T-cell subsets and cytokines are indicative of neoadjuvant chemoimmunotherapy responses in NSCLC.

PURPOSE: Neoadjuvant PD-1 blockade combined with chemotherapy is a promising treatment for resectable non-small cell lung cancer (NSCLC), yet the immunological mechanisms contributing to tumor regression and biomarkers corresponding to different pathological responses remain unclear. METHODS: Using dynamic and paired blood samples from NSCLC patients receiving neoadjuvant chemoimmunotherapy, we analyzed the frequencies of CD8 + T-cell and Treg subsets and their dynamic changes during neoadjuvant treatment through flow cytometry. Cytokine profiles and function-related gene expression of CD8 + T cells and Tregs were analyzed through flow cytometry and mRNA-seq. Infiltrating T-cell subsets in resected tissues from patients with different pathological responses were analyzed through multiplex immunofluorescence. RESULTS: Forty-two NSCLC patients receiving neoadjuvant chemoimmunotherapy were enrolled and then underwent surgical resection and pathological evaluation. Nineteen patients had pCR (45%), 7 patients had MPR (17%), and 16 patients had non-MPR (38%). In patients with pCR, the frequencies of CD137 + CD8 + T cells (P = 0.0475), PD-1 + Ki-67 + CD8 + T cells (P = 0.0261) and Tregs (P = 0.0317) were significantly different from those of non-pCR patients before treatment. pCR patients usually had low frequencies of CD137 + CD8 + T cells, PD-1 + Ki-67 + CD8 + T cells and Tregs, and their AUCs were higher than that of tissue PD-L1 expression. Neoadjuvant chemoimmunotherapy markedly improved CD8 + T-cell proliferation and activation, especially in pCR patients, as the frequencies of CD137 + CD8 + (P = 0.0136) and Ki-67 + CD8 + (P = 0.0391) T cells were significantly increased. The blood levels of cytokines such as IL-2 (P = 0.0391) and CXCL10 (P = 0.0195) were also significantly increased in the pCR group, which is consistent with the high density of activated cytotoxic T cells at the tumor site (P < 0.0001). CONCLUSION: Neoadjuvant chemoimmunotherapy drives CD8 + T cells toward a proliferative and active profile. The frequencies of CD137 + CD8 + T cells, PD-1 + Ki-67 + CD8 + T cells and Tregs at baseline might predict the response to neoadjuvant chemoimmunotherapy in NSCLC patients. The increase in IL-2 and CXCL10 might reflect the chemotaxis and enrichment of cytotoxic T cells at the tumor site and a better response to neoadjuvant chemoimmunotherapy.

Protein-Integrated Hydrogen-Bonded Organic Frameworks: Chemistry and Biomedical Applications.

Hydrogen-bonded organic frameworks (HOFs) are porous nanomaterials that offer exceptional biocompatibility and versatility for integrating proteins for biomedical applications. This minireview concisely discusses recent advancements in the chemistry and functionality of protein-HOF interfaces. It particularly focuses on strategic methodologies, such as the careful selection of building blocks and the genetic engineering of proteins, to facilitate protein-HOF interactions. We examine the role of enzyme encapsulation within HOFs, highlighting its capability to preserve enzyme function, a crucial aspect for applications in biosensing and disease diagnosis. Moreover, we discuss the emerging utility of nanoscale HOFs for intracellular protein delivery, illustrating their applicability as nanoreactors for intracellular catalysis and neuroprotective biorthogonal catalysis within cellular compartments. We highlight the significant advancement of designing biodegradable HOFs tailored for cytosolic protein delivery, underscoring their promising application in targeted cancer therapies. Finally, we provide a perspective viewpoint on the design of biocompatible protein-HOF assemblies, underlining their promising prospects in drug delivery, disease diagnosis, and broader biomedical applications.

TMEM119 (c.G143A, p.S48L) Mutation Is Involved in Primary Failure of Eruption by Attenuating Glycolysis-Mediated Osteogenesis.

Primary failure of eruption (PFE) is a rare oral disease with an incidence rate of 0.06%. It is characterized by abnormal eruption mechanisms that disrupt tooth eruption. The underlying pathogenic genetic variant and mechanism of PFE remain largely unknown. The purpose of this study was to explore the role of a novel transmembrane protein 119 (TMEM119) mutation in two PFE patients in a Chinese family. Information collection was performed on the family with a diagnosis of PFE, and blood samples from patients and healthy family members were extracted. Whole-exome sequencing was performed. Bioinformatics analysis revealed that a heterozygous variant in the TMEM119 gene (c.G143A, p.S48L) was a disease-associated mutation in this family. Recombinant pcDNA3.1 plasmid-containing wild-type and mutant TMEM119 expression cassettes were successfully constructed and transfected into MC3T3-E1 cells, respectively. The results of in vitro analysis suggested that the subcellular distribution of the TMEM119 protein was transferred from the cell cytoplasm to the nucleus, and the ability of cells to proliferate and migrate as well as glycolytic and mineralized capacities were reduced after mutation. Furthermore, rescue assays showed that activating transcription factor 4 (ATF4) overexpression rescued the attenuated glycolysis and mineralization ability of cells. Results of in vivo analysis demonstrated that TMEM119 was mainly expressed in the alveolar bone around the mouse molar germs, and the expression level increased with tooth eruption, demonstrated using immunohistochemistry and immunofluorescence. Collectively, the novel TMEM119 mutation is potentially pathogenic in the PFE family by affecting the glucose metabolism and mineralized function of osteoblasts, including interaction with ATF4. Our findings broaden the gene mutation spectrum of PFE and further elucidate the pathogenic mechanism of PFE.

Unleashing the Power of Proenzyme Delivery for Targeted Therapeutic Applications Using Biodegradable Lipid Nanoparticles.

ConspectusProenzymes, functioning as inactive precursor forms of enzymes, hold significant promise for regulating essential biological processes. Their inherent property of latency, remaining inert until they arrive at the intended site of action, positions them as particularly promising candidates for the development of targeted therapeutics. Despite this potential, the therapeutic potential of proenzymes is challenged by designing proenzymes with excellent selectivity for disease cells. This limitation is further exacerbated by the inability of proenzymes to spontaneously cross the cell membrane, a biological barrier that impedes the cellular internalization of exogenous macromolecules. Therefore, efficacious intracellular delivery is paramount to unlocking the full therapeutic potency of proenzymes.In this Account, we first elucidate our recent advancements made in designing biodegradable lipid nanoparticles (LNPs) for the cell-specific delivery of biomacromolecules, including proteins and nucleic acids. Using a strategy of parallel synthesis, we have constructed an extensive library of ionizable lipids, each integrated with different biodegradable moieties. This combinatorial approach has led to the identification of LNPs that are particularly efficacious for the delivery of biomacromolecules specifically to tumor cells. This innovation capitalizes on the unique intracellular environment of cancer cells to control the degradation of LNPs, thereby ensuring the targeted release of therapeutics within tumor cells. Additionally, we discuss the structure-activity relationship governing the delivery efficacy of these LNPs and their applicability in regulating tumor cell signaling, specifically through the delivery of bacterial effector proteins.In the second segment, we aim to provide an overview of our recent contributions to the field of proenzyme design, where we have chemically tailored proteins to render them responsive to the unique milieu of tumor cells. Specifically, we elaborate on the chemical principles employed to modify proteins and DNAzymes, thereby priming them for activation in the presence of NAD(P)H:quinone oxidoreductase 1 (NQO1), an enzyme that is prevalently upregulated within tumor cells. We summarize the methodologies for intracellular delivery of these proenzymes using biodegradable LNPs, both in vitro and in vivo. The concomitant intracellular delivery and activation of proenzymes are examined in the context of enhanced therapeutic outcomes and targeted CRISPR/Cas9 genome editing.In conclusion, we offer a perspective on the chemical principles that could be leveraged to optimize LNPs for tissue-specific delivery of proenzymes. We also explore chemical strategies for the irreversible modulation of proenzyme activity within living cells and in vivo. Through this discussion, we provide insights into potential avenues for overcoming existing limitations and enhancing the delivery of proenzymes using LNPs, particularly for developing tumor-targeted therapies and genome editing applications.

The Impact of Inadequate Energy Intake on Readmission Burden of Patients With Heart Failure.

BACKGROUND: Adequate energy intake is essential for good clinical outcomes. The association between energy intake and readmission burden of patients with heart failure (HF) still needs to be clarified. OBJECTIVE: In this study, our aim was to determine the association between energy intake and readmission in patients with HF. METHODS: A total of 311 inpatients with HF were recruited. Demographic and clinical information were collected during hospitalization; the daily diets of the participants were collected in the second week after discharge using the 3-day diet record, and the energy intake was calculated using a standardized nutrition calculator. The inadequate energy intake was defined as <70% × 25 kcal/kg of ideal body weight. The participants were followed up for 12 weeks after discharge. The number, reasons, and length of stay of unplanned readmissions were collected. Regression analyses were used to evaluate the associations between inadequate energy intake, and readmission rate and readmission days. RESULTS: The median of the energy intake of participants was 1032 (interquartile range, 809-1266) kcal/d. The prevalence of inadequate energy intake was 40%. Patients with inadequate energy intake had a higher risk of unplanned readmission (odds ratio, 5.616; 95% confidence interval, 3.015-10.462; P < .001) and more readmission days (incidence rate ratio, 5.226; 95% confidence interval, 3.829-7.134, P < .001) after adjusting for potential confounders. CONCLUSIONS: Patients with HF had a high incidence of inadequate dietary energy intake, and it increases the burden of readmission.

Efficient image reconstruction for a small animal PET system with dual-layer-offset detector design.

BACKGROUND: A compact PET/SPECT/CT system Inliview-3000B has been developed to provide multi-modality information on small animals for biomedical research. Its PET subsystem employed a dual-layer-offset detector design for depth-of-interaction capability and higher detection efficiency, but the irregular design caused some difficulties in calculating the normalization factors and the sensitivity map. Besides, the relatively larger (2 mm) crystal cross-section size also posed a challenge to high-resolution image reconstruction. PURPOSE: We present an efficient image reconstruction method to achieve high imaging performance for the PET subsystem of Inliview-3000B. METHODS: List mode reconstruction with efficient system modeling was used for the PET imaging. We adopt an on-the-fly multi-ray tracing method with random crystal sampling to model the solid angle, crystal penetration and object attenuation effect, and modify the system response model during each iteration to improve the reconstruction performance and computational efficiency. We estimate crystal efficiency with a novel iterative approach that combines measured cylinder phantom data with simulated line-of-response (LOR)-based factors for normalization correction before reconstruction. Since it is necessary to calculate normalization factors and the sensitivity map, we stack the two crystal layers together and extend the conventional data organization method here to index all useful LORs. Simulations and experiments were performed to demonstrate the feasibility and advantage of the proposed method. RESULTS: Simulation results showed that the iterative algorithm for crystal efficiency estimation could achieve good accuracy. NEMA image quality phantom studies have demonstrated the superiority of random sampling, which is able to achieve good imaging performance with much less computation than traditional uniform sampling. In the spatial resolution evaluation based on the mini-Derenzo phantom, 1.1 mm hot rods could be identified with the proposed reconstruction method. Reconstruction of double mice and a rat showed good spatial resolution and a high signal-to-noise ratio, and organs with higher uptake could be recognized well. CONCLUSION: The results validated the superiority of introducing randomness into reconstruction, and demonstrated its reliability for high-performance imaging. The Inliview-3000B PET subsystem with the proposed image reconstruction can provide rich and detailed information on small animals for preclinical research.

An Ultraflexible Electrode Array for Large-Scale Chronic Recording in the Nonhuman Primate Brain.

Single-unit (SU) recording in nonhuman primates (NHPs) is indispensible in the quest of how the brain works, yet electrodes currently used for the NHP brain are limited in signal longevity, stability, and spatial coverage. Using new structural materials, microfabrication, and penetration techniques, we develop a mechanically robust ultraflexible, 1 µm thin electrode array (MERF) that enables pial penetration and high-density, large-scale, and chronic recording of neurons along both vertical and horizontal cortical axes in the nonhuman primate brain. Recording from three monkeys yields 2,913 SUs from 1,065 functional recording channels (up to 240 days), with some SUs tracked for up to 2 months. Recording from the primary visual cortex (V1) reveals that neurons with similar orientation preferences for visual stimuli exhibited higher spike correlation. Furthermore, simultaneously recorded neurons in different cortical layers of the primary motor cortex (M1) show preferential firing for hand movements of different directions. Finally, it is shown that a linear decoder trained with neuronal spiking activity across M1 layers during monkey's hand movements can be used to achieve on-line control of cursor movement. Thus, the MERF electrode array offers a new tool for basic neuroscience studies and brain-machine interface (BMI) applications in the primate brain.

Policy instruments facilitate China's COVID-19 work resumption.

Governments worldwide have announced stimulus packages to remobilize the labor force after COVID-19 and therefore to cope with the COVID-19-related recession. However, it is still unclear how to facilitate large-scale work resumption. This paper aims to clarify the issue by analyzing the large-scale prefecture-level dataset of human mobility trajectory information for 320 million workers and about 500,000 policy documents in China. We model work resumption as a collective behavioral change due to configurations of capacity, motivation, and policy instruments by using qualitative comparative analysis. We find that the effectiveness of post-COVID-19 recovery stimulus varied across China depending on the fiscal and administrative capacity and the policy motivation of the prefecture. Subnational fiscal and procurement policies were more effective for the wholesale and retail sector and the hotel and catering sector, whereas the manufacturing and business services sectors required more effort regarding employment policies. Due to limited prefectural capacity and wavering policy motivation, the simultaneous adoption of fiscal, employment, and procurement policy interventions endangered post-COVID-19 work resumption. We highlight the necessity of tailored postcrisis recovery strategies based on local fiscal and administrative capacity and the sectoral structure.

Rapid design of hybrid mechanism metasurface with random coding for terahertz dual-band RCS reduction.

In this paper, a hybrid mechanism metasurface (HMM) employing 1-bit random coding is proposed to achieve polarization-insensitive and dual-wideband monostatic/bistatic radar cross section (RCS) reduction under a wide range of incident angles. The anisotropic unit cell is designed by the combination of the multi-objective particle swarm optimization (MOPSO) algorithm and Python-CST joint simulation, which facilitates the rapid acquisition of the desired unit cell with excellent dual-band absorption conversion capability. The unit cell and its mirrored version are used to represent the units "0" and "1", respectively. In addition, the array distribution with random coding of the units "0" and "1" is optimized under different incident angles, polarizations and frequencies, which enables better diffusion-like scattering. Simulation results demonstrate that the proposed coding HMM can effectively reduce the monostatic/bistatic RCS by over 10 dB within the dual-band frequency ranges of 2.07-3.02 THz and 3.78-4.71 THz. Furthermore, the specular and bistatic RCS reduction performances remain stable at oblique incident angles up to 45° for both TE and TM polarizations.

JARID2 coordinates with the NuRD complex to facilitate breast tumorigenesis through response to adipocyte-derived leptin.

BACKGROUND: Proteins containing the Jumonji C (JmjC) domain participated in tumorigenesis and cancer progression. However, the mechanisms underlying this effect are still poorly understood. Our objective was to investigate the role of Jumonji and the AT-rich interaction domain-containing 2 (JARID2) - a JmjC family protein - in breast cancer, as well as its latent association with obesity. METHODS: Immunohistochemistry, The Cancer Genome Atlas, Gene Expression Omnibus, and other databases were used to analyze the expression of JARID2 in breast cancer cells. Growth curve, 5-ethynyl-2-deoxyuridine (EdU), colony formation, and cell invasion experiments were used to detect whether JARID2 affected breast cancer cell proliferation and invasion. Spheroidization-based experiments and xenotumor transplantation in NOD/SCID mice were used to examine the association between JARID2 and breast cancer stemness. RNA-sequencing, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis were used to identify the cell processes in which JARID2 participates. Immunoaffinity purification and silver staining mass spectrometry were conducted to search for proteins that might interact with JARID2. The results were further verified using co-immunoprecipitation and glutathione S-transferase (GST) pull-down experiments. Using chromatin immunoprecipitation (ChIP) sequencing, we sought the target genes that JARID2 and metastasis-associated protein 1 (MTA1) jointly regulated; the results were validated by ChIP-PCR, quantitative ChIP (qChIP) and ChIP-reChIP assays. A coculture experiment was used to explore the interactions between breast cancer cells and adipocytes. RESULTS: In this study, we found that JARID2 was highly expressed in multiple types of cancer including breast cancer. JARID2 promoted glycolysis, lipid metabolism, proliferation, invasion, and stemness of breast cancer cells. Furthermore, JARID2 physically interacted with the nucleosome remodeling and deacetylase (NuRD) complex, transcriptionally repressing a series of tumor suppressor genes such as BRCA2 DNA repair associated (BRCA2), RB transcriptional corepressor 1 (RB1), and inositol polyphosphate-4-phosphatase type II B (INPP4B). Additionally, JARID2 expression was regulated by the obesity-associated adipokine leptin via Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway in the breast cancer microenvironment. Analysis of various online databases also indicated that JARID2/MTA1 was associated with a poor prognosis of breast cancer. CONCLUSION: Our data indicated that JARID2 promoted breast tumorigenesis and development, confirming JARID2 as a target for cancer treatment.

Effects of weight loss in heart failure patients with overweight and obesity: a systematic review and meta-analysis.

AIMS: To perform a systematic review and meta-analysis to evaluate the impact of weight loss (WL) on the prognosis of overweight and obese patients with heart failure (HF). METHODS AND RESULTS: We reviewed the literature up to 1 February 2023 from PubMed, Web of Science, Embase, Cochrane Library, and Chinese databases for cohort studies, and randomized controlled trials (RCTs). Data from eligible studies were extracted, and statistical analyses were performed using Review Manager 5.3. A total of 19 studies (involving 449 882 patients) were included in the systematic review and meta-analyses. The results showed that WL did not reduce the mortality and rehospitalization rates in overweight and obese HF patients, but could improve the quality of life (P = 0.002), cardiac function (P = 0.0001), and exercise capacity (P = 0.03). The subgroup analysis showed that WL from bariatric surgery (BS) reduced the risk of death (P < 0.00001), WL from medication or exercise was not significantly associated with the risk of death (P = 0.18), and WL was associated with a higher mortality in the subgroup with unspecified WL modality or unintentional WL (P < 0.00001). In addition, it did not reduce the risk of short-term rehospitalization (P = 0.11), but reduced the rehospitalization rates over the long-term (P = 0.03). CONCLUSION: WL improves the long-term rehospitalization (>3 months), quality of life, cardiac function, and exercise capacity in overweight and obese HF patients. Although overall WL is not proven effective, subgroup analysis shows that BS can reduce mortality.

We used mortality, rehospitalization rates, quality of life, the New York Heart Association (NYHA), and 6-min walk test (6 MWT) to assess the impact of weight loss (WL) on the prognosis of overweight and obese heart failure (HF) patients. Key findings: WL is associated with improvements in long-term rehospitalization rates, quality of life, cardiac function, and exercise capacity.Bariatric surgery (BS) may reduce mortality in overweight and obese HF patients. Unintentional WL of more than 5% may mean a bad condition and could increase mortality.

High-sensitivity cardiac SPECT system design with collimator-less interspaced mosaic-patterned scintillators.

Purpose: Single-photon emission computed tomography (SPECT) is an important tool for myocardial perfusion imaging (MPI). Mechanical collimators cause the resolution-sensitivity trade-off in the existing cardiac SPECT systems, which hinders fast cardiac scan capability. In this work, we propose a novel collimator-less cardiac SPECT system with interspaced mosaic-patterned scintillators, aiming to significantly improve sensitivity and reduce scan time without trading-off image resolution. Methods: We propose to assemble a collimator-less cardiac SPECT with 7 mosaic-patterned detector modules forming a half-ring geometry. The detector module consists of 10 blocks, each of which is assembled with 768 sparsely distributed scintillators with a size of 1.68 mm × 1.68 mm × 20 mm, forming a mosaic pattern in the trans-axial direction. Each scintillator bar contains 5 GAGG(Ce) scintillators and 5 optical-guide elements, forming a mosaic pattern in the axial direction. In the Monte Carlo simulations, the in-plane resolution and axial resolution are evaluated using a hot-rod phantom and 5 disk phantoms, respectively. We simulate a cardiac phantom that is placed in a water-filled cylinder and evaluate the image performance with different data acquisition time. We perform image reconstruction with the expectation-maximization algorithm using system matrices derived from the simulation of a uniform cylindrical source filling the field-of-view (FOV). Besides, a 2-D prototype system is designed to demonstrate the feasibility of the collimator-less imaging concept. Results: In the simulation system, the sensitivity is 16.31% ± 8.85% in a 180 mm (Φ) × 100 mm (L) FOV. The 6-mm rods in the hot rod phantom and the 5-mm disks in the disk phantom are clearly separable. Satisfactory MPI image quality is achieved in the cardiac phantom study with an acquisition time of 30 s. In prototype experiments, the point sources with an 8 mm center-to-center distance are clearly separable at different positions across the FOV. Conclusion: The study reveals a promising approach to high-sensitivity SPECT imaging without a heavy-metal collimator. In cardiac imaging, this approach opens the way to a very fast cardiac scan with good resolution. Further works are ongoing to build a practical 3-D imaging system based on the existing design.

Artificial Intelligence and Machine (Deep) Learning in Otorhinolaryngology: A Bibliometric Analysis Based on VOSviewer and CiteSpace.

BACKGROUND: Otorhinolaryngology diseases are well suited for artificial intelligence (AI)-based interpretation. The use of AI, particularly AI based on deep learning (DL), in the treatment of human diseases is becoming more and more popular. However, there are few bibliometric analyses that have systematically studied this field. OBJECTIVE: The objective of this study was to visualize the research hot spots and trends of AI and DL in ENT diseases through bibliometric analysis to help researchers understand the future development of basic and clinical research. METHODS: In all, 232 articles and reviews were retrieved from The Web of Science Core Collection. Using CiteSpace and VOSviewer software, countries, institutions, authors, references, and keywords in the field were visualized and examined. RESULTS: The majority of these papers came from 44 nations and 498 institutions, with China and the United States leading the way. Common diseases used by AI in ENT include otosclerosis, otitis media, nasal polyps, sinusitis, and so on. In the early years, research focused on the analysis of hearing and articulation disorders, and in recent years mainly on the diagnosis, localization, and grading of diseases. CONCLUSIONS: The analysis shows the periodical hot spots and development direction of AI and DL application in ENT diseases from the time dimension. The diagnosis and prognosis of otolaryngology diseases and the analysis of otolaryngology endoscopic images have been the focus of current research and the development trend of future.

Cinnamon oil solid self-microemulsion mediates chronic mild stress-induced depression in mice by modulating monoamine neurotransmitters, corticosterone, inflammation cytokines, and intestinal flora.

Cinnamon oil (CO) is a classic Chinese medicine with excellent soothing effects on exhaustion, weakness and depression. Cinnamaldehyde is the main active ingredient of cinnamic oil. Although CO have antidepression-like effects, limited information is available. Furthermore, the disadvantages of CO, such as low oral availability and difficult portability, limit its development. In this study, a Cinnamon Oil Solid Self-Microemulsifying Drug Delivery System (CO-S-SME) was designed, prepared. In addition, we explored the effects and mechanisms of CO-S-SME on chronic unpredictable mild stress (CUMS)-induced depression-like behavior, monoamine neurotransmitters, inflammatory factors, intestinal flora in mice. Mice were subjected CUMS to establish the depression model. The antidepressant effect of CO-S-SME was evaluated by behavioral tests. In addition, the expression levels of neurotransmitters, corticosterone (CORT) and inflammatory factors in CUMS mice were analyzed by enzyme-linked immunosorbent assay. In addition, we explored the effects of CO-S-SME on the diversity and richness of intestinal flora of mice in each group. Behavioral tests showed that CO-S-SME could effectively improve depression-like behaviors in CUMS mice. Specifically, CO-S-SME treatment effectively increased neurotransmitter levels and reduced the expressions of corticosterone and inflammatory factors in CUMS mice. CO-S-SME also changed the intestinal flora composition, decreased the ratio of Firmicutes to Bacteroidetes, reduced relative abundances of Lactobacillus, modulated Alpha diversity and beta diversity. These results suggest that CO-S-SME an act as a good antidepressant, exhibiting effects via monoamine neurotransmitters, CORT, inflammation cytokines, and intestinal flora.

Safety of deep intravenous propofol sedation in the dental treatment of children in the outpatient department.

Background/purpose: Intravenous sedation with propofol in the dental treatment offers an alternative to inhalation sedation or general anesthesia. The aim of this study was to evaluate the safety and identify risk factors for intraoperative complications. Materials and methods: Uncooperative children who could not complete dental treatment under non-pharmacological behavior management or mild-to-moderate sedation in the outpatient pediatric department were selected. Details and time of dental treatment; intraoperative vital signs data, including blood pressure, heart rate, respiratory rate, pulse oxygen saturation (SpO2), end-tidal carbon dioxide, and electrocardiogram; and incidence of intraoperative and postoperative complications were recorded. Results: Overall, 344 children were selected, with 342 completing dental treatment. The dental treatment time was 20-155 (median, 85; interquartile range, 70-100) min. The number of treated teeth was at least 1 and at most 13 (median, 6; interquartile range, 5-8). Among 342 children, 35 (10.2%) had their treatment interrupted temporarily due to choking cough. No serious complications occurred; the incidence rate of minor complications was 47/342 (13.7%). Tachycardia was observed in 5/342 (1.5%) cases, oxygen desaturation (SpO2 < 95%) in 18, and hypoxemia (SpO2 ≤ 90%) in 25. The treatment duration was significant longer in cases with than without complications (P < 0.05), and children coughing during treatment were more likely to have complications (P < 0.05). Postoperative restlessness occurred in six children, but there was no vomiting, aspiration, or respiratory obstruction. Conclusion: Decreased oxygen saturation is the most common complications. Cough during treatment and longer treatment duration were risk factors for complications.

Local Phase Segregation Induced by Ion Milling in 2:17-Type Sm-Co Based Magnets.

Transmission electron microscopy (TEM) is indispensable to reveal the cellular nanostructure of the 2:17-type Sm-Co based magnets which act as the first choice for high-temperature magnet-associated devices. However, structural deficiencies could be introduced into the TEM specimen during the ion milling process, which would provide misleading information to understand the microstructure-property relationship of such magnets. In this work, we performed a comparative investigation of the microstructure and microchemistry between two TEM specimens prepared under different ion milling conditions in a model commercial magnet Sm13Gd12Co50Cu8.5Fe13Zr3.5 (wt.%). It is found that additional low-energy ion milling will preferably damage the 1:5H cell boundaries, while having no influence on the 2:17R cell phase. The structure of cell boundary transforms from hexagonal into face-centered-cubic. In addition, the elemental distribution within the damaged cell boundaries becomes discontinuous, segregating into Sm/Gd-rich and Fe/Co/Cu-rich portions. Our study suggested that in order to reveal the true microstructure of the Sm-Co based magnets, the TEM specimen should be carefully prepared to avoid structural damage and artificial deficiencies.

Prognostic analysis of patients with breast cancer based on tumor mutational burden and DNA damage repair genes.

Background: Breast cancer has a high tumor-specific death rate and poor prognosis. In this study, we aimed to provide a basis for the prognostic risk in patients with breast cancer using significant gene sets selected by analyzing tumor mutational burden (TMB) and DNA damage repair (DDR). Methods: Breast cancer genomic and transcriptomic data were obtained from The Cancer Genome Atlas (TCGA). Breast cancer samples were dichotomized into high- and low-TMB groups according to TMB values. Differentially expressed DDR genes between high- and low-TMB groups were incorporated into univariate and multivariate cox regression model to build prognosis model. Performance of the prognosis model was validated in an independently new GEO dataset and evaluated by time-dependent ROC curves. Results: Between high- and low-TMB groups, there were 6,424 differentially expressed genes, including 67 DDR genes. Ten genes associated with prognosis were selected by univariate cox regression analysis, among which seven genes constituted a panel to predict breast cancer prognosis. The seven-gene prognostic model, as well as the gene copy numbers are closely associated with tumor-infiltrating immune cells. Conclusion: We established a seven-gene prognostic model comprising MDC1, PARP3, PSMB1, PSMB9, PSMD2, PSMD7, and PSMD14 genes, which provides a basis for further exploration of a population-based prediction of prognosis and immunotherapy response in patients with breast cancer.

The Influence of Informal Caregivers' Preparedness on Psychological Symptoms and Quality of Life Among Patients With Heart Failure And Insufficient Self-care.

BACKGROUND: Most patients with heart failure find self-care difficult to perform and rely on family caregivers for support. Informal caregivers, however, often face insufficient psychological preparation and challenges in providing long-term care. Insufficient caregiver preparedness not only results in psychological burden for the informal caregivers but may also lead to a decline in caregiver contributions to patient self-care that affects patient outcomes. OBJECTIVE: Our objective was to test (1) the association of baseline informal caregivers' preparedness with psychological symptoms (anxiety and depression) and quality of life 3 months after baseline among patients with insufficient self-care and (2) the mediating effects of caregivers' contributions to self-care of heart failure (CC-SCHF) on the relationship of caregivers' preparedness with patients' outcomes at 3 months. METHODS: A longitudinal design was used to collect data between September 2020 and January 2022 in China. Data analyses were conducted using descriptive statistics, correlations, and linear mixed models. We used model 4 of the PROCESS program in SPSS with bootstrap testing to evaluate the mediating effect of CC-SCHF of informal caregivers' preparedness at baseline with psychological symptoms or quality of life among patients with HF 3 months later. RESULTS: Caregiver preparedness was positively associated with CC-SCHF maintenance ( r = 0.685, P < .01), CC-SCHF management ( r = 0.403, P < .01), and CC-SCHF confidence ( r = 0.600, P < .01). Good caregiver preparedness directly predicted lower psychological symptoms (anxiety and depression) and higher quality of life for patients with insufficient self-care. The associations of caregiver preparedness with short-term quality of life and depression of patients with HF with insufficient self-care were mediated by CC-SCHF management. CONCLUSIONS: Enhancing the preparedness of informal caregivers may improve psychological symptoms and quality of life of heart failure patients with insufficient self-care.

Characterization and Assessment of Projection Probability Density Function and Enhanced Sampling in Self-Collimation SPECT.

We have recently reported a self-collimation SPECT (SC-SPECT) design concept that constructs sensitive detectors in a multi-ring interspaced mosaic architecture to simultaneously improve system spatial resolution and sensitivity. In this work, through numerical and Monte-Carlo simulation studies, we investigate this new design concept by analyzing its projection probability density functions (PPDF) and the effects of enhanced sampling, i.e. having rotational and translational object movements during imaging. We first quantitatively characterize PPDFs by their widths and edge slopes. Then we compare the PPDFs of an SC-SPECT and a series of multiple-pinhole SPECT (MPH-SPECT) systems and assess the impact of PPDFs - combined with enhanced sampling - on image contrast recovery coefficient and variance through phantom studies. We show the PPDFs of SC- SPECT have steeper edges and a wider range of width, and these attributes enable SC-SPECT to achieve better performance.

Local-to-global spatial learning for whole-slide image representation and classification.

Whole-slide image (WSI) provides an important reference for clinical diagnosis. Classification with only WSI-level labels can be recognized for multi-instance learning (MIL) tasks. However, most existing MIL-based WSI classification methods have moderate performance on correlation mining between instances limited by their instance- level classification strategy. Herein, we propose a novel local-to-global spatial learning method to mine global position and local morphological information by redefining the MIL-based WSI classification strategy, better at learning WSI-level representation, called Global-Local Attentional Multi-Instance Learning (GLAMIL). GLAMIL can focus on regional relationships rather than single instances. It first learns relationships between patches in the local pool to aggregate region correlation (tissue types of a WSI). These correlations then can be further mined to fulfill WSI-level representation, where position correlation between different regions can be modeled. Furthermore, Transformer layers are employed to model global and local spatial information rather than being simply used as feature extractors, and the corresponding structure improvements are present. In addition, we evaluate GIAMIL on three benchmarks considering various challenging factors and achieve satisfactory results. GLAMIL outperforms state-of-the-art methods and baselines by about 1 % and 10 %, respectively.