Examining the cultural influence on online stances towards COVID-19 preventive measures and their impact on incidence and mortality: A global stance detection analysis of tweets.

During the COVID-19 pandemic, nations implemented various preventive measures, triggering varying online responses. This study examines cultural influences on public online stances toward these measures and their impacts on COVID-19 cases/deaths. Stance detection analysis was used to analyze 16,428,557 Tweets regarding COVID-19 preventive measures from 95 countries, selected based on Hofstede's cultural dimensions. To ensure the variety of population, countries were chosen based on Twitter data availability and a minimum sample size of 385 tweets, achieving a 95% confidence level with a 5% margin of error. The weighted regression analysis revealed that the relationship between culture and online stances depends on the cultural congruence of each measure. Specifically, power distance positively predicted stances for all measures, while indulgence had a negative effect overall. Effects of other cultural indices varied across measures. Individualism negatively affected face coverings stances. Uncertainty avoidance influenced lockdown and vaccination stances negatively but had a positive effect on social distancing stances. Long-term orientation negatively affected lockdown and social distancing stances but positively influenced quarantine stances. Cultural tightness only negatively affected face coverings and quarantine stances. Online stances toward face coverings mediated the relationship between cultural indices and COVID-19 cases/deaths. As such, public health officials should consider cultural profiles and use culturally congruent communication strategies when implementing preventive measures for future pandemics. Furthermore, leveraging digital tools is vital in navigating and shaping online stances to enhance the effectiveness of these measures.

Molecular Hydrogen as a Promising Therapy Could Be Linked With Increased Resting Treg Cells or Decreased Fas+ T Cell Subsets in a IgG4-PF-ILD Patient: A Case Report.

BACKGROUND/AIM: Progressive fibrosing interstitial lung disease (PF-ILD) refers to a group of chronic lung conditions commonly associated with immunoglobulin G4-related disorders. It is characterized by progressive scarring (fibrosis) within the pulmonary interstitium, resulting in respiratory failure and early mortality. Some patients do not respond to standard therapeutic interventions. Numerous studies have confirmed the anti-inflammatory and antioxidant properties of molecular hydrogen in various disease models. CASE REPORT: In this report, we present a case study of an 85-year-old female diagnosed with suspected IgG4-related PF-ILD complicated by hospital-acquired pneumonia. On the fourth day of hydrogen-assisted therapy, a noticeable improvement in lung infiltrations was observed in chest X-rays as the patient gradually progressed towards weaning off mechanical ventilation. To assess treatment responses, we compared immune phenotypes before and after hydrogen treatment. A marked increase was observed in resting regulatory T cell levels after treatment, accompanied by a notable decrease in Fas+ helper T cell and cytotoxic T cell subtypes. CONCLUSION: This case study highlights the effectiveness of hydrogen-assisted therapy in managing PF-ILD complicated by pneumonia, warranting further research in the future.

Emergence of eravacycline heteroresistance in carbapenem-resistant Acinetobacter baumannii isolates in China.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is resistant to almost all antibiotics. Eravacycline, a newer treatment option, has the potential to treat CRAB infections, however, the mechanism by which CRAB isolates develop resistance to eravacycline has yet to be clarified. This study sought to investigate the features and mechanisms of eravacycline heteroresistance among CRAB clinical isolates. A total of 287 isolates were collected in China from 2020 to 2022. The minimum inhibitory concentration (MIC) of eravacycline and other clinically available agents against A. baumannii were determined using broth microdilution. The frequency of eravacycline heteroresistance was determined by population analysis profiling (PAP). Mutations and expression levels of resistance genes in heteroresistant isolates were determined by polymerase chain reaction (PCR) and quantitative real-time PCR (qRT-PCR), respectively. Antisense RNA silencing was used to validate the function of eravacycline heteroresistant candidate genes. Twenty-five eravacycline heteroresistant isolates (17.36%) were detected among 144 CRAB isolates with eravacycline MIC values ≤4 mg/L while no eravacycline heteroresistant strains were detected in carbapenem-susceptible A. baumannii (CSAB) isolates. All eravacycline heteroresistant strains contained OXA-23 carbapenemase and the predominant multilocus sequence typing (MLST) was ST208 (72%). Cross-resistance was observed between eravacycline, tigecycline, and levofloxacin in the resistant subpopulations. The addition of efflux pump inhibitors significantly reduced the eravacycline MIC in resistant subpopulations and weakened the formation of eravacycline heteroresistance in CRAB isolates. The expression levels of adeABC and adeRS were significantly higher in resistant subpopulations than in eravacycline heteroresistant parental strains (P < 0.05). An ISAba1 insertion in the adeS gene was identified in 40% (10/25) of the resistant subpopulations. Decreasing the expression of adeABC or adeRS by antisense RNA silencing significantly inhibited eravacycline heteroresistance. In conclusion, this study identified the emergence of eravacycline heteroresistance in CRAB isolates in China, which is associated with high expression of AdeABC and AdeRS.

Gate-tunable circular phonon dichroism effect in bilayer graphene.

Circular phonon dichroism effect has been proposed in two-dimensional materials; however, the lack of tunability hinders the exploration of the effect. Here, we investigate the role of dual-gating-induced inversion symmetry breaking in the circular phonon dichroism effect in bilayer graphene. We find that the introduction of inversion symmetry breaking modifies the response in the layer-symmetric and layer-antisymmetric channels, and results in the occurrence of phonon dichroism in the cross-channel. In the layer representation, the inversion symmetry breaking breaks the equality of intralayer circular phonon dichroism and enhances the interlayer response. Our results suggest that layer degree of freedom provides possibilities to tune phonon dynamics, which paves a way toward different physics and applications of two-dimensional acoustoelectronics and layertronics.

Bridging Reduced Grip Strength and Altered Executive Function: Specific Brain White Matter Structural Changes in Patients with Alzheimer's Disease.

Objective: To investigate the correlation between specific fiber tracts and grip strength and cognitive function in patients with Alzheimer's disease (AD) by fixel-based analysis (FBA). Methods: AD patients were divided into AD with low grip strength (AD-LGS, n=29) and AD without low grip strength (AD-nLGS, n=25), along with 31 normal controls (NC). General data, neuropsychological tests, grip strength and cranial magnetic resonance imaging (MRI) scans were collected. FBA evaluated white matter (WM) fiber metrics, including fiber density (FD), fiber cross-sectional (FC), and fiber density and cross-sectional area (FDC). The mean fiber indicators of the fiber tracts of interest (TOI) were extracted in cerebral region of significant statistical differences in FBA to further compare the differences between groups and analyze the correlation between fiber properties and neuropsychological test scores. Results: Compared to AD-nLGS group, AD-LGS group showed significant reductions in FDC in several cerebral regions. In AD patients, FDC values of bilateral uncinate fasciculus and left superior longitudinal fasciculus were positively correlated with Clock Drawing Test scores, while FDC of splenium of corpus callosum, bilateral anterior cingulate tracts, forceps major, and bilateral inferior longitudinal fasciculus were positively correlated with the Executive Factor Score of Memory and Executive Screening scale scores. Conclusion: Reduced grip strength in AD patients is associated with extensive impairment of WM structural integrity. Changes in FDC of specific WM fiber tracts related to executive function play a significant mediating role in the reduction of grip strength in AD patients.

tRF3-IleAAT reduced extracellular matrix synthesis in diabetic kidney disease mice by targeting ZNF281 and inhibiting ferroptosis.

It is well established that the synthesis of extracellular matrix (ECM) in mesangial cells is a major determinant of diabetic kidney disease (DKD). Elucidating the major players in ECM synthesis may be helpful to provide promising candidates for protecting against DKD progression. tRF3-IleAAT is a tRNA-derived fragment (tRF) produced by nucleases at tRNA-specific sites, which is differentially expressed in the sera of patients with diabetes mellitus and DKD. In this study we investigated the potential roles of tRFs in DKD. Db/db mice at 12 weeks were adapted as a DKD model. The mice displayed marked renal dysfunction accompanied by significantly reduced expression of tRF3-IleAAT and increased ferroptosis and ECM synthesis in the kidney tissues. The reduced expression of tRF3-IleAAT was also observed in high glucose-treated mouse glomerular mesangial cells. We administered ferrostatin-1 (1 mg/kg, once every two days, i.p.) to the mice from the age of 12 weeks for 8 weeks, and found that inhibition of the onset of ferroptosis significantly improved renal function, attenuated renal fibrosis and reduced collagen deposition. Overexpression of tRF3-IleAAT by a single injection of AAV carrying tRF3-IleAAT via caudal vein significantly inhibited ferroptosis and ECM synthesis in DKD model mice. Furthermore, we found that the expression of zinc finger protein 281 (ZNF281), a downstream target gene of tRF3-IleAAT, was significantly elevated in DKD models but negatively regulated by tRF3-IleAAT. In high glucose-treated mesangial cells, knockdown of ZNF281 exerted an inhibitory effect on ferroptosis and ECM synthesis. We demonstrated the targeted binding of tRF3-IleAAT to the 3'UTR of ZNF281. In conclusion, tRF3-IleAAT inhibits ferroptosis by targeting ZNF281, resulting in the mitigation of ECM synthesis in DKD models, suggesting that tRF3-IleAAT may be an attractive therapeutic target for DKD.

IVIG as a Promising Therapy for Methotrexate-induced Life-threatening Neutropenic Enterocolitis in an Elderly Patient With Rheumatoid Arthritis: A Case Report and Literature Review.

BACKGROUND/AIM: Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with the functional impairment of multiple joints and the destruction of bone and cartilage. Methotrexate (MTX) is a first-line drug commonly used to treat RA; however, even low doses of MTX can potentially cause rare but severe adverse reactions, such as neutropenic enterocolitis (NE), a life-threatening disease characterized by intestinal mucosal damage and immunodeficiency. CASE REPORT: Here, we report on an 82-year-old RA patient who developed life-threatening NE after ten years of low-dose MTX treatment. The condition of the patient rapidly worsened, requiring emergency electrical cardioversion and intravenous treatment with immunoglobulin (IVIG). Immunophenotypic responses were analyzed before and after treatment to evaluate therapeutic efficacy. CONCLUSION: This case highlights the importance of monitoring elderly patients with RA receiving low-dose MTX treatment for the potential accumulation of MTX toxicity. Our findings also illustrate the importance of providing timely IVIG therapy for MTX-induced NE.

SiSGC: A Drug Repositioning Prediction Model Based on Heterogeneous Simplifying Graph Convolution.

Drug repositioning plays a key role in disease treatment. With the large-scale chemical data increasing, many computational methods are utilized for drug-disease association prediction. However, most of the existing models neglect the positive influence of non-Euclidean data and multisource information, and there is still a critical issue for graph neural networks regarding how to set the feature diffuse distance. To solve the problems, we proposed SiSGC, which makes full use of the biological knowledge information as initial features and learns the structure information from the constructed heterogeneous graph with the adaptive selection of the information diffuse distance. Then, the structural features are fused with the denoised similarity information and fed to the advanced classifier of CatBoost to make predictions. Three different data sets are used to confirm the robustness and generalization of SiSGC under two splitting strategies. Experiment results demonstrate that the proposed model achieves superior performance compared with the six leading methods and four variants. Our case study on breast neoplasms further indicates that SiSGC is trustworthy and robust yet simple. We also present four drugs for breast cancer treatment with high confidence and further give an explanation for demonstrating the rationality. There is no doubt that SiSGC can be used as a beneficial supplement for drug repositioning.

Global, regional, and national prevalence of hearing loss from 1990 to 2019: A trend and health inequality analyses based on the Global Burden of Disease Study 2019.

As a severe public health issue, hearing loss has caused an increasingly disease burden, especially in the elderly population. Hearing loss may inevitably induce asymmetric hearing, which makes it difficult for elderly individuals to locate sound sources, therefore resulting in increased postural instability and falling risk. To emphasize the public health emergence of hearing loss, we investigated the temporal trend of prevalence of hearing loss over the last 30 years and further predicted its changes in the next 20 years, decomposed the trend according to demographic factors and epidemiological changes, and quantified the cross-country healthy inequalities, using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. In 2019, there were more than 140 million cases of hearing loss worldwide, a 93.89% increase from 70 million cases in 1990. The age-standardized rate (ASR) also increased with an estimated annual percentage change of 0.08% per year. Population growth and aging are the major drivers contributing to the changes, accounting for 60.83% and 35.35%. Of note, the contribution of aging varies showing a gradual increasing trend with sociodemographic index (SDI) elevating. Also notable, there were significant health inequalities across 204 countries and territories, with slope index of inequality rising over time. Projection of the global burden of hearing loss from 2020 to 2040 indicated progressive increases in both case number and ASR. These reflect the heavy disease burden of hearing loss that needed more targeted and efficient strategies in its prevention and management.

Construction of clinical research nurse training program based on position competence.

BACKGROUND: As one of the most important members in clinical trials, the number of clinical research nurses (CRN) can't keep up with the growth of experimental projects, so it is urgent to build clinical research training and strengthen the background knowledge of nurses. AIM: To construct CRN training program based on position competence, accelerate the construction of CRN talent pool, and provide scientific guidance significance for CRN training. METHODS: Based on the position competence model, combined with literature research and qualitative interview results, the first draft was prepared of the CRN training program. Two rounds of correspondence with 16 experts were conducted using the Delphi method to determine the training program. RESULTS: The effective recovery rate of the expert correspondence questionnaire was 100% and the authority coefficients of the 2 rounds of experts were 0.826 and 0.895. Finally, 4 first-level indicators and determine 15 s-level indicators of training objectives. The training program included 4 first-level indicators, training requirements, content, methods, assessment and evaluation, 15 s-level indicators, and 74 third-level indicators. CONCLUSION: The CRN training program based on position competence is scientific and extendable, providing a basis for participation in CRN training.

Coexistence of Incoherent and Ultrafast Coherent Exciton Transport in a Two-Dimensional Superatomic Semiconductor.

Fully leveraging the remarkable properties of low-dimensional semiconductors requires developing a deep understanding of how their structure and disorder affect the flow of electronic energy. Here, we study exciton transport in single crystals of the two-dimensional superatomic semiconductor CsRe6Se8I3, which straddles a photophysically rich yet elusive intermediate electronic-coupling regime. Using femtosecond scattering microscopy to directly image exciton transport in CsRe6Se8I3, we reveal the rare coexistence of coherent and incoherent exciton transport, leading to either persistent or transient electronic delocalization depending on temperature. Notably, coherent excitons exhibit ballistic transport at speeds approaching an extraordinary 1600 km/s over 300 fs. Such fast transport is mediated by J-aggregate-like superradiance, owing to the anisotropic structure and long-range order of CsRe6Se8I3. Our results establish superatomic crystals as ideal platforms for studying the intermediate electronic-coupling regime in highly ordered environments, in this case displaying long-range electronic delocalization, ultrafast energy flow, and a tunable dual transport regime.

Optical Imaging of Ultrafast Phonon-Polariton Propagation through an Excitonic Sensor.

Hexagonal boron nitride (hBN) hosts phonon polaritons (PhP), hybrid light-matter states that facilitate electromagnetic field confinement and exhibit long-range ballistic transport. Extracting the spatiotemporal dynamics of PhPs usually requires "tour de force" experimental methods such as ultrafast near-field infrared microscopy. Here, we leverage the remarkable environmental sensitivity of excitons in two-dimensional transition metal dichalcogenides to image PhP propagation in adjacent hBN slabs. Using ultrafast optical microscopy on monolayer WSe2/hBN heterostructures, we image propagating PhPs from 3.5 K to room temperature with subpicosecond and few-nanometer precision. Excitons in WSe2 act as transducers between visible light pulses and infrared PhPs, enabling visible-light imaging of PhP transport with far-field microscopy. We also report evidence of excitons in WSe2 copropagating with hBN PhPs over several micrometers. Our results provide new avenues for imaging polar excitations over a large frequency range with extreme spatiotemporal precision and new mechanisms to realize ballistic exciton transport at room temperature.

Functional implications of rs9373441 with FOXP3+Treg and Tr1 for the clinical effectiveness of csDMARDs in rheumatoid arthritis.

Rheumatoid arthritis (RA) is characterized by a deficiency in regulatory T cells (Treg), which play a crucial role in immune regulation. While conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are widely used, there remains a challenge as efficacy varies among patients. In this genome-wide association study (GWAS) involving 410 RA patients, rs9373441 emerged as the most significantly linked single-nucleotide polymorphism (SNP) to csDMARDs response. This non-coding variant functions as a cis-acting regulatory element within the UTRN gene, which is associated with cortical erosion and osteoporosis. Particularly, individuals with the TT allele at rs9373441 exhibited a more favorable response, characterized by a significant increase in FOXP3 + Treg and Type 1 regulatory T cells (Tr1) (p = 0.04, 0.02) and a decrease in Effector T helper cells (Effector Th) (p = 0.03). The GATA3-GCM2-PTH and GATA3-FOXO1-FOXP3 pathways were implicated. RNA-sequencing (RNA-seq) analysis revealed increased expression levels of UTRN, PTH2R, FOXO1, and FOXO3 in good and moderate responders (p = 0.01, 0.03, 0.0005, and 0.02). Notably, the change in FOXP3 + Treg and Tr1 was positively correlated with UTRN expression (both p = 0.03). These findings underscore the critical link between rs9373441 and the response to csDMARDs, empowering clinicians to tailor treatments for enhanced outcomes in patients with RA.

[Spatio-temporal Variations in PM2.5and Its Influencing Factors in the Yangtze River Delta Urban Agglomeration].

To coordinate the contradiction between economic development and environmental pollution and achieve the sustainable development of the economy and society, the spatio-temporal variations in PM2.5 were analyzed based on PM2.5 concentration and meteorological data of the Yangtze River Delta (YRD) urban agglomeration. Wavelet transform coherence (WTC), partial wavelet coherence (PWC), and multiple wavelet coherence (MWC) were used to analyze the multi-scale coupling oscillation between PM2.5 and meteorological factors in the time-frequency domain. The results showed that:① the concentration of PM2.5 in the YRD decreased from northwest to southeast, and the spatial range with high PM2.5 concentration decreased annually. The spatial distribution characteristics of the seasonal average PM2.5 concentration were similar to those of the annual average PM2.5 concentration. PM2.5 concentration exhibited the seasonal variation characteristics of high in winter, low in summer, and transitioning between spring and autumn. ② PM2.5 concentration decreased from 2015 to 2021, and the compliance rate increased. The difference in annual average PM2.5 concentration was decreased with dynamic convergence characteristics. The convergence of PM2.5 concentration in summer was greater than that in winter. During the whole study period, the daily average PM2.5 concentration showed a "U" distribution, and the proportion of days with excellent and good PM2.5 levels were 49.72% and 41.45%, respectively. ③ The wavelet coherence between PM2.5 and meteorological factors was different in different time-frequency domains. The main factors affecting PM2.5 were different in different time-frequency scales. At all time-frequency scales, WTC and PWC showed that wind speed and temperature were the best explanatory variables of PM2.5 variation, respectively. ④ The larger the time-frequency scale, the stronger the interaction of multi-factor combinations to explain PM2.5 variations. The synergistic effect of temperature and wind speed could better explain the variation in PM2.5. These results can provide reference for air pollution control in the YRD.

Early inoculation of an endophyte alters the assembly of bacterial communities across rice plant growth stages.

The core endophytes of plants are regarded as promising resources in future agroecosystems. How they affect the assembly of rice-related bacterial communities after early inoculation remains unclear. Here, we examined bacterial communities across 148 samples, including bulk and rhizosphere soils, sterilized roots, stems, and seeds at the seedling, tillering, booting, and maturity stages. Tissue cultured rice seedlings were inoculated with Xathomonas sacchari JR3-14, a core endophytic bacterium of rice seeds, before transplanting. The results revealed that α-diversity indices were significantly enhanced in the root and stem endosphere at the seedling stage. ß-diversity was altered at most plant developmental stages, except for the root and stem at the booting stage. Network complexity consequently increased in the root and stem across rice growth stages, other than the stem endosphere at the booting stage. Four abundant beneficial bacterial taxa, Bacillus, Azospira, Azospirillum, and Arthrobacter, were co-enriched during the early growth stage. Infer Community Assembly Mechanisms by Phylogenetic-bin-based null model analysis revealed a higher relative contribution of drift and other eco-evolutionary processes mainly in root compartments across all growth stages, but the opposite pattern was observed in stem compartments. IMPORTANCE Endophytic bacteria are regarded as promising environmentally friendly resources to promote plant growth and plant health. Some of microbes from the seed are able to be carried over to next generation, and contribute to the plant's ability to adapt to new environments. However, the effects of early inoculation with core microbes on the assembly of the plant microbiome are still unclear. In our study, we demonstrate that early inoculation of the rice seed core endophytic bacterium Xanthomonas sacchari could alter community diversity, enhance complexity degree of network structure at most the growth stages, and enrich beneficial bacteria at the seedling stage of rice. We further analyzed the evolutionary processes caused by the early inoculation. Our results highlight the new possibilities for research and application of sustainable agriculture by considering the contribution of seed endophytes in crop production and breeding.

Theoretical studies of magneto-optical Kerr and Faraday effects in two-dimensional second-order topological insulators.

Optical approaches are useful for studying the electronic and spin structure of materials. Here, based on the tight-binding model and linear response theory, we investigate the magneto-optical Kerr and Faraday effects in two-dimensional second-order topological insulators (SOTI) with external magnetization. We find that orbital-dependent Zeeman term induces band crossings for SOTI phase, which are absent for trivial phase. In the weak-magnetization regime, these crossings give rise to giant jumps (peaks) of Kerr and Faraday angles (ellipticity) for SOTI phase. In the strong-magnetization regime, we find that two nearly flat bands are formed at the high-symmetry point of Brillouin zone of SOTI phase. These flat bands give rise to two successive giant jumps (peaks) of Kerr and Faraday angles (ellipticity). These phenomena provide new possibilities to characterize and detect the two-dimensional SOTI phase.

Relationship between sarcopenic obesity and cognitive function in patients with mild to moderate Alzheimer's disease.

BACKGROUND: Previous research has linked sarcopenic obesity (SO) to cognitive function; however, the relationship between cognitive performance and SO Alzheimer's disease (AD) patients remains unclear. This study aimed to investigate their relationship in AD patients. METHODS: One hundred and twenty mild to moderate AD patients and 56 normal controls were recruited. According to sarcopenia or obesity status, AD patients were classified into subgroups: normal, obesity, sarcopenia, and SO. Body composition, demographics, and sarcopenia parameters were assessed. Cognitive performance was evaluated using neuropsychological scales. RESULTS: Among the 176 participants, the prevalence of SO in the moderate AD group was higher than in the normal control group. The moderate AD group had the lowest appendicular skeletal muscle mass index (ASMI) and the highest percentage of body fat (PBF). Hypertension and diabetes were more prevalent in the SO group than in the normal group among the subgroups. The sarcopenia and SO groups exhibited worse global cognitive function compared to the normal and obesity groups. Partial correlation analysis revealed that ASMI, PBF, and visceral fat area were associated with multiple cognitive domains scores. In logistic regression analysis, after adjusting for confounders, obesity was not found to be associated with AD. However, sarcopenia (odds ratio (OR) = 5.35, 95% CI: 1.27-22.46) and SO (OR = 5.84, 95% CI: 1.26-27.11) were identified as independent risk factors for AD. CONCLUSIONS: SO was associated with cognitive dysfunction in AD patients. Moreover, the impact of SO on cognitive decline was greater than that of sarcopenia. Early identification and intervention for SO may have a positive effect on the occurrence and progression of AD.

Using Treg, Tr1, and Breg Expression Levels to Predict Clinical Responses to csDMARD Treatment in Drug-naive Patients With Rheumatoid Arthritis.

BACKGROUND/AIM: Regulatory T cells (Treg) play a crucial role in maintaining immune tolerance and preventing autoimmune diseases. Recent data also indicate that type 1 regulatory T (Tr1) and regulatory B (Breg) cells play an inhibitory (i.e., protective) role in autoimmune diseases. Conventional synthetic disease-modifying antirheumatic drugs (csDMARD) are a first-line therapy for rheumatoid arthritis (RA), and our aim was to predict clinical responses of this treatment using immunophenotyping. MATERIALS AND METHODS: We first detected the presence of immune cells in fresh blood from 16 healthy controls (HC) and 26 patients with RA (14 drug-naive and 12 csDMARD-experienced). Then, we recorded immunophenotypic changes in 14 drug-naive RA (naive RA) patients prior to csDMARD treatment (i.e., day 0) and after receiving treatment for 6 months. The observed changes were also compared with other clinical indicators, including the presence of anti-citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF) levels, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels. RESULTS: Naive RA patients had significantly lower Tregs than HC and csDMARD-experienced patients (both p<0.0001) and the number of Tregs correlated with the diagnosis of RA and therapeutic efficacy of csDMARD treatment. Furthermore, lower baseline levels of Treg, memory Treg, Tr1, and higher PD-1+ Marginal B, Breg cells were significantly associated with decreased development of the 28-joint Disease Activity Score (DAS28) (all p<0.05), revealing better medical response. Multiple regression and principal component analysis identified Treg, Tr1, and Breg as potential predictors of csDMARD responses (Area under curve: 0.9; Accuracy: 92.86%). Furthermore, elevated Treg, Tr1, and Breg cells were associated with decreased DAS28, ESR, and CRP (all p<0.05); changes in Treg and Breg cell expression were also more pronounced among double negative anti-CCP and RF in RA patients with better outcomes (p<0.05). CONCLUSION: Immunophenotyping can be an adjunct clinical tool to identify patients who are poor candidates for csDMARD therapy. Alternative therapeutic interventions in the early stages of disease should be formulated for these patients.

Predicting the clinical efficacy of JAK inhibitor treatment for patients with rheumatoid arthritis based on Fas+ T cell subsets.

Rheumatoid arthritis (RA) is a common autoimmune disease. Janus kinase inhibitors (JAKi) have been approved for the treatment of RA; however, the impact of JAKi on immune cells remains inconclusive. This study investigated the response of immune cells to JAKi treatment to identify biomarkers by which to evaluate and predict clinical outcomes. Blood samples were collected from RA patients before and after JAKi treatment for the analysis of immunophenotypes. Our results revealed that JAKi mainly inhibited Fas+ T cell subsets. The percentage changes of Th Fas+ and Naive Th Fas+ cells were positively correlated with the 28-joint Disease Activity Score with erythrocyte sedimentation rate (DAS28-ESR) values. Following treatment, moderate response (MR) RA patients presented a decrease in the number of Naive Th Fas+ cells (p = 0.0001). Initial percentages of 14 T cell and 20 B cell subsets were correlated with percentage changes in DAS28-ESR. Overall, 16 cell subsets presented significant differences between the non-response (NR) and MR groups. Excluding the multicollinearity of the immune cells, we constructed a JAKi treatment response prediction index (JRPI) using 5 subsets of T/B cells, the results of which were strongly correlated with percentage changes in DAS28-ESR (receiver operating characteristic curve of 1). Note that the NR group was clearly distinguished from the MR group (p = 0.0167). In conclusion, the efficacy of JAKi can be attributed mainly to the suppression of Fas+ T cell subsets. A positive correlation was shown between the therapeutic efficacy of JAKi and the percentage changes in both Th Fas+ cells and Naive Th Fas+ cells. Furthermore, the proposed JRPI could potentially be used as an indicator to predict the efficacy of JAKi prior to treatment in RA patients. These findings may contribute to the development of personalized treatment strategies for RA patients using JAKi.