Direct prediction of carbapenem resistance in Pseudomonas aeruginosa by whole genome sequencing and metagenomic sequencing.

Carbapenem resistance is a major concern in the management of antibiotic-resistant Pseudomonas aeruginosa infections. The direct prediction of carbapenem-resistant phenotype from genotype in P. aeruginosa isolates and clinical samples would promote timely antibiotic therapy. The complex carbapenem resistance mechanism and the high prevalence of variant-driven carbapenem resistance in P. aeruginosa make it challenging to predict the carbapenem-resistant phenotype through the genotype. In this study, using whole genome sequencing (WGS) data of 1,622 P. aeruginosa isolates followed by machine learning, we screened 16 and 31 key gene features associated with imipenem (IPM) and meropenem (MEM) resistance in P. aeruginosa, including oprD(HIGH), and constructed the resistance prediction models. The areas under the curves of the IPM and MEM resistance prediction models were 0.906 and 0.925, respectively. For the direct prediction of carbapenem resistance in P. aeruginosa from clinical samples by the key gene features selected and prediction models constructed, 72 P. aeruginosa-positive sputum samples were collected and sequenced by metagenomic sequencing (MGS) based on next-generation sequencing (NGS) or Oxford Nanopore Technology (ONT). The prediction applicability of MGS based on NGS outperformed that of MGS based on ONT. In 72 P. aeruginosa-positive sputum samples, 65.0% (26/40) of IPM-insensitive and 63.2% (24/38) of MEM-insensitive P. aeruginosa were directly predicted by NGS-based MGS with positive predictive values of 0.897 and 0.889, respectively. By the direct detection of the key gene features associated with carbapenem resistance of P. aeruginosa, the carbapenem resistance of P. aeruginosa could be directly predicted from cultured isolates by WGS or from clinical samples by NGS-based MGS, which could assist the timely treatment and surveillance of carbapenem-resistant P. aeruginosa.

Residential greenness exposure and decreased prevalence of diabetic retinopathy: A nationwide analysis in China.

OBJECTIVE: Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness among diabetics. We aimed to explore whether long-term exposure to residential greenness was beneficial to DR. RESEARCH DESIGN AND METHODS: We used data from a large-scale, cross-sectional screening survey conducted in 129 cities of 27 provincial regions of China from 2018 to 2021 among patients with diabetes. We measured residential greenness exposure as the 3-year average of annual maximum Normalized Difference Vegetation Index (NDVI) at a spatial resolution of 250 m. DR was assessed by ophthalmologists based on fundus photographs. The primary outcome was DR, and secondary outcome included DR severity status (i.e., nonproliferative and proliferative), hallmarks of retinal lesions and macular oedema. RESULTS: A total of 484,380 adult participants with diabetes were included in the current analysis, and 15.7% of them were diagnosed with DR. NDVI was inversely and linearly associated with DR prevalence, and an increment of 0.1 NDVI was associated with a 10% (9%-10%) decrease in DR prevalence. Significant and inverse associations were further found for nonproliferative and proliferative DR, hallmarks of lesions and macular oedema. The association between greenness and DR was stronger among participants who were older, obese, lived in the south, had longer duration of diabetes or did not take antidiabetic medications. CONCLUSIONS: This large-scale nationwide study provides the first-hand epidemiological evidence on the associations of residential greenness with DR. Our findings highlight the importance of residential greenness in alleviating DR risk especially in an era of aging and urbanization.

Benefit or Risk in Patient with Type 1 Diabetes Based on Appropriated Dosage of Dapagliflozin: A Case Report.

Purpose: Dapagliflozin has been used extensively in patients with type 2 diabetes mellitus (T2DM). However, due to the potential diabetic ketoacidosis (DKA) risk of dapagliflozin, its use in type 1 diabetes mellitus (T1DM) is limited. Here, we reported an obese patient with T1DM and inadequate glycemic control. We carefully recommended she use dapagliflozin as an insulin adjuvant to achieve better glycemia control and to assess possible benefits and risks. Methods and Results: The patient was a 27-year-old female who had underlying T1DM for 17 years with a body weight of 75.0 kg, body mass index (BMI) of 28.2 kg/m2, and glycated hemoglobin (HbA1c) 7.7% when admitted. To treat her diabetes, she had used an insulin pump for 15 years (the recent dosage of insulin was 45 IU/d) and oral metformin for 3 years (0.5 g qid). In order to decrease body weight and achieve better glycemic control, dapagliflozin (FORXIGA, AstraZeneca, Indiana) was administered as an insulin adjuvant. The patient presented sever DKA with a euglycemia (euDKA) after two days of the administration of dapagliflozin at a dose of 10 mg/d. euDKA occurred again after the administration of dapagliflozin at a dose of 3.3 mg/d. However, after using a smaller dose of dapagliflozin (1.5 mg/d), this patient achieved better glycemia control, with a significant reduction in daily insulin dosage and gradual weight loss, without significant hypoglycemia or DKA occurring. At the sixth month of the administration of dapagliflozin, the HbA1c was 6.2% for the patient, her daily insulin dosage was 22.5 IU, and her body weight was 60.2 kg. Conclusions: The appropriate dose of dapagliflozin is critical for a patient with T1DM patient therapy in order to find a correct balance between the benefits and risks.

Lithium-ion battery state of health and failure analysis with mixture weibull and equivalent circuit model.

Existing methods for interpreting Electrochemical Impedance Spectroscopy data involve various models, which face significant challenges in parameterization and physical interpretation and fail to comprehensively reflect the electrochemical behavior within batteries. To address these issues, this study proposes a Temperature-Controlled Second-Order R-CPE Equivalent Circuit Model to capture the non-ideal capacitive characteristics of electrode surfaces. Additionally, the study employs a Copula based Joint Mixture Weibull Model and multi-output Gaussian Process Regression to enhance the precision in capturing the distribution of battery electrochemical parameters and predict SoH curves. Experimental validation shows that the model used in this article has an average RMSE error of 8.5%, and the prediction of the SoH curve after the 100th cycle can achieve an average RMSE error of 9.2%. These findings provide insightful implications for understanding the electrochemical complexities and parameter interdependencies in the battery aging process, offering a robust framework for future research in battery diagnostics.

Soil warming affects sap flow and stomatal gas exchange through altering functional traits in a subtropical forest.

Climate warming influences the structure and function of ecosystems. However, the mechanisms of plant water use and gas exchange responses to climate warming have been less studied, especially from the perspective of different functional traits. We conducted a field experiment to investigate how soil warming (+2 °C) affects sap flow and stomatal gas exchange through plant functional traits and nutrient characteristics in a subtropical forest. We measured stomatal gas exchange of trees (Acacia auriculiformis and Schima superba) and shrubs (Castanea henryi and Psychotria asiatica), and monitored long-term sap flow of both tree species. Besides, plant leaf nutrient contents, functional traits, and soil nutrients were also studied. It is demonstrated that soil warming significantly increased maximum sap flow density (Js_max, 35.1 %) and whole-tree transpiration (EL, 46.0 %) of A. auriculiformis, but decreased those of S. superba (15.6 % and 14.9 %, respectively). Warming increased the photosynthetic rate of P. asiatica (18.0 %) and water use efficiency of S. superba (47.2 %). Leaf nutrients and stomatal anatomical characteristics of shrubs were less affected by soil warming. Soil warming increased (+42.7 %) leaf K content of A. auriculiformis in dry season. Decomposition of soil total carbon, total nitrogen, and available nitrogen was accelerated under soil warming, and soil exchangeable Ca2+ and Mg2+ were decreased. Trees changed stomatal and anatomic traits to adapt to soil warming, while shrubs altered leaf water content and specific leaf area under soil warming. Warming had a greater effect on sap flow of trees, as well as on their leaf gas exchange (total effect: -0.27) than on that of shrubs (total effect: 0.06). In summary, our results suggest that the combination of functional and nutrient traits can help to better understand plant water use and gas exchange responses under climate warming.

Association of long-term ozone air pollution and age-related macular degeneration in older Chinese population.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of legal blindness. It remains unclear whether and to what extent the ambient ozone pollution could increase the risk of AMD. METHODS: A nationwide cross-sectional survey was conducted in 129 major cities in 27 of 31 provincial regions across China from 2018 to 2021. Data in relation to demographics, residential address, and medical histories were collected. The exposure-response relationship between ozone exposure and AMD was explored using the restricted cubic splines. A piecewise logistic regression model was used to examine the magnitudes of the association, after adjusting demographic, social-economic and co-pollutants. Residential ozone exposures were estimated using a satellite-based model. RESULTS: A total of 624,167 middle-aged and older participants were included in the final analyses, the overall prevalence of AMD was 16.76 %. The risk of AMD was consistently increasing with higher warm-season ozone concentration, and the risk became much larger after the cut-off of 110 µg/m3 (approximately 50 ppb). Every 10 µg/m3 increment in warm-season ozone concentration, the adjusted odds ratio (OR) for AMD were 1.15 (1.13, 1.16) and 1.66 (1.63, 1.69) when the warm-season ozone concentration was below or above 110 µg/m3, respectively. CONCLUSION: This large-scale nationwide study provides the first epidemiological evidence demonstrating significant associations between long-term residential ozone exposure and AMD prevalence. Based on our findings, in conjunction with WHO global air quality guidelines, we suggest that a warm-season ozone of 110 µg/m3 should be adopted for middle-aged and older populations to reduce the risk of AMD. Ongoing efforts to reduce ozone exposure in communities through improved air quality regulations and public education are essential for the improvement of public health.

Association of exposure to ultraviolet radiation and warm-season ozone air pollution with incident age-related macular degeneration: A nationwide cohort study in China.

BACKGROUND: As the leading cause of blindness, age-related macular degeneration (AMD) performs an adverse impact on human health and disability. AMD have been reported to be associated with environmental factors; however, the association between ultraviolet (UV) radiation, warm-season ambient ozone pollution, and incident AMD remains unclear. METHODS: In this study, 19,707 participants without AMD at baseline were included from a nationwide longitudinal cohort in China. UV radiation and warm-season ozone exposure were evaluated through satellite-based models. Incident AMD was diagnosed via ophthalmological fundus images. Cox proportional hazard regression models were employed to explore the association of UV radiation and warm-season ozone with incident AMD, and the hazard ratios (HRs) and 95 % confidence intervals (CIs) were reported. RESULTS: During 312,935 person-month of follow-up, 3774 participants developed to AMD. High exposure to both UV radiation and warm-season ozone was associated with increasing risk of incident AMD, with HRs and 95 % CIs of 1.32 (1.23, 1.41) and 1.20 (1.11, 1.29) in two-exposure models, respectively. Moreover, negative interaction between UV radiation and warm-season ozone was identified, and it was found that exposure to high UV radiation and low ozone presented the highest hazard for AMD. Subgroup analyses showed that the UV-AMD association was stronger in southern China, while the ozone-AMD association was greater in northern China and rural areas. CONCLUSION: Our study provides the first epidemiological evidence that both UV radiation and warm-season ozone would elevate the risk of incident AMD, and the hazard of higher UV radiation may be attenuated by exposure to ozone. Strategies for decreasing AMD burden should jointly consider environmental exposures and geographic locations.

A pilot study on Paxlovid therapy for hemodialysis patients with severe acute respiratory syndrome coronavirus 2 infections.

We aimed to investigate the safety and efficacy of nirmatrelvir/ritonavir (Paxlovid) therapy for hemodialysis-dependent patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Thirteen hemodialysis patients infected with the Omicron variant of SARS-CoV-2 from April 3 to May 30, 2022, were recruited. Laboratory parameters and chest CT (computed tomography) imaging were analyzed. The treatment group included six patients who received 150 mg/100 mg of Paxlovid orally once daily for 5 days, whereas the control group included seven patients who received basic treatment. No serious adverse reactions or safety events were recorded. Four control patients progressed to moderate disease, and none in the treatment group showed progression of chest CT findings (P < 0.05). Paxlovid therapy tended toward early viral clearance and low viral load on Day 8. Moreover, 83.3% of the patients in the treatment group and 57.1% of the patients in the control group turned negative within 22 days. In the Paxlovid treatment group, we found significantly increased levels of lymphocytes (P=0.03) and eosinophils (P=0.02) and decreased levels of D-dimer on Day 8 compared with those on Day 1. Paxlovid therapy showed a potential therapeutic effect with good tolerance in hemodialysis patients. The optimal dose and effectiveness evaluation must be further investigated in a largeer cohort.

Clinical characteristics and microbial signatures in the lower airways of diabetic and nondiabetic patients with pneumonia.

Background: The microbial signatures in diabetes with pneumonia and the risk factors of severe pneumonia (SP) in diabetic patients are not clear. Our study explored microbial signatures and the association between clinical characteristics and SP then constructed a risk model to find effective biomarkers for predicting pneumonia severity. Methods: Our study was conducted among 273 patients with pneumonia diagnosed and treated in our hospital from January 2018 to May 2021. Bronchoalveolar lavage fluid (BALF) samples and clinical data were collected. Metagenomic sequencing was applied after extracting the DNA from samples. Appropriate statistical methods were used to compare the microbial signatures and clinical characteristics in patients with or without diabetes mellitus (DM). Results: In total, sixty-one pneumonia patients with diabetes and 212 pneumonia patients without diabetes were included. Sixty-six differential microorganisms were found to be associated with SP in diabetic patients. Some microbes correlated with clinical indicators of SP. The prediction model for SP was established and the receiver operating characteristic (ROC) curve demonstrated its accuracy, with the sensitivity and specificity of 0.82 and 0.91, respectively. Conclusions: Some microorganisms affect the severity of pneumonia. We identified the microbial signatures in the lower airways and the association between clinical characteristics and SP. The predictive model was more accurate in predicting SP by combining microbiological indicators and clinical characteristics, which might be beneficial to the early identification and management of patients with SP.

Probiotics intervention in preventing conversion of impaired glucose tolerance to diabetes: The PPDP follow-on study.

Objectives: The purpose of this study was to assess the incidence of type 2 diabetes mellitus (T2DM) after 6 years in patients with IGT who received early probiotic intervention in the Probiotics Prevention Diabetes Program (PPDP) trial. Methods: 77 patients with IGT in the PPDP trial were randomized to either probiotic or placebo. After the completion of the trial, 39 non-T2DM patients were invited to follow up glucose metabolism after the next 4 years. The incidence of T2DM in each group was assessed using Kaplan-Meier analysis. The 16S rDNA sequencing technology was used to analyze gut microbiota's structural composition and abundance changes between the groups. Results: The cumulative incidence of T2DM was 59.1% with probiotic treatment versus 54.5% with placebo within 6 years, there was no significant difference in the risk of developing T2DM between the two groups (P=0.674). Conclusions: Supplemental probiotic therapy does not reduce the risk of IGT conversion to T2DM. Clinical Trial Registration: https://www.chictr.org.cn/showproj.aspx?proj=5543, identifier ChiCTR-TRC-13004024.

Eosinophil and IFN-γ associated with immune-related adverse events as prognostic markers in patients with non-small cell lung cancer treated with immunotherapy.

Objectives: Immune checkpoint inhibitors (ICIs) alone or combined with other antitumor agents are largely used in lung cancer patients, which show both positive effects and side effects in particular subjects. Our study aims to identify biomarkers that can predict response to immunotherapy or risk of side effects, which may help us play a positive role and minimize the risk of adverse effects in clinical practice. Methods: We retrospectively collected data from patients with advanced non-small cell lung cancer (NSCLC) treated with ICIs at our center. Patients who received initial ICI therapy for >1 year without progression of disease were classified as long-term treatment (LT) group, while others were classified as the non-long-term treatment (NLT) group. Multivariate logistic analysis was performed to identify independent risk factors of progression-free survival (PFS) and immune-related adverse events (irAEs). Results: A total of 83 patients (55.7%) had irAEs. The median PFS for patients in grades 1-2 of irAEs vs. grades 3-4 vs non-irAEs groups was (undefined vs. 12 vs. 8 months; p = 0.0025). The 1-year PFS rate for multisystem vs. single vs. non-irAE groups was 63%, 56%, and 31%, respectively. Signal transduction of inflammatory cytokines improves clinical prognosis through immunomodulatory function, but the benefit is also limited by the resulting organ damage, making it a complex immune balance. Serum biomarkers including EOS% of ≥ 1.15 (HR: 8.30 (95% CI, 2.06 to 33.42); p = 0.003) and IFN-γ of ≥ 3.75 (HR: 5.10 (95% CI, 1.29 to 20.15), p = 0.02) were found to be predictive for irAEs. Conclusion: EOS% of ≥1.15% and IFN-γ of ≥3.75 ng/L were considered peripheral-blood markers for irAEs and associated with improved clinical outcomes for immunotherapy in patients with advanced NSCLC.

Associations between blood pressure levels and diabetic retinopathy in patients with diabetes mellitus: A population-based study.

Purpose: To evaluate the associations of blood pressure levels with diabetic retinopathy (DR), proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) in patients with diabetes mellitus. Design: A cross-sectional, population-based study. Subjects: A total of 152,844 patients with diabetes from 90 major cities in 19 provincial regions of mainland China during 2018-2021 were finally recruited. Methods: Blood pressure was graded into 5 levels: normal (without hypertension and <120/80 mmHg), normal high (without hypertension and ≥120/80 mmHg), HT-intensive (hypertension and <120/80 mmHg), HT-moderate (hypertension and blood pressure between 120/80 mmHg and 140/90 mmHg) and HT-high (hypertension and ≥140/90 mmHg). Logistic regression was employed to verify the associations of hypertension and blood pressure levels with DR, PDR and DME. The impacts of blood pressure levels on the outcomes were qualified with nomogram models. Main outcome measures: The main outcome was DR. Results: There were 16,685 (10.92%) participants having DR, 2841 (1.86%) having PDR, and 1566 (1.02%) having DME. There were 8126 (5.32%) patients without hypertension and 1350 (0.88%) patients with hypertension having blood pressure <120/80 mmHg. When compared to the normal group with covariates adjusted, an increased prevalence of DR was observed in normal high (adjusted odds ratio [OR] = 1.114, 95% confidence interval [CI] = 1.033-1.202), HT-moderate (adjusted OR = 1.163, 95% CI = 1.065-1.271), and HT-high (adjusted OR = 1.203, 95% CI = 1.114-1.300). Conclusions: There were associations between hypertension and DR, PDR, and DME in the diabetic population. Increased prevalence of DR was found with blood pressure >120/80 mmHg in both patients with and without hypertension. A nomogram was developed for DR prediction based on blood pressure levels.

Chronic obstructive pulmonary disease alters the genetic landscape and tumor immune microenvironment in lung cancer patients.

Background: Chronic obstructive pulmonary disease (COPD) and lung cancer are leading causes of morbidity and mortality worldwide. Studies have reported molecular alterations in patients with lung cancer and in patients with COPD. However, few investigation has been conducted on the molecular characteristics of lung cancer patients with COPD. Materials and methods: We performed a retrospective cohort study that included 435 patients with pathologically confirmed lung cancer at the Ruijin Hospital. For patients with documented spirometry, Global Initiative for Chronic Obstructive Lung Disease criteria were used to define COPD. For patients without documented spirometry, chest computed tomography and other clinical information were used to define COPD. Tumor tissue DNA was extracted from formalin-fixed paraffin-embedded samples. DNA mutation analysis, multiplex immunohistochemistry (mIHC), calculation of tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), and predication of neoantigens were performed. Results: Although SNV mutations in lung cancer patients with COPD (G1 group) were generally higher than those in lung cancer patients without COPD (G2 group), the difference in the number of mutations was insignificant between the two groups. Of the 35 mutated genes, the number of them was higher in G1 than in G2, except that of EGFR. PI3K-Akt signaling pathway was enriched from significantly different genes. While TMB and MATH levels were not significantly different, the tumor neoantigen burdenwas markedly higher in G1 than that in G2. The level of CD68+ macrophages was significant higher in the stroma and total areas in the G1 group than in G2 group. The level of CD8+ lymphocytes was markedly higher in the stroma and showed a clear tendency forhigher expression in the G1 group than inthe G2 group. No significant differences were observed for the level of programmed death-ligand 1+ (PD-L1+), programmed death 1+ (PD-1+), and CD68PD-L1 in the stroma, tumor and total areas. Conclusion: Our study revealed different genetic aberrations and pathways, higher neoantigen burden, and higher level of CD68+ macrophages and CD8+ T lymphocytes in lung cancer patients with COPD. Our investigation implies that the existence of COPD should be considered and immunotherapy is a potential choice when treating lung cancer patients with COPD.

Quantitative analyzes of the variability in airways via four-dimensional dynamic ventilation CT in patients with chronic obstructive pulmonary disease: correlation with spirometry data and severity of airflow limitation.

Background: In chronic obstructive pulmonary disease (COPD) patients, the diagnosis and assessment of disease severity are mainly based on spirometry, which may lead to misjudgments due to poor patient compliance. Thoracic four-dimensional dynamic ventilation computed tomography (4D-CT) provides more airway data approximating true physiological function than conventional CT. We aimed to determine dynamic changes in airways to elucidate the pathological mechanism underlying COPD and predict the severity of airflow limitation in patients. Methods: Forty-two COPD patients underwent 4D-CT and spirometry. The minimum lumen diameter changed with the breathing cycle in 4th-generation airways and was continuously measured in the apical (RB1), lateral (RB4) and posterior basal segments (RB10) of the right lung. The minimum lumen diameter in the peak inspiration and peak expiration as well as the peak expiratory/peak inspiratory ratio (E/I ratio), and dynamic coefficient of variance (CV) were calculated. Results: Correlations of FEV1% with the CV of minimum lumen diameter in RB1 (ρ=-0.473, P=0.002) and in RB10 (ρ=-0.480, P=0.005) were observed, suggesting that the dynamic variability in 4th-generation airways was associated with airflow limitation in COPD patients. The CV of the minimum lumen diameter in RB1 significantly differed between the GOLD I + II and GOLD III + IV groups {8.59 [interquartile range (IQR), 6.63-14.86] vs. 14.64 (10.65-25.88), respectively; P=0.016}, suggesting that the dynamic CV in RB1 increased significantly in the GOLD III + IV group, which had worse pulmonary ventilation function. Based on the receiver operating characteristic (ROC) curve analysis, CV-RB1 predicted FEV1% <50% with an optimal cut-off of 9.43% [sensitivity 85.7%, specificity 57.1%, area under the curve (AUC) 0.717]. Conclusions: 4D-CT might be an available method to help diagnose and evaluate the severity of COPD.

Association Between Circulating Levels of C1q/TNF-Related Protein-9 and Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

CONTEXT: According to growing research, C1q/TNF-Related Protein-9 (CTRP9) appears to be linked to type 2 diabetes mellitus (T2DM). But the literature on circulating levels of CTRP9 in patients with T2DM has been contradictory. OBJECTIVE: This is a systematic review and meta-analysis to reassess the circulating level of CTRP9 in patients with T2DM, with and without complications. METHODS: Relevant studies published until October 31, 2021, were identified from the PubMed, Embase, Web of Science, Cochrane Library, WanFang, CNKI, VIP, and CBM databases. Participants with age ≥18 years with clinically diagnosed T2DM were included. Sex and diabetes complications were not restricted. The data were extracted by 2 reviewers independently using a standard data collection form. RESULTS: Analysis demonstrated significantly lower circulating levels of CTRP9 in patients with T2DM than in patients without diabetes (standardized mean difference [SMD] = -1.36; 95% CI -1.78 to -0.93; P < .001), I2 = 97.5%, P < .001). Furthermore, the circulating level of CTRP9 in patients with T2DM-related complications was lower than that in patients with T2DM without complications, regardless of macrovascular complications or microvascular complications (SMD = -1.062; 95% CI -1.466 to -0.658; P < .001, I2 = 91.3%, P < .001). Subgroup analyses revealed that factors such as body mass index, T2DM duration, and fasting blood glucose were the sources of heterogeneity (P = .047, P = .034, and P = .07, respectively). CONCLUSION: The present systematic review and meta-analysis found CTRP9 levels were lower in T2DM patients with or without complications. However, since this was a meta-analysis of most observational studies, these findings still need to be verified by further studies with a large sample size.

Risk of reactive cutaneous capillary endothelial proliferation induced by camrelizumab in patients with non-small cell lung cancer: a retrospective study.

Background: Reactive cutaneous capillary endothelial proliferation (RCCEP) is a common immune-related adverse event (irAE) related to camrelizumab. This study aimed to investigate the risk factors of RCCEP and its association with patients' survival. Methods: This retrospective study collected the data of consecutive patients with non-small cell lung cancer (NSCLC) who received camrelizumab between January 2019 and December 2021. Baseline characteristics and peripheral blood biomarkers were collected. The outcomes were the occurrence of RCCEP and progression-free survival (PFS). The factors associated with RCCEP were analyzed using univariable and multivariable logistic regression. The association between PFS and RCCEP occurrence was analyzed by the log-rank test. Results: Among the 80 patients included, 24 (30.0%) developed RCCEP, and 56 did not. Among the patients with RCCEP, only four reported the occurrence of grade 3-4 RCCEP. The multivariable analysis revealed that a percentage of eosinophil (EOS%) >1.75% was significantly associated with a higher risk of RCCEP [odds ratio (OR) =4.484; 95% confidence interval (CI): 1.139-17.651] and camrelizumab combined with an anti-angiogenic agent was significantly associated with a lower risk of RCCEP (OR =0.188; 95% CI: 0.055-0.639). The median PFS was numerically longer in patients with RCCEP than in those who did not (17 vs. 9 months, P=0.069). Patients who had baseline EOS% >1.75% and received camrelizumab without an anti-angiogenic agent had a longer median PFS than those who did not (17 vs. 9 months, P=0.011). Conclusions: Baseline EOS% >1.75% and camrelizumab without an anti-angiogenic agent were risk factors of RCCEP and might be associated with better survival in patients with NSCLC.

Functional recovery after intravitreal bevacizumab treatments for idiopathic choroidal neovascularization in young adults.

PURPOSE: To evaluate the morphology and functional recovery of the retina after treatment of idiopathic choroidal neovascularization using intravitreal injections of bevacizumab in young adults. METHODS: For this interventional case series, 20 eyes of 19 patients with idiopathic choroidal neovascularization were treated with multiple intravitreal injections of bevacizumab. Changes in best-corrected visual acuity before the treatment and at follow-up visits were recorded. Structural changes were evaluated using optical coherence tomography and functional changes were assessed using microperimetry. RESULTS: Twenty eyes were followed for 12 months after their first injection. The eyes underwent an average of 3.95 injections. All eyes had a stable or an improved vision. The mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.43 to 0.06 (Wilcoxon signed-ranks test, P < 0.005). Improvement in macular function was detected as early as 1 month after the treatment and lasted for at least 6 months. Microperimetry demonstrated that mean retinal sensitivities within the central 10° field (10.29 ± 5.12 dB) at baseline improved to 13.98 ± 3.96 dB at the last visit. Dense scotomas were found in 13 of the 20 eyes at baseline and 5 of the 20 eyes at the last visit. Stable fixation (6 of 20 at baseline) was found in 17 of the 20 eyes at the last visit. Twelve of the 14 eyes with either a predominantly eccentric or poor central fixation at baseline established central fixation at 12 months. No serious local or systemic complications were encountered. CONCLUSION: In young adults with idiopathic choroidal neovascularization, an improvement in visual acuity and macular function was detected after intravitreal injections of bevacizumab.

Variations in leaf and stem traits across two elevations in subtropical forests.

Understanding the variations in plant traits across elevations may provide valuable insights into the species structure and function of forests and their responses to climate change. To explore the patterns of trait variation across elevations, we analysed 14 leaf and stem traits associated with resource acquisition and stress tolerance in Schima superba Gardner & Champion, Castanopsis chinensis (Sprengel) Hance, and Pinus massoniana Lambert trees at two elevations in a subtropical forest in southern China. Wood density increased, whereas crown width, leaf water potential at 0700 hours (Ψ L-0700 ), and leaf δ 18 O decreased in high-elevation plants. Vessel diameter, daily maximum sap flux density, leaf δ 13 C, and leaf C and N concentrations per unit mass were comparable across elevations. We found species-specific variations in specific leaf area, midday leaf water potential, and leaf P concentration across elevations. Decreasing crown width with increasing elevation was associated with decreasing leaf δ 18 O and Ψ L-0700 , suggesting that higher stomatal conductance may moderate the loss of carbon assimilation. We elucidated the adaptive strategies of plants in response to environmental change, and showed that physiological traits varied in coordination with structural traits. Future studies incorporating multi-dimensional trait analyses can improve our understanding of the responses of forest ecosystems to climate change and global warming.

Use of GLP-1 Receptor Agonists and Occurrence of Thyroid Disorders: a Meta-Analysis of Randomized Controlled Trials.

The association between glucagon-like peptide-1 (GLP-1) receptor agonists and the risk of various kinds of thyroid disorders remains uncertain. We aimed to evaluate the relationship between the use of GLP-1 receptor agonists and the occurrence of 6 kinds of thyroid disorders. We searched PubMed (MEDLINE), EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science from database inception to 31 October 2021 to identify eligible randomized controlled trials (RCTs). We performed meta-analysis using a random-effects model to calculate risk ratios (RRs) and 95% confidence intervals (CIs). A total of 45 trials were included in the meta-analysis. Compared with placebo or other interventions, GLP-1 receptor agonists' use showed an association with an increased risk of overall thyroid disorders (RR 1.28, 95% CI 1.03-1.60). However, GLP-1 receptor agonists had no significant effects on the occurrence of thyroid cancer (RR 1.30, 95% CI 0.86-1.97), hyperthyroidism (RR 1.19, 95% CI 0.61-2.35), hypothyroidism (RR 1.22, 95% CI 0.80-1.87), thyroiditis (RR 1.83, 95% CI 0.51-6.57), thyroid mass (RR 1.17, 95% CI 0.43-3.20), and goiter (RR 1.17, 95% CI 0.74-1.86). Subgroup analyses and meta-regression analyses showed that underlying diseases, type of control, and trial durations were not related to the effect of GLP-1 receptor agonists on overall thyroid disorders (all P subgroup > 0.05). In conclusion, GLP-1 receptor agonists did not increase or decrease the risk of thyroid cancer, hyperthyroidism, hypothyroidism, thyroiditis, thyroid mass and goiter. However, due to the low incidence of these diseases, these findings need to be examined further. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/prospero/, identifier: CRD42021289121.

A new handheld fundus camera combined with visual artificial intelligence facilitates diabetic retinopathy screening.

AIM: To explore the performance in diabetic retinopathy (DR) screening of artificial intelligence (AI) system by evaluating the image quality of a handheld Optomed Aurora fundus camera in comparison to traditional tabletop fundus cameras and the diagnostic accuracy of DR of the two modalities. METHODS: Overall, 630 eyes were included from three centers and screened by a handheld camera (Aurora, Optomed, Oulu, Finland) and a table-top camera. Image quality was graded by three masked and experienced ophthalmologists. The diagnostic accuracy of the handheld camera and AI system was evaluated in assessing DR lesions and referable DR. RESULTS: Under nonmydriasis status, the handheld fundus camera had better image quality in centration, clarity, and visible range (1.47, 1.48, and 1.40) than conventional tabletop cameras (1.30, 1.28, and 1.18; P<0.001). Detection of retinal hemorrhage, hard exudation, and macular edema were comparable between the two modalities, in principle, with the area under the curve of the handheld fundus camera slightly lower. The sensitivity and specificity for the detection of referable DR with the handheld camera were 82.1% (95%CI: 72.1%-92.2%) and 97.4% (95%CI: 95.4%-99.5%), respectively. The performance of AI detection of DR using the Phoebus Algorithm was satisfactory; however, Phoebus showed a high sensitivity (88.2%, 95%CI: 79.4%-97.1%) and low specificity (40.7%, 95%CI: 34.1%-47.2%) when detecting referable DR. CONCLUSION: The handheld Aurora fundus camera combined with autonomous AI system is well-suited in DR screening without mydriasis because of its high sensitivity of DR detection as well as its image quality, but its specificity needs to be improved with better modeling of the data. Use of this new system is safe and effective in the detection of referable DR in real world practice.