Effect of corneal diameter on preoperative screening results for corneal refractive surgery.

AIMS: To investigate the impact of different corneal diameters on corneal morphology and biomechanical outcome during preoperative screening for corneal refractive surgery. METHODS: A retrospective analysis was conducted on 300 patients who underwent corneal refractive surgery at Eye and ENT Hospital, Fudan University between October 2023 and December 2023. All patients had no history of keratoconus or previous corneal surgery. Patients were categorized into two groups based on corneal topography measurements: (1) normal corneal diameter group (n=159), those with corneal diameter ranging from 11.5 mm to 12.0 mm; (2) abnormal corneal diameter group (n=141), those with corneal diameter smaller than 10.0 mm or larger than 12.5 mm. Corneal thickness, morphologic data, and biomechanical data were measured using Pentacam corneal topography. Correlation analysis was conducted to explore the relationship between corneal diameter and various corneal topography and biomechanical data. RESULTS: Significant differences were observed in corneal topography data including BFSf (F=43.21), BFSb (F=30.24), Df (F=15.32), Dp (F=32.36), Da (F=9.66), D (F=58.36), PPIavg (F=32.64), and ARTmax (F=12.06) between the groups (P<0.05). Additionally, BFSf, BFSb, Db, Dp, D, and PPIavg exhibited statistically significant differences between any two groups (P<0.05). Significant differences were also found in Df, Da, and ARTmax between small and large corneas, as well as between normal-sized and large corneas (P<0.05). Correlation analysis indicated negative correlations between corneal diameter and A1V (r=-0.12), HCdArcLength (r=-0.17), CBI (r=-0.27), bIOP (r=-0.13), Df (r=-0.025), PPIavg (r=-0.028), and TBI (r=-0.27). Conversely, BFSf (r=0.009), BFSb (r=0.001), PD (r=0.15), and ARTH (r=0.37) displayed positive correlations with corneal diameter. CONCLUSIONS: Corneal diameter significantly affects preoperative screening for corneal refractive surgery. Smaller corneal diameters exhibit a greater influence on the corneal topography BAD analysis system.

Trends in utilization patterns of newer glucose-lowering drugs in US adults with type 2 diabetes and a history of coronary heart disease or heart failure: 2005-2019.

BACKGROUND: The newer glucose-lowering drugs (GLDs), including Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), have demonstrated superior cardio- and renal protective benefits compared to older GLDs in individuals with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). OBJECTIVE: This study examined the trends of the newer GLDs use in people with T2D who had a history of coronary heart disease or heart failure in the United States. METHOD: We used 2005-2019 data from the Medical Expenditure Panel Survey (MEPS). Individuals with self-reported diabetes and CVD history were identified. RESULTS: There was a steady increase in the use of GLP-1RA only from 2008 (3 %) to 2019 (21 %) and SGLT2i only from 2014 (5 %) to 2019 (12 %). Individuals with dual use of both newer GLD classes increased from 0.62 % in 2015 to 6 % in 2019. The overall uptake of these two newer drugs in 2019 was less than 40 %. In other words, 60 % of individuals who can substantially benefit from these newer treatments did not use the treatments. CONCLUSION: The use of GLP-1RA and SGLT2i among individuals with T2D and a history of CVD was low and varied by insurance type. Policy-level interventions are needed to improve the use of these newer treatments further. SUMMARY: We examined how newer glucose-lowering drugs are used among individuals with type 2 diabetes and at high risk for coronary heart disease or heart failure in the US. We found that 60 % of individuals who can substantially benefit from these newer treatments did not use the treatments due to the variation of insurance type.

KDM1A, a potent and selective target, for the treatment of DNMT3A-deficient non-small cell lung cancer.

BACKGROUND: DNMT3A is a crucial epigenetic regulation enzyme. However, due to its heterogeneous nature and frequent mutation in various cancers, the role of DNMT3A remains controversial. Here, we determine the role of DNMT3A in non-small cell lung cancer (NSCLC) to identify potential treatment strategies. METHODS: To investigate the role of loss-of-function mutations of DNMT3A in NSCLC, CRISPR/Cas9 was used to induce DNMT3A-inactivating mutations. Epigenetic inhibitor library was screened to find the synthetic lethal partner of DNMT3A. Both pharmacological inhibitors and gene manipulation were used to evaluate the synthetic lethal efficacy of DNMT3A/KDM1A in vitro and in vivo. Lastly, MS-PCR, ChIP-qPCR, dual luciferase reporter gene assay and clinical sample analysis were applied to elucidate the regulation mechanism of synthetic lethal interaction. RESULTS: We identified DNMT3A is a tumour suppressor gene in NSCLC and KDM1A as a synthetic lethal partner of DNMT3A deletion. Both chemical KDM1A inhibitors and gene manipulation can selectively reduce the viability of DNMT3A-KO cells through inducing cell apoptosis in vitro and in vivo. We clarified that the synthetic lethality is not only limited to the death mode, but also involved into tumour metastasis. Mechanistically, DNMT3A deficiency induces KDM1A upregulation through reducing the methylation status of the KDM1A promoter and analysis of clinical samples indicated that DNMT3A expression was negatively correlated with KDM1A level. CONCLUSION: Our results provide new insight into the role of DNMT3A in NSCLC and elucidate the mechanism of synthetic lethal interaction between KDM1A and DNMT3A, which might represent a promising approach for treating patients with DNMT3A-deficient tumours.

Glucagon-Like Peptide-1 Receptor Agonists and Risk for Suicidal Ideation and Behaviors in U.S. Older Adults With Type 2 Diabetes : A Target Trial Emulation Study.

BACKGROUND: A major concern has recently emerged about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and increased risk for suicidal ideation and behaviors based on International Classification of Diseases codes. OBJECTIVE: To investigate the association between GLP-1 RAs, compared with sodium-glucose cotransporter-2 inhibitors (SGLT2is) or dipeptidyl peptidase-4 inhibitors (DPP4is), and risk for suicidal ideation and behaviors in older adults with type 2 diabetes (T2D). DESIGN: Two target trial emulation studies comparing propensity score (PS)-matched cohorts for GLP-1 RAs versus SGLT2is and GLP-1 RAs versus DPP4is. SETTING: U.S. national Medicare administrative data from January 2017 to December 2020. PATIENTS: Older adults (≥66 years) with T2D; no record of suicidal ideation or behaviors; and a first prescription for a GLP-1 RA, SGLT2i, or DPP4i. MEASUREMENTS: The primary end point was a composite of suicidal ideation and behaviors. New GLP-1 RA users were matched 1:1 on PS to new users of an SGLT2i or DPP4i in each pairwise comparison. A Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% CIs within matched groups. RESULTS: This study included 21 807 pairs of patients treated with a GLP-1 RA versus an SGLT2i and 21 402 pairs of patients treated with a GLP-1 RA versus a DPP4i. The HR of suicidal ideation and behaviors associated with GLP-1 RAs relative to SGLT2is was 1.07 (95% CI, 0.80 to 1.45; rate difference, 0.16 [CI, -0.53 to 0.86] per 1000 person-years); the HR relative to DPP4is was 0.94 (CI, 0.71 to 1.24; rate difference, -0.18 [CI, -0.92 to 0.57] per 1000 person-years). LIMITATIONS: Low event rate; imprecise estimates; unmeasured confounders, such as body mass index; and potential misclassification of outcomes. CONCLUSION: Among Medicare beneficiaries with T2D, this study found no clear increased risk for suicidal ideation and behaviors with GLP-1 RAs, although estimates were imprecise and a modest adverse risk could not be ruled out. PRIMARY FUNDING SOURCE: American Foundation for Pharmaceutical Education, Pharmaceutical Research and Manufacturers of America Foundation, National Institute on Aging, and National Institute of Diabetes and Digestive and Kidney Diseases.

Clinical Predictors of Cisplatin Chemoradiation-Induced Ototoxicity in HPV-Positive Oropharyngeal Squamous Cell Carcinoma: A Case-Control Study.

BACKGROUND: Cisplatin-based chemoradiation is a standard treatment for many patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), an etiologically distinct subset of head and neck cancer. Although associated with good long-term survival, clinical risk factors for ototoxicity have been understudied in this population. This study aimed to evaluate clinical predictors associated with ototoxicity in HPV-positive OPSCC patients treated with cisplatin chemoradiation. METHODS: This retrospective case-control study included 201 adult patients (>18 years) with histologically confirmed HPV-positive OPSCC who received cisplatin chemoradiation as their primary treatment from 2001 and 2019 at a single tertiary cancer center. Ototoxicity was determined using baseline and follow-up audiometry and the Common Terminology Criteria for Adverse Events v5.0 grading criteria (Grade ≥2). Multivariable logistic regression [adjusted odds ratio (aOR)] identified significant predictors that increased the odds of ototoxicity. RESULTS: A total of 201 patients [165 males; median (IQR) age, 57 (11) years] were included in the study. The incidence of ototoxicity in the worst ear was 56.2%, with the greatest hearing loss occurring at high frequencies (4-8 kHz), resulting in a loss of 12.5 dB at 4 to 6 kHz and 20 dB at 6 to 8 kHz. High-dose cisplatin administration compared to weekly administration [aOR 4.93 (95% CI: 1.84-14.99), P = .003], a higher mean cochlear radiation dose [aOR 1.58 (95% CI: 1.12-2.30), P = .01], smoking history [aOR 2.89 (95% CI: 1.51-5.63), P = .001], and a 10 year increase in age [aOR 2.07 (95% CI: 1.25-3.52), P = .006] were each independently associated with increased odds of ototoxicity. CONCLUSIONS: Clinical predictors of ototoxicity in HPV-positive OPSCC patients treated with cisplatin-based chemoradiation include the use of a high-dose cisplatin regimen, higher cochlear radiation doses, a history of smoking, and older age. With the rising incidence of this malignancy in Western countries and overall improved survivorship, our research motivates future studies into risk stratification and earlier interventions to mitigate and reduce the risk of ototoxicity.

Development and validation of a predictive model for postpartum endometritis.

OBJECTIVE: The aim was to develop a predictive tool for anticipating postpartum endometritis occurrences and to devise strategies for prevention and control. METHODS: Employing a retrospective approach, the baseline data of 200 women diagnosed with postpartum endometritis in a tertiary maternity hospital in Zhejiang Province, spanning from February 2020 to September 2022, was examined. Simultaneously, the baseline data of 1,000 women without endometritis during the same period were explored with a 1:5 ratio. Subsequently, 1,200 women were randomly allocated into a training group dataset and a test group dataset, adhering to a 7:3 split. The selection of risk factors for postpartum endometritis involved employing random forests, lasso regression, and traditional univariate and multifactor logistic regression on the training group dataset. A nomogram was then constructed based on these factors. The model's performance was assessed using the area under the curve (AUC), calculated through plotting the receiver operating characteristic (ROC) curve. Additionally, the Brier score was employed to evaluate the model with a calibration curve. To gauge the utility of the nomogram, a clinical impact curve (CIC) analysis was conducted. This comprehensive approach not only involved identifying risk factors but also included a visual representation (nomogram) and thorough evaluation metrics, ensuring a robust tool for predicting, preventing, and controlling postpartum endometritis. RESULTS: In the multivariate analysis, six factors were identified as being associated with the occurrence of maternal endometritis in the postpartum period. These factors include the number of negative finger tests (OR: 1.159; 95%CI: 1.091-1.233; P < 0.05), postpartum hemorrhage (1.003; 1.002-1.005; P < 0.05), pre-eclampsia (9.769; 4.64-21.155; P < 0.05), maternity methods (2.083; 1.187-3.7; P < 0.001), prenatal reproductive tract culture (2.219; 1.411-3.47; P < 0.05), and uterine exploration (0.441; 0.233-0.803; P < 0.001).A nomogram was then constructed based on these factors, and its predictive performance was assessed using the area under the curve (AUC). The results in both the training group data (AUC: 0.803) and the test group data (AUC: 0.788) demonstrated a good predictive value. The clinical impact curve (CIC) further highlighted the clinical utility of the nomogram. CONCLUSION: The development of an individualized nomogram for postpartum endometritis infection holds promise for doctors in screening high-risk women, enabling early intervention and ultimately reducing the rate of postpartum endometritis infection. This comprehensive approach, integrating key risk factors and predictive tools, enhances the potential for timely and targeted medical intervention.

Renal function as an effect modifier of intensive glucose control in delaying cognitive function decline among individuals with type 2 diabetes: A revisit to the ACCORD MIND trial.

AIM: Dysglycaemia accelerates cognitive decline. Intensive glucose control may help delay or prevent cognitive function decline (CFD). We aimed to determine how patient characteristics influence the effect of intensive glucose control [glycated haemoglobin (HbA1c) <6.0%] on delaying CFD in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this post-hoc analysis of 2977 type 2 diabetes participants from the ACCORD MIND trial, we applied the causal forest and causal tree algorithms to identify the effect modifier of intensive glucose control in delaying CFD from 68 variables (demographics, disease history, medications, vitals and baseline biomarkers). The exposure was intensive versus standard glucose control (HbA1c <6.0% vs. 7.0%-7.9%). The main outcome was cognitive function changes from baseline to the 40th month follow-up, which were evaluated using the digit symbol substitution test, Rey auditory verbal learning test, mini-mental state examination and Stroop test. We used Cohen's d, a measure of standardized difference, to quantify the effect size of intensive glucose control on delaying CFD. RESULTS: Among all the baseline characteristics, renal function was the most significant effect modifier. Participants with urinary albumin levels <0.4 mg/dl [absolute function change (AFC): 0.51 in mini-mental state examination, 95% confidence interval (CI): 0.04, 0.98, Cohen's d: 0.25] had slower CFD with intensive glucose control. Patients with preserved renal function (estimated glomerular filtration rate between 60 and 90 ml/min/1.73 m2) were associated with small benefits (AFC: 1.28 in Stroop, 95% CI: 0.28, 2.27, Cohen's d: 0.12) when undergoing intensive glucose control. Conversely, participants with an estimated glomerular filtration rate <60 ml/min/1.73 m2 (AFC: -0.57 in the Rey auditory verbal learning test, 95% CI: -1.09, -0.05, Cohen's d: -0.30) exhibited faster CFD when undergoing intensive glucose control. Participants who were <60 years old showed a significant benefit from intensive glucose control in delaying CFD (AFC: 1.08 in the digit symbol substitution test, 95% CI: 0.06, 2.10, Cohen's d: 0.13). All p < .05. CONCLUSIONS: Our findings linked renal function with the benefits of intensive glucose control in delaying CFD, informing personalized HbA1c goals for those with diabetes and at risk of CFD.

High expression of circulating exosomal PD-L1 contributes to immune escape of hepatocellular carcinoma and immune clearance of chronic hepatitis B.

OBJECTIVE: To investigate the expression of programmed death ligand-1 (PD-L1) in circulating exosomes, and to define the role of exosomal PD-L1 in promoting immune escape mechanism during chronic hepatitis B infection (CHB) and related liver diseases. METHODS: The levels of PD-L1 expressed in exosomes were detected by ELISA. CD8+T cells were sorted and cytotoxicity test was assessed by flow cytometry. PD-L1 protein expression in hepatocellular carcinoma (HCC) and normal adjacent tissues were detected by immunohistochemistry. RESULTS: Circulating exosomal PD-L1 levels were significantly higher in patients with CHB and HCC than in healthy controls (F =7.46, P=0.001). Levels of CD107a on CD8+T cells in patients with CHB receiving PD-L1 blocking antibody were significantly lower than in patients receiving isotype blocking antibody (t = 4.96, P < 0.01). Levels of TNF-α in cell culture supernatants of the PD-L1 blocking antibody group were significantly higher than in the isotype blocking antibody group (t =5.92, P < 0.01). Compared with patients receiving isotype blocking antibody, levels of CD107a on CD8+T cells significantly increased in patients with HCC receiving anti-PD-L1 antibody (t = 3.51, P<0.05). Compared with adjacent tissues, the levels of PD-L1 protein expression in HCC tissues were slightly higher; however, no significant difference between the two groups was observed. CONCLUSIONS: PD-L1 blockade in exosomes might promote the cytotoxic function of CD8+T cells and inhibit immune evasion during progression of HCC. Blocking PD-L1 in exosomes reduced the cytotoxic function of CD8+T cells in patients with CHB while enhancing the production of proinflammatory cytokines.

Identification and Functional Characterization of Carboxylesterase Genes Involved in Spirodiclofen Resistance in Panonychus citri (McGregor).

Overexpression of carboxyl/cholinesterase (CCE) genes has been reported to be associated with many cases of pesticide resistance in arthropods. However, it has been rarely documented that CCE genes participate in spirodiclofen resistance in Panonychus citri. In previous research, we found that spirodiclofen resistance is related to increased P450 and CCE enzyme activities in P. citri. In this study, we identified two CCE genes, PcCCE3 and PcCCE5, which were significantly upregulated in spirodiclofen-resistant strain and after exposure to spirodiclofen. RNA interference of PcCCE3 and PcCCE5 increased the spirodiclofen susceptibility in P. citri. In vitro metabolism indicated that PcCCE3 and PcCCE5 could interact with spirodiclofen, but metabolites were detected only in the PcCCE3 treatment. Our results indicated that PcCCE3 participates in spirodiclofen resistance through direct metabolism, and PcCCE5 may be involved in the spirodiclofen resistance by passive binding and sequestration, which provides new insights into spirodiclofen resistance in P. citri.

A 52-week follow-up, multi-center, randomized, double-blinded comparison of efficacy and safety of two hyaluronic acid fillers for the treatment of moderate-to-severe nasolabial folds in Chinese population.

INTRODUCTION: To investigate the efficacy and safety of Cutegel® MAX (Cutegel) in the correction of moderate-to-severe nasolabial folds (NLFS) compared to Restylane® (Restylane, control). METHODS: This study was a 52-week, multicenter, randomized, double-blinded, active-controlled clinical trial. Qualified participants with moderate-to-severe NLFs were randomly assigned in a 1:1 ratio to receive Cutegel or Restylane. For the primary efficacy endpoint, the response rate was defined as the percentage of subjects exhibiting an improvement of at least one-point based on blinded evaluation of Wrinkle Severity Rating Scale (WSRS) at 24 weeks after injection. Other secondary efficacy endpoints and treatment-emergent adverse events (TEAEs) were assessed. RESULTS: Of 340 subjects randomized, 317 completed the week 52 visit. In the per protocol set (PPS), the blinded evaluator-assessed response rates at week 24 were 81.17% for Cutegel versus 77.56% for Restylane (p = 0.327). The between-group treatment differences in response rates were 3.60% [95% confidence interval (CI) = (-5.39%, 12.60%)], which demonstrated the noninferiority of Cutegel. Other secondary efficacy endpoints supported this. No significant differences were observed in the occurrence of adverse events between the two groups. CONCLUSION: Similar to Restylane, Cutegel was effective and well tolerated in correcting moderate-to-severe NLFs among the Chinese population.

Nasolabial folds (NLFs) are among the early indicators of facial aging process. In the past, rhytidectomy has been considered a safe procedure, yet it continues to carry risks such as hematoma, skin necrosis, nerve injury, and infection. With the ongoing development of biomaterials including hyaluronic acid (HA), minimally invasive injection procedures for the aesthetic correction of NLFs have become the preferred choice in recent years. The widespread use of HA has resulted in the development of various types of commercial HA fillers, such as Cutegel and Restylane. It is well known that HA filler products produce varying effects, attributable to differences in their components and physical properties. Previous studies have established that Restylane is a safe and effective HA dermal filler for the correction of NLFs. However, there is a lack of studies on both the cosmetic results and safety data for Cutegel in the published literature. Therefore, a randomized, double-blinded, active-controlled clinical trial was conducted at seven Chinese hospitals to evaluate the efficacy and safety of Cutegel for the correction of moderate-to-severe NLFs, compared to the approved Restylane in China. Among the 340 randomized subjects, 170 subjects received Cutegel, and 169 subjects received Restylane. Both groups reported similar improvements in WSRS (the between-group treatment differences in response rates exceeded the prespecified noninferiority margins), and also in other efficacy evaluations. Additionally, the two treatment groups showed similar safety profiles. In summary, Cutegel proved to be well tolerated and effective in this randomized, active-controlled clinical study, demonstrating its noninferiority to Restylane and validating its use as an alternative treatment for Chinese subjects with moderate-to-severe NLFs.

Nanoscale Surface and Bulk Electronic Properties of Ti3C2Tx MXene Unraveled by Multimodal X-Ray Spectromicroscopy.

2D layered materials, such as transition metal carbides or nitrides, known as MXenes, offer an ideal platform to investigate charge transfer processes in confined environment, relevant for energy conversion and storage applications. Their rich surface chemistry plays an essential role in the pseudocapacitive behavior of MXenes. However, the local distribution of surface functional groups over single flakes and within few- or multilayered flakes remains unclear. In this work, scanning X-ray microscopy (SXM) is introduced with simultaneous transmission and electron yield detection, enabling multimodal nanoscale chemical imaging with bulk and surface sensitivity, respectively, of individual MXene flakes. The Ti chemical bonding environment is found to significantly vary between few-layered hydrofluoric acid-etched Ti3C2Tx MXenes and multilayered molten salt (MS)-etched Ti3C2Tx MXenes. Postmortem analysis of MS-etched Ti3C2Tx electrodes cycled in a Li-ion battery further illustrates that simultaneous bulk and surface chemical imaging using SXM offers a method well adapted to the characterization of the electrode-electrolyte interactions at the nanoscale.

Radiology-Pathology Concordance and Prognostication of Nodal Features in pN+ Oral Cavity Cancer.

BACKGROUND AND PURPOSE: The aims of our study are to evaluate the diagnostic performance and prognostic value of radiological lymph node (LN) characteristics in pN+ oral cavity squamous carcinoma (OSCC). MATERIALS AND METHODS: pN+ OSCC treated between 2012 and 2020 were included. Preoperative imaging was reviewed by a single radiologist blinded to pathologic findings for the following nodal features: imaging-positive LN (iN+), laterality and total number, and image-identified extranodal extension (iENE). The sensitivity of iN+ for pN+ was calculated. The diagnostic performance of other nodal features was evaluated in the iN+ subgroup. The association of radiologic nodal features with overall survival (OS) was evaluated. Inter-rater kappa for radiologic nodal features was assessed in 100 randomly selected cases. RESULTS: Of 406 pN+ OSCC, 288 were iN+. The sensitivity of iN+ for pN+ was 71% overall, and improved to 89% for pN+ LN >1.5 cm. Within iN+, sensitivity/specificity for LN size (>3 cm), total LN number (>4), and ENE were 0.44/0.95, 0.57/0.84, and 0.27/0.96, respectively. Sensitivity of iENE was higher in the subset, with major (>2 mm) versus minor (≤2 mm) pENE (43% vs. 13%, p = 0.001). Reduced OS was observed in iN+ versus iN- (p = 0.006), iENE+ versus iENE- (p = 0.004), LN size >3 versus ≤3 cm (p < 0.001), and higher LN number (p < 0.001). Inter-rater kappa for iN+, laterality, total LN number, and presence of iENE were 0.71, 0.57, 0.78, and 0.69, respectively. CONCLUSION: Our study shows that despite modest sensitivity of most radiological nodal features, the specificity of image-identified nodal features is high and their prognostic values are retained in pN+ OSCC. LEVEL OF EVIDENCE: Level 3 (retrospective review comparing cases and controls) Laryngoscope, 2024.

Standardised definitions and diagnostic criteria for extranodal extension detected on histopathological examination in head and neck cancer: Head and Neck Cancer International Group consensus recommendations.

Detection of extranodal extension on histopathology in surgically treated head and neck squamous cell carcinoma indicates poor prognosis. However, there is no consensus on the diagnostic criteria, interpretation, and reporting of histology detected extranodal extension, which has contributed to conflicting evidence in the literature, and likely clinical inconsistency. The Head and Neck Cancer International Group conducted a three-round modified Delphi process with a group of 19 international pathology experts representing 15 national clinical research groups to generate consensus recommendations for histology detected extranodal extension diagnostic criteria. The expert panel strongly agreed on terminology and diagnostic features for histology detected extranodal extension and soft tissue metastasis. Moreover, the panel reached consensus on reporting of histology detected extranodal extension and on nodal sampling. These consensus recommendations, endorsed by 19 organisations representing 34 countries, are a crucial development towards standardised diagnosis and reporting of histology detected extranodal extension, and more accurate data collection and analysis.

Criteria for the diagnosis of extranodal extension detected on radiological imaging in head and neck cancer: Head and Neck Cancer International Group consensus recommendations.

Extranodal extension of tumour on histopathology is known to be a negative prognostic factor in head and neck cancer. Compelling evidence suggests that extranodal extension detected on radiological imaging is also a negative prognostic factor. Furthermore, if imaging detected extranodal extension could be identified reliably before the start of treatment, it could be used to guide treatment selection, as patients might be better managed with non-surgical approaches to avoid the toxicity and cost of trimodality therapy (surgery, chemotherapy, and radiotherapy together). There are many aspects of imaging detected extranodal extension that remain unresolved or are without consensus, such as the criteria to best diagnose them and the associated terminology. The Head and Neck Cancer International Group conducted a five-round modified Delphi process with a group of 18 international radiology experts, representing 14 national clinical research groups. We generated consensus recommendations on the terminology and diagnostic criteria for imaging detected extranodal extension to harmonise clinical practice and research. These recommendations have been endorsed by 19 national and international organisations, representing 34 countries. We propose a new classification system to aid diagnosis, which was supported by most of the participating experts over existing systems, and which will require validation in the future. Additionally, we have created an online educational resource for grading imaging detected extranodal extensions.

Bacterial Symbionts Contribute to Insecticide Susceptibility of Diaphorina citri via Changing the Expression Level of Host Detoxifying Genes.

Insecticide susceptibility is mainly determined by the insect host, but symbiotic bacteria are also an important affecting factor. In this study, we investigate the relationship between the structure of gut bacterial symbionts and insecticide susceptibility in Diaphorina citri, the important carrier of Candidatus Liberibacter asiaticus (CLas), the causal agent of Huanglongbing (HLB). Our results indicated that antibiotic treatment significantly increased the susceptibility of D. citri to bifenthrin and thiamethoxam, and significantly decreased the relative abundance of Wolbachia and Profftella, enzyme activities of CarEs, and expression level of multiple CarE genes. The relative loads of Wolbachia and Profftella were positively correlated with DcitCCE13, DcitCCE14, DcitCCE15, and DcitCCE16. RNAi and prokaryotic expression revealed that DcitCCE15 is associated with bifenthrin metabolism. These results revealed that bacterial symbionts might regulate DcitCCE15 expression, which is involved in the susceptibility of D. citri to bifenthrin.

Natural Prenylflavonoids from Sophora flavescens Root Bark against Multidrug-Resistant Methicillin-Sensitive Staphylococcus aureus Targeting the Membrane Permeability.

The overuse of antibiotics in animal farming and aquaculture has led to multidrug-resistant methicillin-sensitive Staphylococcus aureus (MR-MSSA) becoming a common pathogen in foodborne diseases. Sophora flavescens Ait. serves as a traditional plant antibacterial agent and functional food ingredient. A total of 30 compounds (1-30) were isolated from the root bark of S. flavescens, consisting of 20 new compounds (1-20). In the biological activity assay, compound 1 demonstrated a remarkable inhibitory effect on MR-MSSA, with an MIC of 2 µg/mL. Furthermore, 1 was found to rapidly eliminate bacteria, inhibit biofilm growth, and exhibit exceptionally low cytotoxicity. Mechanistic studies have revealed that 1 possesses an enhanced membrane-targeting ability, binding to the bacterial cell membrane components phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and cardiolipin (CL). This disruption of bacterial cell membrane integrity increases intracellular reactive oxygen species, protein and DNA leakage, reduced bacterial metabolism, and ultimately bacterial death. In summary, these findings suggest that compound 1 holds promise as a lead compound against MR-MSSA.

The Development of Visible-Light Organic Photocatalysts for Atom Transfer Radical Polymerization via Conjugation Extension.

This work aimed to develop organic photocatalysts (PCs) that could mediate organocatalytic atom transfer radical polymerization (O-ATRP) under visible light. Through the core-modification of known chromophoric structures and ring-locking to reach a conjugation extension, annulated N-aryl benzo[kl]acridines were identified as effective visible light-responsive photocatalysts. The corresponding selenium-doped structure showed excellent performance in the O-ATRP of methacrylates, which could afford polymer products with controlled molecular weights and low dispersities under the irradiation of visible light at a 100 ppm catalyst loading.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.