A bibliometric analysis based on hotspots and frontier trends of positron emission tomography/computed tomography utility in bone and soft tissue sarcoma.

Purpose: This study aimed to analyze articles on the diagnosis and treatment of bone and soft tissue sarcoma using positron emission tomography (PET)/computed tomography (CT) published in the last 13 years. The objective was to conduct a bibliometric analysis and identify the research hotspots and emerging trends. Methods: Web of Science was used to search for articles on PET/CT diagnosis and treatment of bone and soft tissue sarcoma published from January 2010 to June 2023. CiteSpace was utilized to import data for bibliometric analysis. Results: In total, 425 relevant publications were identified. Publications have maintained a relatively stable growth rate for the past 13 years. The USA has the highest number of published articles (139) and the highest centrality (0.35). The UDICE-French Research Universities group is the most influential institution. BYUN BH is a prominent contributor to this field. The Journal of Clinical Oncology has the highest impact factor in the field. Conclusion: The clinical application of PET/CT is currently a research hotspot. Upcoming areas of study concentrate on the merging of PET/CT with advanced machine learning and/or alternative imaging methods, novel imaging substances, and the fusion of diagnosis and therapy. The use of PET/CT has progressively become a crucial element in the identification and management of sarcomas. To confirm its efficacy, there is a need for extensive, multicenter, prospective studies.

Catalyst and base-free, direct oxidation of chitin to lactic acid with hydrogen peroxide.

In recent years, the research on the conversion of chitin to high value-added chemicals has attracted more and more attention. At present, the method of preparing lactic acid from chitin mostly uses strong base or catalyst. The reaction system under alkaline condition not only corrodes the container but also easily harms the human body. Herein, a simple and effective method to convert chitin to organic acids in catalyst and base-free conditions is developed. The use of H2O2 only can efficiently convert chitin to organic acids in the absence of bases and catalysts. Under the optimal conditions of 30 mg chitin, 2.1 mL water, 0.9 mL H2O2 at 230 °C for 1.5 h, the lactic acid yield of chitin can reach 58.2 % and the total organic acid yield can reach 84.0 %. This work provides an efficient method for the resource utilization of chitin biomass.

Dietary patterns in the progression of metabolic dysfunction-associated fatty liver disease to advanced liver disease: a prospective cohort study.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant health problem. Dietary intervention plays an important role in patients with MAFLD. OBJECTIVE: We aimed to provide a reference for dietary patterns in patients with MAFLD. METHODS: The presence of MAFLD was determined in the UK Biobank cohort. Nine dietary pattern scores were derived from the dietary records. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). The contrast test was employed to calculate the heterogeneity across MAFLD statuses. RESULTS: We identified 175,300 patients with MAFLD at baseline. Compared with non-MAFLD, MAFLD was significantly associated with chronic liver disease (CLD) (HR: 3.48, 95% CI: 3.15-3.84), severe liver disease (SLD) (HR: 2.87, 95% CI: 2.63-3.14), liver cancer (HR: 1.93, 95% CI: 1.67-2.23), and liver-related death (LRD) (HR: 1.93, 95% CI: 1.67-2.23). In the overall cohort, the alternate Mediterranean diet (aMED) (HRCLD: 0.53, 95% CI: 0.37-0.76; HRSLD: 0.52, 95% CI: 0.37-0.72), Planetary Health Diet (PHD) (HRCLD: 0.62, 95% CI: 0.47-0.81; HRSLD: 0.65, 95% CI: 0.51-0.83) , plant based Low-carbohydrate Diet (pLCD) (HRCLD: 0.65, 95% CI: 0.49-0.86; HRSLD: 0.66, 95% CI: 0.51-0.85), and healthful Plant-based Diet Index (hPDI) (HRCLD: 0.63, 95% CI: 0.47-0.84; HRSLD: 0.61, 95% CI: 0.47-0.78) were associated with a lower risk of CLD and SLD. Additionally, unhealthful Plant-based Diet Index (uPDI) was associated with increased risk of CLD (HR: 1.42, 95% CI: 1.09-1.85), SLD (HR: 1.50, 95% CI: 1.19-1.90), and LRD (HR: 1.88, 95% CI: 1.28-2.78). The aforementioned associations remained consistently strong within the MAFLD subgroup, while exhibiting less pronounced in the non-MAFLD group. However, no significant heterogeneity was observed across different MAFLD statuses. CONCLUSION: These findings highlight the detrimental effects of MAFLD on the development of subsequent liver diseases and the importance of dietary patterns in managing MAFLD.

Eye-brain connections revealed by multimodal retinal and brain imaging genetics.

The retina, an anatomical extension of the brain, forms physiological connections with the visual cortex of the brain. Although retinal structures offer a unique opportunity to assess brain disorders, their relationship to brain structure and function is not well understood. In this study, we conducted a systematic cross-organ genetic architecture analysis of eye-brain connections using retinal and brain imaging endophenotypes. We identified novel phenotypic and genetic links between retinal imaging biomarkers and brain structure and function measures from multimodal magnetic resonance imaging (MRI), with many associations involving the primary visual cortex and visual pathways. Retinal imaging biomarkers shared genetic influences with brain diseases and complex traits in 65 genomic regions, with 18 showing genetic overlap with brain MRI traits. Mendelian randomization suggests bidirectional genetic causal links between retinal structures and neurological and neuropsychiatric disorders, such as Alzheimer's disease. Overall, our findings reveal the genetic basis for eye-brain connections, suggesting that retinal images can help uncover genetic risk factors for brain disorders and disease-related changes in intracranial structure and function.

Combining CD38 antibody with CD47 blockade is a promising strategy for treating hematologic malignancies expressing CD38.

Background: CD38 and CD47 are expressed in many hematologic malignancies, including multiple myeloma (MM), B-cell non-Hodgkin lymphoma (NHL), B-cell acute lymphoblastic leukemia (ALL), and B-cell chronic lymphocytic leukemia (CLL). Here, we evaluated the antitumor activities of CD38/CD47 bispecific antibodies (BsAbs). Methods: Five suitable anti-CD38 antibodies for co-targeting CD47 and CD38 BsAb were developed using a 2 + 2 "mAb-trap" platform. The activity characteristics of the CD38/CD47 BsAbs were evaluated using in vitro and in vivo systems. Results: Using hybridoma screening technology, we obtained nine suitable anti-CD38 antibodies. All anti-CD38 antibodies bind to CD38+ tumor cells and kill tumor cells via antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Five anti-CD38 antibodies (4A8, 12C10, 26B4, 35G5, and 65A7) were selected for designing CD38/CD47 BsAbs (IMM5605) using a "mAb-trap" platform. BsAbs had higher affinity and binding activity to the CD38 target than those to the CD47 target, decreasing the potential on-target potential and off-tumor effects. The CD38/CD47 BsAbs did not bind to RBCs and did not induce RBC agglutination; thus, BsAbs had much lower blood toxicity. The CD38/CD47 BsAbs had a greater ability to block the CD47/SIRPα signal in CD38+/CD47+ tumor cells than IMM01 (SIRPα Fc fusion protein). Through Fc domain engineering, CD38/CD47 BsAbs were shown to kill tumors more effectively by inducing ADCC and ADCP. IMM5605-26B4 had the strongest inhibitory effect on cellular CD38 enzymatic activity. IMM5605-12C10 had the strongest ability to directly induce the apoptosis of tumor cells. The anti-CD38 antibody 26B4 combined with the SIRPα-Fc fusion proteins showed strong antitumor effects, which were better than any of the mono-therapeutic agents used alone in the NCI-H929 cell xenograft model. The CD38/CD47 BsAbs exhibited strong antitumor effects; specifically, IMM5605-12C10 efficiently eradicated all established tumors in all mice. Conclusion: A panel of BsAbs targeting CD38 and CD47 developed based on the "mAb-tarp" platform showed potent tumor-killing ability in vitro and in vivo. As BsAbs had lower affinity for binding to CD47, higher affinity for binding to CD38, no affinity for binding to RBCs, and did not induce RBC agglutination, we concluded that CD38/CD47 BsAbs are safe and have a satisfactory tolerability profile.

Comparison of 68Ga-FAP-2286 and 18F-FDG PET/CT in the diagnosis of advanced lung cancer.

Purpose: The 68Ga/177Lu-FAP-2286 is a newly developed tumor imaging agent that shows potential for visualizing and treating tumor stroma. The objective of this research was to evaluate the effectiveness of 68Ga-FAP-2286 PET/CT and 18F-FDG PET/CT in diagnosing advanced lung cancer. Methods: In this prospective study, patients with lung cancer who underwent 68Ga-FAP-2286 and 18F-FDG PET/CT examinations between September 2022 and June 2023 were analyzed. Lesion uptake was converted to SUVmax. A paired T-test was used to compare the SUVmax, and the number of positive lesions detected by the two methods was recorded. Results: In total, 31 participants (median age: 56 years) were assessed. The uptake of 68Ga-FAP-2286 was significantly higher than that of 18F-FDG in primary lesions (9.90 ± 5.61 vs. 6.09 ± 2.84, respectively, P < 0.001), lymph nodes (7.95 ± 2.75 vs. 5.55 ± 1.59, respectively, P=0.01), and bone metastases (7.74 ± 3.72 vs. 5.66 ± 3.55, respectively, P=0.04). Furthermore, the detection sensitivity of lymph nodes using 68Ga-FAP-2286 PET/CT was superior to that with 18F-FDG PET/CT [100% (137/137) vs. 78.8% (108/137), respectively], as well as for bone metastases [100% (384/384) vs. 68.5% (263/384), respectively]. However, the detection sensitivity for primary tumors using both modalities was comparable [100% (13/13) for both]. Conclusion: Compared to 18F-FDG PET/CT, 68Ga-FAP-2286 PET/CT demonstrated better lesion detection capabilities for lung cancer, particularly in lymph nodes and bone metastases, providing compelling imaging evidence for the efficacy of 177Lu-FAP-2286 treatment.

Comparison for the diagnostic performance of early diagnostic methods for biliary atresia: a systematic review and network meta-analysis.

BACKGROUND: Biliary atresia (BA), a progressive condition affecting canalicular-bile duct function/anatomy, requires prompt surgical intervention for favorable outcomes. Therefore, we conducted a network meta-analysis of common diagnostic methods to assess their performance and provide evidence-based support for clinical decision-making. METHODS: We reviewed literature in PubMed, EMBASE, and Cochrane for BA diagnostics. The search included gamma-glutamyl transferase (GGT), direct/combined bilirubin, matrix metalloproteinase 7 (MMP-7), ultrasonic triangular cord sign (TCS), hepatic scintigraphy (HS), and percutaneous cholangiocholangiography/percutaneous transhepatic cholecysto-cholangiography (PCC/PTCC). QUADAS-2 assessed study quality. Heterogeneity and threshold effect were evaluated using I2 and Spearman's correlation. We combined effect estimates, constructed SROC models, and conducted a network meta-analysis based on the ANOVA model, along with meta-regression and subgroup analysis, to obtain precise diagnostic performance assessments for BA. RESULTS: A total of 40 studies were included in our analysis. GGT demonstrated high diagnostic accuracy for BA with a sensitivity of 81.5% (95% CI 0.792-0.836) and specificity of 72.1% (95% CI 0.693-0.748). Direct bilirubin/conjugated bilirubin showed a sensitivity of 87.6% (95% CI 0.833-0.911) but lower specificity of 59.4% (95% CI 0.549-0.638). MMP-7 exhibited a total sensitivity of 91.5% (95% CI 0.893-0.934) and a specificity of 84.3% (95% CI 0.820-0.863). TCS exhibited a sensitivity of 58.1% (95% CI 0.549-0.613) and high specificity of 92.9% (95% CI 0.911-0.944). HS had a high sensitivity of 98.4% (95% CI 0.968-0.994) and moderate specificity of 79.0% (95% CI 0.762-0.816). PCC/PTCC exhibited excellent diagnostic performance with a sensitivity of 100% (95% CI 0.900-1.000) and specificity of 87.0% (95% CI 0.767-0.939). Based on the ANOVA model, the network meta-analysis revealed that MMP-7 ranked second overall, with PCC/PTCC ranking first, both exhibiting superior diagnostic accuracy compared to other techniques. Our analysis showed no significant bias in most methodologies, but MMP-7 and hepatobiliary scintigraphy exhibited biases, with p values of 0.023 and 0.002, respectively. CONCLUSION: MMP-7 and ultrasound-guided PCC/PTCC show diagnostic potential in the early diagnosis of BA, but their clinical application is restricted due to practical limitations. Currently, the cutoff value of MMP-7 is unclear, and further evidence-based medical research is needed to firmly establish its diagnostic value. Until more evidence is available, MMP-7 is not suitable for widespread diagnostic use. Therefore, considering cost and operational simplicity, liver function tests combined with ultrasound remain the most clinically valuable non-invasive diagnostic methods for BA.

Diluted contrast media combined with high-resolution C-arm CT for evaluating apposition of flow diversions in a porcine model.

BACKGROUND: In intracranial stenting, good stent apposition is crucial, and high-resolution C-arm computer tomography (CT) is utilized to assess whether stent apposition is complete. This study was aimed at finding optimal hypertonic or isotonic contrast media injection concentration for high-resolution C-arm CT to assess apposition of flow diversion (FD) after carotid artery stenting in swine. METHODS: Twelve FD stents were implanted into the left carotid artery of Bama swine through the endovascular method. During high-resolution C-arm CT scanning, 6%, 8%, 10%, 12%, and 14% dilution percentages of hypertonic contrast media (iopromide 370 mg/ml) and 10%, 12%, 14%, 16%, and 18% dilution percentages of isotonic contrast media (iodixanol 320 mg/ml) were separately injected. A radiologist and a neuro-interventional specialist evaluated and qualitatively scored the post-processed images, and intravascular ultrasound (IVUS) was used to verify the accuracy of these images. RESULTS: Overall, 12 FD stents were implanted into the left common carotid artery of 12 swine, with a technical success rate of 100%. The best reconstructed images used to observe stent apposition were achieved with iopromide diluted to a concentration of 12% (all P < .05) or iodixanol diluted to a concentration of 16% (all P < .05). Malapposition was noted in one case, and good apposition was noted in 11 cases. These results were consistent with IVUS observations. CONCLUSION: Injecting iopromide or iodixanol diluted to 12% or 16% during high-resolution C-arm CT scanning, respectively, can help evaluate FD stent apposition and obtain optimal image quality.

A universal solvent-replacement strategy to convert alginate hydrogels into mechanically strong and transparent alginate eutectogels for sensitive strain sensors.

Eutectogels based on natural polymers have attracted significant attention as an alternative to easily dehydrated hydrogels and expensive ionogels in the development of flexible strain sensors. The feasibility of employing eutectogels derived from pure natural polymers could be greatly enhanced if their mechanical properties satisfy the requirements of applications. Herein, alginate eutectogels (AEs) with high mechanical properties (tensile strain 217 % and strength 2.26 MPa at fracture), and excellent transparency (over 90 %) are acquired via CaCl2 inducing ionic crosslinking and subsequent deep eutectic solvents (DESs, composed of glycerol and choline chloride) initiating physical crosslinking with a universal solvent- replacement strategy. Among them, sodium alginate, a natural polysaccharide polymer, is selected as representative supporting scaffolds and forms water-insoluble alginate hydrogels (AHs) in CaCl2 coagulation bath. The exchange of DESs with water of AHs not only restrengthens the polymer network by physical crosslinking, but also endows the obtained AEs with long-term solvent retention and high temperature resistance. In addition, the AEs not only have high reliability but also exhibit better linear sensitivity in a wide strain range (0-200 %). In particular, the AEs display multiple sensitivity to stretching, bending, and human motions, demonstrating feasibility as sensitive strain sensors.

Use of the Neuroform Atlas Stent or LVIS Jr Stent for Treatment of Unruptured Intracranial Aneurysms in Parent Arteries of <2 mm in Diameter: A Multicenter Experience.

BACKGROUND AND PURPOSE: The Neuroform Atlas stent and the LVIS Jr stent are intracranial microstent systems for the treatment of wide-neck intracranial aneurysms. Hence, this study aimed to compare the efficacy and safety of the Neuroform Atlas stent and the LVIS Jr stent for the treatment of unruptured intracranial aneurysms in parent arteries of <2 mm in diameter. MATERIALS AND METHODS: From March 2022 to April 2023, the clinical and imaging data of 135 patients with unruptured intracranial aneurysms treated with stent-assisted coiling using the Neuroform Atlas or LVIS Jr stent in parent arteries of <2 mm in diameter were retrospectively analyzed. Stent apposition was evaluated by high-resolution conebeam CT (HR-CBCT). Immediate aneurysm-embolization attenuation and occlusion at 6-month follow-up were evaluated using 2D DSA and the modified Raymond-Roy classification. Adverse events were recorded. Multivariate logistic regression analysis was undertaken to determine the independent factors affecting incomplete stent apposition. RESULTS: One hundred thirty-five patients (135 aneurysms) underwent stent-assisted coiling (66 Neuroform Atlas stents and 69 LVIS Jr stents). Intraoperative HR-CBCT showed that 1 Neuroform Atlas stent and 11 LVIS Jr stents had incomplete stent apposition at the aneurysm neck (P < .05). Perioperative complications occurred in 3 cases (2.22%). These comprised 2 cases of neurologic complications (1 case of distal intracranial vascular embolism and 1 case of cerebral parenchymal hemorrhage) and 1 case of severe postprocedural gastrointestinal hemorrhage. DSA follow-up showed 3 cases of aneurysm recurrence in the LVIS Jr group. Multivariate regression analysis showed that a stent angle of ≥75° (OR, 23.963; P = .005) or a parent artery diameter mismatch ratio of ≥1.25 (OR, 8.043; P = .037) were risk factors for incomplete stent apposition, especially for the LVIS Jr stent (OR, 20.297; P = .015). CONCLUSIONS: The Neuroform Atlas stent and LVIS Jr stent are efficacious in the treatment of unruptured intracranial aneurysms in parent arteries of <2 mm in diameter. Apposition of the LVIS Jr stent was worse than in the Neuroform Atlas stent at the neck of some aneurysms.

Multi-organ imaging-derived polygenic indexes for brain and body health.

The UK Biobank (UKB) imaging project is a crucial resource for biomedical research, but is limited to 100,000 participants due to cost and accessibility barriers. Here we used genetic data to predict heritable imaging-derived phenotypes (IDPs) for a larger cohort. We developed and evaluated 4,375 IDP genetic scores (IGS) derived from UKB brain and body images. When applied to UKB participants who were not imaged, IGS revealed links to numerous phenotypes and stratified participants at increased risk for both brain and somatic diseases. For example, IGS identified individuals at higher risk for Alzheimer's disease and multiple sclerosis, offering additional insights beyond traditional polygenic risk scores of these diseases. When applied to independent external cohorts, IGS also stratified those at high disease risk in the All of Us Research Program and the Alzheimer's Disease Neuroimaging Initiative study. Our results demonstrate that, while the UKB imaging cohort is largely healthy and may not be the most enriched for disease risk management, it holds immense potential for stratifying the risk of various brain and body diseases in broader external genetic cohorts.

Endovascular thrombectomy versus medical management on outcomes with infarct volumes more than 70 mL.

OBJECTIVE: Endovascular thrombectomy (EVT) in patients with large infarct volume remains controversial. The aim of this study is to compare clinical outcomes between EVT and medical management in acute large vessel occlusion with infarct volumes larger than 70 mL on diffusion-weighted magnetic resonance imaging (DWI). METHODS: A prospective observational cohort study was conducted, including patients with anterior cerebral circulation occlusion due to ischemic stroke with infarct volumes larger than 70 mL within 24 h of onset between July 2018 and June 2023. Eligible patients were divided into two groups: the EVT group and the medical management (non-EVT) group. The main outcomes were functional independence and mortality at 90 days. To assess clinical endpoints, we selected variables including age, NIHSS score, infarct volume, and occlusion location for 1:1 propensity score (PS) matching and PS adjustment using inverse probability of treatment weighting (IPTW). RESULTS: Among the 131 identified patients (mean [SD] age, 69.9 [13.7] years; 58 female), the median infarct volume was 123.6 mL. Of these patients, 75 (57.3%) underwent EVT. After PS adjustment, EVT was not associated with functional independence (10.9% vs. 10.9%; p = 1.000) or mortality (43.5% vs. 47.8%; p = 0.675). Additionally, after PS adjustment using IPTW, EVT was also not associated with a functional independence (15.8% vs. 13.7%; p = 0.767) or mortality (46.8% vs. 44.0%; p = 0.762). CONCLUSION: This study provides real-world evidence regarding infarct volumes larger than 70 mL, indicating that EVT does not provide benefits compared to medical management alone when considering age, NIHSS score, infarct volume, and occlusion location.

A clinical comparative study of dual LVIS devices and single flow diversion stenting for the treatment of unruptured V3-V4 vertebral artery dissection.

PURPOSE: This study aims to compare the efficacy and safety of using overlapping low-profile visualized intraluminal support (LVIS) devices and flow diversion (FD) for the treatment of unruptured vertebral artery dissection (VAD) in the V3-V4 segments. METHODS: The clinical and imaging data of 71 patients with unruptured VAD in the V3-V4 segments who underwent either dual LVIS stenting (d-LVIS group) or single FD stenting (FD group) at our center from September 2014 to December 2021 were retrospectively analyzed. RESULTS: Immediate postoperative angiography revealed no significant difference in the degree of occlusion between the two groups in treating vertebral artery dissecting aneurysms (with or without noncompact coiling). However, the d-LVIS group had significantly higher fluoroscopy exposure time and total radiation exposure dose compared to the FD group. During the perioperative period, two cases of pontine infarction and one case of acute thrombosis were encountered. One patient died from subarachnoid hemorrhage during the follow-up period. For dissecting the aneurysm, angiographic follow-up (8.56 ± 1.96 months) showed similar healing outcomes between the two groups (with or without noncompact coiling). However, seven patients (7/40, 17.5%) showed poor healing and one patient showed mild in-stent stenosis. For simple dissection, angiographic follow-up (8.78 ± 1.83 months) showed patent lumens in both groups, with all dissections healing well, and two patients having mild in-stent stenosis. CONCLUSION: Both methods could effectively treat unruptured VAD in V3-V4 segments. Nevertheless, simple FD implantation is relatively easier to perform and involves lower radiation exposure.

Prediction of Cognitive Impairment Risk among Older Adults: A Machine Learning-Based Comparative Study and Model Development.

INTRODUCTION: The prevalence of cognitive impairment and dementia in the older population is increasing, and thereby, early detection of cognitive decline is essential for effective intervention. METHODS: This study included 2,288 participants with normal cognitive function from the Ma'anshan Healthy Aging Cohort Study. Forty-two potential predictors, including demographic characteristics, chronic diseases, lifestyle factors, anthropometric indices, physical function, and baseline cognitive function, were selected based on clinical importance and previous research. The dataset was partitioned into training, validation, and test sets in a proportion of 60% for training, 20% for validation, and 20% for testing, respectively. Recursive feature elimination was used for feature selection, followed by six machine learning algorithms that were employed for model development. The performance of the models was evaluated using area under the curve (AUC), specificity, sensitivity, and accuracy. Moreover, SHapley Additive exPlanations (SHAP) was conducted to access the interpretability of the final selected model and to gain insights into the impact of features on the prediction outcomes. SHAP force plots were established to vividly show the application of the prediction model at the individual level. RESULTS: The final predictive model based on the Naive Bayes algorithm achieved an AUC of 0.820 (95% CI, 0.773-0.887) on the test set, outperforming other algorithms. The top ten influential features in the model included baseline Mini-Mental State Examination (MMSE), education, self-reported economic status, collective or social activities, Pittsburgh sleep quality index (PSQI), body mass index, systolic blood pressure, diastolic blood pressure, instrumental activities of daily living, and age. The model demonstrated the potential to identify individuals at a higher risk of cognitive impairment within 3 years from older adults. CONCLUSION: The predictive model developed in this study contributes to the early detection of cognitive impairment in older adults by primary healthcare staff in community settings.

SIRT5 exacerbates eosinophilic chronic rhinosinusitis by promoting polarization of M2 macrophage.

BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.

How consistent are the key recommendations, and what is the quality of guidelines and expert consensus regarding paediatric cow's milk protein allergy?

The objective of this study was to assess the quality and consistency of recommendations in clinical practice guidelines (CPGs) and expert consensus on paediatric cow's milk protein allergy (CMPA) to serve as a foundation for future revisions and enhancements of clinical guidelines and consensus documents. We conducted a comprehensive literature search across several databases, including the Chinese Biomedical Literature Database (CBM), PubMed, Embase, Web of Science, UpToDate, ClinicalKey, DynaMed Plus and BMJ Best Practice. We spanned the search period from the inception of each database through October 1, 2023. We integrated subject headings (MeSH/Emtree) and keywords into the search strategy, used the search methodologies of existing literature and developed it in collaboration with a librarian. Two trained researchers independently conducted the literature screening and data extraction. We evaluated methodological quality and recommendations by using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) and AGREE-Recommendations for Excellence (AGREE-REX) tools. Moreover, we compared and summarized key recommendations from high-quality CPGs. Our study included 27 CPGs and expert consensus documents on CMPA. Only four CPGs (14.8%) achieved a high-quality AGREE II rating. The four high-quality CPGs consistently provided recommendations for CMPA. The highest scoring domains for AGREE II were 'scope and purpose' (77 ± 12%) and 'clarity of presentation' (75 ± 22%). The lowest scoring domains were 'stakeholder involvement' (49 ± 21%), 'rigor of development' (34 ± 20%) and 'applicability' (12 ± 20%). Evaluation with AGREE-REX generally demonstrated low scores across its domains.   Conclusion: Recommendations within high-quality CPGs for the paediatric CMPA showed fundamental consistency. Nevertheless, the methodology and recommendation content of CPGs and the expert consensus exhibited low quality, thus indicating a substantial scope for enhancement. Guideline developers should rigorously follow the AGREE II and AGREE-REX standards in creating CPGs or expert consensuses to guarantee their clinical efficacy in managing paediatric CMPA. What is Known: • The quality of clinical practice guidelines and expert consensus on paediatric cow's milk protein allergy (CMPA) remains uncertain. • There is a lack of clarity regarding the consistency of crucial recommendations for CMPA management. What is New: • Improving the methodological quality of guidelines and consensus on CMPA requires greater emphasis on stakeholder engagement, rigorous development processes, and practical applicability. • The recommendations from four high-quality guidelines align. However, addressing clinical applicability, integrating values and preferences, and ensuring actionable implementation are critical to improving the quality of all guidelines.

Physician estimate of inflammation vs global assessment in explaining variations in swollen joint counts in rheumatoid arthritis patients.

Objective: To analyse patients with RA for inflammatory activity by physician estimate of global assessment (DOCGL) vs an estimate of inflammatory activity (DOCINF) to explain variation in the swollen joint count (SJC). Methods: Patients with RA were studied at routine care visits. Patients completed a multidimensional health assessment questionnaire (MDHAQ) and the physician completed a 28-joint count for swollen (SJC), tender (TJC) and deformed (DJC) joints and a RheuMetric checklist with a 0-10 DOCGL visual numeric scale (VNS) and 0-10 VNS estimates of inflammation (DOCINF), damage (DOCDAM) and patient distress (DOCSTR). The disease activity score in 28 joints with ESR (DAS28-ESR), Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) were calculated. Individual scores and RA indices were compared according to Spearman correlation coefficients and regression analyses. Results: A total of 104 unselected patients were included, with a median age and disease duration of 54.5 and 5 years, respectively. The median DAS28-ESR was 2.9 (Q1-Q3: 2.0-3.7), indicating low activity. DOCINF was correlated significantly with DOCGL (ρ = 0.775). Both DOCGL and DOCINF were correlated significantly with most other measures; correlations with DOCGL were generally higher than with DOCINF other than for SJC. In regression analyses, DOCINF was more explanatory of variation in SJC than DOCGL and other DAS28-ESR components. Conclusions: Variation in SJC is explained more by a 0-10 DOCINF VNS than the traditional DOCGL or any other measure in RA patients seen in routine care. DOCINF on a RheuMetric checklist can provide informative quantitative scores concerning inflammatory activity in RA patients monitored over long periods.

Artificial intelligence as a prediction tool for orthognathic surgery assessment.

INTRODUCTION: An ideal orthodontic treatment involves qualitative and quantitative measurements of dental and skeletal components to evaluate patients' discrepancies, such as facial, occlusal, and functional characteristics. Deciding between orthodontics and orthognathic surgery remains challenging, especially in borderline patients. Advances in technology are aiding clinical decisions in orthodontics. The increasing availability of data and the era of big data enable the use of artificial intelligence to guide clinicians' diagnoses. This study aims to test the capacity of different machine learning (ML) models to predict whether orthognathic surgery or orthodontics treatment is required, using soft and hard tissue cephalometric values. METHODS: A total of 920 lateral radiographs from patients previously treated with either conventional orthodontics or in combination with orthognathic surgery were used, comprising n = 558 Class II and n = 362 Class III patients, respectively. Thirty-two measures were obtained from each cephalogram at the initial appointment. The subjects were randomly divided into training (n = 552), validation (n = 183), and test (n = 185) datasets, both as an entire sample and divided into Class II and Class III sub-groups. The extracted data were evaluated using 10 machine learning models and by a four-expert panel consisting of orthodontists (n = 2) and surgeons (n = 2). RESULTS: The combined prediction of 10 models showed top-ranked performance in the testing dataset for accuracy, F1-score, and AUC (entire sample: 0.707, 0.706, 0.791; Class II: 0.759, 0.758, 0.824; Class III: 0.822, 0.807, 0.89). CONCLUSIONS: The proposed combined 10 ML approach model accurately predicted the need for orthognathic surgery, showing better performance in Class III patients.

A case report of sustained remission after radiotherapy combined with ICI in NEPC with primary drug resistance to chemotherapy.

Advanced prostate cancer (PCa) is usually treated initially with androgen deprivation therapy (ADT). Although they experience a period of disease regression, most patients progress to metastatic castration-resistant prostate cancer (mCRPC). Patients with mCRPC now have an unprecedented number of approved treatment options, including chemotherapies, hormone therapies, targeted therapies, etc. However, the improvement of overall survival (OS) in patients with mCRPC and its special subtype neuroendocrine prostate cancer (NEPC) is limited. In recent years, with the use of immune checkpoint inhibitors (ICIs), such as PD1/PDL1 and CTLA4 inhibitors, immunotherapy has once again become a promising treatment choice to stimulate antitumor immunity. However, the efficacy of NEPC receiving ICI has not been reported. Here, we describe a patient with mCRPC who developed primary resistance to current endocrine and chemotherapy regimens and progressed to mCRPC with NEPC as the main component, showing a significant and lasting response to PD1 monoclonal antibody combined with radiotherapy.

Exploring causality with biliary atresia at different levels: two-sample Mendelian randomization study.

Background: In recent years, Mendelian randomization (MR) has been widely used to infer causality of related disease risk exposures. However, this strategy has not been applied to biliary atresia (BA). Methods: Genome-wide association studies (GWAS) data of 41 inflammatory cytokines, 731 immune cell traits, and 1400 metabolites were obtained from public databases as exposure factors. The outcome information was obtained from a GWAS meta-analysis of 499 children with BA and 1928 normal controls. Inverse variance weighting was the primary causality analysis. Cochran Q-test, MR-Egger intercept, MR pleiotropy residual sum and outlier, and 'leave-one-out' analyses were used for sensitivity analysis. Reverse MR, MR-Steiger, and Linkage Disequilibrium Score were used to exclude the effects of reverse causality, genetic association, and linkage disequilibrium. Results: MR results showed that a total of seven traits had potential causal relationships with BA, including three inflammatory cytokines: eotaxin (odds ratio (OR)=1.45, 95% confidence interval (CI): 1.08 to 1.95, p FDR=0.18), G-CSF (OR=4.21, 95% CI: 1.75 to 10.13, p FDR=0.05) and MCP-1/MCAF (OR=1.53, 95% CI: 1.12 to 2.10, p FDR=0.14); three immune cell traits: CD8dim NKT/T cells ratio (OR=0.59, 95% CI: 0.45 to 0.77, p FDR=0.06), CD8dim NKT counts (OR=0.58, 95% CI: 0.43 to 0.78, p FDR=0.06), CD8dim NKT/lymphocyte ratio (OR=0.63, 95% CI: 0.49 to 0.81, p FDR=0.06); one metabolite: X-12261 levels (OR=2.86, 95% CI: 1.73 to 4.74, p FDR=0.06). Conclusions: In this study, eotaxin, G-CSF, MCP-1/MCAF, and X-12261 levels were shown to be risk factors for BA. However, CD8dim NKT/T cells ratio, CD8dim NKT counts, and CD8dim NKT/lymphocyte ratio were protective factors for BA. These findings provided a promising genetic basis for the etiology, diagnosis, and treatment of BA.