period lower in the 6 and 9 moxa cones groups (P<0.05). The CMSS-T and CMSS-S scores of the 6 and 9 moxa cones groups were lower than those of the 3 moxa cones group in the third cycle and follow-up period (P<0.05). The CMSS-T and CMSS-S scores of the 9 moxa cones group were lower than those of the 6 moxa cones group during the follow-up period (P<0.05). CONCLUSIONS: Grain-Sized moxibustion has dose-effect relationship in the treatment of PD. Compared with 3 and 6 moxa cones groups, 9 moxa cones group has advantages in improving uterine artery blood flow parameters and alleviating dysmenorrhea symptoms in PD patients.

High Healthcare Costs in Childhood Inflammatory Bowel Disease: Development of a Prediction Model Using Linked Clinical and Health Administrative Data.

BACKGROUND: The incidence of pediatric-onset inflammatory bowel disease (IBD) and the costs of caring for individuals with IBD are both increasing. We calculated the direct healthcare costs of pediatric IBD in the first year after diagnosis and developed a model to predict children who would have high costs (top 25th percentile). METHODS: Using data from the Canadian Children IBD Network inception cohort (≤16 years of age, diagnosed between 2013 and 2019) deterministically linked to health administrative data from Ontario, Canada, we estimated direct healthcare and medication costs accrued between 31 and 365 days after diagnosis. Candidate predictors included age at diagnosis, sex, rural/urban residence location, distance to pediatric center, neighborhood income quintile, IBD type, initial therapy, disease activity, diagnostic delay, health services utilization or surgery around diagnosis, regular primary care provider, and receipt of mental health care. Logistic regression with stepwise elimination was used for model building; 5-fold nested cross-validation optimized and improved model accuracy while limiting overfitting. RESULTS: The mean cost among 487 children with IBD was CA$15 168 ± 15 305. Initial treatment (anti-tumor necrosis factor therapy, aminosalicylates, or systemic steroids), having a mental health care encounter, undergoing surgery, emergency department visit at diagnosis, sex, and age were predictors of increased costs, while having a regular primary care provider was a predictor of decreased costs. The C-statistic for our model was 0.71. CONCLUSIONS: The cost of caring for children with IBD in the first year after diagnosis is immense and can be predicted based on characteristics at diagnosis. Efforts that mitigate rising costs without compromising quality of care are needed.

Cost of caring for children with IBD is high­CA$15 168 between 31 and 365 days from diagnosis in 487 Canadian children. Predictors of high costs included anti-tumor necrosis factor therapy and mental health care, with lower costs in those with a primary-care provider.

Electroacupuncture Alleviates Memory Deficits in APP/PS1 Mice by Targeting Serotonergic Neurons in Dorsal Raphe Nucleus.

OBJECTIVE: Alzheimer's disease (AD) has become a significant global concern, but effective drugs able to slow down AD progression is still lacked. Electroacupuncture (EA) has been demonstrated to ameliorate cognitive impairment in individuals with AD. However, the underlying mechanisms remains poorly understood. This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD. METHODS: APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu (BL 23) and Baihui (GV 20). Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus (DRN). Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests. Golgi staining, western blot, and immunostaining were utilized to determine EA-induced neuroprotection. RESULTS: EA at Shenshu (BL 23) and Baihui (GV 20) effectively ameliorated learning and memory impairments in APP/PS1 mice. EA attenuated dendritic spine loss, increased the expression levels of PSD95, synaptophysin, and brain-derived neurotrophic factor in hippocampus. Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT1B. Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory. CONCLUSION: EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN. Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD.

LncRNA MALAT1-miR-339-5p-NIS axis is involved in the increased level of thyroid stimulating hormone (TSH) induced by combined exposure of high iodine and hyperlipidemia.

Hypothyroidism and subclinical hypothyroidism were both characterized by elevated levels of thyroid stimulating hormone (TSH). Previous studies had found that high iodine or hyperlipidemia alone was associated with increased TSH level. However, their combined effects on TSH have not been elucidated. In this study, combination of high iodine and hyperlipidemia was established through the combined exposure of high-water iodine and high fat diet in Wistar rats. The results showed that combined exposure of high iodine and high fat can induce higher TSH level. The mRNA and protein levels of sodium iodide transporters (NIS) and type 1 deiodinase (D1) in thyroid tissues, which were crucial genes in the synthesis of thyroid hormones, decreased remarkably in combined exposure group. Mechanistically, down-regulated long non-coding RNA (lncRNA) metastasis associated in lung denocarcinoma transcript 1 (MALAT1) may regulate the expression of NIS by increasing miR-339-5p, and regulating D1 by increasing miR-224-5p. Then, the above findings were explored in subjects exposed to high water iodine and hyperlipidemia. The results indicated that in population combined with high iodine and hyperlipidemia, TSH level increased to higher level and lncRNA MALAT1-miR-339-5p-NIS axis was obviously activated. Collectively, this study found that combined exposure of high iodine and hyperlipidemia induced a higher level of TSH, and lncRNA MALAT1-miR-339-5p-NIS axis may play important role.

Metal-Free Cascade Formation of C-C and C-N Bond for the Construction of 3-Cyano-2-Pyridones with Insecticidal Properties.

A straightforward and efficient methodology has been developed for the synthesis of 3-cyano-2-pyridones via the C-C and C-N bond formation processes. A total of 51 diverse 3-cyano-2-pyridone derivatives were obtained in moderate to excellent yields. This reaction featured advantages such as a metal-free process, wide functional group tolerance, simple operation, and mild conditions. A plausible mechanism for the reaction was proposed. 3-cyano-2-pyridones as ricinine analogues for insecticidal properties were evaluated, and the compound 3ci (LC50 = 2.206 mg/mL) showed the best insecticidal property.

A bibliometric analysis of the knowledge related to mental health during and post COVID-19 pandemic.

Objective: COVID-19 led to a horrific global pandemic, with strict lockdowns and prolonged indoor stays increasing the risk of mental health problems, affecting people of different ages, genders, regions, and types of work to varying degrees. This study provides a bibliometric summary of the knowledge map related to mental health during and post COVID-19 pandemic. Methods: Publications related to mental health during and post COVID-19 pandemic were searched in the Web of Science Core Collection (WoSCC) database through March 19, 2024. After screening the search results, the literature included in the final was first quantitatively analyzed using GraphPad Prism software and then visualized using VOSviewer, CiteSpace, and R (the bibliometrix package). Results: The 7,047 publications from 110 countries were included, with the highest number of publications from China and the United States, and the number of publications related to mental health during and post the COVID-19 pandemic increased annually until 2023, after which it began to decline. The major institutions were University of Toronto, University of London, Harvard University, King's College London, University College London, University of California System, University of Melbourne, Institut National De La Sante Et De La Recherche Medicale (Inserm), Mcgill University, and University of Ottawa; Frontiers in Psychiatry had the highest number of publications, and the Journal of Affective Disorders had the highest number of co-citations; 36,486 authors included, with Xiang, Yu-Tao, Cheung, Teris, Chung, Seockhoon published the most papers, and World Health Organization, Kroenke K, and Wang CY were the most co-cited; epidemiologically relevant studies on mental health related to COVID-19, and the importance of mental health during normalized epidemic prevention and control are the main directions of this research area, especially focusing on children's mental health; "pandemic," "sars-cov-2," "epidemic," "depression," "coronavirus anxiety," "anxiety," "longitudinal," "child," "coronavirus anxiety," "longitudinal," "child," and "coronavirus" are the top keywords in recent years. Conclusion: This comprehensive bibliometric study summarizes research trends and advances in mental health during and after the COVID-19 Pandemic. It serves as a reference for mental health research scholars during and after the COVID-19 pandemic, clarifying recent research preoccupations and topical directions.

Efficacy and safety of mesenchymal stem cells therapy in COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The coronavirus disease 2019 (COVID-19) has become a serious public health issue. In COVID-19 patients, the elevated levels of inflammatory cytokines lead to the manifestation of COVID-19 symptoms, such as lung tissue edema, lung diffusion dysfunction, acute respiratory distress syndrome (ARDS), secondary infection, and ultimately mortality. Mesenchymal stem cells (MSCs) exhibit anti-inflammatory and immunomodulatory properties, thus providing a potential treatment option for COVID-19. The number of clinical trials of MSCs for COVID-19 has been rising. However, the treatment protocols and therapeutic effects of MSCs for COVID-19 patients are inconsistent. This meta-analysis was performed to systematically determine the safety and efficacy of MSC infusion in COVID-19 patients. METHODS: We conducted a comprehensive literature search from PubMed/Medline, Web of Science, EMBASE, and Cochrane Library up to 22 November 2023 to screen for eligible randomized controlled trials. Inclusion and exclusion criteria for searched literature were formulated according to the PICOS principle, followed by the use of literature quality assessment tools to assess the risk of bias. Finally, outcome measurements including therapeutic efficacy, clinical symptoms, and adverse events of each study were extracted for statistical analysis. RESULTS: A total of 14 randomized controlled trials were collected. The results of enrolled studies demonstrated that patients with COVID-19 pneumonia who received MSC inoculation showed a decreased mortality compared with counterparts who received conventional treatment (RR: 0.76; 95% CI [0.60, 0.96]; p = 0.02). Reciprocally, MSC inoculation improved the clinical symptoms in patients (RR: 1.28; 95% CI [1.06, 1.55]; p = 0.009). In terms of immune biomarkers, MSC treatment inhibited inflammation responses in COVID-19 patients, as was indicated by the decreased levels of CRP and IL-6. Importantly, our results showed that no significant differences in the incidence of adverse reactions or serious adverse events were monitored in patients after MSC inoculation. CONCLUSION: This meta-analysis demonstrated that MSC inoculation is effective and safe in the treatment of patients with COVID-19 pneumonia. Without increasing the incidence of adverse events or serious adverse events, MSC treatment decreased patient mortality and inflammatory levels and improved the clinical symptoms in COVID-19 patients. However, large-cohort randomized controlled trials with expanded numbers of patients are required to further confirm our results.

Aqueous extract of Phellinus igniarius ameliorates hyperuricemia and renal injury in adenine/potassium oxonate-treated mice.

Phellinus igniarius is an important medicinal and edible fungus with diverse biological activities. This study aimed to investigate the effects of aqueous extract from P. igniarius (API) on the treatment of hyperuricemia (HUA) and related kidney damage. The chemical constituents of API were determined. The therapeutic effects of API on HUA and renal injury were assessed in adenine/potassium oxonate (PO)-treated mice. The constituent analysis of API revealed a predominance of polysaccharides (33.4 %), followed by total flavonoids (9.1 %), and total triterpenoids (3.5 %). Compared to control, the adenine/PO treatment greatly elevated serum uric acid (UA) levels but this elevation was attenuated by API. In the liver, the expression and activity of xanthine oxidase (XOD) were increased by HUA which were diminished by API. Furthermore, API was found to enhance the expression of UA transporter ABCG2 in the kidney and intestine of HUA mice, suggesting elevating UA excretion. Additionally, API ameliorated HUA-induced renal injury, as indicated by reduced serum BUN/creatinine levels, decreased glomerular and tubular damage, and lowered fibrotic levels. Network pharmacology analysis predicted that P. igniarius may regulate mitochondrial function to improve HUA-related renal injury. This prediction was then substantialized by the API-induced upregulation of NAD+/NADH ratio, ATP level, SOD2 activity, and expression of SOD2/PCG-1α/PPARγ in the kidney of HUA mice. Our results demonstrate that API may effectively ameliorate HUA by reducing UA production in the liver and enhancing UA excretion in the kidney and intestine, and it might be a potential therapy to HUA-related renal injury.

N-Acyl-N-Alkyl Sulfonamide Probes for Ligand-Directed Covalent Labeling of GPCRs: The Adenosine A2B Receptor as Case Study.

Small molecular tool compounds play an essential role in the study of G protein-coupled receptors (GPCRs). However, tool compounds most often occupy the orthosteric binding site, hampering the study of GPCRs upon ligand binding. To overcome this problem, ligand-directed labeling techniques have been developed that leave a reporter group covalently bound to the GPCR, while allowing subsequent orthosteric ligands to bind. In this work, we applied such a labeling strategy to the adenosine A2B receptor (A2BAR). We have synthetically implemented the recently reported N-acyl-N-alkyl sulfonamide (NASA) warhead into a previously developed ligand and show that the binding of the A2BAR is not restricted by NASA incorporation. Furthermore, we have investigated ligand-directed labeling of the A2BAR using SDS-PAGE, flow cytometric, and mass spectrometry techniques. We have found one of the synthesized probes to specifically label the A2BAR, although detection was hindered by nonspecific protein labeling most likely due to the intrinsic reactivity of the NASA warhead. Altogether, this work aids the future development of ligand-directed probes for the detection of GPCRs.

Newborn readmissions and virtual primary care delivery: a population-based case-control study.

BACKGROUND: Early post-discharge assessments for newborns are recommended. Virtual care has become more prevalent during the pandemic, providing an opportunity to better understand its impact on the quality of post-discharge newborn care. The objective of this study was to understand whether primary care visit modality (in-person vs. virtual) is associated with early newborn hospital readmissions and emergency department (ED) visits. METHODS: We conducted a population-based, case-control study using linked health administrative databases between September 1, 2020 and March 31, 2022 in Ontario, Canada. We compared the modality of primary care visits among cases (hospital readmission within 14 days of life) and controls (newborns without a readmission), matched on infant sex, gestational age, and maternal parity. We included an alternative definition of cases as a composite of either a newborn hospital readmission or emergency department (ED) visit or in-hospital death within the first 14 days of life. Conditional logistic regression models were used to model odds ratios (ORs), comparing those exposed to a virtual visit versus in-person visit, adjusting for infant birth weight, birth hospitalization length of stay, neighbourhood level material deprivation, rurality and presence of active maternal comorbidities. RESULTS: Among 73,324 eligible newborns, 2,220 experienced a hospital readmission within 14 days of life and were matched to 8,880 controls. Jaundice was the primary reason for readmission (75% of readmissions). Compared to newborns who were seen in-person post-discharge, newborns who were seen virtually had higher odds of hospital readmission (adjusted odds ratio [aOR] 1.41 (95% CI 1.09, 1.83); the magnitude of effect was not different using the composite outcome (aOR 1.35, 95% CI 1.05, 1.75). CONCLUSIONS: Newborns who receive a virtual post-discharge visit are more likely than those who receive an in-person visit to require hospital readmission.

Bio-inspired foveal super-resolution method for multi-focal-length images based on local gradient constraints.

Most existing super-resolution (SR) imaging systems, inspired by the bionic compound eye, utilize image registration and reconstruction algorithms to overcome the angular resolution limitations of individual imaging systems. This article introduces a multi-aperture multi-focal-length imaging system and a multi-focal-length image super-resolution algorithm, mimicking the foveal imaging of the human eye. Experimental results demonstrate that with the proposed imaging system and an SR imaging algorithm inspired by the human visual system, the proposed method can enhance the spatial resolution of the foveal region by up to 4 × compared to the original acquired image. These findings validate the effectiveness of the proposed imaging system and computational imaging algorithm in enhancing image texture and spatial resolution.

Seeing Beyond the Surface: Superior performance of Ultrasound elastography over Milan ultrasound criteria in distinguishing fibrosis of ulcerative colitis.

BACKGROUND: Colonic fibrosis has important clinical implications in ulcerative colitis. Ultrasound imaging has emerged as a convenient and reliable tool in diagnosis of inflammatory bowel disease. We aimed to explore the potential use of ultrasound to evaluate UC fibrosis. METHODS: Consecutive UC patients who had proctocolectomy from July 2022 to Sep 2023 were enrolled in the study. Patients underwent bowel ultrasound examination and ultrasound elastography imaging prior to surgery. Milan ultrasound criteria (MUC) was calculated and bowel wall stiffness was determined using two mean strain ratios (MSRs). Degree of colonic fibrosis and inflammation was measured upon histological analysis. ROC analysis was used to evaluate the performance of ultrasound-derived parameters to predict fibrosis. RESULTS: Fifty-six patients were enrolled with 112 segments included in analysis. The median fibrosis score was 2 (0-4) and the median Geboes score was 5 (0-13) and these two scores were significantly correlated (p<0.001). The muscularis mucosa thickness was significantly higher in moderate-severe fibrosis than none-mild fibrosis (p=0.003) but bowel wall thickness was not (p=0.082). The strain ratios (p<0.001) and MUC (p=0.010) was significantly higher in involved than non-involved segments. The strain ratios were correlated with fibrosis score (p<0.001) but not MUC (p=0.387). At ROC analysis, MSR1 had an AUC of 0.828 (cutoff value 3.07, 95% CI 0.746-0.893, p<0.001) to predict moderate-severe fibrosis. CONCLUSION: Ultrasound elastography imaging could predict the degree of colonic fibrosis in UC. Application of this technique could help disease monitoring and decision-making of UC patients.