Effect of disease duration on the use of tofacitinib: a real-world study in elderly patients with rheumatoid arthritis.

This study aims to test the hypothesis that disease duration may affect the response to generic tofacitinib (TOF) and investigate the influence of concomitant medications with TOF on elderly rheumatoid arthritis (RA). This study retrospectively collected 76 elderly patients (age > 60) treated with TOF from 2019 to 2023 and grouped them according to age of disease onset. Data were collected from baseline to the last follow-up visit within 24 months. The demographic characteristics and follow-up results were compared. TOF retention and the effect of concomitant drugs (methotrexate, MTX, prednisone) were analyzed using Kaplan-Meier plots and COX regression analysis. Canonical correlation analysis (CCA) was used to explore the correlation among demographic characteristics, medication regimen, and improved clinical outcomes. There was no significant difference in the proportion of patients achieving low disease activity (LDA) between different disease duration groups. Patients in the group of MTX had a shorter time of using TOF in follow-up (log-rank p = 0.041). Prednisone dosage at baseline had a predictive value for functionally disabled situation. We found significant associations between discontinuation of TOF in the last follow-up and getting LDA. A total result of CCA yielded a significant positive correlation with set 1 (demographic characteristics and medication regimen) and set 2 (improved clinical outcomes) (canonical coefficient = 0.887, p < 0.001). Disease duration may not affect response to generic TOF and medication regimen was the factor related to efficacy of generic TOF in elderly RA in the real world. Demographic characteristics and medication regimen were correlated positively with improved clinical outcomes. Key Points • There is scarce data from the western area of China regarding the use of tofacitinib in elderly rheumatoid arthritis patients, despite widespread use. • In this retrospective analysis of 76 elderly patients at a single center, we found disease duration may not affect response to generic TOF. • Concomitant MTX might contribute to better control of the disease activity. • Concomitant prednisone dosage at baseline was the independent risk factor for functionally disabled situation.

Metagenomic analysis demonstrates distinct changes in the gut microbiome of Kawasaki diseases children.

Background: Kawasaki disease (KD) has been considered as the most common required pediatric cardiovascular diseases among the world. However, the molecular mechanisms of KD were not fully underlined, leading to a confused situation in disease management and providing precious prognosis prediction. The disorders of gut microbiome had been identified among several cardiovascular diseases and inflammation conditions. Therefore, it is urgent to elucidate the characteristics of gut microbiome in KD and demonstrate its potential role in regulating intravenous immunoglobulin (IVIG) resistance and coronary artery injuries. Methods: A total of 96 KD children and 62 controls were enrolled in the study. One hundred forty fecal samples had been harvested from KD patients, including individuals before or after IVIG treatment, with or without early coronary artery lesions and IVIG resistance. Fecal samples had been collected before and after IVIG administration and stored at -80°C. Then, metagenomic analysis had been done using Illumina NovaSeq 6000 platform. After that, the different strains and functional differences among comparisons were identified. Results: First, significant changes had been observed between KD and their controls. We found that the decrease of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides uniformis, and Bacteroides ovatus and the increase of pathogenic bacteria Finegoldia magna, Abiotrophia defectiva, and Anaerococcus prevotii perhaps closely related to the incidence of KD. Then, metagenomic and responding functional analysis demonstrated that short-chain fatty acid pathways and related strains were associated with different outcomes of therapeutic efficacies. Among them, the reduction of Bacteroides thetaiotaomicron, the enrichment of Enterococcus faecalis and antibiotic resistance genes had been found to be involved in IVIG resistance of KD. Moreover, our data also revealed several potential pathogenetic microbiome of that KD patients with coronary artery lesions. Conclusion: These results strongly proved that distinct changes in the gut microbiome of KD and the dysfunction of gut microbiomes should be responsible for the pathogenesis of KD and significantly impact the prognosis of KD.

Individualized music induces theta-gamma phase-amplitude coupling in patients with disorders of consciousness.

Objective: This study aimed to determine whether patients with disorders of consciousness (DoC) could experience neural entrainment to individualized music, which explored the cross-modal influences of music on patients with DoC through phase-amplitude coupling (PAC). Furthermore, the study assessed the efficacy of individualized music or preferred music (PM) versus relaxing music (RM) in impacting patient outcomes, and examined the role of cross-modal influences in determining these outcomes. Methods: Thirty-two patients with DoC [17 with vegetative state/unresponsive wakefulness syndrome (VS/UWS) and 15 with minimally conscious state (MCS)], alongside 16 healthy controls (HCs), were recruited for this study. Neural activities in the frontal-parietal network were recorded using scalp electroencephalography (EEG) during baseline (BL), RM and PM. Cerebral-acoustic coherence (CACoh) was explored to investigate participants' abilitiy to track music, meanwhile, the phase-amplitude coupling (PAC) was utilized to evaluate the cross-modal influences of music. Three months post-intervention, the outcomes of patients with DoC were followed up using the Coma Recovery Scale-Revised (CRS-R). Results: HCs and patients with MCS showed higher CACoh compared to VS/UWS patients within musical pulse frequency (p = 0.016, p = 0.045; p < 0.001, p = 0.048, for RM and PM, respectively, following Bonferroni correction). Only theta-gamma PAC demonstrated a significant interaction effect between groups and music conditions (F (2,44) = 2.685, p = 0.036). For HCs, the theta-gamma PAC in the frontal-parietal network was stronger in the PM condition compared to the RM (p = 0.016) and BL condition (p < 0.001). For patients with MCS, the theta-gamma PAC was stronger in the PM than in the BL (p = 0.040), while no difference was observed among the three music conditions in patients with VS/UWS. Additionally, we found that MCS patients who showed improved outcomes after 3 months exhibited evident neural responses to preferred music (p = 0.019). Furthermore, the ratio of theta-gamma coupling changes in PM relative to BL could predict clinical outcomes in MCS patients (r = 0.992, p < 0.001). Conclusion: Individualized music may serve as a potential therapeutic method for patients with DoC through cross-modal influences, which rely on enhanced theta-gamma PAC within the consciousness-related network.

Identifying biomarkers related to motor function in chronic stroke: A fNIRS and TMS study.

BACKGROUND: Upper limb motor impairment commonly occurs after stroke, impairing quality of life. Brain network reorganization likely differs between subgroups with differing impairment severity. This study explored differences in functional connectivity (FC) and corticospinal tract (CST) integrity between patients with mild/moderate versus severe hemiplegia poststroke to clarify the neural correlates underlying motor deficits. METHOD: Sixty chronic stroke patients with upper limb motor impairment were categorized into mild/moderate and severe groups based on Fugl-Meyer scores. Resting-state FC was assessed using functional near-infrared spectroscopy (fNIRS) to compare connectivity patterns between groups across motor regions. CST integrity was evaluated by inducing motor evoked potentials (MEP) via transcranial magnetic stimulation. RESULTS: Compared to the mild/moderate group, the severe group exhibited heightened premotor cortex-primary motor cortex (PMC-M1) connectivity (t = 4.56, p < 0.01). Absence of MEP was also more frequent in the severe group (χ2 = 12.31, p = 0.01). Bayesian models effectively distinguished subgroups and identified the PMC-M1 connection as highly contributory (accuracy = 91.30%, area under the receiver operating characteristic curve [AUC] = 0.86). CONCLUSION: Distinct patterns of connectivity and corticospinal integrity exist between stroke subgroups with differing impairments. Strengthened connectivity potentially indicates recruitment of additional motor resources to compensate for damage. These findings elucidate the neural correlates underlying motor deficits poststroke and could guide personalized, network-based therapies targeting predictive biomarkers to improve rehabilitation outcomes.

Effect of Flammulina velutipes polysaccharide on mitochondrial apoptosis in lung adenocarcinoma A549 cells.

FVP is a polysaccharide extracted from Flammulina velutipes with immunomodulatory, anti-tumor, and anti-oxidation activities. In this study, we obtained the crude polysaccharide FVP-C from the water extract of Flammulina velutipes, and its main component FVP-S1 was obtained after further purification. Upon structural identification, we found that FVP-C is a neutral polysaccharide, and FVP-S1 was an acidic golden mushroom polysaccharide, consisting of glucuronic acid, xylose, and glucose. Lung adenocarcinoma (A549) was treated with FVP-S1 and FVP-C, respectively, and we found that FVP-S1 and FVP-C inhibited the proliferation and migration ability of tumor cells, as well as changed the morphology of the tumor cells and caused chromosome sheteropythosis, among which FVP-S1 had the best inhibition effect. The results of flow cytometry experiments and mitochondrial membrane potential, RT-qPCR, and Western blot showed that FVP-S1 and FVP-C were able to decrease the mitochondrial membrane potential, increase the expression level of apoptotic proteins Casepase-3 and Casepase-9 proteins, and at the same time, increase the ratio of Bax and Bcl-2, which promoted apoptosis of tumor cells. In conclusion, these data indicated that FVP-S1 and FVP-C were able to induce apoptosis in A549 cells through the mitochondrial pathway, which played an important role in inhibiting tumor cells.

Assessing green production efficiency and spatial characteristics of China's real estate industry based on the undesirable super-SBM model.

As China strives to balance rapid urbanization with environmental conservation, increasing attention is being paid to the pursuit of green production efficiency (GPE) in the real estate industry. The undesirable super-SBM model was used to calculate the GPE of China's real estate industry from 2001 to 2020. Additionally, GPE spatial distribution characteristics in China's real estate industry were analyzed using the standard deviation ellipse (SDE), Moran's index, Theil index, random kernel density estimation (RKDA), and spatial Markov chain (SMC) methods. The GPE exhibited a U-shaped trend, with 2008 as the inflection point, first decreasing and then increasing. It reached a maximum value of 0.747 in 2020. The Theil index increased from 0.043 to 0.121 nationwide, indicating the overall characteristics of low-level slow growth, and imbalance. Discrepancies in input-output scales, the southward shift of economic centers, and population movements contribute significantly to the disparities between the east and west, north and south, and regions divided by the Hu Huanyong Line (Hu Line). The GPE exhibited club convergence characteristics; however, polarization phenomena exist in local areas. Spatial spillover effects were also observed in GPE. Finally, we provide recommendations for promoting green development in the real estate industry, including green building technology, fiscal subsidy investment, and population migration management.

Integrated miRNA and mRNA Sequencing Reveals the Sterility Mechanism in Hybrid Yellow Catfish Resulting from Pelteobagrus fulvidraco (♀) × Pelteobagrus vachelli (♂).

The hybrid yellow catfish exhibits advantages over pure yellow catfish in terms of fast growth, fast development, a high feeding rate, and strong immunity; additionally, it is almost sterile, thus ensuring the conservation of the genetic stock of fish populations. To investigate the sterility mechanism in hybrid yellow catfish (P. fulvidraco (♀) × P. vachelli (♂)), the mRNA and miRNA of the gonads of P. fulvidraco, P. vachelli, and a hybrid yellow catfish were analyzed to characterize the differentially expressed genes; this was carried out to help establish gene expression datasets to assist in the further determination of the mechanisms of genetic sterility in hybrid yellow catfish. In total, 1709 DEGs were identified between the hybrid and two pure yellow catfishes. A KEGG pathway analysis indicated that several genes related to reproductive functions were upregulated, including those involved in the cell cycle, progesterone-mediated oocyte maturation, and oocyte meiosis, and genes associated with ECM-receptor interaction were downregulated. The spermatogenesis-related GO genes CFAP70, RSPH6A, and TSGA10 were identified as being downregulated DEGs in the hybrid yellow catfish. Sixty-three DEmiRNAs were identified between the hybrid and the two pure yellow catfish species. The upregulated DEmiRNAs ipu-miR-194a and ipu-miR-499 were found to target the spermatogenesis-related genes CFAP70 and RSPH6A, respectively, playing a negative regulatory role, which may underscore the miRNA-mRNA regulatory mechanism of sterility in hybrid yellow catfish. The differential expression of ipu-miR-196d, ipu-miR-125b, and ipu-miR-150 and their target genes spidr, cep85, and kcnn4, implicated in reproductive processes, was verified via qRT-PCR, consistent with the transcriptome sequencing expression trends. This study provides deep insights into the mechanism of hybrid sterility in vertebrate groups, thereby contributing to achieving a better understanding and management of fish conservation related to hybrid sterility.

Plasma BDNF/Irisin Ratio Associates with Cognitive Function in Older People.

Background: Reliable blood biomarkers are crucial for early detection and treatment evaluation of cognitive impairment, including Alzheimer's disease and other dementias. Objective: To examine whether plasma biomarkers and their combination are different between older people with mild cognitive impairment (MCI) and cognitively normal individuals, and to explore their relations with cognitive performance. Methods: This cross-sectional study included 250 older adults, including 124 participants with MCI, and 126 cognitively normal participants. Plasma brain-derived neurotrophic factor (BDNF), irisin and clusterin were measured, and BDNF/irisin ratio was calculated. Global cognition was evaluated by the Montreal Cognitive Assessment. Results: Plasma irisin levels, but not BDNF, were significantly different between MCI group and cognitively normal group. Higher irisin concentration was associated with an increased probability for MCI both before and after controlling covariates. By contrast, plasma BDNF concentration, but not irisin, was linearly correlated with cognitive performance after adjusting for covariates. Higher BDNF/irisin ratios were not only correlated with better cognitive performance, but also associated with lower risks of MCI, no matter whether we adjusted for covariates. Plasma BDNF and irisin concentrations increased with aging, whereas BDNF/irisin ratios remained stable. No significant results of clusterin were observed. Conclusions: Plasma BDNF/irisin ratio may be a reliable indicator which not only reflects the odds of the presence of MCI but also directly associates with cognitive performance.

GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines.

BACKGROUND: Thrombocytopenia 2, an autosomal dominant inherited disease characterized by moderate thrombocytopenia, predisposition to myeloid malignancies and normal platelet size and function, can be caused by 5'-untranslated region (UTR) point mutations in ankyrin repeat domain containing 26 (ANKRD26). Runt related transcription factor 1 (RUNX1) and friend leukemia integration 1 (FLI1) have been identified as negative regulators of ANKRD26. However, the positive regulators of ANKRD26 are still unknown. AIM: To prove the positive regulatory effect of GATA binding protein 2 (GATA2) on ANKRD26 transcription. METHODS: Human induced pluripotent stem cells derived from bone marrow (hiPSC-BM) and urothelium (hiPSC-U) were used to examine the ANKRD26 expression pattern in the early stage of differentiation. Then, transcriptome sequencing of these iPSCs and three public transcription factor (TF) databases (Cistrome DB, animal TFDB and ENCODE) were used to identify potential TF candidates for ANKRD26. Furthermore, overexpression and dual-luciferase reporter experiments were used to verify the regulatory effect of the candidate TFs on ANKRD26. Moreover, using the GENT2 platform, we analyzed the relationship between ANKRD26 expression and overall survival in cancer patients. RESULTS: In hiPSC-BMs and hiPSC-Us, we found that the transcription levels of ANKRD26 varied in the absence of RUNX1 and FLI1. We sequenced hiPSC-BM and hiPSC-U and identified 68 candidate TFs for ANKRD26. Together with three public TF databases, we found that GATA2 was the only candidate gene that could positively regulate ANKRD26. Using dual-luciferase reporter experiments, we showed that GATA2 directly binds to the 5'-UTR of ANKRD26 and promotes its transcription. There are two identified binding sites of GATA2 that are located 2 kb upstream of the TSS of ANKRD26. In addition, we discovered that high ANKRD26 expression is always related to a more favorable prognosis in breast and lung cancer patients. CONCLUSION: We first discovered that the transcription factor GATA2 plays a positive role in ANKRD26 transcription and identified its precise binding sites at the promoter region, and we revealed the importance of ANKRD26 in many tissue-derived cancers.

Functional near-infrared spectroscopy evidence of cognitive-motor interference in different dual tasks.

Dual tasks (DTs) combining walking with a cognitive task can cause various levels of cognitive-motor interference, depending on which brain resources are recruited in each case. However, the brain activation and functional connectivity underlying cognitive-motor interferences remain to be elucidated. Therefore, this study investigated the neural correlation during different DT conditions in 40 healthy young adults (mean age: 27.53 years, 28 women). The DTs included walking during subtraction or N-Back tasks. Cognitive-motor interference was calculated, and brain activation and functional connectivity were analysed. Portable functional near-infrared spectroscopy was utilized to monitor haemodynamics in the prefrontal cortex (PFC), motor cortex and parietal cortex during each task. Walking interference (decrease in walking speed during DT) was greater than cognitive interference (decrease in cognitive performance during DT), regardless of the type of task. Brain activation in the bilateral PFC and parietal cortex was greater for walking during subtraction than for standing subtraction. Furthermore, brain activation was higher in the bilateral motor and parietal and PFCs for walking during subtraction than for walking alone, but only increased in the PFC for walking during N-Back. Coherence between the bilateral lateral PFC and between the left lateral PFC and left motor cortex was significantly greater for walking during 2-Back than for walking. The PFC, a critical brain region for organizing cognitive and motor functions, played a crucial role in integrating information coming from multiple brain networks required for completing DTs. Therefore, the PFC could be a potential target for the modulation and improvement of cognitive-motor functions during neurorehabilitation.

Age-related changes in meningeal lymphatic function are closely associated with vascular endothelial growth factor-C expression.

Meningeal lymphatic vessels (MLVs) have crucial roles in removing metabolic waste and toxic proteins from the brain and transporting them to the periphery. Aged mice show impaired meningeal lymphatic function. Nevertheless, as the disease progresses, and significant pathological changes manifest in the brain, treating the condition becomes increasingly challenging. Therefore, investigating the alterations in the structure and function of MLVs in the early stages of aging is critical for preventing age-related central nervous system degenerative diseases. We detected the structure and function of MLVs in young, middle-aged, and aged mice. Middle-aged mice, compared with young and aged mice, showed enhanced meningeal lymphatic function along with MLV expansion and performed better in the Y maze test. Moreover, age-related changes in meningeal lymphatic function were closely associated with vascular endothelial growth factor-C (VEGF-C) expression in the brain cortex. Our data suggested that the cerebral cortex may serve as a target for VEGF-C supplementation to ameliorate meningeal lymphatic dysfunction, thus providing a new strategy for preventing age-related central nervous system diseases.

DNA methylation and transcriptome analysis reveal epigenomic differences among three macaque species.

Macaques (genus Macaca) are the most widely distributed non-human primates, and their evolutionary history, gene expression profiles, and genetic differences have been extensively studied. However, the DNA methylomes of macaque species are not available in public databases, which hampers understanding of epigenetic differences among macaque species. Epigenetic modifications can potentially affect development, physiology, behavior, and evolution. Here, we investigated the methylation patterns of the Tibetan macaque (M. thibetana; TM), Chinese rhesus macaque (M. mulatta lasiota; CR), and crab-eating macaque (M. fascicularis; CE) through whole-genome bisulfite sequencing from peripheral blood. We compared genome-wide methylation site information for the three species. We identified 12,128 (CR vs. CE), 59,165 (CR vs. TM), and 39,751 (CE vs. TM) differentially methylated regions (DMRs) in the three macaques. Furthermore, we obtained the differentially expressed genes (DEGs) among the three macaque species. The differences between CR and CE were smaller at both the methylome and transcriptome levels than compared with TM (CR vs. TM and CE vs. TM). We also found a change in the density of single nucleotide mutations in DMRs relative to their flanking regions, indicating a potential mechanism through which genomic alterations may modulate methylation landscapes, thereby influencing the transcriptome. Functional enrichment analyses showed the DMR-related genes were enriched in developmental processes and neurological functions, such as the growth hormone-related pathway, insulin secretion pathway, thyroid hormone synthesis pathway, morphine addiction, and GABAergic synapses. These differences may be associated with variations in physiology and habitat among the macaques. Our study provides one of the first genome-wide comparisons of genetic, gene expression, and epigenetic variations across different macaques. Our results should facilitate further research on comparative genomic and genetic differences in macaque species.

Interpretation of vaginal metagenomic characteristics in different types of vaginitis.

Although vaginitis is closely related to vaginal microecology in females, the precise composition and functional potential of different types of vaginitis remain unclear. Here, metagenomic sequencing was applied to analyze the vaginal flora in patients with various forms of vaginitis, including cases with a clue cell proportion ranging from 1% to 20% (Clue1_20), bacterial vaginitis (BV), vulvovaginal candidiasis (VVC), and BV combined with VVC (VVC_BV). Our results identified Prevotella as an important biomarker between BV and Clue1_20. Moreover, a gradual decrease was observed in the relative abundance of shikimic acid metabolism associated with bacteria producing indole as well as a decline in the abundance of Gardnerella vaginalis in patients with BV, Clue1_20, and healthy women. Interestingly, the vaginal flora of patients in the VVC_BV group exhibited structural similarities to that of the VVC group, and its potentially functional characteristics resembled those of the BV and VVC groups. Finally, Lactobacillus crispatus was found in high abundance in healthy samples, greatly contributing to the stability of the vaginal environment. For the further study of L. crispatus, we isolated five strains of L. crispatus from healthy samples and evaluated their capacity to inhibit G. vaginalis biofilms and produce lactic acid in vitro to select the potential probiotic candidate for improving vaginitis in future clinical studies. Overall, we successfully identified bacterial biomarkers of different vaginitis and characterized the dynamic shifts in vaginal flora between patients with BV and healthy females. This research advances our understanding and holds great promise in enhancing clinical approaches for the treatment of vaginitis. IMPORTANCE: Vaginitis is one of the most common gynecological diseases, mostly caused by infections of pathogens such as Candida albicans and Gardnerella vaginalis. In recent years, it has been found that the stability of the vaginal flora plays an important role in vaginitis. Furthermore, the abundant Lactobacillus-producing rich lactic acid in the vagina provides a healthy acidic environment such as Lactobacillus crispatus. The metabolites of Lactobacillus can inhibit the colonization of pathogens. Here, we collected the vaginal samples of patients with bacterial vaginitis (BV), vulvovaginal candidiasis (VVC), and BV combined with VVC to discover the differences and relationships among the different kinds of vaginitis by metagenomic sequencing. Furthermore, because of the importance of L. crispatus in promoting vaginal health, we isolated multiple strains from vaginal samples of healthy females and chose the most promising strain with potential probiotic benefits to provide clinical implications for treatment strategies.

Cortical activation and brain network efficiency during dual tasks: An fNIRS study.

OBJECTIVE: Dual task (DT) is a commonly used paradigm indicative of executive functions. Brain activities during DT walking is usually measured by portable functional near infrared spectroscopy (fNIRS). Previous studies focused on cortical activation in prefrontal cortex and overlooked other brain regions such as sensorimotor cortices. This study is aimed at investigating the modulations of cortical activation and brain network efficiency in multiple brain regions from single to dual tasks with different complexities and their relationships with DT performance. METHODS: Forty-two healthy adults [12 males; mean age: 27.7 (SD=6.5) years] participated in this study. Participants performed behavioral tasks with portable fNIRS simultaneous recording. There were three parts of behavioral tasks: cognitive tasks while standing (serial subtraction of 3's and 7's), walking alone and DT (walk while subtraction, including serial subtraction of 3's and 7's). Cognitive cost, walking cost and cost sum (i.e., sum of cognitive and walking costs) were calculated for DT. Cortical activation, local and global network efficiency were calculated for each task. RESULTS: The cognitive cost was greater and the walking cost was less during DT with subtraction 3's compared with 7's (P's = 0.032 and 0.019, respectively). Cortical activation and network efficiency were differentially modulated among single and dual tasks (P's < 0.05). Prefrontal activation during DT was positively correlated with DT costs, while network efficiency was negatively correlated with DT costs (P's < 0.05). CONCLUSIONS: Our results revealed prefrontal over-activation and reduced network efficiency in individuals with poor DT performance. Our findings suggest that reduced network efficiency could be a possible mechanism contributing to poor DT performance, which is accompanied by compensatory prefrontal over-activation.

Electroencephalography oscillations can predict the cortical response following theta burst stimulation.

BACKGROUND: Continuous theta burst stimulation and intermittent theta burst stimulation are clinically popular models of repetitive transcranial magnetic stimulation. However, they are limited by high variability between individuals in cortical excitability changes following stimulation. Although electroencephalography oscillations have been reported to modulate the cortical response to transcranial magnetic stimulation, their association remains unclear. This study aims to explore whether machine learning models based on EEG oscillation features can predict the cortical response to transcranial magnetic stimulation. METHOD: Twenty-three young, healthy adults attended two randomly assigned sessions for continuous and intermittent theta burst stimulation. In each session, ten minutes of resting-state electroencephalography were recorded before delivering brain stimulation. Participants were classified as responders or non-responders based on changes in resting motor thresholds. Support vector machines and multi-layer perceptrons were used to establish predictive models of individual responses to transcranial magnetic stimulation. RESULT: Among the evaluated algorithms, support vector machines achieved the best performance in discriminating responders from non-responders for intermittent theta burst stimulation (accuracy: 91.30%) and continuous theta burst stimulation (accuracy: 95.66%). The global clustering coefficient and global characteristic path length in the beta band had the greatest impact on model output. CONCLUSION: These findings suggest that EEG features can serve as markers of cortical response to transcranial magnetic stimulation. They offer insights into the association between neural oscillations and variability in individuals' responses to transcranial magnetic stimulation, aiding in the optimization of individualized protocols.

Red pandas with different diets and environments exhibit different gut microbial functional composition and capacity.

The red panda (Ailurus fulgens) is a distinctive mammal known for its reliance on a diet primarily consisting of bamboo. The gut microbiota and overall health of animals are strongly influenced by diets and environments. Therefore, conducting research to explore the taxonomical and functional variances within the gut microbiota of red pandas exposed to various dietary and environmental conditions could shed light on the dynamic complexities of their microbial communities. In this study, normal fecal samples were obtained from red pandas residing in captive and semi-free environments under different dietary regimes and used for metabolomic, 16S rRNA, and metagenomic sequencing analysis, with the pandas classified into four distinct cohorts according to diet and environment. In addition, metagenomic sequencing was conducted on mucus fecal samples to elucidate potential etiological agents of disease. Results revealed an increased risk of gastrointestinal diseases in red pandas consuming bamboo shoots due to the heightened presence of pathogenic bacteria, although an increased presence of microbiota-derived tryptophan metabolites appeared to facilitate intestinal balance. The red pandas fed bamboo leaves also exhibited a decrease in gut microbial diversity, which may be attributed to the antibacterial flavonoids and lower protein levels in leaves. Notably, red pandas residing in semi-free environments demonstrated an enriched gut microbial diversity. Moreover, the occurrence of mucus secretion may be due to an increased presence of species associated with diarrhea and a reduced level of microbiota-derived tryptophan metabolites. In summary, our findings substantiate the influential role of diet and environment in modulating the gut microbiota of red pandas, offering potential implications for improved captive breeding practices.

Angiographic microvascular resistance in patients with obstructive hypertrophic cardiomyopathy.

BACKGROUND: Coronary microvascular dysfunction (CMD) is an important feature of obstructive hypertrophic cardiomyopathy (oHCM). Angiographic microvascular resistance (AMR) offers a potent means for assessing CMD. This study sought to evaluate the prognostic value of CMD burden calculated by AMR among oHCM patients. METHODS: We retrospectively screened all patients diagnosed with oHCM from Fuwai Hospital between January 2017 and November 2021. Off-line AMR assessments were performed for all 3 major coronary vessels by the independent imaging core laboratory. Patients were followed every 6 months post discharge via office visit or telephone contacts. The primary outcome was major adverse cardiovascular events (MACE), including all-cause death, and unplanned rehospitalization for heart failure. RESULTS: A total of 342 patients presented with oHCM diseases enrolled in the present analyses. Mean age was 49.7, 57.6 % were men, mean 3-vessel AMR was 6.9. At a median follow-up of 18 months, high capability of 3-vessel AMR in predicting MACE was identified (AUC: 0.70) with the best cut-off value of 7.04. The primary endpoint of MACE was significantly higher in high microvascular resistance group (3-vessel AMR ≥ 7.04) as compared with low microvascular resistance group (56.5 % vs. 16.5 %; HR: 5.13; 95 % CI: 2.46-10.7; p < 0.001), which was mainly driven by the significantly higher risk of heart failure events in high microvascular resistance group. Additionally, 3-vessel AMR (HR: 4.37; 95 % CI: 1.99-9.58; p < 0.001), and age (per 1 year increase, HR: 1.03; 95 % CI: 1.01-1.06; p = 0.02) were independently associated with MACE. CONCLUSION: The present retrospective study demonstrated that the novel angiography-based AMR was a useful tool for CMD evaluation among patients with oHCM. High microvascular resistance as identified by 3-vessel AMR (≥7.04) was associated with worse prognosis.

Oral frailty: A concept analysis.

AIM: To clarify the concept of oral frailty to provide a clear and standardized conceptual basis for further research in older people. DESIGN: Rodgers and Knafl's evolutionary concept analysis approach. METHODS: The narrative analysis detailedly extracted and synthesized the attributes of oral frailty, as well as its antecedents, consequences and related terms under the guidance of Rodgers' evolutionary method. DATA SOURCES: Multiple databases including Pubmed, CINAHL and Cochrane were searched using selected search terms 'oral frail*', 'oral health' and 'aged' respectively. Articles written between 2013 and 2023 were included, and grey literature was excluded. RESULTS: A total of 32 articles were included for further analysis and synthesis. The attributes of oral frailty were hypofunction, predisposing in nature, non-specific and multidimensional. Antecedents of prefrailty were classified into four categories, namely, sociodemographic characteristics, comorbidity, physical function and psychosocial factors. Consequences of oral frailty include three themes: increased risk of adverse outcomes, poor nutritional status and possibility of social withdrawal. Related terms that had shared attributes with oral frailty were oral health, functional dentition, oral hypofunction and deterioration of oral function. CONCLUSIONS: Oral frailty is an age-related phenomenon reflected in decreased oral function. The findings of this concept analysis are conducive to understanding and clarifying the oral frailty, which can help clinicians or other healthcare providers to consider how to distinguish oral frailty in older adults and further promote the development of this field. IMPACT: Oral frailty is increasingly recognized as an age-related phenomenon reflected in decreased oral function. As it is newly proposed, no consensus has been reached regarding the theoretical and operational concept of it. Through clarifying the concept, this paper will guide future healthcare research on oral frailty regarding the influencing factors, mechanisms and interventions, thus raising the awareness with regard to oral health among older adults. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: In the context of older adults, oral frailty is a concept that requires further research to guide future theoretical development, and the influencing factors, mechanisms and interventions need to be further studied. Raise awareness with regard to oral health among older people and more attention will be paid to the early identification and intervention of oral frailty, so as to further improve the quality of life of older adults.

Neurophysiological characterization of stroke recovery: A longitudinal TMS and EEG study.

AIMS: Understanding the neural mechanisms underlying stroke recovery is critical to determine effective interventions for stroke rehabilitation. This study aims to systematically explore how recovery mechanisms post-stroke differ between individuals with different levels of functional integrity of the ipsilesional corticomotor pathway and motor function. METHODS: Eighty-one stroke survivors and 15 age-matched healthy adults participated in this study. We used transcranial magnetic stimulation (TMS), electroencephalography (EEG), and concurrent TMS-EEG to investigate longitudinal neurophysiological changes post-stroke, and their relationship with behavioral changes. Subgroup analysis was performed based on the presence of paretic motor evoked potentials and motor function. RESULTS: Functional connectivity was increased dramatically in low-functioning individuals without elicitable motor evoked potentials (MEPs), which showed a positive effect on motor recovery. Functional connectivity was increased gradually in higher-functioning individuals without elicitable MEP during stroke recovery and influence from the contralesional hemisphere played a key role in motor recovery. In individuals with elicitable MEPs, negative correlations between interhemispheric functional connectivity and motor function suggest that the influence from the contralesional hemisphere may be detrimental to motor recovery. CONCLUSION: Our results demonstrate prominent clinical implications for individualized stroke rehabilitation based on both functional integrity of the ipsilesional corticomotor pathway and motor function.

Metagenomic analysis of oral and intestinal microbiome of patients during the initial stage of orthodontic treatment.

INTRODUCTION: This prospective study analyzed changes in the oral and intestinal microbiomes in patients before and after fixed orthodontic treatment, elucidating the impacts of fixed orthodontic treatment on patient health and metabolism. METHODS: Metagenomic analysis was conducted on stool, dental plaque, and saliva samples from 10 fixed orthodontic patients. All the samples were sequenced with Illumina NovaSeq 6000 with a paired-end sequencing length of 150 bp. Identification of taxa in metagenomes and functional annotation of genes of the microbiota were performed using the data after quality control. Clinical periodontal parameters, including the gingiva index, plaque index, and pocket probing depth, were examined at each time point in triplicates. Patients also received a table to record their oral hygiene habits of brushing, flossing, and dessert consumption frequency over 1 month. RESULTS: The brushing and flossing times per day of patients were significantly increased after treatment compared with baseline. The number of times a patient ate dessert daily was also fewer after treatment than at baseline. In addition, the plaque index decreased significantly, whereas the pH value of saliva, gingiva index, and pocket probing depth did not change. No significant differences were observed between the participants before and after orthodontic treatment regarding alpha-diversity analysis of the gut, dental plaque, or saliva microbiota. However, on closer analysis, periodontal disease-associated bacteria levels in the oral cavity remain elevated. Alterations in gut microbiota were also observed after orthodontic treatment. CONCLUSIONS: The richness and diversity of the microbiome did not change significantly during the initial stage of fixed orthodontic treatment. However, the levels of periodontal disease-associated bacteria increased.