Extreme terahertz magnon multiplication induced by resonant magnetic pulse pairs.

Nonlinear interactions of spin-waves and their quanta, magnons, have emerged as prominent candidates for interference-based technology, ranging from quantum transduction to antiferromagnetic spintronics. Yet magnon multiplication in the terahertz (THz) spectral region represents a major challenge. Intense, resonant magnetic fields from THz pulse-pairs with controllable phases and amplitudes enable high order THz magnon multiplication, distinct from non-resonant nonlinearities such as the high harmonic generation by below-band gap electric fields. Here, we demonstrate exceptionally high-order THz nonlinear magnonics. It manifests as 7th-order spin-wave-mixing and 6th harmonic magnon generation in an antiferromagnetic orthoferrite. We use THz two-dimensional coherent spectroscopy to achieve high-sensitivity detection of nonlinear magnon interactions up to six-magnon quanta in strongly-driven many-magnon correlated states. The high-order magnon multiplication, supported by classical and quantum spin simulations, elucidates the significance of four-fold magnetic anisotropy and Dzyaloshinskii-Moriya symmetry breaking. Moreover, our results shed light on the potential quantum fluctuation properties inherent in nonlinear magnons.

[Jianpi Zishen granule inhibits podocyte autophagy in systemic lupus erythematosus: a network pharmacology and clinical study].

OBJECTIVE: To explore the therapeutic mechanism of Jianpi Zishen (JPZS) granules for systemic lupus erythematosus(SLE) in light of podocyte autophagy regulation. METHODS: TCMSP, GeneCards, OMIM, and TTD databases were used to obtain the targets of JPZS granules, SLE, and podocyte autophagy. The protein-protein interaction network was constructed using Cytoscape, and the key active ingredients and targets were screened for molecular docking. In the clinical study, 46 patients with SLE were randomized into two groups to receive baseline treatment with prednisone acetate and mycophenolate mofetil (control group) and additional treatment with JPZS granules (observation group) for 12 weeks, with 10 healthy volunteers as the healthy control group. Urinary levels of nephrin and synaptopodin of the patients were detected with ELISA. Western blotting was performed to determine peripheral blood levels of p-JAK1/JAK1, p-STAT1/STAT1, LC3II/LC3I, and p62 proteins of the participants. RESULTS: Four key active ingredients and 5 core target genes (STAT1, PIK3CG, MAPK1, PRKCA, and CJA1) were obtained, and enrichment analysis identified the potentially involved signaling pathways including AGE-RAGE, JAK/STAT, EGFR, and PI3K/Akt. Molecular docking analysis showed that STAT1 was the most promising target protein with the highest binding activity, suggesting its role as an important mediator for signal transduction after JPZS granule treatment. In the 43 SLE patients available for analysis, treatment with JPZS granule significantly reduced serum levels of p-JAK1/JAK1, p-STAT1/STAT1, and LC3II/LC3I (P < 0.05 or 0.01), increased the protein level of P62 (P < 0.05), and reduced urinary levels of nephrin and synaptopodin (P < 0.05). CONCLUSION: The therapeutic effect of JPZS granules on SLE is mediated probably by coordinated actions of quercetin, kaempferol, ß-sitosterol, and isorhamnetin on their target gene STAT1 to inhibit the JAK/STAT pathway, thus suppressing autophagy and alleviating podocyte injuries in SLE.

[Epidemic characteristics and trend analysis of major injuries deaths among children and adolescents in Jiangsu Province from 2012 to 2021].

Objective: To understand the situation and epidemic characteristics of injury deaths among children aged 5 to 24 years in Jiangsu Province from 2012 to 2021 and the trend of annual changes. Methods: The main injury mortality data of children and adolescents was collected, and the crude and standardized mortality rates of road traffic accidents, drowning, suicide, and accidental falls among children and adolescents over a decade and the annual average percentage of change (AAPC) were calculated. The main injury mortality characteristics and trends of children and adolescents of different age groups and genders were analyzed. Results: The total number of injury deaths among 5 to 24 adolescents in Jiangsu Province was 16 052, with a standardized mortality rate of 9.58/100 000. There was no significant trend in the overall standardized mortality rate of injuries (AAPC=-3.450%, P=0.055). The standardized mortality rate of road traffic injuries among children and adolescents showed a decreasing trend over the past decade, with statistical significance (AAPC=-9.406%, P<0.001). The standardized suicide mortality rate showed an upward trend over the past decade, with statistical significance (AAPC=9.000%, P=0.001). The overall injury mortality rate showed an upward trend with age. Suicide rates in males and females were on the rise and both have statistical significance (AAPC=9.420% and AAPC=9.607%, both P<0.05). The standardized mortality rates of female traffic accidents, drowning, and male traffic accidents showed a decreasing trend and were statistically significant (AAPC for female traffic accidents=-7.364%, AAPC for female drowning=-5.352%, and AAPC for male traffic accidents=-10.242%, all P<0.05). The standardized mortality rate of urban and rural traffic accidents showed a decreasing trend and was statistically significant(AAPC=-7.899% and AAPC=-9.421%, both P<0.001). The standardized suicide mortality rate showed an upward trend and statistical significance (AAPC=11.009% and AAPC=7.528%, both P<0.05). Conclusions: The overall injury situation of children and adolescents in Jiangsu Province improved in the past decade from 2012 to 2021, but the suicide mortality rate was on the rise. It is necessary to focus on the mental health issues of this age group and to strengthen the prevention and control of suicide among children and adolescents, in Jiangsu.

Application of machine learning techniques in the diagnostic approach of PTSD using MRI neuroimaging data: A systematic review.

Background: At present, the diagnosis of post-traumatic stress disorder（PTSD） mainly relies on clinical symptoms and psychological scales, and finding objective indicators that are helpful for diagnosis has always been a challenge in clinical practice and academic research. Neuroimaging is a useful and powerful tool for discovering the biomarkers of PTSD,especially functional MRI (fMRI), structural MRI (sMRI) and Diffusion Weighted Imaging（DTI）are the most commonly used technologies, which can provide multiple perspectives on brain function, structure and its connectivity. Machine learning (ML) is an emerging and potentially powerful method, which has aroused people's interest because it is used together with neuroimaging data to define brain structural and functional abnormalities related to diseases, and identify phenotypes, such as helping physicians make early diagnosis. Objectives: According to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) declaration, a systematic review was conducted to assess its accuracy in distinguishing between PTSD patients, TEHC(Trauma-Exposed Healthy Controls), and HC(healthy controls). Methods: We searched PubMed, Embase, and Web of Science using common words for ML methods and PTSD until June 2023, with no language or time limits. This review includes 13 studies, with sensitivity, specificity, and accuracy taken from each publication or acquired directly from the authors. Results: All ML techniques have an diagnostic accuracy rate above 70%，and support vector machine（SVM） are the most commonly used techniques. This series of studies has revealed significant neurobiological differences in key brain regions among individuals with PTSD, TEHC, and HC. The connectivity patterns of regions such as the Insula and Amygdala hold particular significance in distinguishing these groups. TEHC exhibits more normal connectivity patterns compared to PTSD, providing valuable insights for the application of machine learning in PTSD diagnosis. Conclusion: In contrast to any currently available assessment and clinical diagnosis, ML techniques can be used as an effective and non-invasive support for early identification and detection of patients as well as for early screening of high-risk populations.

HEIDI: an experiment-management platform enabling high-throughput fragment and compound screening.

The Swiss Light Source facilitates fragment-based drug-discovery campaigns for academic and industrial users through the Fast Fragment and Compound Screening (FFCS) software suite. This framework is further enriched by the option to utilize the Smart Digital User (SDU) software for automated data collection across the PXI, PXII and PXIII beamlines. In this work, the newly developed HEIDI webpage (https://heidi.psi.ch) is introduced: a platform crafted using state-of-the-art software architecture and web technologies for sample management of rotational data experiments. The HEIDI webpage features a data-review tab for enhanced result visualization and provides programmatic access through a representational state transfer application programming interface (REST API). The migration of the local FFCS MongoDB instance to the cloud is highlighted and detailed. This transition ensures secure, encrypted and consistently accessible data through a robust and reliable REST API tailored for the FFCS software suite. Collectively, these advancements not only significantly elevate the user experience, but also pave the way for future expansions and improvements in the capabilities of the system.

The efficacy and safety of venetoclax combined with demethylating agents in elderly patients with acute myeloid leukemia: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to evaluate the efficacy and adverse effects of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia. MATERIALS AND METHODS: A comprehensive literature search identified related studies from PubMed, Medline, Embase, Scopus, and Cochrane Library. Overall complete remission (CR) and overall response rate (ORR) were applied to evaluate the efficacy of venetoclax in combination with hypomethylating agents in elderly with acute myeloid leukemia, and incidence of grade 3-4 adverse events were used to evaluate the safety. RESULTS: 10 studies, including a total of 930 patients, were identified in our study and analyzed using the random-effects model. Meta-analysis showed the pooled overall CR rate of 70% (95% CI: 63-77%), the pooled ORR rate of 53% (95% CI: 39-67%), and the median overall survival ranged from 7.7 to 16.9 months. A total of 6 studies reported related adverse events, mainly including thrombocytopenia, febrile neutropenia, neutropenia, leukopenia, anemia, and pneumonia. The pooled incidence of overall adverse events was 30% (95% CI: 22-38%), and all adverse events were tolerable and resolved with treatment. CONCLUSIONS: The combination of venetoclax and demethylating drugs has a good therapeutic effect on elderly patients with acute myeloid leukemia, but it also induces some adverse events. Although this therapy has a small impact on the quality of life, further attention is still needed to reduce the occurrence of such adverse events.

[Prognostic significance of textbook outcome in advanced gastric patients who underwent neoadjuvant chemotherapy followed by surgical resection].

Objective: To investigate the risk factors and prognostic value of the textbook outcome (TO) in patients with advanced gastric cancer (AGC) who underwent neoadjuvant chemotherapy followed by surgical resection. Methods: This is a retrospective cohort study. A total of 253 patients with AGC who underwent neoadjuvant chemotherapy combined with gastrectomy and D2 lymphadenectomy in the Department of Gastric Surgery, Fujian Medical University Union Hospital from January 2010 to December 2019 were retrospectively included. There were 195 males and 58 females, aged (60.3±10.0) years (range: 27 to 75 years). The patients were then divided into the TO group (n=168) and the non-TO group (n=85). Multivariate Logistic regression was used to analyze the independent predictors of TO. Univariate and multivariate Cox analysis were used to analyze independent prognosis factors for overall survival (OS) and disease-free survival (DFS). Propensity score matching was performed to balance the TO and non-TO groups, and the Kaplan-Meier method was used to calculate survival rates and draw survival curves. Results: Among the 253 patients, 168 patients (66.4%) achieved TO. The Eastern Cooperative Oncology Group score (OR=0.488, 95%CI: 0.278 to 0.856, P=0.012) and ypN stage (OR=0.626, 95%CI:0.488 to 0.805, P<0.01) were independently predictive of TO. Multivariate analysis revealed that TO was an independent risk factor for both OS (HR=0.662, 95%CI: 0.457 to 0.959,P=0.029) and DFS (HR=0.687, 95%CI: 0.483 to 0.976, P=0.036). After matching, the 5-year OS rate (42.2% vs. 27.8%) and the 5-year DFS rate (37.5% vs. 27.8%) were significantly higher in the TO group than in the non-TO group (both P<0.05). Furthermore, patients in the non-TO group benefited significantly from postoperative chemotherapy (both P<0.05), but those in the TO group did not (both P>0.05). Conclusion: TO is an independent prognosis factor in patients undergoing neoadjuvant chemotherapy and surgery for AGC and is associated with postoperative chemotherapy benefits.

[Quality control of gastric resection range in laparoscopic locally advanced gastric cancer].

After nearly 30 years of exploration and practice, minimally invasive surgical techniques represented by laparoscopic technology have become an important means for the surgical treatment of gastric cancer. In China, laparoscopic radical resection for locally advanced gastric cancer has been extensively carried out. However, there are still controversies regarding the gastric resection range and methods for advanced gastric cancer. By reviewing relevant domestic and foreign guideline documents and combining team practice experience, this article elaborates on the key points of quality control of laparoscopic gastric resection range for locally advanced gastric cancer from aspects such as tumor localization and gastric resection range for upper, middle and lower gastric tumors. It aims to provide reference for carrying out and promoting laparoscopic radical gastrectomy more safely.

Robust unfolding of MeV x-ray spectra from filter stack spectrometer data.

We present an inversion method capable of robustly unfolding MeV x-ray spectra from filter stack spectrometer (FSS) data without requiring an a priori specification of a spectral shape or arbitrary termination of the algorithm. Our inversion method is based upon the perturbative minimization (PM) algorithm, which has previously been shown to be capable of unfolding x-ray transmission data, albeit for a limited regime in which the x-ray mass attenuation coefficient of the filter material increases monotonically with x-ray energy. Our inversion method improves upon the PM algorithm through regular smoothing of the candidate spectrum and by adding stochasticity to the search. With these additions, the inversion method does not require a physics model for an initial guess, fitting, or user-selected termination of the search. Instead, the only assumption made by the inversion method is that the x-ray spectrum should be near a smooth curve. Testing with synthetic data shows that the inversion method can successfully recover the primary large-scale features of MeV x-ray spectra, including the number of x-rays in energy bins of several-MeV widths to within 10%. Fine-scale features, however, are more difficult to recover accurately. Examples of unfolding experimental FSS data obtained at the Texas Petawatt Laser Facility and the OMEGA EP laser facility are also presented.

China's prevention and control experience of echinococcosis: A 19-year retrospective.

Echinococcosis poses a significant threat to public health. The Chinese government has implemented prevention and control measures to mitigate the impact of the disease. By analyzing data from the Chinese Center for Disease Control and Prevention and the State Council of the People's Republic of China, we found that implementation of these measures has reduced the infection rate by nearly 50% between 2004 to 2022 (from 0.3975 to 0.1944 per 100,000 person-years). Nonetheless, some regions still bear a significant disease burden, and lack of detailed information limites further evaluation of the effects on both alveolar and cystic echinococcosis. Our analysis supports the continuing implementation of these measures and suggests that enhanced wildlife management, case-based strategies, and surveillance systems will facilitate disease control.

[Research hot spots and trends of keratoconus in China: a bibliometric analysis].

Objective: To review the studies related to keratoconus in China, investigate research hotspots and development trends in this field, and provide reference for future research. Methods: This is a bibliometrics study. The relevant literature written in Chinese was retrieved from the WanFang DATA and the China National Knowledge Infrastructure, English articles were collected from the Web of Science Core Collection database. Searched for journal articles related to keratoconus VOSviewer software, CiteSpace, and Bibliometrix in the R language were employed to create the knowledge map. The analysis encompassed the distribution of published journals, research collaboration networks of countries/regions, institutions, and authors. Additionally, core authors, high-frequency keyword co-occurrence, keyword topic maps, and keyword emergence time ranking were examined. Results: The study ultimately included 1 100 Chinese articles and 668 English articles. Chinese literature and English literature began to increase in 1997 and 2009, respectively, indicating that the field is currently in a developmental stage. The publications involved 244 Chinese journals and 150 English journals, predominantly in the field of ophthalmology. The United States collaborated the most with China, contributing to 123 articles, followed by other countries such as the United Kingdom and Switzerland. Chinese literature and English literature involved 552 and 883 institutions, respectively. The institution with the highest number of Chinese literature publications was the Eye Institute of Shandong First Medical University (63 papers), while Wenzhou Medical University had the highest number of English literature publications (91 papers). Chinese literature involved 2 435 authors, and English literature involved 2 073 authors. The largest collaboration cluster in Chinese literature was formed by the teams of Xie Lixin and Shi Weiyun, while the Gao Hua team formed the largest cluster in English literature. However, collaboration between authors was primarily limited to within each team. A total of 622 and 1 611 keywords were extracted from Chinese and English literature, respectively. The node centrality of the four Chinese keywords, "keratoconus", "cornea", "corneal transplantation" and "myopia" as well as the three English keywords, "keratoconus", "collagen cross-linking" and "penetrating keratoplasty" was greater than 0.1. "Collagen", "riboflavin", "corneal transplantation" and "ultraviolet A" were identified as common core hotspots and important research topics in Chinese and English literature on keratoconus. Keyword emergence analysis indicated that the keywords with the highest intensity of emergence in Chinese and English literature were "myopia" (13.54) and "penetrating keratoplasty" (9.99), respectively. The longest emergence time was observed for "contact lenses" (1995-2006) and "penetrating keratoplasty" (2003-2014). Conclusions: At present, research on keratoconus in China is on the rise, with research hotspots including pathogenesis, various new surgical methods, and improvement in quality of life. The future research trend mainly focuses on early diagnosis and screening methods, artificial intelligence, biomechanical examination, subclinical keratoconus, and small incision lenticule extraction.

[Effect of changes in posterior tibial slope on the mid-term clinical outcomes of Oxford unicompartmental knee arthroplasty].

Objective: To investigate the impact of changes in the posterior tibial slope (PTS) in Oxford unicompartmental knee arthroplasty (OUKA) on the mid-term clinical outcomes of postoperative patients. Methods: This study was a follow-up study. The data of 135 patients (150 knees) who underwent OUKA at the China-Japan Friendship Hospital from January 2012 to January 2013 were analyzed retrospectively. The patients were followed-up for at least ten years. According to the changes in PTS of the medial tibial plateau before and after surgery, patients were divided into three groups: group A (PTS decreased by more than 5°), group B (PTS changed by 5° or less), and group C (PTS increased by more than 5°). The Knee Society Clinical Score (KSS-C), Knee Society Functional Score (KSS-F), Oxford Knee Score (OKS), Forgotten Joint Score (FJS), and knee range of motion (ROM) among the three groups were compared at the last follow-up. Results: Prior to the final follow-up assessment, six patients expired, and an additional nine patients were lost to follow-up. A total of 120 patients (135 knees) were enrolled in this study (30 males and 90 females). The mean age was (66.29±8.62) years, and the follow-up time was (10.54±0.72) years. Group A consisted of 32 patients (34 knees), group B comprised 77 patients (90 knees), and group C included 11 patients (11 knees). One knee in group A suffered prosthesis loosening, and two knees in group C experienced postoperative bearing dislocation, one knee encountered bearing fragmentation. The incidence of postoperative complications differed significantly among the three groups (P<0.05). The preoperative OKS was (33.91±6.59) points, KSS-F was (43.46±8.99) points, KSS-C was (41.05±5.70) points and ROM was 115.23°±13.53°; after the surgery, they changed to (18.82±7.01) points, (81.51±7.34) points, (82.64±7.94) points, and 119.07°±8.62°, respectively, and all the differences were statistically significant (all P<0.001). In terms of postoperative outcomes, group A had an OKS of (21.44±8.46) points and a FJS of (63.83±11.40) points, group B had an OKS of (17.07±5.81) points and a FJS of (70.49±12.45) points, group C had an OKS of (25.09±5.07) points and a FJS score of (59.48±10.09) points; the differences among the three groups were all statistically significant (all P<0.05), but there were no significant differences in the postoperative KSS scores and ROM among the three groups (all P>0.05). Conclusions: After OUKA, better mid-term clinical outcomes are achieved when ΔPTS is<5°. Although the recommended central value for PTS in OUKA is 7° according to Oxford, it should be individualized, and it is recommended to consider the preoperative angle, with a change of less than 5° before and after surgery.

Realization of a crosstalk-avoided quantum network node using dual-type qubits of the same ion species.

Generating ion-photon entanglement is a crucial step for scalable trapped-ion quantum networks. To avoid the crosstalk on memory qubits carrying quantum information, it is common to use a different ion species for ion-photon entanglement generation such that the scattered photons are far off-resonant for the memory qubits. However, such a dual-species scheme can be subject to inefficient sympathetic cooling due to the mass mismatch of the ions. Here we demonstrate a trapped-ion quantum network node in the dual-type qubit scheme where two types of qubits are encoded in the S and F hyperfine structure levels of 171Yb+ ions. We generate ion photon entanglement for the S-qubit in a typical timescale of hundreds of milliseconds, and verify its small crosstalk on a nearby F-qubit with coherence time above seconds. Our work demonstrates an enabling function of the dual-type qubit scheme for scalable quantum networks.

TNFSF14 mediates the impact of docosahexaenoic acid on atopic dermatitis: a Mendelian randomization study.

OBJECTIVE: While current research suggests potential value for docosahexaenoic acid (DHA) in the prevention and management of atopic dermatitis (AD), the causal relationship between DHA and AD remains unclear, and the underlying mechanisms are not well understood. MATERIALS AND METHODS: To investigate the potential causal relationship between DHA and AD, as well as to explore potential mediating mechanisms, we employed the Mendelian randomization (MR) methods. To study these potential relationships, we conducted MR analysis using publicly available Genome-Wide Association Studies (GWAS) data. Effect estimates were computed using the random-effects inverse-variance weighted method. RESULTS: Our study demonstrates a negative correlation between DHA levels and AD risk (OR: 0.915, 95% CI: 0.858-0.975, p=0.007). Furthermore, in MR analysis using tumor necrosis factor ligand superfamily member 14 (TNFSF14) levels as an outcome, DHA levels also show a negative association with TNFSF14 levels (OR: 0.933, 95% CI: 0.879-0.990, p=0.022). Subsequently, we performed further analysis to explore the relationship between TNFSF14 and AD risk, revealing a positive correlation (OR: 1.069, 95% CI: 1.005-1.137, p=0.033). This suggests a potential mediating role of TNFSF14 in the impact of DHA on AD risk. CONCLUSIONS: In summary, our study employs MR analysis to offer genetic evidence indicating a potential role of DHA in reducing the risk of AD, as well as opening avenues for further in-depth investigation into potential mechanisms. These findings emphasize the importance of ongoing research in this field.

Rapid Intrafibrillar Mineralization Strategy Enhances Adhesive-Dentin Interface.

Biomimetic mineralization of dentin collagen appears to be a promising strategy to optimize dentin bonding durability. However, traditional postbonding mineralization strategies based on Ca/P ion release still have some drawbacks, such as being time-consuming, having a spatiotemporal mismatch, and having limited intrafibrillar minerals. To tackle these problems, a prebonding rapid intrafibrillar mineralization strategy was developed in the present study. Specifically, polyacrylic acid-stabilized amorphous calcium fluoride (PAA-ACF) was found to induce rapid intrafibrillar mineralization of the single-layer collagen model and dentin collagen at just 1 min and 10 min, as identified by transmission electron microscopy, scanning electron microscopy, and atomic force microscopy. This strategy has also been identified to strengthen the mechanical properties of demineralized dentin within a clinically acceptable timeframe. Significantly, the bonding strength of the PAA-ACF-treated groups outperformed the control group irrespective of aging modes. In addition, the endogenous matrix metalloproteinases as well as exogenous bacterial erosion were inhibited, thus reducing the degradation of dentin collagen. High-quality integration of the hybrid layer and the underlying dentin was also demonstrated. On the basis of the present results, the concept of "prebonding rapid intrafibrillar mineralization" was proposed. This user-friendly scheme introduced PAA-ACF-based intrafibrillar mineralization into dentin bonding for the first time. As multifunctional primers, PAA-ACF precursors have the potential to shed new light on prolonging the service life of adhesive restorations, with promising significance.

Analysis of Extracellular ATP Distribution in the Intervertebral Disc.

Progressive loss of proteoglycans (PGs) is the major biochemical change during intervertebral disc (IVD) degeneration. Adenosine triphosphate (ATP) as the primary energy source is not only critical for cell survival but also serves as a building block in PG synthesis. Extracellular ATP can mediate a variety of physiological functions and was shown to promote extracellular matrix (ECM) production in the IVD. Therefore, the objective of this study was to develop a 3D finite element model to predict extracellular ATP distribution in the IVD and evaluate the impact of degeneration on extracellular ATP distribution. A novel 3D finite element model of the IVD was developed by incorporating experimental measurements of ATP metabolism and ATP-PG binding kinetics into the mechano-electrochemical mixture theory. The new model was validated by experimental data of porcine IVD, and then used to analyze the extracellular distribution of ATP in human IVDs. Extracellular ATP was shown to bind specifically with PGs in IVD ECM. It was found that annulus fibrosus cells hydrolyze ATP faster than that of nucleus pulposus (NP) cells whereas NP cells exhibited a higher ATP release. The distribution of extracellular ATP in a porcine model was consistent with experimental data in our previous study. The predictions from a human IVD model showed a high accumulation of extracellular ATP in the NP region, whereas the extracellular ATP level was reduced with tissue degeneration. This study provides an understanding of extracellular ATP metabolism and its potential biological influences on the IVD via purinergic signaling.

Multiparametric MRI-based radiomics nomogram for predicting the hormone receptor status of HER2-positive breast cancer.

AIM: To investigate the value of multiparametric magnetic resonance imaging (MRI)-based radiomics nomograms for predicting the hormone receptor (HR) status of HER2-positive breast cancer. MATERIALS AND METHODS: Patients with HER2-positive invasive breast cancer were divided randomly into training (68 patients) and validation (30 patients) sets. All were classified as either HR-positive (HR+) or negative (HR-) at histopathology. Two radiologists outlined the three-dimensional (3D) volumetric regions of interest (VOI) on the MRI images. Features (n=1,096) were extracted from the T2-weighted imaging (WI), apparent diffusion coefficient (ADC), and dynamic contrast-enhanced (DCE) images separately. Dimensionality was reduced using feature screening. Binary radiomics prediction models were established using a logistic regression classifier and were validated in the validation set. To construct a nomogram, independent predictors were identified using multivariate logistic regression analysis. The predictive efficacy of the model was assessed using the area under the receiver operating characteristic curve (AUC). RESULTS: Ten radiomics features were obtained after feature dimensionality reduction based on the merged T2WI, ADC, and DCE images. The diagnostic efficacy of the radiomics signature using the three sequences was better than that of any single sequence (training set AUC: 0.797; validation set AUC: 0.75). Using multivariate logistic regression analysis, the independent predictors for identifying HR status were combined radiomics signature and peritumoural oedema. Nomograms constructed by combining the radiomics signature and peritumoural oedema showed good discrimination in both the training and validation sets (AUC: 0.815 and 0. 805, respectively). CONCLUSION: A multiparametric MRI-based nomogram incorporating the radiomics signature and peritumoural oedema can assess the HR status of HER2-positive breast cancer. The resulting model can improve diagnostic accuracy, improving patient outcomes.

Endochondral Repair of Jawbone Defects Using Periosteal Cell Spheroids.

Recapitulation of the natural healing process is receiving increasing recognition as a strategy to induce robust tissue regeneration. Endochondral ossification has been recognized as an essential reparative approach in natural jawbone defect healing. However, such an approach has been overlooked in the recent development of cell-based therapeutics for jawbone repair. Therefore, this study aimed to explore a bioinspired stem cell-based strategy for jawbone repair by mimicking the mesenchymal condensation of progenitor cells during the early endochondral ossification process. For this purpose, passage 3 of jawbone periosteum-derived cells (jb-PDCs) was cultured in our previously reported nonadherent microwells (200 µm in diameter, 148 µm in depth, and 100 µm space in between) and self-assembled into spheroids with a diameter of 96.4 ± 5.8 µm after 48 h. Compared to monolayer culture, the jb-PDC spheroids showed a significant reduction of stemness marker expression evidenced by flow cytometry. Furthermore, a significant upregulation of chondrogenic transcription factor SOX9 in both gene and protein levels was observed in the jb-PDC spheroids after 48 h of chondrogenic induction. RNA sequencing and Western blotting analysis further suggested that the enhanced SOX9-mediated chondrogenic differentiation in jb-PDC spheroids was attributed to the activation of the p38 MAPK pathway. Impressively, inhibition of p38 kinase activity significantly attenuated chondrogenic differentiation jb-PDC spheroids, evidenced by a significant decline of SOX9 in both gene and protein levels. Strikingly, the jb-PDC spheroids implanted in 6- to 8-wk-old male C57BL/6 mice with critical-size jawbone defects (1.8 mm in diameter) showed an evident contribution to cartilaginous callus formation after 1 wk, evidenced by histological analysis. Furthermore, micro-computed tomography analysis showed that the jb-PDC spheroids significantly accelerated bone healing after 2 wk in the absence of exogenous growth factors. In sum, the presented findings represent the successful development of cell-based therapeutics to reengineer the endochondral bone repair process and illustrate the potential application to improve bone repair and regeneration in the craniofacial skeleton.

Physicians are over optimistic in recognizing inpatients' survival and palliative care needs: a large-scale multi-center study in Taiwan.

BACKGROUND: Physicians' recognition of end of life (EOL) has key influences on patients' 'good death'. AIM: We aimed to study physicians' attitude toward EOL, and to analyze the relationship between physicians' assessment and patients' actual survival and the trigger effect on patient's access to palliative consultation and palliative care. DESIGN: This is a multi-center retrospective cohort study in seven community hospitals in Taiwan. METHODS: Inpatients admitted between 1 March 2016 and 31 December 2020, scored ≥4 points using Taiwan version-Palliative Care Screening Tool (TW-PCST), and expired before 31 December 2020 were enrolled. Physicians answered three questions regarding these inpatients: 'surprised of mortality within 6-12 months', 'EOL' and 'in need of palliative care'. We followed up patients' actual survival and access to palliative consultation and services. RESULTS: We enrolled 10 304 cases. There was high correlation among the three questions. The median survival of patients with 'not surprised of death within 6-12 months', 'EOL', and 'needing palliative care' were 68, 60 and 58 days, respectively. Those with opposite responses were 206, 166 and 186 days, respectively. Patients' main diagnosis, TW-PCST score, physicians' palliative care qualifications and reward measures were all associated with physicians' recognition of EOL. Physicians' assessment, physicians' training, disease characteristics and TW-PSCT scores were all associated with palliative consultation and palliative care. CONCLUSIONS: Physicians are still over optimistic in recognizing inpatients' survival and palliative care needs. EOL talks can be initiated when the TW-PCST score is high. Universal palliative care training can be integrated into medical education.