Comparative efficacy and safety of JAK inhibitors in the treatment of moderate-to-severe alopecia areata: a systematic review and network meta-analysis.

We performed a Bayesian network meta-analysis to indirectly compare the relative efficacy and safety of the latest JAK inhibitors for moderate-to-severe alopecia areata (AA). 13 trials totaling 3,613 patients were included. Two low-dose groups of oral formulations (ritlecitinib 10mg and ivarmacitinib 2mg) and two topical formulations (delgocitinib ointment and ruxolitinib cream) appeared to be relatively ineffective against moderate-to-severe AA. Ranking analysis suggested that brepocitinib 30mg has the best relative effect in reducing the SALT score (sucra = 0.9831), and demonstrated comparable efficacy to deuruxolitinib 12mg (sucra = 0.9245), followed by deuruxolitinib 8mg (sucra = 0.7736). Regarding the SALT50 response, brepocitinib 30mg ranked highest (sucra = 0.9567), followed by ritlecitinib 50mg (sucra = 0.8689) and deuruxolitinib 12mg (sucra = 0.7690). For achieving the SALT75 response, deuruxolitinib 12mg had the highest probability (sucra = 0.9761), followed by deuruxolitinib 8mg (sucra = 0.8678) and brepocitinib 30mg (sucra = 0.8448). Deuruxolitinib 12mg might be the most effective therapy for patients with severe AA (sucra = 0.9395), followed by ritlecitinib 50mg (sucra = 0.8753) and deuruxolitinib 8mg (sucra = 0.8070). Deuruxolitinib 12mg/8mg demonstrated notable efficacy for moderate-to-severe AA, and is expected to be a new treatment option for AA. It was worth noting that deuruxolitinib exhibit a greater likelihood of causing adverse events in comparison to other JAK inhibitors. Ritlecitinib 50mg seemed to exhibit fewer adverse effects in the high-dose groups of oral JAK inhibitors and might be an optimal choice to balance safety and efficacy. The majority of JAK inhibitors exhibited acceptable short-term safety profiles. To enhance the applicability and accuracy of our research, further head-to-head trials with longer follow-up periods are needed. Systematic Review Registration: identifier [CRD42022368012].

Frontiers of soybean pan-genome studies.

Artificial domestication provided the original motivation to the blooming of agriculture, following with the dramatic change of the genetic background of crops and livestock. According to theory and technology upgradation that contributing to the omics, we appreciate using the pan-genome instead of single reference genome for crop study. By comparison and integration of multiple genomes under the guidance of pan-genome theory, we can estimate the genomic information range of a species, leading to a global understanding of its genetic diversity. Combining pan-genome with large size chromosomal structural variations, high throughput population resequencing, and multi-omics data, we can profoundly study the genetic basis behind species traits we focus on. Soybean is one of the most important commercial crops over the world. It is also essential to our food security. Dissecting the formation of genetic diversity and the causal loci of key agricultural traits of soybean will make the modern soybean breeding more efficiently. In this review, we summarize the core idea of pan-genome and clarified the characteristics of construction strategies of pan-genome such as de novo/mapping assembly, iterative assembly and graph-based genome. Then we used the soybean pan-genome work as a case study to introduce the general way to study pan-genome. We highlighted the contribution of structural variation (SV) to the evolution/domestication of soybean and its value in understanding the genetic bases of agronomy traits. By those, we approved the value of graph-based pan-genome for data integration and SV calculation. Future research directions are also discussed for crop genomics and data science.

Arteriovenous Fistula Histology, Hemodynamics, and Wall Mechanics: A Case Report of Successful and Failed Access in a Single Patient.

The low 1-year patency rate of mature arteriovenous fistulas (AVFs) remains a significant clinical problem. Although vessel properties and biomechanics have been suggested to affect AVF function, understanding their roles in AVF patency failure is challenging owing to the heterogeneity within the patient population, including demographics and comorbid conditions. In this study, we present a case of a patient with 2 upper-arm AVFs with different 1-year patency outcomes and investigate whether they had different histologic features before the AVF creation surgery and biomechanics at 1 day and 6 weeks after the AVF creation surgery using magnetic resonance imaging-based fluid structure interaction simulations. Despite both AVFs being in the upper arm, created <1 year apart by the same surgeon, and having similar preoperative vessel diameters, the 1-year patent AVF had less preoperative intimal collagen and higher wall shear stress 1 day after AVF creation, when compared with the AVF that failed by 1 year. Thus, a low intimal collagen content before the AVF surgery and higher wall shear stress immediately after the AVF creation surgery may be important for long-term AVF patency and should be investigated with larger cohorts.

[Survival and Prognosis of Patients with Acute Myeloid Leukemia with Myelodysplasia-Related Changes Transformed from Myelodysplastic Syndrome].

OBJECTIVE: To explore the risk factors affecting the survival and efficacy of patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) transformed from myelodysplastic syndrome (MDS). METHODS: The clinical data of 60 patients with AML-MRC transformed from MDS who hospitalized in The Third Affiliated Hospital of Soochow University from January 2010 to December 2021 were retrospectively analyzed. The demographic data and laboratory parameters, cytogenetic karyotypes, target genes of AML detected by next generation sequence, risk stratification, treatment regimen, therapeutic efficacy and survival outcome were documented. Rank sum test and Chi-square test or Fisher exact test were used to compare the survival and efficacy. The effects of clinical parameters, risk stratification and treatment regimens on the survival and efficacy of the AML-MRC patients were analyzed by univariate and multivariate analysis. RESULTS: The median overall survival (OS) of the AML-MRC patients was 4.5 months, the 1-year OS rate was 28.3%, and the complete remission (CR) rate after treatment was 33.3%. The univariate analysis showed that age≥60 years, leukocytosis, severe thrombocytopenia, poor-risk group and only accepted hypomethylating agents(HMAs) or supportive therapy were the risk factors affecting OS. COX multivariate analysis showed that thrombocytopenia ( HR=4.46), HMAs therapy (compared to transplantation, HR=10.47), supportive therapy (compared to transplantation, HR=25.80) and poor-risk group (compared to medium-risk group, HR=13.86) were independent hazard factors for median OS of patients with AML-MRC. The univariate analysis showed that the risk factors affecting 1-year OS in patients with AML-MRC were age≥60 years, thrombocytopenia, time of transformation from MDS to AML (TTA)≥3 months, fibrinogen-albumin ratio index (FARI)≥0.07, CONUT score≥5, poor-risk group and supportive therapy. Binary logistic regression analysis showed that the independent risk factors for 1-year OS in AML-MRC patients were age≥60 years ( HR=11.23), thrombocytopenia ( HR=8.71), FARI≥0.07 ( HR=5.19) and poor-risk group ( HR=14.00). The risk factors affecting CR of AML-MRC patients in univariate analysis were age≥60 years, thrombocytopenia, FARI≥0.1, CONUT score≥5, poor-risk group and supportive therapy, while binary logistic regression analysis showed that age≥60 years( HR=7.35), CONUT score≥5 ( HR=9.60), thrombocytopenia ( HR=12.05) and poor-risk group ( HR=32.5) were independent risk factors affecting CR of the patients. CONCLUSION: The OS of AML-MRC patients is poor, old age(≥60 years old), supportive therapy, HMA therapy, poor-risk, thrombocytopenia, FARI≥0.07 and CONUT score≥5 may be associated with poor prognosis.

miR-451a was selectively sorted into exosomes and promoted the progression of esophageal squamous cell carcinoma through CAB39.

Exosomes are emerging mediators of cell-cell communication, which are secreted from cells and may be delivered into recipient cells in cell biological processes. Here, we examined microRNA (miRNA) expression in esophageal squamous cell carcinoma (ESCC) cells. We performed miRNA sequencing in exosomes and cells of KYSE150 and KYSE450 cell lines. Among these differentially expressed miRNAs, 20 of the miRNAs were detected in cells and exosomes. A heat map indicated that the level of miR-451a was higher in exosomes than in ESCC cells. Furthermore, miRNA pull-down assays and combined exosomes proteomic data showed that miR-451a interacts with YWHAE. Over-expression of YWHAE leads to miR-451a accumulation in the exosomes instead of the donor cells. We found that miR-451a was sorted into exosomes. However, the biological function of miR-451a remains unclear in ESCC. Here, Dual-luciferase reporter assay was conducted and it was proved that CAB39 is a target gene of miR-451a. Moreover, CAB39 is related to TGF-ß1 from RNA-sequencing data of 155 paired of ESCC tissues and the matched tissues. Western Blot and qPCR revealed that CAB39 and TGF-ß1 were positively correlated in ESCC. Over-expression of CAB39 were cocultured with PBMCs from the blood from healthy donors. Flow cytometry assays showed that apoptotic cells were significantly reduced after CAB39 over-expression and significantly increased after treated with TGF-ß1 inhibitors. Thus, our data indicate that CAB39 weakens antitumor immunity through TGF-ß1 in ESCC. In summary, YWHAE selectively sorted miR-451a into exosomes and it can weaken antitumor immunity promotes tumor progression through CAB39.

The association between wet overactive bladder and consumption of tea, coffee, and caffeine: Results from 2005-2018 National Health and Nutrition Examination Survey.

BACKGROUND & AIMS: Previous studies have reported an inconsistent relationship between overactive bladder (OAB) and the consumption of tea, coffee, and caffeine. Our study aims to determine these associations in a large and nationally representative adult sample. METHODS: This cross-sectional study included 15,379 participants from the 2005-2018 US National Health and Nutrition Examination Survey (NHANES) database. The outcome was the risk of wet OAB that was diagnosed when the OAB symptom score was ≥3 with urgent urinary incontinence and excluded other diseases affecting diagnosis. The exposures were the consumption of tea, coffee, and caffeine. Weighted logistic regression models were established to explore these associations by calculating odds ratios (OR) and 95% confidence intervals (CI), as did restricted cubic splines (RCS) used to analyze the nonlinear associations. RESULT: Of all the participants (n = 15,379), 2207 had wet OAB. Mean [SE] consumption of tea, total coffee, caffeinated coffee, decaffeinated coffee, and caffeine was 233.6 [15.7] g/day, 364.3 [15.5] g/day, 301.6 [14.9] g/day, 62.7 [7.9] g/day, 175.5 [6.6] mg/day in participants with wet OAB, respectively. In the fully adjusted model, compared to those without tea consumption, the high consumption of tea (>481 g/day) was associated with an increased risk of wet OAB (OR: 1.29; 95%CI: 1.01-1.64). Low decaffeinated coffee (0.001-177.6 g/day) had a negative association with the risk (OR: 0.66; 95%CI: 0.49-0.90). In the RCS analysis, tea consumption showed a positive linear association with the risk of wet OAB, and decaffeinated coffee showed a nonlinear relationship with the risk and had a turning point of 78 g/day in the U-shaped curve between 0 and 285 g/day. Besides, total coffee, caffeinated coffee, and caffeine consumption had no significant association with the risk. Interestingly, in the high tea consumption, participants with high total coffee consumption [>527.35 g/day, OR and 95%CI: 2.14(1.16-3.94)] and low caffeine consumption [0.1-74.0 mg/day, OR and 95%CI: 1.50(1.03-2.17)] were positively associated with the risk of wet OAB. CONCLUSION: High tea consumption was associated with the increased risk of wet OAB, especially intake together with high total coffee and low caffeine consumption, but no significant association with the single consumption of total coffee and caffeine. Low decaffeinated coffee was associated with a decreased risk of wet OAB. It is necessary to control tea intake when managing the liquid intake of wet OAB patients.

Research trends and hotspots in the field of electrical impedance tomography for mechanical ventilation: a bibliometric analysis.

Background: Electrical impedance tomography (EIT) is a relatively recent functional imaging technique that is both noninvasive and radiation free. EIT measures the associated voltage when a weak current is applied to the surface of the human body to determine the distribution of electrical resistance within tissues. We performed a bibliometrics-based review to explore the geographic hotspots of current research and future trends developing in the field of EIT for mechanical ventilation. Methods: The Web of Science database was searched from its inception to June 25, 2023. CiteSpace software was used to visualize and analyze the relevant literature and identify the most impactful literature, trends, and hotspots. Results: 363 articles describing EIT use in mechanical ventilation were identified. A fluctuating growth in the number of publications was observed from 1998 to 2023. Germany had the highest number of articles (n=154), followed by Italy (n=53) and China (n=52). A cluster analysis of keyword co-occurrence revealed that "titration", "ventilator-related lung injury", and "oxygenation" were the most actively researched terms associated with the use of EIT in mechanically ventilated patients. Conclusions: Significant progress has been made in EIT research for mechanical ventilation. EIT research is limited to a small number of countries with a present research focus on the prevention and treatment of ventilator-related lung injury, oxygenation status, and prone ventilation. These topics are expected to remain research hotspots in the future.

Integration of multiomics analyses reveals unique insights into CD24-mediated immunosuppressive tumor microenvironment of breast cancer.

BACKGROUND: Tumor immunotherapy brings new light and vitality to breast cancer patients, but low response rate and limitations of therapeutic targets become major obstacles to its clinical application. Recent studies have shown that CD24 is involved in an important process of tumor immune regulation in breast cancer and is a promising target for immunotherapy. METHODS: In this study, singleR was used to annotate each cell subpopulation after t-distributed stochastic neighbor embedding (t-SNE) methods. Pseudo-time trace analysis and cell communication were analyzed by Monocle2 package and CellChat, respectively. A prognostic model based on CD24-related genes was constructed using several machine learning methods. Multiple quantitative immunofluorescence (MQIF) was used to evaluate the spatial relationship between CD24+PANCK+cells and exhausted CD8+T cells. RESULTS: Based on the scRNA-seq analysis, 1488 CD24-related differential genes were identified, and a risk model consisting of 15 prognostic characteristic genes was constructed by combining the bulk RNA-seq data. Patients were divided into high- and low-risk groups based on the median risk score. Immune landscape analysis showed that the low-risk group showed higher infiltration of immune-promoting cells and stronger immune reactivity. The results of cell communication demonstrated a strong interaction between CD24+epithelial cells and CD8+T cells. Subsequent MQIF demonstrated a strong interaction between CD24+PANCK+ and exhausted CD8+T cells with FOXP3+ in breast cancer. Additionally, CD24+PANCK+ and CD8+FOXP3+T cells were positively associated with lower survival rates. CONCLUSION: This study highlights the importance of CD24+breast cancer cells in clinical prognosis and immunosuppressive microenvironment, which may provide a new direction for improving patient outcomes.

Inadequate pregnancy-specific knowledge among patients with inflammatory bowel disease: A multicenter survey in China.

OBJECTIVES: The perceptions and attitudes of inflammatory bowel disease (IBD) patients towards pregnancy may affect their fertility plan and disease progression. We performed a nationwide multicenter survey of pregnancy-related knowledge among gastroenterologists and IBD patients in China to investigate whether specific educational interventions could improve their understanding and broadly influence fertility plan. METHODS: A cross-sectional questionnaire regarding pregnancy-specific knowledge was carried out among 63 IBD centers in China. Questionnaires were collected from 185 physicians and 609 patients. The patients then received education regarding pregnancy during IBD and filled in the same questionnaire again. Their knowledge regarding pregnancy during IBD was compared before and after education. RESULTS: Compared to physicians, patients' knowledge regarding fertility (39.1% vs 70.8%), imaging examinations (22.8% vs 72.4%), endoscopy performed during pregnancy (19.9% vs 71.4%), and vaccination for infants (16.6% vs 46.5%) was significantly more limited (all P < 0.001). There was a lack of knowledge among gastroenterologists regarding the delivery mode (36.8%), medications (36.8%), and emergency surgery (26.5%) during pregnancy in patients with IBD. After education, the patients showed significant improvement in knowledge regarding medications (26.7% vs 51.7%), fertility (45.0% vs 63.3%), heritability (40.0% vs 58.3%), indications for emergency surgery (15.0% vs 53.3%), imaging examinations during pregnancy (20.0% vs 40.0%), and vaccinations for infants (26.7% vs 45.0%) (all P < 0.05). CONCLUSIONS: Pregnancy-specific IBD knowledge needs to be improved among certain gastroenterologists and patients in China. Educational interventions can partially improve the knowledge levels of the patients.

Clinical Characteristics, Management and Prognostic Factors of Immune Checkpoint Inhibitor-Associated Pneumonia in Chinese Cancer Patients.

OBJECTIVE: To investigate the clinical characteristics, treatment methods, outcomes, and variables influencing the outcomes of checkpoint inhibitor-related pneumonitis (CIP) among Chinese cancer patients. STUDY DESIGN: Descriptive Study. Place and Duration of the Study: Department of Pharmacy, Hunan Cancer Hospital, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China, from January 2019 to December 2022. METHODOLOGY: Patients with CIP were inducted. Clinical data including patient characteristics, ICI protocols; and the clinical features, treatments, and outcomes of CIP were collected and analysed. RESULTS: One hundred and forty-six patients were included. Median time to onset in the CIP was 17.0 weeks (range: 0.4 - 74.7). Mild CIP and severe CIP accounted for 84.93% and 15.07% of cases, respectively. All patients with CIP received methylprednisolone treatment, with an average starting dose of 1.64 mg/kg (0.59-6.00 mg/kg), and 79 (54.11%) of them received anti-infective therapy. One hundred and thirteen (77.04%) patients had improved symptoms of pneumonia, with only 33 (22.60%) patients displaying no improvement. Multivariate analysis revealed that the severity of CIP [OR = 0.167 (95% CI 0.061-0.461), p <0.001] and the starting dose of methylprednisolone [OR = 0.314 (95% CI 0.129-0.764), p <0.001] were independent predictors of outcomes of CIP, while the use of antibiotic was not. CONCLUSION: The severity of CIP and the initial dosage of methylprednisolone administered are significant factors that impact the outcomes of CIP in Chinese cancer patients after ICI treatment. Appropriate use of glucocorticoids and antibiotics is a necessary management strategy to control CIP effectively. KEY WORDS: Immune checkpoint inhibitors, Immune-related adverse events, Checkpoint inhibitor-related pneumonitis, Glucocorticosteroids, Antibiotics, Prognostic factors.

Development of machine learning-based malignant pericardial effusion-related model in breast cancer: Implications for clinical significance, tumor immune and drug-therapy.

Background: Malignant pericardial effusion (MPE) is a common complication of advanced breast cancer (BRCA) and plays an important role in BRCA. This study is aims to construct a prognostic model based on MPE-related genes for predicting the prognosis of breast cancer. Methods: The BRCA samples are analyzed based on the expression of MPE-related genes by using an unsupervised cluster analysis method. This study processes the data by least absolute shrinkage and selection operator and multivariate Cox analysis, and uses machine learning algorithms to construct BRCA prognostic model and develop web tool. Results: BRCA patients are classified into three clusters and a BRCA prognostic model is constructed containing 9 MPE-related genes. There are significant differences in signature pathways, immune infiltration, immunotherapy response and drug sensitivity testing between the high and low-risk groups. Of note, a web-based tool (http://wys.helyly.top/cox.html) is developed to predict overall survival as well as drug-therapy response of BRCA patients quickly and conveniently, which can provide a basis for clinicians to formulate individualized treatment plans. Conclusion: The MPE-related prognostic model developed in this study can be used as an effective tool for predicting the prognosis of BRCA and provides new insights for the diagnosis and treatment of BRCA patients.

Discovering ferroptosis-associated tumor antigens and ferroptosis subtypes in pancreatic adenocarcinoma to facilitate mRNA vaccine development.

Pancreatic adenocarcinoma (PAAD) is an aggressive, heterogeneous malignancy. We studied the potential of ferroptosis-related tumor vaccines for PAAD treatment. Ferroptosis-related genes, gene expression profiles, and clinical information were extracted from the FerrDB, UCSC Xena, and International Cancer Genome Consortium databases. Differential expression levels and prognostic indices were calculated, genetic alterations and correlations with immune-infiltrating cells were explored, and consensus clustering analysis was performed to identify ferroptosis subtypes and gene modules. Immune enrichment scores were calculated using gene set enrichment analysis, and gene modules were screened using weighted gene co-expression network analysis. The ferroptosis subtype distribution was visualized using graph learning-based dimensionality reduction analysis of the Monocle package with a Gaussian distribution. We identified four ferroptosis-related tumor antigens, AGPS, KDM5A, NRAS, and OSBPL9, which were associated with pancreatic cancer prognosis and antigen-presenting cell infiltration. We determined three minor ferroptosis subtypes, with different clinical prognosis and tumor immune status. Of the subtypes, FS3 may be more suitable for mRNA therapy. We constructed a PAAD ferroptosis landscape to identify the ferroptosis status of patients and predict their prognosis. Finally, we found that the eigengene of the green module was an independent prognostic factor, with a significantly better prognosis in the high-score group than in the low-score group. In conclusion, we identified four ferroptosis-related genes as targets for mRNA vaccines and three ferroptosis subtypes, providing a theoretical basis for the anti-PAAD mRNA vaccine and defining suitable patients for vaccination.

Bipolar hip arthroplasty using conjoined tendon preserving posterior lateral approach in treatment of displaced femoral neck fractures.

BACKGROUND: Hip fractures account for 23.8% of all fractures in patients over the age of 75 years. More than half of these patients are older than 80 years. Bipolar hemiarthroplasty (BHA) was established as an effective management option for these patients. Various approaches can be used for the BHA procedure. However, there is a high risk of postoperative dislocation. The conjoined tendon-preserving posterior (CPP) lateral approach was introduced to reduce postoperative dislocation rates. AIM: To evaluate the effectiveness and safety of the CPP lateral approach for BHA in elderly patients. METHODS: We retrospectively analyzed medical data from 80 patients with displaced femoral neck fractures who underwent BHA. The patients were followed up for at least 1 year. Among the 80 patients, 57 (71.3%) were female. The time to operation averaged 2.3 d (range: 1-5 d). The mean age was 80.5 years (range: 67-90 years), and the mean body mass index was 24.9 kg/m2 (range: 17-36 kg/m2). According to the Garden classification, 42.5% of patients were type Ⅲ and 57.5% of patients were type Ⅳ. Uncemented bipolar hip prostheses were used for all patients. Torn conjoined tendons, dislocations, and adverse complications during and after surgery were recorded. RESULTS: The mean postoperative follow-up time was 15.3 months (range: 12-18 months). The average surgery time was 52 min (range: 40-70 min) with an average blood loss of 120 mL (range: 80-320 mL). The transfusion rate was 10% (8 of 80 patients). The gemellus inferior was torn in 4 patients (5%), while it was difficult to identify in 2 patients (2.5%) during surgery. The posterior capsule was punctured by the fractured femoral neck in 3 patients, but the conjoined tendon and the piriformis tendon remained intact. No patients had stem varus greater than 3 degrees or femoral fracture. There were no patients with stem subsidence more than 5 mm at the last follow-up. No postoperative dislocations were observed throughout the follow-up period. No significance was found between preoperative and postoperative mean Health Service System scores (87.30 ± 2.98 vs 86.10 ± 6.10, t = 1.89, P = 0.063). CONCLUSION: The CPP lateral approach can effectively reduce the incidence of postoperative dislocation without increasing perioperative complications. For surgeons familiar with the posterior lateral approach, there is no need for additional surgical instruments, and it does not increase surgical difficulty.

Global Regulatory Frameworks for the Use of Artificial Intelligence (AI) in the Healthcare Services Sector.

The healthcare sector is faced with challenges due to a shrinking healthcare workforce and a rise in chronic diseases that are worsening with demographic and epidemiological shifts. Digital health interventions that include artificial intelligence (AI) are being identified as some of the potential solutions to these challenges. The ultimate aim of these AI systems is to improve the patient's health outcomes and satisfaction, the overall population's health, and the well-being of healthcare professionals. The applications of AI in healthcare services are vast and are expected to assist, automate, and augment several healthcare services. Like any other emerging innovation, AI in healthcare also comes with its own risks and requires regulatory controls. A review of the literature was undertaken to study the existing regulatory landscape for AI in the healthcare services sector in developed nations. In the global regulatory landscape, most of the regulations for AI revolve around Software as a Medical Device (SaMD) and are regulated under digital health products. However, it is necessary to note that the current regulations may not suffice as AI-based technologies are capable of working autonomously, adapting their algorithms, and improving their performance over time based on the new real-world data that they have encountered. Hence, a global regulatory convergence for AI in healthcare, similar to the voluntary AI code of conduct that is being developed by the US-EU Trade and Technology Council, would be beneficial to all nations, be it developing or developed.

Rice straw-derived chitosan-enhanced plasticizers as biologically and environmentally friendly alternatives for sustainable materials.

Plasticizers like Bis(2-ethylhexyl)phthalate (DEHP) are commonly used to enhance plastic properties but pose environmental and health risks. This study successfully derived plasticizers X and Y from rice straws, demonstrating efficacy in chitosan polymer coatings. Chitosan-based polymers exhibit exceptional hardness, with a value of 300 MPa, due to their enriched structure and robust chitosan bonding. This surpasses the hardness of DEHP. Zebrafish exposure over 5 days revealed that X and Y had no significant behavioral impact, while DEHP caused noticeable toxic effects. Maternal DEHP exposure reduced placental cell growth, unlike X and Y, which had no adverse effects on uterine differentiation or placenta formation, suggesting their safety in human pregnancy. The successful development of X and Y represents a crucial step towards greener plasticizers, addressing environmental concerns and promoting safer alternatives in various industries.

A prospective study of zanubrutinib, a Bruton tyrosine kinase inhibitor, in relapsed/refractory idiopathic multicentric Castleman disease.

Relapsed and refractory (R/R) idiopathic multicentric Castleman disease (iMCD) is a clinical challenge with no standard treatment. In this preliminary clinical trial, we investigated the efficacy and safety profiles of a Bruton tyrosine kinase inhibitor (BTKi), zanubrutinib, in patients with R/R iMCD. The primary endpoint was the overall response rate at Week 12 according to the Castleman Disease Collaborative Network (CDCN) response criteria. The trial was terminated early due to a lack of treatment response in the first enrolled 5 patients. Although 3 patients achieved symptomatic response, none of the 5 patients had an overall response by Week 12. One patient had progressive disease and the other 4 had stable disease. The study drug was well tolerated without grade 2 or higher adverse events. Our findings suggest that BTKi therapy is not effective for iMCD, and further attempts at single-agent therapy with zanubrutinib or other BTKis for iMCD should be considered with caution and probably avoided. This trial was registered at www.clinialtrials.gov as #NCT04743687.

[Effectiveness of unilateral biportal endoscopy combined with percutaneous pedicle screw fixation in treatment of lumbar burst fractures with neurological symptoms].

Objective: To evaluate the effectiveness of spinal canal decompression assisted by unilateral biportal endoscopy (UBE) and percutaneous uniplanar pedicle screw internal fixation in the treatment of lumbar burst fractures with neurological symptoms. Methods: Between June 2021 and December 2022, 10 patients with single level lumbar burst fracture with neurological symptoms were treated with spinal canal decompression assisted by UBE and percutaneous uniplanar pedicle screw internal fixation. There were 7 males and 3 females with an average age of 43.1 years (range, 21-57 years). The injured vertebrae located at L 1 in 2 cases, L 2 in 4 cases, L 3 in 3 cases, and L 4 in 1 case. There were 7 cases of AO type A3 fractures and 3 cases of AO type A4 fractures. The total operation time, the time of operation under endoscopy, and complications were recorded. Pre- and post-operative visual analogue scale (VAS) score and American Spinal Injury Association (ASIA) scale (grading A-E corresponding to assigning 1-5 points for statistical analysis) were used to evaluate effectiveness. X-ray film and CT were performed to observe the fracture healing, and the ratio of anterior vertebral body height, Cobb angle, and rate of spinal canal invasion were measured to evaluate the reduction of fracture. Results: All operations was successfully completed, and the spinal canal decompression and the bone fragment in spinal canal reduction completed under the endoscopy. Total operation time was 119 minutes on average (range, 95-150 minutes), and the time of operation under endoscopy was 46 minutes on average (range, 35-55 minutes). There was no complication such as dural sac, nerve root, or blood vessel injury during operation. All incisions healed by first intention. All patients were followed up 18.7 months on average (range, 10-28 months). The VAS score after operation significantly decreased when compared with that before operation ( P<0.05), and further improved at last follow-up ( P<0.05). The ASIA scale after operation significantly improved when compared with that before operation ( P<0.05), and there was no significant difference ( P>0.05) in the ASIA scale between at 1 week after operation and at last follow-up. The imaging examination showed that the screw position was good and the articular process joint was preserved. During follow-up, there was no loosening, fracture, or fixation failure of the internal fixation. The ratio of anterior vertebral body height and Cobb angle significantly improved, the rate of spinal canal invasion significantly decreased after operation ( P<0.05), and without significant loss of correction during the follow-up ( P>0.05). Conclusion: Spinal canal decompression assisted by UBE and percutaneous uniplanar pedicle screw fixation is a feasible minimally invasive treatment for lumbar burst fractures with neurological symptoms, which can effectively restore the vertebral body sequence, as well as relieve the compression of spinal canal, and improve the neurological function.

Parametric Analysis of Donor Activation for Glycosylation Reactions.

The chemical synthesis of complex oligosaccharides relies on efficient and highly reproducible glycosylation reactions. The outcome of a glycosylation is contingent upon several environmental factors, such as temperature, acidity, the presence of residual moisture, as well as the steric, electronic, and conformational aspects of the reactants. Each glycosylation proceeds rapidly and with a high yield within a rather narrow temperature range. For better control over glycosylations and to ensure fast and reliable reactions, a systematic analysis of 18 glycosyl donors revealed the effect of reagent concentration, water content, protecting groups, and structure of the glycosyl donors on the activation temperature. With these insights, we parametrize the first step of the glycosylation reaction to be executed reliably and efficiently.

Beta-informativeness-diffusion multilayer graph embedding for brain network analysis.

Brain network analysis provides essential insights into the diagnosis of brain disease. Integrating multiple neuroimaging modalities has been demonstrated to be more effective than using a single modality for brain network analysis. However, a majority of existing brain network analysis methods based on multiple modalities often overlook both complementary information and unique characteristics from various modalities. To tackle this issue, we propose the Beta-Informativeness-Diffusion Multilayer Graph Embedding (BID-MGE) method. The proposed method seamlessly integrates structural connectivity (SC) and functional connectivity (FC) to learn more comprehensive information for diagnosing neuropsychiatric disorders. Specifically, a novel beta distribution mapping function (beta mapping) is utilized to increase vital information and weaken insignificant connections. The refined information helps the diffusion process concentrate on crucial brain regions to capture more discriminative features. To maximize the preservation of the unique characteristics of each modality, we design an optimal scale multilayer brain network, the inter-layer connections of which depend on node informativeness. Then, a multilayer informativeness diffusion is proposed to capture complementary information and unique characteristics from various modalities and generate node representations by incorporating the features of each node with those of their connected nodes. Finally, the node representations are reconfigured using principal component analysis (PCA), and cosine distances are calculated with reference to multiple templates for statistical analysis and classification. We implement the proposed method for brain network analysis of neuropsychiatric disorders. The results indicate that our method effectively identifies crucial brain regions associated with diseases, providing valuable insights into the pathology of the disease, and surpasses other advanced methods in classification performance.