Ablating Myocardium Using Nanosecond Pulsed Electric Fields: Preclinical Assessment of Feasibility, Safety, and Durability.

BACKGROUND: Unlike conventional microsecond pulsed electrical fields that primarily target the cell membranes, nanosecond pulses are thought to primarily electroporate intracellular organelles. We conducted a comprehensive preclinical assessment of catheter-based endocardial nanosecond pulsed field ablation in swine. METHODS: A novel endocardial nanosecond pulsed field ablation system was evaluated in a total of 25 swine. Using either a low-dose (5-second duration) or high-dose (15-second duration) strategy, thoracic veins and discrete atrial and ventricular sites were ablated. Swine survived for <1 (n=1), ≈2 (n=7), ≈7 (n=6), 14 (n=2), or ≈28 (n=9) days, and venous isolation was assessed before euthanize. Safety assessments included evaluation of esophageal effects, phrenic nerve function, and changes in venous caliber. All tissues were subject to careful gross pathological and histopathologic examination. RESULTS: All (100%) veins (13 low-dose, 34 high-dose) were acutely isolated, and all reassessed veins (6 low-dose, 15 high-dose) were durably isolated. All examined vein lesions (10 low-dose, 22 high-dose) were transmural. Vein diameters (n=15) were not significantly changed. Of the animals assessed for phrenic palsy (n=9), 3 (33%) demonstrated only transient palsy. There were no differences between dosing strategies. Thirteen mitral isthmus lesions were analyzed, and all 13 (100%) were transmural (depth, 6.4±0.4 mm). Ventricular lesions were 14.7±4.5 mm wide and 7.1±1.3 mm deep, with high-dose lesions deeper than low-dose (7.9±1.2 versus 6.2±0.8 mm; P=0.007). The esophagus revealed nontransmural adventitial surface lesions in 5 of 5 (100%) animals euthanized early (2 days) post-ablation. In the 10 animals euthanized later (14-28 days), all animals demonstrated significant esophageal healing-8 with complete resolution, and 2 with only trace fibrosis. CONCLUSIONS: A novel, endocardial nanosecond pulsed field ablation system provides acute and durable venous isolation and linear lesions. Transient phrenic injury and nontransmural esophageal lesions can occur with worst-case assessments suggesting limits to pulsed field ablation tissue selectivity and the need for dedicated assessments during clinical studies.

CT-based radiomics and clinical characteristics for predicting bone metastasis in lung adenocarcinoma patients.

Background: The occurrence of bone metastasis (BM) will seriously shorten the survival time of lung adenocarcinoma patients and aggravate the suffering of patients. Computed tomography (CT)-based clinical radiomics nomogram may help clinicians stratify the risk of BM in lung adenocarcinoma patients, thereby enabling personalized individualized clinical decision making. Methods: A total of 501 patients with lung adenocarcinoma from March 2017 to March 2019 were enrolled in the study. Based on plain chest CT images, 1130 radiomics features were extracted from each lesion. One-way analysis of variance (ANOVA) and least absolute shrinkage selection operator (LASSO) algorithm were used for radiomics features selection. Univariate and multivariate analyses were used to screen for clinical characteristics and identify independent predictors of BM. Three models (radiomics model, clinical model and combined model) were constructed to predict BM in lung adenocarcinoma patients. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were used to evaluate the performance of the three models. The DeLong test was used to compare the performance of the models. Results: Finally, the clinical model for predicting BM in lung adenocarcinoma patients was constructed based on 5 independent predictors: cytokeratin 19-fragments (CYFRA21-1), stage, Ki-67, edge, and lobulation. The radiomics model was constructed based on 5 radiomics features. The combined model incorporating clinical independent predictors and radiomics was constructed. In the validation cohort, the area under the curve (AUC) of the clinical model, radiomics model and combined model was 0.824, 0.842 and 0.866, respectively. Delong test showed that in the training cohort, the AUC values of the radiomics model and the combined model were statistically different (P=0.03), and the AUC values of the other models were not statistically different. DCA showed that the nomogram had a highest net clinical benefit. Conclusions: The CT-based clinical radiomics nomogram can be used as a non-invasive and quantitative method to help clinicians stratify the risk of BM in patients with lung adenocarcinoma, thereby enabling personalized clinical decision making.

Pop-Out Myocardial Infarction Induction in Mice.

Myocardial infarction (MI) in mice is a widely used surgical model in preclinical cardiac repair studies to recapitulate human cardiovascular ischemic disease. Induction of reproducible infarct size is crucial for quantitative and analytical purpose. Here we describe a quick and reliable method to induce consistent infarct size in mice in less than a minute.

Ct-based intratumoral and peritumoral radiomics for predicting prognosis in osteosarcoma: A multicenter study.

PURPOSE: To evaluate the performance of CT-based intratumoral, peritumoral and combined radiomics signatures in predicting prognosis in patients with osteosarcoma. METHODS: The data of 202 patients (training cohort:102, testing cohort:100) with osteosarcoma admitted to the two hospitals from August 2008 to February 2022 were retrospectively analyzed. Progression free survival (PFS) and overall survival (OS) were used as the end points. The radiomics features were extracted from CT images, three radiomics signatures（RSintratumoral, RSperitumoral, RScombined）were constructed based on intratumoral, peritumoral and combined radiomics features, respectively, and the radiomics score (Rad-score) were calculated. Kaplan-Meier survival analysis was used to evaluate the relationship between the Rad-score with PFS and OS, the Harrell's concordance index (C-index) was used to evaluate the predictive performance of the radiomics signatures. RESULTS: Finally, 8, 6, and 21 features were selected for the establishment of RSintratumoral, RSperitumoral, and RScombined, respectively. Kaplan-Meier survival analysis confirmed that the Rad-scores of the three RSs were significantly correlated with the PFS and OS of patients with osteosarcoma. Among the three radiomics signatures, RScombined had better predictive performance, the C-index of PSF prediction was 0.833 in the training cohort and 0.814 in the testing cohort, the C-index of OS prediction was 0.796 in the training cohort and 0.764 in the testing cohort. CONCLUSIONS: CT-based intratumoral, peritumoral and combined radiomics signatures can predict the prognosis of patients with osteosarcoma, which may assist in individualized treatment and improving the prognosis of osteosarcoma patients.

Oral microbiome associated with differential ratios of Porphyromonas gingivalis and Streptococcus cristatus.

Periodontitis has recently been defined as a dysbiotic disease caused by an imbalanced oral microbiota. The transition from commensal microbial communities to periodontitis-associated ones requires colonization by specific pathogens, including Porphyromonas gingivalis. We previously reported an antagonistic relationship between Streptococcus cristatus and P. gingivalis. To determine the role of S. cristatus in altering the interactions of P. gingivalis with other oral bacteria in a complex context, we collected dental plaque samples from patients with periodontitis and assigned them to two groups based on the ratios of S. cristatus and P. gingivalis. We then characterized the microbial profiles of the dental plaque samples using shotgun metagenomic sequencing and compared the oral microbial composition and functional capabilities of the group with high S. cristatus-P. gingivalis ratios with the low ratio group. Taxonomic annotation revealed significant differences in the microbial composition at both the genus and species levels between the low and high S. cristatus-P. gingivalis ratio groups. Notably, a higher microbial diversity was observed in the samples with low S. cristatus-P. gingivalis ratios. Furthermore, the antibiotic resistance gene profiles of the two groups were also distinct, with a significantly increased abundance of the genes in the dental plaque samples with low S. cristatus-P. gingivalis ratios. It, therefore, indicates that the S. cristatus-P. gingivalis ratios influenced the virulence potential of the oral microbiome. Our work shows that enhancing the S. cristatus-P. gingivalis ratio in oral microbial communities can be an attractive approach for revising the dysbiotic oral microbiome.IMPORTANCEPeriodontitis, one of the most common chronic diseases, is linked to several systemic diseases, such as cardiovascular disease and diabetes. Although Porphyromonas gingivalis is a keystone pathogen that causes periodontitis, its levels, interactions with accessory bacteria and pathobionts in the oral microbiome, and its association with the pathogenic potential of the microbial communities are still not well understood. In this study, we revealed the role of Streptococcus cristatus and the ratios of S. cristatus and P. gingivalis in modulating the oral microbiome to facilitate a deeper understanding of periodontitis and its progression. The study has important clinical implications as it laid a foundation for developing novel non-antibiotic therapies against P. gingivalis and improving the efficiency of periodontal treatments.

Using chitosan nanofibers to simultaneously improve the toughness and sensing performance of chitosan-based ionic conductive hydrogels.

Conductive hydrogels, especially polysaccharide-based ionic conductive hydrogels, have received increasing interest in the field of wearable sensors due to their similarity to human skin. Nevertheless, it is still a challenging task to simultaneously prepare a self-healed and adhesive conductive hydrogel with good toughness, temperature tolerance and high sensing performance, especially with high sensitivity and a low detection limit. Herein, we developed a new strategy to improve the toughness and sensing performance of a multifunctional conductive hydrogel by simultaneously using dissolved chitosan (CS) and solid chitosan nanofibers (CSFs) to induce the formation of hierarchical polymeric networks in the hydrogel. The tensile strength and elongation at break of the hydrogel could be improved from 70.3 kPa and 1005 % to 173.9 kPa and 1477 %, respectively, simply by introducing CSFs to the hydrogel, and its self-healing, adhesive and antibacterial properties were effectively retained. When serving as a resistive sensing material, the introduction of CSFs increased the gauge factor of the hydrogel-based strain sensor from 8.25 to 14.27. Moreover, the hydrogel-based strain sensor showed an ultralow detection limit of 0.2 %, excellent durability and stability (1000 cycles) and could be used to detect various human activities. In addition, the hydrogel prepared by using a water-glycerol binary solvent system showed temperature-tolerant performance and possessed adequate sensitivity when serving as a resistive sensing material. Therefore, this work provides a new way to prepare multifunctional conductive hydrogels with good toughness, sensing performance and temperature tolerance to expand the application range of hydrogel-based strain sensors.

Using chitosan nanofibers to synergistically construct a highly stretchable multi-functional liquid mental-based hydrogel for assembling strain sensor with high sensitivity and broad working range.

Liquid metal (LM) microdroplets have garnered significant interest as conductive materials for initiating free radical polymerization in the development of conductive hydrogels suited for strain sensors. However, crafting multi-functional conductive hydrogels that boast both high stretchability and superior sensing capabilities remains as a challenge. In this study, we have successfully synthesized LM-based conductive hydrogels characterized by remarkable stretchability and sensing performance employing acrylic acid (AA) to evenly distribute chitosan nanofibers (CSFs) and to subsequently catalyze the free radical polymerization of AA. The resultant polymer network was crosslinked within situ polyacrylic acid (PAA), facilitated by Ga3+ in conjunction with guar gum (GG)-stabilized Ga droplets. The strategic interplay between the rigid, and protonated CSFs and the pliable PAA matrix, coupled with the ionic crosslinking of Ga3+, endows the resulting GG-Ga-CSF-PAA hydrogel with high stretchability (3700 %), ultrafast self-healing, robust moldability, and strong adhesiveness. When deployed as a strain sensing material, this hydrogel exhibits a high gauge factor (38.8), a minimal detection threshold, enduring durability, and a broad operational range. This versatility enables the hydrogel-based strain sensor to monitor a wide spectrum of human motions. Remarkably, the hydrogel maintains its stretchability and sensing efficacy under extreme temperatures after a simple glycerol solution treatment.

Discovery of a multipotent cell type from the term human placenta.

We report a unique population of multipotent cells isolated from the term human placenta, for the first time, that can differentiate into cardiomyocytes and vascular cells with clonal proliferative ability, migratory ability, and trancriptomic evidence of immune privilege. Caudal-type homeobox-2 (CDX2) is a conserved factor that regulates trophectoderm formation and placentation during early embryonic development but has not previously been implicated in developmentally conserved regenerative mechanisms. We had earlier reported that Cdx2 lineage cells in the mouse placenta are capable of restoring cardiac function after intravenous delivery in male mice with experimental cardiac injury (myocardial infarction). Here we demonstrate that CDX2-expressing cells are prevalent in the human chorion and are poised for cardiovascular differentiation. We examined the term placentas from 106 healthy patients and showed that isolated CDX2 cells can spontaneously differentiate into cardiomyocytes, functional vascular cells, and retain homing ability in vitro. Functional annotation from transcriptomics analysis supports enhanced cardiogenesis, vasculogenesis, immune modulation, and chemotaxis gene signatures in CDX2 cells. CDX2 cells can be clonally propagated in culture with retention of cardiovascular differentiation. Our data supports further use of this accessible and ethically feasible cell source in the design of therapeutic strategies for cardiovascular disease.

Ultrastructural insights from myocardial ablation lesions from microsecond pulsed field vs radiofrequency energy.

BACKGROUND: Ultrastructural findings immediately after pulsed field ablation (PFA) of the myocardium have not been described. OBJECTIVES: The purpose of this study was to elucidate ultrastructural characteristics and differences between microsecond PFA at the 1- and 4-hour timepoints after pulse delivery and to compare them to irrigated radiofrequency ablation (RFA) lesions. METHODS: Healthy swine underwent endocardial PFA or RFA followed by necropsy. Discrete microsecond PFA and irrigated RFA lesions were created in the ventricles with a lattice tip ablation catheter. Lesions were delivered in a manner so as to allow sampling to occur 1 and 4 hours after ablation. All lesions were located at necropsy, and samples were carefully obtained from within the lesion core, lesion periphery, and adjacent healthy myocardium. Transmission electron microscopic assessment was performed after fixation using paraformaldehyde and glutaraldehyde. RESULTS: One hour after microsecond PFA delivery, myocytes were noted to be significantly and uniformly disrupted. Clustered, misaligned, swollen mitochondria coupled with degenerating nuclei and condensed chromatin were visualized. These findings progressed over the subsequent few hours with worsening edema. Similar changes were seen with RFA but reduced in severity. However, there was prominent extravasation of red blood cells with occlusion of capillaries that was not seen in PFA. At the lesion periphery, an abrupt change in the degree of myocyte damage was observed with PFA but not RFA. CONCLUSION: Transmission electron microscopy demonstrates evidence of widespread destruction of myocytes as early as an hour after PFA and corroborates known histologic features such as sparing of vessels and sharp lesion margins.

Prognostic Value of Tumor Size in Colon Cancer-Smaller is Better?

BACKGROUND: The prognostic value of tumor size in colon cancer remains controversial. This study aimed to reveal the correlation between tumor size and prognosis of colon cancer. METHODS: A total of 491 patients with colon cancer were included in this study. The correlation of tumor size with prognosis, mismatch repair status, and other clinicopathological characteristics as well as tumor microenvironment was analyzed. RESULTS: For stage IIA microsatellite stable (MSS) colon cancer, tumors sized <3.5 cm and ≥5 cm were associated with a poorer disease free survival (DFS) compared with tumors sized between 3.5 and 5 cm (P = .002). Small tumor size (HR = 5.098, P = .001) and large tumor size (HR = 2.749, P = .029) were found to be independent prognostic factors for stage IIA MSS colon cancer. Moreover, high expression of transgelin (TAGLN), a marker of cancer-associated fibroblasts (CAFs), was found to be an independent prognostic factor for poorer DFS (HR = 9.651, P = .009), which was also associated with smaller tumor size (P = .027). CONCLUSION: Small (<3.5 cm) and large (≥5 cm) tumor sizes are associated with decreased DFS in stage IIA MSS colon cancer. Enrichment of TAGLN+ CAFs is associated with decreased DFS and small tumor size.

Tyrosine kinase receptor ErbB4 in Advillin-positive neurons contributes to inflammatory pain hypersensitivity in mouse DRG.

Inflammatory pain is a common type of pathological pain. Although the dorsal root ganglion (DRG) is key to pathogenesis of inflammatory pain, the underlying specific molecular and cellular mechanisms remain unclear. In this study, we used mouse models of acute or chronic inflammatory pain, induced by formalin or complete Freund' s adjuvant (CFA), respectively, to explore whether tyrosine kinase receptor ErbB4 participates in the pathogenesis of inflammatory pain. Firstly, we found that both the expression of Neuregulin 1 (Nrg1) and phosphorylation of ErbB4 receptor were upregulated in DRG after inflammatory pain, implying the activation of ErbB4 in DRG. Using ErbB4-mutant mice, we found reduced pain sensitivity of mice when ErbB4 gene expression was largely ablated; furthermore, ErbB4 deletion decreased the inflammatory pain hypersensitivity of either formalin- or CFA-induced mouse models. Moreover, the pain sensitivity was reduced in mice with specific deletion of ErbB4 on advillin-positive neurons within DRG. Importantly, pain hypersensitivity also decreased in Advillin-Cre;ErbB4-/- cKO mice after formalin- or CFA-induced inflammatory pain. Finally, gene quantification differential expression analysis, using RNAseq technology in combination with GO and KEGG enrichment analysis, suggested that calcium signaling pathway possibly mediated the roles of ErbB4 on DRG sensory neurons in inflammatory pain models. Together, these results indicate that ErbB4 on advillin-positive sensory neurons enhances inflammatory pain sensitivity, providing new clues towards the pathogenic mechanisms of inflammatory pain.

Safety and immunogenicity of the COVID-19 mRNA vaccine CS-2034: A randomized, double-blind, dose-exploration, placebo-controlled multicenter Phase I clinical trial in healthy Chinese adults.

BACKGROUND: The novel coronavirus pneumonia (COVID-19) is an infectious disease caused by the infection of a novel coronavirus known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which has resulted in millions of deaths. We aimed to evaluate the safety and immunogenicity of the COVID-19 mRNA vaccine (CS-2034, CanSino, Shanghai, China) in adults without COVID-19 infection from China. METHOD: This is a multicenter Phase I clinical trial with a randomized, double-blinded, dose-exploration, placebo-controlled design. The trial recruited 40 seronegative participants aged 18-59 years who had neither received any COVID-19 vaccine nor been infected before. They were divided into a low-dose group (administered with either the CS-2034 vaccine containing 30 µg of mRNA or a placebo of 0.3 ml type 5 adenovirus vector) and a high-dose group (administered with either the CS-2034 vaccine containing 50 µg of mRNA or a placebo of 0.5 ml type 5 adenovirus vector). Participants were randomly assigned in a 3:1 ratio to receive either the mRNA vaccine or a placebo on days 0 and 21 according to a two-dose immunization schedule. The first six participants in each dosage group were assigned as sentinel subjects. Participants were sequentially enrolled in a dose-escalation manner from low to high dose and from sentinel to non-sentinel subjects. Blood samples were collected from all participants on the day before the first dose (Day 0), the day before the second dose (day 21), 14 days after the second dose (day 35), and 28 days after the second dose (day 49) to evaluate the immunogenicity of the CS-2034 vaccine. Participants were monitored for safety throughout the 28-day follow-up period, including solicited adverse events, unsolicited adverse events, adverse events of special interest (AESI), and medically attended adverse events (MAE). This report focuses solely on the safety and immunogenicity analysis of adult participants aged 18-59 years, while the long-term phase of the study is still ongoing. This study is registered at ClinicalTrials.gov, NCT05373485. FINDINGS: During the period from May 17, 2022, to August 8, 2022, a total of 155 participants aged 18-59 years were screened for this study. Among them, 115 participants failed the screening process, and 40 participants were randomly enrolled (15 in the low-dose group, 15 in the high-dose group, and 10 in the placebo group). Throughout the 28-day follow-up period, the overall incidence of adverse reactions (related to vaccine administration) in the low-dose group, high-dose group, and placebo group was 93.33% (14/15), 100.00% (15/15), and 80.00% (8/10), respectively. There was a statistically significant difference in the incidence of local adverse reactions (soreness, pruritus, swelling at the injection site) among the low-dose group, high-dose group, and placebo group (P = 0.002). All adverse reactions were mainly of severity grade 1 (mild) or 2 (moderate), and no adverse events of severity grade 4 or higher occurred. Based on the analysis of Spike protein Receptor Binding Domain (S-RBD) IgG antibodies against the BA.1 strain, the seroconversion rates of antibodies at day 21 after the first dose were 86.67%, 93.33%, and 0.00% in the low-dose group, high-dose group, and placebo group, respectively. The geometric mean titer (GMT) of antibodies was 61.2(95%CI 35.3-106.2), 55.4(95%CI 36.3-84.4), and 15.0(95%CI 15.0-15.0), and the geometric mean fold increase (GMI) was 4.08(95%CI 2.35-7.08), 3.69(95%CI 2.42-5.63), and 1.00(95%CI 1.00-1.00) for each group. At day 28 after the full vaccination, the seroconversion rates of antibodies were 100.00%, 93.33%, and 0.00%, and the GMT of antibodies was 810.0(95%CI 511.4-1283.0), 832.2(95%CI 368.1-1881.6), and 15.0(95%CI 15.0-15.0), and the GMI was 54.00(95%CI 34.09-85.53), 55.48(95%CI 24.54-125.44), and 1.00(95%CI 1.00-1.00) for each group, respectively. Based on the analysis of CD3+/CD4+ cell cytokine response, the percentages of IL-2+, IL-4+, IFN-γ+, and TNF-α+ cells increased after 14 days and 28 days of full vaccination in both the low-dose group and high-dose group. The increase was most pronounced in the high-dose group. INTERPRETATION: At day 28 after the full vaccination, both the low-dose and the high-dose CS-2034 vaccine were able to induce the production of high titers of S-RBD IgG antibodies against the BA.1 strain. Adverse reactions in the low-dose and high-dose groups were mainly of severity grade 1 or 2, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine.

Oral microbiome associated with differential ratios of Porphyromonas gingivalis and Streptococcus cristatus.

Background: Periodontitis has been recently defined as a dysbiotic disease resulting from imbalanced oral microbiota. The transition of microbial communities from commensal to periodontitis-associated ones likely requires colonization by specific pathogens, including Porphyromonas gingivalis. We previously reported an antagonistic relationship between Streptococcus cristatus and P. gingivalis and the role of S. cristatus in inhibition of the biofilm formation, invasion, and gingipain enzymatic activity of P. gingivalis. Given the importance of P. gingivalis as a keystone pathogen of polymicrobial communities, the determinants of P. gingivalis levels, its interaction with the core microbiota, and association with the pathogenic potential of the microbial communities need to be addressed. Results: This present study intends to determine the role of S. cristatus in altering interactions of P. gingivalis with other oral bacteria in a complex context. We collected dental plaque samples from periodontitis patients and assigned them into two groups based on their ratios of S. cristatus and P. gingivalis. We then characterized microbial profiles of the dental plaque samples using shotgun metagenomic sequencing and subsequently compared oral microbial composition and functional capabilities between groups with high or low S. cristatus-P. gingivalis ratios. Taxonomic annotation showed significant differences in microbial compositions at both genus and species levels between the two groups. Notably, a higher microbial composition diversity was observed in the samples with low S. cristatus-P. gingivalis ratios. The antibiotic resistance gene profiles of the two groups are also distinct, with significantly increased diversity and abundance of antibiotic resistance genes in the dental plaque samples with low S. cristatus-P. gingivalis ratios, which likely lead to elevated virulence potential. Conclusions: Overall, our work highlights the importance of S. cristatus-P. gingivalis ratios in influencing the virulence of the oral microbiome. Approaches to enhance S. cristatus-P. gingivalis ratios in oral microbial communities will be attractive for revising the dysbiotic oral microbiome.

Influences of race/ethnicity in periodontal treatment response and bacterial distribution, a cohort pilot study.

Objectives: Periodontitis disproportionately affects different racial and ethnic populations. We have previously reported the higher levels of Porphyromonas gingivalis and lower ratios of Streptococcus cristatus to P. gingivalis may contribute to periodontal health disparities. This prospective cohort study was designed to investigate if ethnic/racial groups responded differently to non-surgical periodontal treatment and if the treatment outcomes correlated to the bacterial distribution in patients with periodontitis before treatment. Methods: This prospective cohort pilot study was carried out in an academic setting, at the School of Dentistry, University of Texas Health Science Center at Houston. Dental plaque was collected from a total of 75 African Americans, Caucasians and Hispanics periodontitis patients in a 3-year period. Quantitation of P. gingivalis and S. cristatus was carried out using qPCR. Clinical parameters including probing depths and clinical attachment levels were determined before and after nonsurgical treatment. Data were analyzed using one-way ANOVA, the Kruskal-Wallis test, the paired samples t-test and the chi-square test. Results: The gains in clinical attachment levels after treatment significantly differed amongst the 3 groups-Caucasians responded most favorably, followed by African-Americans, lastly Hispanics, while numbers of P. gingivalis were highest in Hispanics, followed by African-Americans, and lowest in Caucasians (p = 0.015). However, no statistical differences were found in the numbers of S. cristatus amongst the 3 groups. Conclusion: Differential response to nonsurgical periodontal treatment and distribution of P. gingivalis are present in different ethnic/racial groups with periodontitis.

Corrigendum: The effects of intermittent theta burst stimulation of the unilateral cerebellar hemisphere on swallowing-related brain regions in healthy subjects.

[This corrects the article DOI: 10.3389/fnhum.2023.1100320.].

Regulation of Cardiomyocyte Division During Cardiac Regeneration.

PURPOSE OF REVIEW: This review explores efforts made over the previous three decades to determine mechanisms of cardiomyocyte cell division. Many investigators have explored cell therapy strategies in animal models and clinical trials over the past 2 decades with marginal results thus far in clinical testing. Hence, there is a greater focus now on strategies to induce cardiomyocyte proliferation. RECENT FINDINGS: Reports to induce reactivation of the cardiomyocyte cell cycle predated the focus on cell therapy, and we summarize the literature on this topic, which began with the very first transgenic mouse studies in cardiovascular science. These earlier studies form the foundation for the use of cell cycle manipulation in cardiac repair and should inform current and future investigations with respect to rigor of assessment in the degree of cardiomyocyte cell division and gold standard measures of cardiac functional improvement.

Convex and Nonconvex Optimization Are Both Minimax-Optimal for Noisy Blind Deconvolution under Random Designs.

We investigate the effectiveness of convex relaxation and nonconvex optimization in solving bilinear systems of equations under two different designs (i.e. a sort of random Fourier design and Gaussian design). Despite the wide applicability, the theoretical understanding about these two paradigms remains largely inadequate in the presence of random noise. The current paper makes two contributions by demonstrating that: (1) a two-stage nonconvex algorithm attains minimax-optimal accuracy within a logarithmic number of iterations, and (2) convex relaxation also achieves minimax-optimal statistical accuracy vis-à-vis random noise. Both results significantly improve upon the state-of-the-art theoretical guarantees.

Regional differences and driving factors of carbon emission intensity in China's electricity generation sector.

As an industry with immense decarbonization potential, the low-carbon transformation of the power sector is crucial to China's carbon emission (CE) reduction commitment. Based on panel data of 30 provinces in China from 2000 to 2019, this research calculates and analyzes the provincial CE intensity in electricity generation (CEIE) and its spatial distribution characteristics. Additionally, the GTWR model based on the construction explains the regional heterogeneity and dynamic development trend of each driving factor's influence on CEIE from time and space. The main results are as follows: CEIE showed a gradual downward trend in time and a spatial distribution pattern of high in the northeast and low in the southwest. The contribution of driving factors to CEIE has regional differences, and the power structure contributes most to the CEIE of the power sector, which promotes regional CE. Concurrently, most provinces with similar economic development, technological level, geographic location, or resource endowment characteristics show similar spatial and temporal trends. These detections will furnish broader insights into implementing CE reduction policies for the regional power sector.

The effects of intermittent theta burst stimulation of the unilateral cerebellar hemisphere on swallowing-related brain regions in healthy subjects.

Objective: We aimed to investigate the effects and mechanisms of swallowing-related brain regions using resting-state functional magnetic resonance imaging (rs-fMRI) in healthy subjects who underwent intermittent theta burst stimulation (iTBS) on dominant or non-dominant cerebellar hemispheres. Methods: Thirty-nine healthy subjects were randomized into three groups that completed different iTBS protocols (dominant cerebellum group, non-dominant cerebellum group and sham group). Before iTBS, the resting motor threshold (rMT) was measured by single-pulse transcranial magnetic stimulation (sTMS) on the cerebellar representation of the suprahyoid muscles, and the dominant cerebellar hemisphere for swallowing was determined. Forty-eight hours after elution, iTBS protocols were completed: in the dominant cerebellum group, iTBS was administered to the dominant cerebellar hemisphere, and the non-dominant cerebellar hemisphere was given sham stimulation; in the non-dominant cerebellum group, iTBS was administered to the non-dominant cerebellar hemisphere, and sham stimulation was delivered to the dominant cerebellar hemisphere; in the sham group, sham stimulation was applied to the cerebellum bilaterally. Rs-fMRI was performed before and after iTBS stimulation to observe changes in the fractional amplitude of low-frequency fluctuation (fALFF) in the whole brain. Results: Compared with baseline, the dominant cerebellum group showed increased fALFF in the ipsilateral cerebellum, and decreased fALFF in the ipsilateral middle temporal gyrus and contralateral precuneus after iTBS; the iTBS of the non-dominant cerebellum group induced increased fALFF in the ipsilateral superior frontal gyrus, the calcarine fissure and the surrounding cortex, and the contralateral inferior parietal lobule; and in the sham group, there was no significant difference in fALFF. Exploring the effects induced by iTBS among groups, the dominant cerebellum group showed decreased fALFF in the contralateral calcarine fissure, and surrounding cortex compared with the sham group. Conclusion: Intermittent theta burst stimulation of the dominant cerebellar hemisphere for swallowing excited the ipsilateral cerebellum, and stimulation of the non-dominant cerebellar hemisphere increased the spontaneous neural activity of multiple cerebrocortical areas related to swallowing. In conclusion, regardless of which side of the cerebellum is stimulated, iTBS can facilitate part of the brain neural network related to swallowing. Our findings provide supporting evidence that cerebellar iTBS can be used as a potential method to modulate human swallowing movement.