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Education policies align with evolving needs and changes in education. Two years ago, the double reduction policy was widely welcomed. But new challenges have emerged now, it is necessary to examine whether it still meets parental expectations, and whether adjustments in details are needed. We investigated parents' perception of policy implementation intensity; and its relationship with parents' perception of educational involution; and parents' educational anxiety, as well as the roles played by gender. Findings highlight parents who perceive a stronger policy implementation intensity experience higher levels of educational anxiety and are more likely to feel educational involution; education anxiety acts as a mediator, while gender plays a moderating role. We highlighted policy's advantages while emphasizing the necessity to avoid policy rigidity and one‐size‐fits‐all. We recommend establishing a flexible, real‐time parental feedback mechanism and promoting continuous monitoring and evaluation. This approach would enable it to meet the changing demands of education. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are widely used in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC); however, the toxicity profiles are inconclusive. Methods: Clinical trials evaluating ICIs for R/M HNSCC were searched from online databases. The characteristics of the studies and the results of incidences of any grade treatment‐related adverse events (trAEs), grade three or more trAEs, treatment‐related deaths, trAEs leading to discontinuation of treatment, and specific trAEs were extracted. Results: Twenty studies with 3756 patients were included. The pooled incidences of any grade trAEs, grade three or more trAEs, treatment‐related deaths, trAEs leading to discontinuation of treatment for overall population were 62.07% (95% CI, 59.07%–65.02%), 13.82% (95% CI, 11.23%–16.62%), 0.39% (95% CI, 0.15%–0.71%), 3.99% (95% CI, 2.36%–5.95%), respectively. Programmed cell death protein 1 (PD‐1) inhibitors monotherapy and ICIs combination therapy had significantly higher incidences of any grade trAEs (odds ratio [OR], 1.25, 95% CI, 1.05–1.49 and 1.36, 95% CI, 1.15–1.60, respectively), grade three or more trAEs (OR, 1.41, 95% CI, 1.08–1.84 and 1.79, 95% CI, 1.39–2.30, respectively), trAEs leading to discontinuation of treatment (OR, 3.98, 95% CI, 2.06–7.70 and 10.14, 95% CI, 5.49–18.70, respectively) compared with programmed death‐ligand 1 (PD‐L1) inhibitors monotherapy. ICIs combination therapy had a significantly higher incidence of grade three or more trAEs compared with PD‐1 inhibitors monotherapy (OR, 1.27, 95% CI, 1.03–1.55); however, the incidences of any grade trAEs and trAEs leading to discontinuation of treatment were not significant different. Conclusions: Our study suggests that the incidences of grade three or more trAEs, treatment‐related deaths, and trAEs leading to discontinuation of treatment are low in R/M HNSCC patients treated with ICIs. PD‐L1 inhibitors monotherapy may be safer compared with PD‐1 inhibitors monotherapy and ICIs combination therapy. [ABSTRACT FROM AUTHOR]

Aims: A therapeutic strategy for chronic heart failure (HF) is to lower resting heart rate (HR). Ivabradine is a well‐known HR‐lowering agent, but limited prospective data exist regarding its use in Chinese patients. This study aimed to evaluate the effectiveness and safety of ivabradine in Chinese patients with chronic HF. Methods and results: This multicentre, single‐arm, prospective, observational study enrolled Chinese patients with chronic HF. The primary outcome was change from baseline in HR at 1 and 6 months, measured by pulse counting. Effectiveness was also evaluated using laboratory tests, the Kansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score (CSS) and overall summary score (OSS), and New York Heart Association (NYHA) class. Treatment‐emergent adverse events (TEAEs) were assessed. A post hoc analysis examined the effectiveness and safety of ivabradine combined with an angiotensin receptor–neprilysin inhibitor (ARNI) or beta‐blocker. A total of 1003 patients were enrolled [mean age 54.4 ± 15.0 years, 773 male (77.1%), mean baseline HR 88.5 ± 11.3 b.p.m., mean blood pressure 115.7/74.4 ± 17.2/12.3 mmHg, mean left ventricular ejection fraction 30.9 ± 7.6%, NYHA Classes III and IV in 48.8% and 22.0% of patients, respectively]. HR decreased by a mean of 12.9 and 16.1 b.p.m. after 1 and 6 months, respectively (both P < 0.001). At Month 6, improvements in the KCCQ CSS and OSS of ≥5 points were observed in 72.1% and 74.1% of patients, respectively (both P < 0.001). Left ventricular ejection fraction increased by 12.1 ± 11.6 (P < 0.001), and 66.7% of patients showed improvement in NYHA class (P < 0.001). At Month 6, the overall proportion of patients in NYHA Classes III and IV was reduced to 13.5% and 2.1%, respectively. Serum brain natriuretic peptide (BNP) and N‐terminal pro‐BNP changed by −331.9 ng/L (−1238.6, −134.0) and −1113.8 ng/L (−2202.0, −297.2), respectively (P < 0.001). HR reductions and improvements in NYHA and KCCQ scores with ivabradine were similar with and without use of ARNIs or beta‐blockers. Of 498 TEAEs in 296 patients (29.5%), 73 TEAEs in 55 patients (5.5%) were considered related to ivabradine [most frequent sinus bradycardia (n = 7) and photopsia (n = 7)]. TEAEs were reported in a similar number of patients in ARNI and beta‐blocker subgroups (21.9–35.6%). Conclusions: Ivabradine treatment reduced HR and improved cardiac function and health‐related quality of life in Chinese patients with chronic HF. Benefits were seen irrespective of whether or not patients were also taking ARNIs or beta‐blockers. Treatment was well tolerated with a similar profile to previous ivabradine studies. [ABSTRACT FROM AUTHOR]

Bullous pemphigoid (BP) is a severe autoimmune blistering disease affecting patients' quality of life. Gut microbiota (GM) dysbiosis have been investigated to be associated with multiple autoimmune diseases. However, the relationship between GM and BP onset and remission remains to be established by a systematic study. We conducted a study that enrolled 24 patients with BP onset (BP group), 24 patients under remission stage (BP‐R group) and 24 healthy controls (HC group). We applied 16S rRNA sequencing on faecal samples and revealed a separation of the microbiota structure. At the family level, Lachnospiraceae, Prevotellaceae and Veillonellaceae were more abundant in the HC and BP‐R groups, while Bacteroidaceae, Ruminococcaceae and Enterobacteriaceae were more abundant in the BP group. Bugbase analysis revealed the potentially pathogenic bacteria had an increasing trend in the BP group compared with the HC group and this variation vanished in the BP‐R group. At the amplicon sequence variants (ASV) level, Bacteroides ovatus (ASV40) and Veillonella dispar (ASV140) significantly decreased, while Prevotella copri (ASV54) increased in the BP group compared to the HC and BP‐R groups. The HC group and BP‐R group shared similar abundance. Furthermore, by correlation analysis, we investigated key ASVs correlated with clinical parameters and found some discriminate biomarkers between the BP and BP‐R groups. Our study established a dynamic GM profile in BP patients under different disease activity, providing a new direction to understand the role of GM in BP pathogenesis and therapeutic effects. [ABSTRACT FROM AUTHOR]

Background and purpose: Intracranial atherosclerotic disease (ICAD) is a major cause of ischemic stroke in China, but the prevalence and prognosis of asymptomatic ICAD detected using high‐resolution magnetic resonance imaging (HR‐MRI) is largely unknown. The aim of this study was to investigate the prevalence and prognosis in order to guide neurologists in interpreting ICAD detected on HR‐MRI. Methods: We included stroke‐free participants from a community‐based prospective cohort (Shunyi study participants) who underwent HR‐MRI between July 2014 and April 2016. The participants were divided into two groups: those with or without ICAD (ICAD+ and ICAD−, respectively). ICAD included intracranial artery stenosis and non‐stenotic plaque. The primary outcome was ischemic stroke. Cox proportional hazard models were used to evaluate the association between ICAD and event outcomes. Results: A total of 1060 stroke‐free participants evaluated by HR‐MRI were included from the Shunyi study. The median age at HR‐MRI was 56 years and 64.7% were female. The ICAD prevalence was 36.3% (n = 385). The ICAD+ group was older and had more cerebrovascular risk factors. The rates of ischemic stroke in the ICAD− and ICAD+ groups were 1.3% (n = 9) and 5.2% (n = 20), respectively, with a median follow‐up time of 54 months. ICAD was associated with an increased risk of ischemic stroke in the unadjusted and adjusted Cox models, with hazard ratios of 4.12 (95% confidence interval [CI] 1.87–9.05) and 2.50 (95% CI 1.05–5.94), respectively. The greatest risk of an event outcome was observed in participants with ≥70% stenosis or occlusion. The features of high‐risk plaques were also identified. Conclusions: We found that ICAD detected using HR‐MRI increases the long‐term risk of a first‐ever ischemic stroke in a stroke‐free population, suggesting that the current primary prevention protocol of stroke awaits further optimization. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to explore the efficacy and safety of toripalimab combined with anlotinib in patients with advanced non‐small cell lung cancer (NSCLC) who acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs). Materials and Methods: Patients who developed resistance after using first‐ or second‐generation EGFR‐TKIs as their first‐line regimen without EGFR T790M mutation or had disease progression after being treated with third‐generation EGFR‐TKIs as first‐ or second‐line therapy were enrolled. All patients received toripalimab (240 mg/day on Day 1, intravenously) combined with anlotinib (12 mg/day, Days 1–14, orally) once every 3 weeks. Treatment continued until disease progression, or if toxicity was intolerable. The primary endpoint was the objective response rate (ORR) assessed by the investigator. The secondary endpoint was the progression‐free survival (PFS). Results: In total, 19 patients were enrolled between May 2020 and October 2021.The ORR was 0%, and a median PFS was 2.1 months (95% CI 0.251–3.949). Grade ≥3 treatment‐related adverse events (AEs) occurred in 11% patients. Common adverse events included hypothyroidism (12/19), fatigue (9/19), and hypertension (8/19). Patients in stable disease (SD) group had lower abundance of EGFR mutation allele frequency (AF) before enrollment than those in progressive disease (PD) group (p = 0.031). Patients without detectable EGFR mutation (EGFR−) had longer PFS compared to the ones with EGFR mutations (p = 0.059). Patients with high levels of soluble programmed cell death ligand 1 (PD‐L1) at baseline also tended to have longer PFS (p = 0.160). Conclusion: Toripalimab combined with anlotinib was tolerable in EGFR‐TKI‐resistant advanced NSCLC patients not previously treated with chemotherapy. Patients without detectable EGFR mutation and high soluble PD‐L1 levels may benefit from this chemotherapy‐free treatment. [ABSTRACT FROM AUTHOR]

Summary: Tiller number per plant—a cardinal component of ideal plant architecture—affects grain yield potential. Thus, alleles positively affecting tillering must be mined to promote genetic improvement. Here, we report a Tiller Number 1 (TN1) protein harbouring a bromo‐adjacent homology domain and RNA recognition motifs, identified through genome‐wide association study of tiller numbers. Natural variation in TN1 affects its interaction with TIF1 (TN1 interaction factor 1) to affect DWARF14 expression and negatively regulate tiller number in rice. Further analysis of variations in TN1 among indica genotypes according to geographical distribution revealed that low‐tillering varieties with TN1‐hapL are concentrated in Southeast Asia and East Asia, whereas high‐tillering varieties with TN1‐hapH are concentrated in South Asia. Taken together, these results indicate that TN1 is a tillering regulatory factor whose alleles present apparent preferential utilization across geographical regions. Our findings advance the molecular understanding of tiller development. [ABSTRACT FROM AUTHOR]

Background: Currently, survival benefit of immunotherapy in advanced non‐small cell lung cancer (NSCLC) with EGFR exon 20 insertions (ex20ins) is controversial, though it generally indicates poor response and activity. Compared with standard chemotherapy in combination with bevacizumab, first‐line chemotherapy plus immune checkpoint inhibitor (ICI) in advanced NSCLC with EGFR ex20ins remains elusive and lacks real‐world evidence. Patients and Methods: A retrospective real‐world study was conducted to evaluate clinical outcomes of chemotherapy alone (C), chemotherapy plus ICI (C + I), or chemotherapy plus angiogenesis inhibitors (C + A) as first‐line strategies for advanced NSCLC patients with EGFR ex20ins. Investigator‐assessed response and survival outcomes were compared between subgroups. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to reveal concomitant alterations and explore the molecular landscape of ex20ins. Results: A total of 164 patients were screened, identifying 35 kinds of ex20ins, and 122 cases treated with C, C + I, and C + A were finally included in the first‐line analysis. C + A achieved much better objective response rate (ORR, 38.1% vs. 18.2%) and significant progression‐free survival (PFS) benefit compared with C (median, 7.73 vs.5.93 months, HR = 0.60, 95% CI: 0.40–0.90, p = 0.014), and it showed similar ORR (38.1% vs. 40.0%), but higher disease control rate (DCR, 96.8% vs. 80.0%) and numerically longer median PFS (7.73 vs. 6.53 months, HR = 0.83, 95% CI: 0.44–1.56, p = 0.30) than C + I. There was no PFS difference between C + I and C, despite of PD‐L1 expression or tumor mutational burden. KEGG analysis revealed concomitant upregulation of PI3K/AKT signaling might mediate intrinsic resistance to ICI in ex20ins. Conclusion: First‐line chemotherapy plus angiogenesis inhibitors might yield more survival benefits than chemotherapy alone for NSCLC with EGFR ex20ins, whereas, it suggests that chemotherapy in combination with ICI might not obtain a better survival benefit for this subset of patients. Activation of PI3K/AKT signaling might mediate intrinsic immunosuppression in NSCLC with EGFR ex20ins. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitor (ICI) combined with chemotherapy is one of the standards of care for advanced non–small cell lung cancer (NSCLC) without driver mutations. However, the biomarker of combination therapy is still unknown. Although previous studies have confirmed that low allele frequency adjusted blood‐based tumor mutational burden (LAF‐bTMB) is associated with the efficacy of ICI monotherapy, there has been no report on the correlation between the efficacy of LAF‐bTMB and ICI combined chemotherapy. This study aimed to explore whether LAF‐bTMB can be used as a predictive biomarker for the efficacy of immunotherapy combined with chemotherapy in advanced NSCLC. Methods: This study enrolled patients diagnosed with advanced NSCLC and who received ICI combined with chemotherapy for first‐line therapy from May 2020 to December 2021 at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Clinical information, treatment information, survival data, and peripheral blood samples of every patient before treatment were collected. Next‐generation sequencing was performed on plasma samples to estimate bTMB and LAF‐bTMB. Results: A total of 42 patients with NSCLC were enrolled. In this cohort, 19 patients achieved partial response (PR), and the objective response rate (ORR) was 45.2%. The median progression‐free survival (PFS) of all patients was 13.4 months (95% CI, 7.49–19.72). Both PFS and the overall survival (OS) were significantly longer in the responder (R) group than in the non‐responder (NR) group (median PFS, 16.4 months vs. 7.2 months, p = 0.028; median OS, NE vs. 9.3 months, p = 0.016). There was no significant difference in bTMB and LAF‐BTMB between the R and NR group. The ORR of patients with LAF‐bTMB≤8muts/Mb was significantly higher than that of patients with LAF‐bTMB >8muts/Mb (ORR, 61% vs. 26%, respectively, p = 0.033). When LAF‐bTMB ≤8muts/Mb or > 20muts/Mb, ORR was significantly higher than that of patients with LAF‐bTMB between 8 and 20muts/Mb (ORR were 57% and 21%, p = 0.047). No correlation has been found between LAF‐bTMB and PFS or OS. Conclusions: This study confirmed that neither bTMB nor LAF‐bTMB is feasible as a potential predictor of first‐line immunochemotherapy for advanced NSCLC. More suitable biomarkers need to be explored to screen patients with better efficacy of immunotherapy combined with chemotherapy in the future. [ABSTRACT FROM AUTHOR]

Background: The application of immune checkpoint inhibitors (ICIs) represents a breakthrough in the current landscape for the treatment of extensive‐stage small‐cell lung cancer (ES‐SCLC), but the real‐world outcome is limited. This study aimed to investigate the treatment options and efficacy evaluation of first‐line, second‐line, and subsequent‐line immunotherapy in routine practice. Methods: A retrospective analysis of ES‐SCLC patients treated with ICIs was conducted between May 2016 and September 2021. Objective response rate, disease control rate, progression‐free survival (PFS) and overall survival were assessed between groups to explore the value of ICIs at different treatment time periods. PFS1 and PFS2 were defined as the duration from initial therapy to disease progression or death in first‐line or second‐line treatment. Results: Ninety‐six patients with ES‐SCLC were included. PFS1 was prolonged in patients treated with first‐line ICIs‐combined therapy (median PFS1 7.20 months vs. 5.30 months, hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.36–087, p = 0.0085). For patients who progressed after first‐line ICIs treatment (N = 22), PFS1 + PFS2 was longer in the second‐line ICIs continuation group with no significant difference (median PFS1 + PFS2 11.27 months vs. 7.20 months, HR 0.45, 95% CI 0.14–1.51, p = 0.19). For patients who experienced a progression event after first‐line chemotherapy (N = 50), PFS2 and PFS1 + PFS2 were prolonged in patients who accepted second‐line ICIs‐combined therapy without significant difference (median PFS2 4.00 months vs. 2.43 months, HR 0.59, 95% CI 0.33–1.05, p = 0.070; median PFS1 + PFS2 11.30 months vs. 8.70 months, HR 0.53, 95% CI 0.29–0.98, p = 0.056). Conclusion: First‐line ICIs plus chemotherapy should be applied in the clinical practice of ES‐SCLC. If patients did not receive ICIs plus chemotherapy in first‐line treatment, therapies that include ICIs in second‐line treatment should be considered. [ABSTRACT FROM AUTHOR]

Localized scleroderma (LoS) is a rare chronic disease with extensive tissue fibrosis, inflammatory infiltration, microvascular alterations, and epidermal appendage lesions. However, a deeper understanding of the pathogenesis and treatment strategies of LoS is currently limited. In the present work, a proteome map of LoS skin is established, and the pathological features of LoS skin are characterized. Most importantly, a human‐induced pluripotent stem cell‐derived epithelial and mesenchymal (EM) organoids model in a 3D culture system for LoS therapy is established. According to the findings, the application of EM organoids on scleroderma skin can significantly reduce the degree of skin fibrosis. In particular, EM organoids enhance the activity of epidermal stem cells in the LoS skin and promotes the regeneration of sweat glands and blood vessels. These results highlight the potential application of organoids for promoting the recovery of scleroderma associated phenotypes and skin‐associated functions. Furthermore, it can provide a new therapeutic alternative for patients suffering from disfigurement and skin function defects caused by LoS. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) patients with impact on skin and hair loss are reported. Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is detected in the skin of some patients; however, the detailed pathological features of skin tissues from patients infected with SARS‐CoV‐2 at a molecular level are limited. Especially, the ability of SARS‐CoV‐2 to infect skin cells and impact their function is not well understood. A proteome map of COVID‐19 skin is established here and the susceptibility of human‐induced pluripotent stem cell (hiPSC)‐derived skin organoids with hair follicles and nervous system is investigated, to SARS‐CoV‐2 infection. It is shown that KRT17+ hair follicles can be infected by SARS‐CoV‐2 and are associated with the impaired development of hair follicles and epidermis. Different types of nervous system cells are also found to be infected, which can lead to neuron death. Findings from the present work provide evidence for the association between COVID‐19 and hair loss. hiPSC‐derived skin organoids are also presented as an experimental model which can be used to investigate the susceptibility of skin cells to SARS‐CoV‐2 infection and can help identify various pathological mechanisms and drug screening strategies. [ABSTRACT FROM AUTHOR]

Background: There was no standard treatment for patients who acquired resistance to osimertinib mediated by epidermal growth factor receptor (EGFR) T790M‐cis‐C797S. The aim of this study was to investigate the association between different therapeutic strategies and survival outcomes among these patients. Methods: This retrospective cohort study analyzed 46 patients with metastatic lung adenocarcinoma and EGFR T790M‐cis‐C797S after osimertinib progression from January 1, 2017 to October 31, 2020. Among them, 13 patients received brigatinib‐based therapy, 23 patients received chemotherapy in combination of anti‐angiogenics or not, and 10 patients received other targeted treatments like dacomtinib, bevacizumab, or a combined therapy of osimertinib and other targeted drugs. Results: Compared to other targeted therapy, brigatinib‐based therapy (median progression‐free survival [mPFS]: 4.40 vs. 1.63 months, hazard ratio [HR] = 0.39, 95% confidence interval [CI]: 0.21–0.73, p = 0.001) and chemotherapy‐based treatment (mPFS: 4.70 vs. 1.63 months, HR = 0.18, 95% CI: 0.06–0.50, p < 0.001) presented a better survival outcome and there was no significant difference between brigatinib‐based therapy and chemotherapy‐based treatment (mPFS: 4.40 vs. 4.70 months, HR = 1.24, 95% CI: 0.57–2.67, p = 0.58). Chemotherapy combined with anti‐angiogenics achieved a better efficacy than only chemotherapy (mPFS: 5.50 vs. 1.03 months, HR = 0.30, 95% CI: 0.11–0.83, p = 0.02). Patients carrying EGFR exon 19 deletion mutation had a longer PFS than those who harboring EGFR exon 21 p.L858R mutation (4.57 vs. 1.03 months, HR = 0.18, 95% CI: 0.06–0.54, p = 0.001), no matter they received brigatinib‐based therapy (mPFS: 5.00 vs. 3.23 months, HR = 0.19, 95% CI: 0.01–0.96, p = 0.05) or chemotherapy‐based treatment (mPFS: 7.23 vs. 1.03 months, HR = 0.05, 95% CI 0.01–0.49, p < 0.001). Conclusion: Brigatinib‐based therapy and chemotherapy plus anti‐angiogenics could be considered beyond progression from osimertinib therapy. For patients harboring EGFR exon 19 deletion/T790M/cis‐C797S mutation, the clinical efficacy was superior to patients harboring EGFR exon 21 p.L858R/T790M/cis‐C797S mutation. [ABSTRACT FROM AUTHOR]

Background: Hereditary angioedema (HAE) is a rare disease with heterogeneous clinical symptoms. It is vitally important to predict whether an HAE patient will develop severe symptoms in clinical practice, but there are currently no predictive biomarkers for HAE stratification. Plasma N‐glycomes are disease‐specific and have great potential for the discovery of non‐invasive biomarkers. In this study, we profiled the plasma N‐glycome of HAE patients from two independent cohorts to identify candidate biomarkers. Methods: Linkage‐specific sialylation derivatization combined with matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry detection and automated data processing was employed to analyze the plasma N‐glycome of two independent type‐1 HAE cohorts. Results: HAE patients had abnormal glycan complexity, galactosylation, and α2,3‐ and α2,6‐linked sialylation compared to healthy controls (HC). The classification models based on dysregulated glycan traits could successfully discriminate between HAE and HC with area under the curves (AUCs) being greater than 0.9. Some of the aberrant glycans showed response to therapy. Moreover, we identified a series of glycan traits with strong associations with the occurrence of laryngeal or gastrointestinal angioedema or disease severity score. Predictive models based on these traits could be used to predict disease severity (AUC > 0.9). These results were replicated in an independent cohort. Conclusions: We reported the full plasma N‐glycomic signature of HAE for the first time, and identified potential biomarkers. These findings may play a critical role in predicting disease severity and guide the treatment of HAE in clinical practice. Further protein‐specific and prospective studies are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Background: Low‐grade fetal adenocarcinoma of the lung (L‐FLAC) is a rare subtype of lung adenocarcinoma with undetermined histological features and genetic abnormalities. In this study, we attempted to investigate the pathological characteristics and genomic profiles of L‐FLAC. Methods: Among 9839 cases of primary lung adenocarcinoma resected at Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College between January 2011 and June 2016, three cases diagnosed with L‐FLAC were selected. An immunohistochemical profile and whole exome sequencing (WES) using tumor and normal tissues was conducted. The last follow‐up date of patients was January 2021. Results: Three cases diagnosed with L‐FLAC were finally screened, suggesting a percentage of 0.03%. All three patients were male and diagnosed as stage I following radical lobectomy. The missense variant was found to be the major gene mutation type using WES. CTNNB1 and DICER1 were the two most frequent gene mutations. All cases demonstrated positive TTF‐1 expression. In addition, two patients showed positive expression of β‐catenin (nuclear/cytoplasmic expression), CgA and Sny. Negative expression of PD‐L1 in tumor cells was observed in all three cases. One case with a relatively high tumor mutation burden (TMB) (2.18 mut/Mb) had an inferior overall survival of 11.5 months. However, the other two cases with a lower TMB (0.12 and 0.74 mut/Mb) still acquired disease‐free status up to the last follow‐up date. Conclusions: L‐FLAC has a specific molecular background which is different from lung adenocarcinoma. Furthermore, gene heterogeneity was found and might be the reason for a dramatically different prognosis in these L‐FLAC patients. [ABSTRACT FROM AUTHOR]

Background and purpose: Cerebral small vessel disease (CSVD) is a clinical imaging syndrome with diverse etiology. Total homocysteine (HCY) level might increase the risk of myocardial and cerebral infarction by damaging the vascular endothelium. We aimed to explore the correlation between total HCY and CSVD imaging burden, based on Mendelian randomization methods. Methods: A total of 1,023 participants of the Shunyi study, a population‐based cohort study, were included. Vascular risk factors, total HCY levels and methylenetetrahydrofolate reductase (MTHFR) gene mutations (C677T and A1298C) were examined. CSVD imaging markers, including lacunes, cerebral microbleeds, white matter hyperintensity, enlarged perivascular space and brain parenchymal fraction (BPF) were also assessed. Results: Mutations of C677T were significantly correlated with increased total HCY levels (CC→TT: β = 0.28, p < 0.0001), while mutations of A1298C were correlated with decreased total HCY levels (AA→AC: β = −0.13, p < 0.0001; AA→CC: β = −0.25, p = 0.004). In the Mendelian randomization study, the C677T genotype was significantly associated with lacunes (CC→CT: odds ratio [OR] 2.76, p = 0.008; CC→TT: OR 2.50, p = 0.018), and the A1298C genotype was significantly correlated with BPF (AA→CC: β = 1.32, p = 0.015). Similarly, in multivariate regression analysis, total HCY levels were significantly correlated with lacunes (OR 2.14, p < 0.0001) and negatively correlated with BPF (β = −0.55, p = 0.004). Age, sex and vascular risk factors were adjusted for. Conclusions: Total HCY level was correlated with imaging burden of CSVD, especially with lacunes and brain volume loss. For individuals with risk genetic predisposition, enhanced homocysteine‐lowering strategies might be necessary to reduce the risk and progress of CSVD. [ABSTRACT FROM AUTHOR]

Background: The emergence of COVID‐19 has become a global health emergency. The transmissibility of the disease is of great interest to healthcare workers and scientists alike. The primary route of transmission is via respiratory droplets, but viral RNA has also been found in feces and body fluids such as urine, serum, and semen. So far, there has been no report on whether SARS‐CoV‐2 is present in the exudates of cutaneous lesions. This study was designed to investigate whether SARS‐CoV‐2 can be found in the pressure injury exudates in patients with severe COVID‐19 infections. Methods: 46 critically ill COVID‐19 patients who were admitted to the ICU of the Sino‐French New City Branch of Tongji Hospital in Wuhan between February 4 and April 12 developed pressure injuries. 22 patients with pressure injuries had wound exudates. Wound and pharyngeal swabs of the 22 patients were collected and RT‐PCRs were conducted to detect SARS‐CoV‐2 viral RNA. Results: At the time of pressure injury, 5 patients still tested positive by pharyngeal swabs, the rest of the 17 patients tested negative. However, none of the wound exudate swabs from the participants tested positive for SARS‐CoV‐2 by RT‐PCR. Conclusion: Our study suggests that it is rather unlikely that COVID‐19 can be transmitted via pressure injury exudates, but we still recommend standardized personal protective equipment, face shield and an additional pair of gloves when treating pressure injuries. [ABSTRACT FROM AUTHOR]

Aims: Cardiac complications are common and associated with mortality in critically ill patients with COVID‐19; however, the diagnostic and prognostic implications of critical care echocardiography (CCE) have not been studied. Methods and results: A cohort of 43 patients with COVID‐19 who were in the intensive care unit (ICU) underwent bedside CCE during their disease course. Demographic, clinical, and survival data were collected. The echocardiographic analyses revealed high frequencies of pericardial effusion (90.7%), increased left ventricular mass index (60.5%), elevated relative wall thickness (76.7%), and reduced left ventricular stroke volume index (LVSVi; 53.5%) and cardiac index (51.2%). Twenty‐two (51.2%) patients died in the ICU. In multivariate Cox regression, the strongest predictor of in‐ICU death was decreased cardiac index [hazard ratio (HR), 0.67, 95% confidence interval (CI), 0.45–0.98; P = 0.041], after adjusting for male sex, shock status, high‐sensitivity cardiac troponin I, and N‐terminal pro‐B‐type natriuretic peptide. Negative associations with mortality were observed for LVSVi (HR, 0.91, 95% CI 0.85–0.96; P = 0.002), tricuspid annular plane systolic excursion (HR, 0.74, 95% CI 0.64–0.84; P < 0.001), and S′ (HR, 0.78, 95% CI 0.69–0.88; P < 0.001). Kaplan–Meier analyses indicated that reductions in LVSVi, cardiac index, TAPSE, and S′ were associated with a shorter survival time. Conclusions: Pericardial effusion and increased ventricular mass in COVID‐19 might indicate a swollen heart. Both left and right heart dysfunction and a reduced cardiac index may lead to an increased risk of mortality. Clinicians should pay special attention to cardiac haemodynamic disorders in critical patients with COVID‐19. [ABSTRACT FROM AUTHOR]

Aims: To explore the relevance of disease duration with axial skeletal lesions in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome based on computed tomography (CT). Methods: Patients who had undergone whole‐spine CT were included from a previously reported single‐center cohort of SAPHO syndrome. Patients with previous treatments of bisphosphates, biological agents or surgeries were excluded. Sites of axial skeletal involvement were reviewed including the spine, sacroiliac joints, and anterior chest wall. Duration of osteoarticular involvement was defined as the interval between the onset of osteoarticular symptoms and the CT evaluation. Results: Eighty‐one patients (54 female and 27 male) were included in the study. The mean disease duration was 26.9 ± 34.9 months. Fifty (63.0%) patients showed spinal lesions on CT. The average numbers of involved vertebral segments for corner and endplate lesions were 3.16 ± 3.51 and 0.73 ± 1.85 respectively. Sixty‐eight (84.0%) patients exhibited abnormalities in the anterior chest wall. The number of involved vertebral segments showed poor correlation with disease duration for both corner lesions (r2 = 0.051, P = 0.043) and endplate lesions (r2 = 0.137, P = 0.001). Patients with costoclavicular involvement showed remarkably longer disease duration than those without (49.3 ± 47.7 months vs 18.0 ± 23.5 months, P = 0.006), while no significant difference was detected regarding other structures in the anterior chest wall. Conclusion: Costoclavicular involvement is a hallmark of long disease duration in SAPHO syndrome. Corner and endplate lesions in the vertebrae and sacroiliac involvement may not relate to disease course. [ABSTRACT FROM AUTHOR]

Finite‐difference modeling with a cross‐rhombus stencil with high‐order accuracy in both spatial and temporal derivatives is a potential method for efficient seismic simulation. The finite‐difference coefficients determined by Taylor‐series expansion usually preserve the dispersion property in a limited wavenumber range and fixed angles of propagation. To construct the dispersion‐relationship‐preserving scheme for satisfying high‐wavenumber components and multiple angles, we expand the dispersion relation of the cross‐rhombus stencil to an over‐determined system and apply a regularization method to obtain the stable least‐squares solution of the finite‐difference coefficients. The new dispersion‐relationship‐preserving based scheme not only satisfies several designated wavenumbers but also has high‐order accuracy in temporal discretization. The numerical analysis demonstrates that the new scheme possesses a better dispersion characteristic and more relaxed stability conditions compared with the Taylor‐series expansion based methods. Seismic wave simulations for the homogeneous model and the Sigsbee model demonstrate that the new scheme yields small dispersion error and improves the accuracy of the forward modelling. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is causing considerable morbidity and mortality worldwide. Multiple reports have suggested that patients with heart failure (HF) are at a higher risk of severe disease and mortality with COVID-19. Moreover, evaluating and treating HF patients with comorbid COVID-19 represents a formidable clinical challenge as symptoms of both conditions may overlap and they may potentiate each other. Limited data exist regarding comprehensive management of HF patients with concomitant COVID-19. Since these issues pose serious new challenges for clinicians worldwide, HF specialists must develop a structured approach to the care of patients with COVID-19 and be included early in the care of these patients. Therefore, the Heart Failure Association of the European Society of Cardiology and the Chinese Heart Failure Association & National Heart Failure Committee conducted web-based meetings to discuss these unique clinical challenges and reach a consensus opinion to help providers worldwide deliver better patient care. The main objective of this position paper is to outline the management of HF patients with concomitant COVID-19 based on the available data and personal experiences of physicians from Asia, Europe and the United States. [ABSTRACT FROM AUTHOR]

A rather low crystallization rate has greatly limited the application of poly(l‐lactide) (PLLA) in many fields. Thus, functionalized cellulose nanoparticles (CPNs) were prepared based on cellulose aerogel through a novel and simple approach and were then applied as biobased nucleating agents to improve the crystallization rate of PLLA. First, isolated individual CPNs with a mean diameter around 37.2 nm and regular circular shape were obtained. Subsequently, PLLA based nanocomposites with various contents of CPNs were prepared by solution blending. As a result, CPNs promoted the crystallization rate of PLLA significantly. Compared with that of neat PLLA, the crystallinity (Xc) of the nanocomposites increased dramatically more than 30 times to 36.65% at a CPN loading of 0.5 wt%, and the half‐crystal time (t1/2) at 130 °C decreased by about 91%. Furthermore, due to the presence of CPNs, which provided a large number of nucleation sites in the PLLA matrix, the chain conformational and crystallization kinetics behavior of the PLLA based nanocomposites during isothermal crystallization were changed in the early stages, and based on this result a proposal for the nucleation process for CPNs in a PLLA matrix is presented. © 2018 Society of Chemical Industry The schematic diagram represents the preparation of functionalized cellulose nanoparticles and their effect on the crystallization behavior of poly(l‐lactide) matrix. [ABSTRACT FROM AUTHOR]

Increasing demand for effective energy‐storage systems derived from low‐cost and ecofriendly raw materials has aroused wide concern. In this contribution, we propose nitrogen‐abundant amorphous micron‐sized carbon ribbons (AMCRs) originating from biomass raupo as a novel substrate due to their specific quasi 2D morphologies and outstanding dispersion ability. Owing to the innate nitrogen atoms on the surface of AMCRs, ultrathin binary and ternary metal oxide (NiO, CoO, and NiCo2O4) nanosheets can be uniformly developed under benign conditions. These three composites were separately fabricated as electrodes for supercapacitors in a three‐electrode system and exhibited favorable activities. Among them, the ternary metal oxide composites NiCo2O4@AMCRs delivered the supreme specific capacitance of 1691 F g−1 and best cycling stability (89 % capacity retention over 10,000 cycles). Moreover, symmetric supercapacitors (NiCo2O4@AMCRs//NiCo2O4@AMCRs) were assembled inside sleeve devices with 2 m KOH aqueous electrolyte, which demonstrated admirable cyclic stability (79.1 % capacity retention over 8,000 cycles), and an excellent energy density of 26 Wh kg−1 at the power density of 1.8 kW kg−1. Nanotechnology: Nitrogen‐abundant amorphous micron‐sized carbon ribbons (AMCRs), originating from biomass raupo, are proposed as a substrate for electronic storage systems. Among those tested, NiCo2O4@AMCRs delivered a supreme specific capacitance of 1691 F g−1 and the best cycling stability (89 % capacity retention over 10,000 cycles; see figure). [ABSTRACT FROM AUTHOR]

ABSTRACT The in situ formation of poly(lactic acid)- b-poly(propylene carbonate) (PLA- b-PPC) block copolymers were carried out by the reaction between PLA and PPC in the presence of tetrabutyl titanate via transesterification. Molecular weight measurements and 13C nuclear magnetic resonance spectroscopy revealed that PLA- b-PPC block copolymers with higher molecular weight were obtained by controlling the reactivity point ratio between PLA chains and PPC chains in PLA/PPC reaction system. The sample with a composition of PLA:PPC = 40:60 (wt %) and a catalyst amount of 0.5 wt % had a more proportionable reactivity point ratio between PLA chains and PPC chains compared with other samples, resulting in a most conspicuous transesterification and inconspicuous chain scission reaction. Therefore, its high molecular weight fraction ( Mw > 40.0 × 104) increased 80%. The formation of macromolecular PLA- b-PPC copolymer could strengthen the entanglement between PLA and PPC molecular chains, which resulted in an increased viscosity of blends at low shear rate. In addition, the elongation at break of sample with a composition of PLA:PPC = 40:60 (wt %) and a catalyst amount of 0.5 wt % was nearly as twice as which without catalyst because of the improving miscibility of PLA domains and PPC matrix by the compatibilization of PLA- b-PPC copolymer. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 46009. [ABSTRACT FROM AUTHOR]

Abstract: Acute heart failure due to myocarditis is not common in Takayasu arteritis, let alone in combination with thrombosis affecting both ventricles and pulmonary arteries. The concomitant infection of non‐tuberculosis mycobacterium further complicates the clinical scenario and poses challenges for implementation of tailored treatments. This case report describes a teenage girl with a history of intermittent claudication and Erythema Nodosum who developed acute heart failure. Detailed clinical investigations and imaging techniques confirmed the diagnosis. [ABSTRACT FROM AUTHOR]

Despite the increasing biomedical applications of gold nanoparticles (AuNPs), their toxicological effects need to be thoroughly understood. In the present study, the genotoxic potential of commercially available AuNPs with varying size (5, 20, and 50 nm) were assessed using a battery of in vitro and in vivo genotoxicity assays. In the comet assay, 20 and 50 nm AuNPs did not induce obvious DNA damage in HepG2 cells at the tested concentrations, whereas 5 nm NPs induced a dose-dependent increment in DNA damage after 24-h exposure. Furthermore, 5 nm AuNPs induced cell cycle arrest in G1 phase in response to DNA damage, and promoted the production of reactive oxygen species (ROS). In the chromosomal aberration test, AuNPs exposure did not increase in the frequency of chromosomal aberrations in Chinese hamster lung (CHL) cells. In the standard in vivo micronucleus test, no obvious increase in the frequency of micronucleus formation was found in mice after 4 day exposure of AuNPs. However, when the exposure period was extended to 14 days, 5 nm AuNPs presented significant clastogenic damage, with a dose-dependent increase of micronuclei frequencies. This finding suggests that particle size plays an important role in determining the genotoxicity of AuNPs. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 710-719, 2017. [ABSTRACT FROM AUTHOR]

ABSTRACT How stress and temperature impact the movement of poly(lactic acid) (PLA) chains in the process of tensile film stretching was studied. The motion mode of chains was investigated through the study of the strain-induced crystallization and orientation through changes in the draw temperature ( Td), draw ratio, and draw rate. The crystallinity and orientation degrees of the PLA films were measured by differential scanning calorimetry, Fourier transform infrared spectroscopy, and polarized optical microscopy. According to the competition between the orientation caused by the stretching and relaxation of chains under the temperature field, the motion modes of PLA chains during strain were divided into four types, modes I-IV. When Td was 100°C, the PLA chains acted in mode I, in which the relaxation rate of chains was so fast that no crystallinity or orientation could be obtained. Beyond a draw rate of 20 mm/min at a Td of 90°C, the type of chain movement changed from mode I to II. In mode II, only crystallites could be reserved after unloading. Chains in the PLA film moved in mode III at a Td of 80°C; then, both the crystallization and orientation were enhanced monophonically with increasing draw rate. Beyond the draw rate of 10 mm/min at a Td of 70°C, the orientation rate of chains was much faster than the relaxation one, and the motion mode transformed from mode III to IV. Then, obvious decreases in the crystallinity and orientation were observed with further increases in the draw rate; this resulted from the destruction of the crystallites. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42969. [ABSTRACT FROM AUTHOR]

Purpose: Accurate detection of pulmonary nodules remains a technical challenge in computer-aided diagnosis systems because some nodules may adhere to the blood vessels or the lung wall, which have low contrast compared to the surrounding tissues. In this paper, the analysis of typical shape features of candidate nodules based on a shape constraint Chan-Vese (CV) model combined with calculation of the number of blood branches adhered to nodule candidates is proposed to reduce false positive (FP) nodules from candidate nodules. Methods: The proposed scheme consists of three major stages: (1) Segmentation of lung parenchyma from computed tomography images. (2) Extraction of candidate nodules. (3) Reduction of FP nodules. A gray level enhancement combined with a spherical shape enhancement filter is introduced to extract the candidate nodules and their sphere-like contour regions. FPs are removed by analysis of the typical shape features of nodule candidates based on the CV model using spherical constraint and by investigating the number of blood branches adhered to the candidate nodules. The constrained shapes of CV model are automatically achieved from the extracted candidate nodules. Results: The detection performance was evaluated on 127 nodules of 103 cases including three types of challenging nodules, which are juxta-pleural nodules, juxta-vascular nodules, and ground glass opacity nodules. The free-receiver operating characteristic (FROC) curve shows that the proposed method is able to detect 88% of all the nodules in the data set with 4 FPs per case. Conclusions: Evaluation shows that the authors' method is feasible and effective for detection of three types of nodules in this study. [ABSTRACT FROM AUTHOR]

Purpose: Effective and accurate segmentation of the aortic valve (AV) from sequenced ultrasound (US) images remains a technical challenge because of intrinsic factors of ultrasound images that impact the quality and the continuous changes of shape and position of segmented objects. In this paper, a novel shape-constraint gradient Chan-Vese (GCV) model is proposed for segmenting the AV from time serial echocardiography. Methods: The GCV model is derived by incorporating the energy of the gradient vector flow into a CV model framework, where the gradient vector energy term is introduced by calculating the deviation angle between the inward normal force of the evolution contour and the gradient vector force. The flow force enlarges the capture range and enhances the blurred boundaries of objects. This is achieved by adding a circle-like contour (constructed using the AV structure region as a constraint shape) as an energy item to the GCV model through the shape comparison function. This shapeconstrained energy can enhance the image constraint force by effectively connecting separate gaps of the object edge as well as driving the evolution contour to quickly approach the ideal object. Because of the slight movement of the AV in adjacent frames, the initial constraint shape is defined by users, with the other constraint shapes being derived from the segmentation results of adjacent sequence frames after morphological filtering. The AV is segmented from the US images by minimizing the proposed energy function. Results: To evaluate the performance of the proposed method, five assessment parameters were used to compare it with manual delineations performed by radiologists (gold standards). Three hundred and fifteen images acquired from nine groups were analyzed in the experiment. The area-metric overlap error rate was 6.89% ± 2.88%, the relative area difference rate 3.94% ± 2.63%, the average symmetric contour distance 1.08 ± 0.43 mm, the root mean square symmetric contour distance 1.37 ± 0.52 mm, and the maximum symmetric contour distance was 3.57 ± 1.72 mm. Conclusions: Compared with the CV model, as a result of the combination of the gradient vector and neighborhood shape information, this semiautomatic segmentation method significantly improves the accuracy and robustness of AV segmentation, making it feasible for improved segmentation of aortic valves from US images that have fuzzy boundaries. [ABSTRACT FROM AUTHOR]

Introduction/Aims Methods Results Discussion Severe spinal deformities and previous spinal orthopedic instrumentation may result in substantial technical challenges for nusinersen delivery through lumbar puncture in patients with spinal muscular atrophy (SMA). The aim of this paper was to review our experience with ultrasound‐guided cervical puncture as an alternative approach for the intrathecal administration of nusinersen.This was a retrospective medical record review of transverse interlaminar ultrasound‐guided C1‐C2 puncture for nusinersen delivery in SMA patients. The details of puncture, complications, and success rate of the procedure were summarized.There were four patients who received a total of 13 cervical punctures for nusinersen delivery. All procedures were technically successful with no major complications. Full doses of nusinersen were delivered intrathecally.Transverse interlaminar ultrasound‐guided C1‐C2 puncture is an alternative approach for administering nusinersen if lumbar puncture fails. The success of the technique requires a thorough preprocedural evaluation of cervical spine imaging, sound knowledge of the cervical sonoanatomy and careful manipulation of the needle. [ABSTRACT FROM AUTHOR]

Biallelic pathogenic variants in CCN6 cause progressive pseudorheumatoid dysplasia (PPD), a rare skeletal dysplasia. The predominant features include noninflammatory progressive joint stiffness and enlargement, which are not unique to this condition. Nearly 100% of the reported variants are single nucleotide variants or small indels, and missing of a second variant has been reported. Genome sequencing (GS) covers various types of variants and deep phenotyping (DP) provides detailed and precise information facilitating genetic data interpretation. The combination of GS and DP improves diagnostic yield, especially in rare and undiagnosed diseases. We identified a novel compound heterozygote involving a disease-causing copy number variant (g.112057664&#95;112064205del) in trans with a single nucleotide variant (c.624dup(p.Cys209MetfsTer21)) in CCN6 in a pair of monozygotic twins, through the methods of GS and DP. The twins had received three nondiagnostic results before. The g.112057664&#95;112064205del variant was missed by all the tests, and the recorded phenotypes were inaccurate or even misleading. The twins were diagnosed with PPD, ending a 13-year diagnostic odyssey. There may be other patients with PPD experiencing underdiagnosis and misdiagnosis due to inadequate genetic testing or phenotyping methods. This case highlights the critical role of GS and DP in facilitating an accurate and timely diagnosis., (© 2024 Wiley Periodicals LLC.)