Search

Mutations in cysteine and glycine-rich protein 3 (CSRP3)/muscle LIM protein (MLP), a key regulator of striated muscle function, have been linked to hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) in patients. However, the roles of CSRP3 in heart development and regeneration are not completely understood. In this study, we characterized a novel zebrafish gene-trap line, gSAIzGFFM218A, which harbors an insertion in the csrp3 genomic locus, heterozygous fish served as a csrp3 expression reporter line and homozygous fish served as a csrp3 mutant line. We discovered that csrp3 is specifically expressed in larval ventricular cardiomyocytes (CMs) and that csrp3 deficiency leads to excessive trabeculation, a common feature of CSRP3-related HCM and DCM. We further revealed that csrp3 expression increased in response to different cardiac injuries and was regulated by several signaling pathways vital for heart regeneration. Csrp3 deficiency impeded zebrafish heart regeneration by impairing CM dedifferentiation, hindering sarcomere reassembly, and reducing CM proliferation while aggravating apoptosis. Csrp3 overexpression promoted CM proliferation after injury and ameliorated the impairment of ventricle regeneration caused by pharmacological inhibition of multiple signaling pathways. Our study highlights the critical role of Csrp3 in both zebrafish heart development and regeneration, and provides a valuable animal model for further functional exploration that will shed light on the molecular pathogenesis of CSRP3-related human cardiac diseases. [ABSTRACT FROM AUTHOR]

Background: The results of several large randomized controlled trials (RCTs) have changed the clinical practice of bariatric surgery. However, the characteristics of global RCTs of bariatric surgery have not been reported internationally and whether there was research waste in these RCTs is unknown. Methods: Search ClinicalTrials.gov for bariatric surgery RCTs registered between January 2000 and December 2022 with the keywords 'Roux-en-Y gastric-bypass' and 'Sleeve Gastrectomy'. The above analysis was conducted in January 2023. Results: A total of 326 RCTs were included in this study. The number of RCTs registered for sleeve gastrectomy and gastric bypass surgery increased year by year globally. Europe has always accounted for the largest proportion, Asia has gradually increased, and North America has decreased. A total of 171 RCTs were included in the analysis of waste, of which 74 (43.8%) were published. Of the 74 published RCTs, 37 (37/74, 50.0%) were judged to be adequately reported and 36 (36/74, 48.6%) were judged to have avoidable design defects. In the end, 143 RCTs (143/171, 83.6%) had at least one research waste. Body weight change as the primary endpoint (OR: 0.266, 95% CI: 0.103-0.687, P=0.006) and enrolment greater than 100 (OR: 0.349, 95% CI: 0.146-0.832, P=0.018) were independent protective factors for research waste. Conclusions: This study for the first time describes the characteristic changes of the mainstream RCT of bariatric surgery globally in the last 20 years and identifies a high research waste burden and predictive factor in this area, which provides reference evidence for carrying out bariatric surgery RCTs more rationally. [ABSTRACT FROM AUTHOR]

The aim was to evaluate the efficacy and safety between the watch-and-wait strategy (WW), radical surgery (RS), and local excision (LE) for rectal cancer with clinical complete response (cCR) after neoadjuvant radiotherapy (nCRT). We searched MEDLINE, EMBASE, the Cochrane Library, and clinical trials to compare WW with RS and LE for patients with cCR until March 2023 and collected the following data: local recurrence (LR), distant metastasis (DM), cancer-related death (CRD), overall survival (OS), and disease-free survival (DFS). In total, 2240 patients from 21 studies were included. Pairwise meta-analysis revealed no statistically significant differences between the three groups in terms of CRD and 2-, 3-, and 5-year OS (P < 0.05). The RS group was significantly better than the WW group in terms of the LR rate (odds ratio [OR] = 0.12, 95 % confidence interval [CI]: 0.06–0.21, P < 0.001, I2 = 0 %], 3-year DFS (OR = 1.56, 95 % CI: 1.10–2.21, P = 0.01, I2 = 38 %), and 5-year DFS (OR = 2.30, 95 % CI: 1.53–3.46, P < 0.001, I2 = 34 %). The results of network meta-analysis were also similar. After sensitivity analysis, the 5-year OS of the RS group was significantly better than that of the WW group (OR = 2.77, 95 % CI: 1.28–6.00, P = 0.009, I2 = 33 %). Nevertheless, neither regression analysis nor subgroup analysis provided meaningful results. However, the cumulative meta-analysis of LR, DM, and 3- and 5-year DFS revealed significant turning points (P < 0.05). Our meta-analysis recommends using the WW strategy for patients with cCR having poor underlying conditions and high surgical risk; however, there is a risk of higher LR and worse survival after 3 years. [ABSTRACT FROM AUTHOR]

To characterize nirsevimab in the prevention of RSV, children from the Phase 3 MELODY trial were followed through their second RSV season. No increase in medically attended RSV lower respiratory tract infections or evidence of antibody-dependent enhancement of infection or disease severity was found for nirsevimab vs placebo recipients. Clinical Trial Registration: Clinicaltrials.gov, NCT03979313, https://clinicaltrials.gov/ct2/show/NCT03979313. [ABSTRACT FROM AUTHOR]

Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients. [ABSTRACT FROM AUTHOR]

This article, published in the Journal of Neurological Surgery, introduces a novel outcome metric called the 30-day hospitalization ratio (HR) for patients with pituitary adenomas. The metric combines the length of stay and readmission rates within a 30-day period to provide a comprehensive measure of the economic burden of treatment. The study analyzed the clinical records of 468 patients who underwent endoscopic endonasal surgery for pituitary adenoma. Factors associated with a high HR included high preoperative ASA scores, postoperative lumbar drain placement, intradural extension, and employment status. Understanding these risk factors can lead to personalized monitoring and care, ultimately reducing burden and improving outcomes. [Extracted from the article]

Background: Indocyanine green (ICG) fluorescence imaging is effective in increasing the number of lymph node dissections during laparoscopic radical gastrectomy; however, no studies have attempted to explain this phenomenon. Methods: This study utilized the data from a previous randomized controlled trial (FUGES-012 study) investigating ICG-guided laparoscopic radical gastrectomy performed between November 2018 and July 2019. The Objective Structured Assessments of Technical Skills (OSATS) scoring system was used to grade videos from the ICG and non-ICG groups. Patients with an OSATS score greater than 29 were classified as the high-OSATS population, while those with an OSATS score less than or equal to 29 were classified as the low-OSATS population. Results: A total of 258 patients were included in the modified intention-to-treat analysis: 129 in the ICG group and 129 in the non-ICG group. The OSATS score of the ICG group was higher than that of the non-ICG group (29.6 ± 2.6 vs. 26.6 ± 3.6; P< 0.001). The ICG group underwent a significantly higher mean total number of lymph node dissections than the non-ICG group (50.5 ± 15.9 vs. 42.0 ± 10.3; adjusted P<0.001). The group assigned to ICG use, better OSATS (high-OSATS) scores were observed, which correlated with greater D2 lymph node retrieval (54.1 ± 15.0 vs. 47.2 ± 8.7; adjusted P =0.039). Finally, the ICG group had a lower rate of lymph node noncompliance than that of the non-ICG group (31.8 vs. 57.4%; P <0.001). Conclusions: By applying the ICG fluorescence navigation technique, better OSATS scores were observed, which correlated with greater lymph node retrieval and a lower lymph node noncompliance rate, as recommended for individualized laparoscopic radical gastrectomy. [ABSTRACT FROM AUTHOR]

Background: How brain neural activity changes at multiple time points throughout the day and the neural mechanisms underlying time‐dependent modulation of vigilance are less clear. Purpose: To explore the effect of circadian rhythms and homeostasis on brain neural activity and the potential neural basis of time‐dependent modulation of vigilance. Study Type: Prospective. Subjects: A total of 30 healthy participants (22–27 years old). Field Strength/Sequence: A 3.0 T, T1‐weighted imaging, echo‐planar functional MRI (fMRI). Assessment: Six resting‐state fMRI (rs‐fMRI) scanning sessions were performed at fixed times (9:00 h, 13:00 h, 17:00 h, 21:00 h, 1:00 h, and 5:00 h) to investigate fractional amplitude of low‐frequency fluctuation (fALFF) and regional homogeneity (ReHo) diurnal variation. The fALFF/ReHo and the result of the psychomotor vigilance task were used to assess local neural activity and vigilance. Statistical Tests: One‐way repeated measures analysis of variance (ANOVA) was used to assess changes in vigilance (P < 0.05) and neural activity in the whole brain (P < 0.001 at the voxel level and P < 0.01 at the cluster level, Gaussian random field [GRF] corrected). Correlation analysis was used to examine the relationship between neural activity and vigilance at all‐time points of the day. Results: The fALFF/ReHo in the thalamus and some perceptual cortices tended to increase from 9:00 h to 13:00 h and from 21:00 h to 5:00 h, whereas the key nodes of the default mode network (DMN) tended to decrease from 21:00 h to 5:00 h. The vigilance tended to decrease from 21:00 h to 5:00 h. The fALFF/ReHo in the thalamus and some perceptual cortices was negatively correlated with vigilance at all‐time points of the day, whereas the fALFF/ReHo in the key nodes of the DMN was positively correlated with vigilance. Data Conclusion: Neural activities in the thalamus and some perceptual cortices show similar trends throughout the day, whereas the key nodes of the DMN show roughly opposite trends. Notably, diurnal variation of the neural activity in these brain regions may be an adaptive or compensatory response to changes in vigilance. Evidence Level: 1. Technical Efficacy: 1. [ABSTRACT FROM AUTHOR]

Cationic polyacrylate latex has attracted extensive attention due to its special properties and potential applications in wood primers, metal coatings, and fabric treatments, etc. However, cationic polyacrylate latex has poor durability and stability, which limits its use in practical applications. In this study, a functional cationic monomer (3-chloro-2-hydroxypropyl) dimethyl [2-[(2-methyl-1-oxoallyl)oxy]ethyl] ammonium chloride (DEAC) was combined with two conventional monomers of methyl methacrylate (MMA) and butyl acrylate (BA) to prepare cationic polyacrylate latex by a semi-continuous emulsion polymerization. The obtained latexes showed typical cationic character with zeta potential in the range of + 40 to + 65 mV. The effect of DEAC on the stability of latex was studied and good alkali resistance could be gained at high DEAC content. Water resistance and mechanical properties of the film before and after crosslinking are studied in detail. The results showed that the water absorption reduced from 60.04% to a minimum of 9.18%, and the tensile strength increased from 3.9 to 8.4 MPa, which was comparable to solvent-based polyacrylate films. This work provides a new strategy for the preparation of waterborne cationic polyacrylate latex with improved water resistance and good mechanical properties, etc., which can be applied in papermaking, textiles, wood primers, and other potential fields. [ABSTRACT FROM AUTHOR]

Citrus maxima (Burm.) Merr. ‘Guanximiyou’ is a major citrus tree largely cultivated in China. A previous study has reported the complete chloroplast genome of C. maxima, but there may be some differences between wild species and cultivating variety. In this study, the complete chloroplast genome sequence of ‘Guanximiyou’ pummelo was characterized using BGISEQ-500 sequencing. The chloroplast genome was 160,186 bp in length and separated into four distinct regions such as large single-copy region (87,939 bp), small single-copy region (18,395 bp), and a pair of inverted repeat regions (26,926 bp). The genome contained a total of 109 genes including 79 protein-coding genes, 29 tRNA genes, and 4 rRNA genes. Phylogenetic maximum-likelihood analysis revealed that ‘Guanximiyou’ pummelo was clustered with other Rutaceae species with high bootstrap values.