Deadly yet Preventable? Lessons From South Korea's Halloween Crowd Crush.

Avoidable disasters are both saddening and baffling. In 2022, 159 people, mostly in their 20s, and 30s were crushed to death in Itaewon's narrow alleyway amid South Korea's first pandemic-restrictions-free Halloween celebration. What is particularly sobering about this tragedy is that although many people called police hotlines as crowds became cramped and static, their calls went unheeded for hours. Rather than order independent investigations into the catastrophe (as of January 2024), the President of South Korea at the time focused on superficial issues such as asking the public to refer to the disaster as an "accident" (which it was not, it was an avoidable disaster) and the casualties as "the dead" (who are casualties indeed, instead of victims of a preventable tragedy). In this paper, we examine how officials' complacency about public health and safety dangers, ineffective disaster prevention, and preparedness systems, as well as the government's chronic lack of prioritization of public health and safety may have contributed to the disaster. Furthermore, we discuss the importance of creating integrated public health and safety protection systems to prevent similar tragedies from happening.

Efficacy and safety of esketamine versus propofol in electroconvulsive therapy for treatment-resistant depression: A randomized, double-blind, controlled, non-inferiority trial.

BACKGROUND: Electroconvulsive therapy (ECT) is a commonly used alternative for treatment-resistant depression (TRD). Although esketamine has a rapid pharmacological antidepressant action, it has not been studied as an ECT anesthetic. The objective of this study was to compare the efficacy and safety of esketamine with propofol when both are used as ECT anesthetic agents. METHODS: Forty patients with TRD were assigned to one of two arms in a double-blind, randomized controlled trial: esketamine or propofol anesthesia for a series of eight ECT sessions. Using a non-inferiority design, the primary outcome was the reduction in HAMD-17 depressive symptoms. The other outcomes were: rates of response and remission, anxiety, suicidal ideation, cognitive function, and adverse events. These were compared in an intention-to-treat analysis. RESULTS: Esketamine-ECT was non-inferior to propofol-ECT for reducing TRD symptoms after 8 sessions (adjusted Δ = 2.0, 95 % CI: -1.2-5.1). Compared to propofol-ECT, esketamine-ECT also had higher depression response (80 % vs. 70 %; p = .06) and remission (65 % vs. 55 %; p = .11) rates but non-inferiority was not established. In four components of cognitive function (speed of processing, working memory, visual learning, and verbal learning) esketamine-ECT was non-inferior to propofol-ECT. The results for anxiety, suicidal ideation, and adverse events (all p's > .05) were inconclusive. CONCLUSION: Esketamine was non-inferior to propofol when both are used as anesthetics for TRD patients undergoing ECT. Replication studies with larger samples are needed to examine the inconclusive results. REGISTRATION NUMBER: ChiCTR2000033715.

Catalyst-Free Dearomative Allylboration of Ketones with Benzo[b]thiophenylmethyl Boronic Acids.

A novel approach to the dearomative allylboration of ketones with benzo[b]thiophenylmethyl boronic acids has been developed. By leveraging the inherent reactivity of the boronic acid unit, this process occurs under mild reaction conditions without the need for a catalyst, leading to the efficient formation of homoallylic tertiary alcohols accompanied by the construction of three-dimensional sulfur-containing alicyclic scaffolds in high yields with excellent stereoselectivities.

Near-Infrared-Light-Induced Iron(I) Dimer-Enabled Radical Cascade Reactions of Fluoroalkyl Bromides for the Synthesis of Ring-Fused Quinazolinones.

The use of an earth-abundant and inexpensive iron complex as a catalyst, coupled with near-infrared (NIR) light as the energy source, for radical reactions with alkyl halides has been far less developed. In this study, we report NIR light-mediated iron(I) dimer-catalyzed radical cascade reactions of fluoroalkyl bromides for the synthesis of ring-fused quinazolinones bearing a difluoromethyl group. In this process, the 3-bromo-1,10-phenanthroline ligand facilitates the reactivity of [CpFe(CO)2]2, thereby improving the efficiency of the reaction.

A machine learning model based on CHAT-23 for early screening of autism in Chinese children.

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental condition that significantly impacts the mental, emotional, and social development of children. Early screening for ASD typically involves the use of a series of questionnaires. With answers to these questionnaires, healthcare professionals can identify whether a child is at risk for developing ASD and refer them for further evaluation and diagnosis. CHAT-23 is an effective and widely used screening test in China for the early screening of ASD, which contains 23 different kinds of questions. Methods: We have collected clinical data from Wuxi, China. All the questions of CHAT-23 are regarded as different kinds of features for building machine learning models. We introduce machine learning methods into ASD screening, using the Max-Relevance and Min-Redundancy (mRMR) feature selection method to analyze the most important questions among all 23 from the collected CHAT-23 questionnaires. Seven mainstream supervised machine learning models were built and experiments were conducted. Results: Among the seven supervised machine learning models evaluated, the best-performing model achieved a sensitivity of 0.909 and a specificity of 0.922 when the number of features was reduced to 9. This demonstrates the model's ability to accurately identify children for ASD with high precision, even with a more concise set of features. Discussion: Our study focuses on the health of Chinese children, introducing machine learning methods to provide more accurate and effective early screening tests for autism. This approach not only enhances the early detection of ASD but also helps in refining the CHAT-23 questionnaire by identifying the most relevant questions for the diagnosis process.

Research progress and considerations on oral rehydration therapy for the prevention and treatment of severe burn shock: A narrative review.

Severe burns are a significant cause of life-threatening conditions in both peacetime and wartime. Shock is a critical complication during the early stages of burn injury, contributing substantially to mortality and long-term disability. Effective fluid resuscitation is crucial for preventing and treating shock, with prompt administration being vital. However, timely intravenous fluid resuscitation is often challenging, and errors in resuscitation significantly contribute to mortality. Therefore, exploring a more rapid and effective non-invasive method of fluid resuscitation is necessary. Oral rehydration therapy (ORT) has shown considerable potential in this regard. This paper reviews ORT's historical development and current research progress, discussing its application in early anti-shock treatment for burns. While ORT is generally safe, potential complications like diarrhoea, vomiting, and abdominal discomfort must be noted, particularly if the rehydration rate is too rapid or if gastrointestinal issues exist. Careful patient assessment and monitoring are essential during ORT administration. Based on a comprehensive review of relevant research, we present provisional guidelines for ORT in burn patients. These guidelines aim to inform clinical practice but should be applied cautiously due to limited clinical evidence. Implementation must be tailored to the patient's condition under healthcare supervision, with adjustments according to evolving circumstances: ① Initiation timing: Start as soon as possible, and the ideal start time is usually within 6 h after injury. ② Rate of application: Employing a fractional administration approach, wherein small quantities of approximately 150-250 millilitres are provided for each instance and the initial fluid rate of oral rehydration can be simplified to 100 mL/kg/24 h. ③ Composition combination: In addition to essential salts and glucose, the oral rehydration solution can incorporate various anti-inflammatory and cellular protection constituents.

Post-heading dry-matter transport and nutrient uptake differentiate hybrid and inbred indica rice in the double-cropping system in South China.

Introduction: Hybrid rice demonstrated superior performance in enhancing yield and efficiency in rice production compared to inbred rice. Nevertheless, the underlying mechanism responsible for the increased yield and efficiency of hybrid rice in South China's double-cropping rice region remains understudied. Methods: Field experiments over two consecutive years were conducted. Firstly, yield variations among 20 inbred and 15 hybrid rice cultivars prevalent in South China's double-cropping rice system were examined. Secondly, selecting representative hybrid and inbred rice cultivars with significant yield disparities were carried out on further analyzing dry-matter production, source-sink relationships, and nutrient absorption and utilization in both rice types. Results: Hybrid rice displayed an average grain yield of 8.07 and 7.22 t hm-2 in the early and late seasons, respectively, which corresponds to a 12.29% and 13.75% increase over inbred rice with statistically significant differences. In comparison to inbred rice, hybrid rice exhibited enhanced nitrogen concentration in leaves at the heading stage (15.48-16.20%), post-heading dry matter accumulation (52.62-73.21%), post-heading dry matter conversion rate (29.23-34.12%), and harvest index (17.31-18.37%). Additionally, grain nitrogen and phosphorus uptake in hybrid rice increased by 11.88-22.50% and 16.38-19.90%. Hybrid rice mainly improved post-heading nitrogen and phosphorus uptake and transport, while not total nitrogen and phosphorus uptake. Internal nitrogen and phosphorus use efficiency enhanced by 9.83%-14.31% and 10.15%-13.66%, respectively. Post-heading dry matter accumulation, harvest index, grain nitrogen and phosphorus uptake, and internal nitrogen and phosphorus use efficiency exhibited significant positive linear correlations with grain yield. Discussion: The period from heading to maturity is critical for enhancing hybrid rice yield and efficiency. Improving photosynthetic capacity during this period and promoting nutrient transport to grains serve as crucial pathways for increasing grain yield and efficiency. This study is of great significance for further improvement grain yield and breeding rice cultivars with high-yield and high nutrients use efficiency for South China's double-cropped rice system.

Global mental health solidarity: strategies and solutions.

Mental health is deteriorating far and fast globally post-COVID. Though there were already over one billion people living with mental disorders pre-pandemic, in the first year of COVID-19 alone, the prevalence of anxiety and depression soared by 25% worldwide. In light of the chronic shortages of mental health resources and talents, along with disruptions of available health services caused by pandemic-related restrictions, technology is widely believed to hold the key to addressing the rising mental health crises. However, hurdles such as fragmented and oftentimes suboptimal patient protection measures substantially undermine technology's potential to address the global mental health crises reliably and at scale. To shed light on these issues, this paper aims to discuss the post-pandemic mental health challenges and opportunities, and the strategies and solutions the global mental health community could leverage to protect and elevate society's mental health in the long run.

Targeting NTCP for liver disease treatment: A promising strategy.

The sodium taurocholate co-transporting polypeptide (NTCP), a bile acids transporter, has been identified as a new therapeutic target for the treatment of liver disease. This paper thoroughly investigates the function of NTCP for regulating bile acid regulation, its correlation with hepatitis B and D infections, and its association with various liver diseases. Additionally, in this review we examine recent breakthroughs in creating NTCP inhibitors and their prospective applications in liver disease treatment. While this review emphasizes the promising potential of targeting NTCP, it concurrently underscores the need for broader and more detailed research to fully understand the long-term implications and potential side effects associated with NTCP inhibition.

Radical Replacement Process for Ligated Boryl Radical-Mediated Activation of Unactivated Alkyl Chlorides for C(sp3)-C(sp3) Bond Formation.

The ligated boryl radical (LBR) has emerged as a potent tool for activating alkyl halides in radical transformations through halogen-atom transfer (XAT). However, unactivated alkyl chlorides still present an open challenge for this strategy. We herein describe a new activation mode of the LBR for the activation of unactivated alkyl chlorides to construct a C(sp3)-C(sp3) bond. Mechanistic studies reveal that the success of the protocol relies on a radical replacement process between the LBR and unactivated alkyl chloride, forming an alkyl borane intermediate as the alkyl radical precursor. Aided with the additive K3PO4, the alkyl borane then undergoes one-electron oxidation, generating an alkyl radical. The incorporation of the radical replacement activation model to activate unactivated alkyl chlorides significantly enriches LBR chemistry, which has been applied to activate alkyl iodides, alkyl bromides, and activated alkyl chlorides via XAT.

Metal-Phosphonate-Organic Network as Ion Enrichment Layer for Sustainable Zinc Metal Electrode with High Rate Capability.

Zinc (Zn) metal batteries could be the technology of choice for sustainable battery chemistries owing to its better safety and cost advantage. However, their cycle life and Coulombic efficiency (CE) are strongly limited by the dendritic growth and side reactions of Zn anodes. Herein, we proposed an in situ construction of a metal-phosphonate-organic network (MPON) with three-dimensional interconnected networks on Zn metal, which can act as an ion enrichment layer for Zn anodes in Zn-metal batteries. This MPON with abundant porous structure and phosphate sites possesses ion enriching properties and high Zn2+ transference number (0.83), which is beneficial for enhancing Zn2+ migration and self-concentrating kinetics. Meanwhile, MPON offers hydrophobicity to effectively inhibit the water-induced Zn anode corrosion. As a result, the Zn electrode exhibits superior Zn/Zn2+ reversibility of over 4 months at 3 mA cm-2 and a high CE of 99.6%. Moreover, the Zn/NaV3O8 ·1.5H2O and Zn/MnO2 full cells using ultrathin Zn anodes (10 µm) exhibit high-capacity retention of 81% and 78% after 1400 and 1000 cycles, respectively. This work provides a unique promise to design high-performance anode for practical Zn-metal-based batteries.

N6-methyladenosine transcriptome-wide profiles of maize kernel development.

Maize (Zea mays L.) kernel development is a complex and dynamic process involving cell division and differentiation, into a variety of cell types. Epigenetic modifications, including DNA methylation, play a pivotal role in regulating this process. N6-methyladenosine modification is a universal and dynamic post-transcriptional epigenetic modification that is involved in the regulation of plant development. However, the role of N6-methyladenosine in maize kernel development remains unknown. In this study, we have constructed transcriptome-wide profiles for maize kernels at various stages of early development. Utilizing a combination of MeRIP-seq and RNA-seq analysis, we identified a total of 11,170, 10,973, 11,094, 11,990, 12,203 and 10,893 N6-methyladenosine peaks in maize kernels at 0, 2, 4, 6, 8, and 12 days after pollination, respectively. These N6-methyladenosine modifications were primarily deposited at the 3'-UTRs and were associated with the conserved motif-UGUACA. Additionally, we found that conserved N6-methyladenosine modification are involved in the regulation of genes that are ubiquitously expressed during kernel development. Further analysis revealed that N6-methyladenosine peak intensity was negatively correlated with the mRNA abundance of these ubiquitously expressed genes. Meanwhile, we employed phylogenetic analysis to predict potential regulatory proteins involved in maize kernels development and identified several that participate in the regulation of N6-methyladenosine modifications. Collectively, our results suggest the existence of a novel post-transcriptional epigenetic modification mechanism involved in the regulation of maize kernels development, thereby providing a novel perspective for maize molecular breeding.

Nickel-catalyzed selective disulfide formation by reductive cross-coupling of thiosulfonates.

Developing innovative methodologies for disulfide preparation is of importance in contemporary organic chemistry. Despite significant advancements in nickel-catalyzed reductive cross-coupling reactions for forming carbon-carbon and carbon-heteroatom bonds, the synthesis of S-S bonds remains a considerable challenge. In this context, we present a novel approach utilizing nickel catalysts for the reductive cross-coupling of thiosulfonates. This method operates under mild conditions, offering a convenient and efficient pathway to synthesize a wide range of both symmetrical and unsymmetrical disulfides from readily available, bench-stable thiosulfonates with exceptional selectivity. Notably, this approach is highly versatile, allowing for the late-stage modification of pharmaceuticals and the preparation of various targeted compounds. A comprehensive mechanistic investigation has been conducted to substantiate the proposed hypothesis.

Suicidality is most centrally situated within network of depression symptom criteria in unipolar depression patients with mood stabilizer in Asia.

Lithium and mood stabilizers are considered effective augmentation agents of antidepressants for treatment-resistant depression. Thus, this study aimed to estimate the network structure of depression symptom criteria among unipolar depression patients with mood stabilizers, using data from the Research on Asian Psychotropic Prescription Patterns for mood stabilizers (REAP-MS). We estimated a network of the 9 depression symptom criteria among 411 unipolar depression patients in Asia. Each of the depression symptom criteria was considered to be a dichotomous categorical variable. Suicidality (suicidal ideation or attempt) was the most centrally situated within the network of depression symptoms, followed by depressed mood, loss of energy, anhedonia and weight loss or gain. Contrastingly, concentration problem was the least interconnected. The depression symptom criteria were organized into 4 clusters by the community detection method. The findings suggest that suicidality may be one of the significant therapeutic target symptoms in unipolar depression patients with mood stabilizers.

Analysis on the epidemiological and drug resistance characteristics of osteoarticular tuberculosis in South-central China.

Objective: Osteoarticular tuberculosis (OATB) is one of the most common forms of extrapulmonary tuberculosis; however, limited epidemiological data are available on this public health concern worldwide, especially in developing countries. This study aimed to analyze the clinical epidemiology and drug resistance characteristics of OATB cases in Hunan province which located in South-central China. Methods: We retrospectively enrolled OATB patients with Mycobacterium tuberculosis culture positive at Hunan Chest Hospital from January 2013 through March 31, 2022. The multiple demographic, clinical variables and drug susceptibility data of the patients were collected from the hospital's electronic patient records. Descriptive statistical methods, Chi-square test and logistic regression analysis were employed as statistical methods. Results: Of the 269 OATB cases, 197 (73.23%) were males, 206 (76.85%) were farmers; patients' ages ranged from 5 to 85 years, 57 (21.19%) aged at 20-29 years old and 52 (19.33%) aged at 60-69 years old. In terms of the disease, 177 (65.80%) had spinal TB with most occurrence in lumbar vertebrae (26.02%, 70/269), multiple spinal sites (18.96%, 51/269) and thoracic vertebrae (15.24%, 41/269). Outside of the spine, OATB mainly occurred in the lower limb (13.38%, 36/269). In terms of drug resistance, 40 (14.87%) and 72 (26.77%) were resistant to rifampicin (RFP) and isoniazid (INH) respectively; 38 (14.13%) were multi-drug resistant (MDR), and a total of 78 (29.00%) isolates were drug resistant. OATB patients aged 40-49 years old (compared to those aged ≥70 years) and from the west of Hunan province, China (compared to those from the center of Hunan) were at risk for developing RR/MDR (ORs were 5.057 and 4.942, respectively; 95% CIs were 1.009-25.342 and 1.458-16.750, respectively). Conclusion: In South-central China, OATB mainly affected males, farmers and those aged 20-29 and 60-69 years old. Spinal TB is prone to occur in the lumbar and multiple spinal sites. The resistance situation of OATB was serious, and people aged 40-49 years old and patients from the west of Hunan were risk factors of RR/MDR. All these findings will help to improve the prevention, diagnosis and treatment strategies of OATB.

Comparing network structures of depressive and anxiety symptoms between demographically-matched heart disease and heart disease free samples using propensity score matching: Findings from the Chinese Longitudinal Healthy Longevity Survey (CLHLS).

BACKGROUND: Older adults with heart disease often experience higher rates of comorbid anxiety and depression. This study examined depression and anxiety network structures among older adults with heart disease and their heart disease free peers. METHODS: Network analyses of secondary cross-sectional data from the 2017 to 2018 wave of CLHLS were used to construct groups of older adults with and without heart disease using propensity score matching. Depression and anxiety symptoms were assessed using Center for Epidemiological Studies Depression Scale and Generalized Anxiety Disorder Scale, respectively. Central symptoms and bridge symptoms were identified using expected influence. RESULTS: 1689 older adults with heart disease and matched control sample of 1689 older adults without heart disease were included. The prevalence and severity of depression and anxiety were significantly higher in older adults with heart disease compared to the control group. There was no significant difference in overall structures of depression and anxiety network models between two the groups. Key central symptoms and bridge symptoms within these groups were highly similar; GAD 2 "Uncontrollable worrying" and GAD 4 "Trouble relaxing" were identified as the most central symptoms, while GAD 1 "Nervousness" and CESD 1 "Feeling bothered" were identified as key bridge symptoms across both network models. CONCLUSION: Depression and anxiety are more prevalent in older adults with heart disease than demographically-matched heart disease free controls. However, network structures of these symptoms do not differ between two groups. Accordingly, depression and anxiety psychosocial interventions developed for older adults without heart disease may also benefit older adults with heart disease.

Gender differences in behavioral and emotional problems among school children and adolescents in China: National survey findings from a comparative network perspective.

BACKGROUND: Behavioral and emotional problems are common and often co-occur during childhood and adolescence. The aim of this study was to assess gender differences in the network structures of behavioral and emotional problems of children and adolescents in China based on a national survey. METHODS: The Parent version of Achenbach's Child Behavior Checklist (CBCL) was used to assess behavioral and emotional problems. To account for potential confounding factors between boys and girls, propensity score matching was utilized. Network model differences were assessed with a Network Comparison Test (NCT). RESULTS: Data from 60,715 children and adolescents were included for analyses. Boys exhibited more severe total behavioral and emotional problems compared to girls. While several edges showed significant differences between boys and girls, the strongest association was consistently found between "Attention problems" (CBCL6) and "Aggressive behavior"(CBCL8) in both boys and girls, regardless of age. Network centrality was higher among adolescents compared to children. The most central problems commonly found across different genders and age groups were "Aggressive behavior" (CBCL8) (centrality values were 1.142 for boys aged 6-11 years, 1.051 for boys aged 12-16 years, 1.148 for girls aged 6-11 years, and 1.028 for girls aged 12-16 years), "Anxious/depressed" (CBCL1) (centrality values of 0.892 for boys aged between 6 and 11 years, 1.031 for boys aged 12-16 years, 0.951 for girls aged 6-11 years, and 1.099 for girls aged 12-16 years) and "Social problems" (CBCL4) (centrality values of 1.080 for boys aged 6-11 years, 0.978 for boys aged 12-16 years, 1.086 for girls aged between 6 and 11 years, and 0.929 for girls aged 12-16 years). CONCLUSION: Development of interventions that address aggressive behavior, anxiety/depression, and social problems may be beneficial for reducing risk of psychopathology among children and adolescents.

Unveiling the Interplay Between Depressive Symptoms' Alleviation and Quality of Life Improvement in Major Depressive Disorder: A Network Analysis Based on Longitudinal Data.

Background: Understanding the dynamic relationship between depressive symptoms and quality of life (QOL) is essential in improving long-term outcomes for patients with Major Depressive Disorder (MDD). While previous studies often relied on cross-sectional data, there is a pressing need for stronger evidence based on longitudinal data to better inform the development of effective clinical interventions. By focusing on key depressive symptoms, such interventions have the potential to ultimately enhance QOL in individuals with MDD. Methods: This multi-center prospective study, conducted between 2016 and 2020, enrolled outpatients and inpatients diagnosed with MDD across twelve psychiatric hospitals in China. Longitudinal data on Patient Health Questionnaire - 9 (PHQ-9) and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) was analyzed using an Extended Bayesian Information Criterion (EBIC) graphical least absolute shrinkage and selection operator (gLASSO) network model to explore the connections between depressive symptom changes and QOL changes. Flow network was applied to investigate relationships between individual symptom changes and overall QOL score change, as well as daily functional independence. Results: This study included 818 participants with complete data after 8-week antidepressant treatment. Apart from the overlapping items from PHQ-9 and Q-LES-Q-SF, the three edges between "mood" (delta-QLES2) and "anhedonia" (delta-DEP1), between "physical health" (delta-QLES1) and "sleep problems" (delta-DEP3), and between "physical health" (delta-QLES1) and "sad mood" (delta-DEP2) were the most strong bridges between the cluster of depressive symptoms alleviation and the cluster of QOL change. "Anhedonia" (delta-DEP1), "sad mood" (delta-DEP2) and "loss of energy" (delta-DEP4) had the highest bridge strength between the alleviations of depressive symptoms and the total score change of Q-LES-Q-SF. Anhedonia had the greatest connection with participants' satisfaction with function in daily life. Conclusion: This study highlighted the potential for developing highly effective interventions by targeting on central symptoms, thereby to ultimately improve QOL for patients with MDD.

Exploring the feasibility of preoperative tumor-bed boost, oncoplastic surgery, and adjuvant radiotherapy schedule in early-stage breast cancer: A phase II clinical trial.

BACKGROUND: Oncoplastic breast-conserving surgery (OBCS) improves satisfaction in patients who would fare otherwise sub-optimal cosmetic outcome, while brings challenge in tumor-bed identification during adjuvant radiotherapy. The ultra-hypofractionated breast radiotherapy further shortens treatment sessions from moderately hypofractionated regimens. To circumscribe the difficulty in tumor-bed contouring and the additional toxicity from larger boost volumes, we propose to move forward the boost session preoperatively from the adjuvant radiation part. Thus, the present study aims to evaluate the feasibility of a new treatment paradigm of preoperative primary-tumor boost before breast-conserving surgery (BCS) or OBCS followed by adjuvant ultra-hypofractionated whole-breast irradiation (u-WBRT) for patients with early-stage breast cancer. METHODS: There was a phase II study. Patients younger than 55 years old, with a biopsy confirmed mono-centric breast cancer, without lymph node involvement were enrolled. Preoperative primary-tumor boost was given by a single 10 Gy in 1 fraction, and BCS or OBCS was conducted within two weeks afterwards. Adjuvant u-WBRT (26 Gy/5.2 Gy/5 f) was given in 6 weeks postoperatively without any boost, after the full recovery from surgery. Surgical complications and patient-reported outcomes, as assessed via Breast-Q questionnaires, were documented. A propensity score matching approach was employed to identify a control group at a 1:1 ratio for BREAST-Q outcomes comparison. RESULTS: From May 2022 to September 2023, 36 patients were prospectively enrolled. Surgical complications were observed in 7 cases (19.4%), including 3 cases with Clavien-Dindo (CD) grade 1-2 and 4 cases with CD grade 3 complications. All but four patients (11.1%) started the planned u-WBRT within one week after the pre-defined due dates postoperatively (≤49 d). Four patients (11.1%) developed grade 2 radiodermatitis after chemotherapy initiation. Compared to the study group, the control patients reported higher scores in chest physical well-being (P=0.045) and in their attitudes towards arm swelling (P=0.01). No significant difference was detected in the other of domains (Satisfaction with Breasts, Sexual and Psychosocial Well-Being, and Adverse Effects of Radiation). With a median follow-up period of 9.8 months (2.4-18.9 mo), none had any sign of relapse. CONCLUSION: This Phase II clinical trial confirmed the technical and safety feasibility of novel radiation schedule in patients undergoing BCS or OBCS. According to the BREAST-Q questionnaire, patients who underwent novel radiation schedules reported lower satisfaction in chest physical well-being. A randomized controlled trial is necessary to further investigate these findings. Additionally, long-term follow-up is required to assess oncological outcomes.

Apoptotic vesicles (apoVs) derived from fibroblast-converted hepatocyte-like cells effectively ameliorate liver fibrosis.

Liver fibrosis is a serious global health issue for which effective treatment remains elusive. Chemical-induced hepatocyte-like cells (ciHeps) have emerged as an appealing source for cell transplantation therapy, although they present several challenges such as the risk of lung thromboembolism or hemorrhage. Apoptotic vesicles (apoVs), small membrane vesicles generated during the apoptosis process, have gained attention for their role in regulating various physiological and pathological processes. In this study, we generated ciHep-derived apoVs (ciHep-apoVs) and investigated their therapeutic potential in alleviating liver fibrosis. Our findings revealed that ciHep-apoVs induced the transformation of macrophages into an anti-inflammatory phenotype, effectively suppressed the activity of activated hepatic stellate cells (aHSCs), and enhanced the survival of hepatocytes. When intravenously administered to mice with liver fibrosis, ciHep-apoVs were primarily engulfed by macrophages and myofibroblasts, leading to a reduction in liver inflammation and fibrosis. Proteomic and miRNA analyses showed that ciHep-apoVs were enriched in various functional molecules that modulate crucial cellular processes, including metabolism, signaling transduction, and ECM-receptor interactions. ciHep-apoVs effectively suppressed aHSCs activity through the synergistic inhibition of glycolysis, the PI3K/AKT/mTOR pathway, and epithelial-to-mesenchymal transition (EMT) cascades. These findings highlight the potential of ciHep-apoVs as multifunctional nanotherapeutics for liver fibrosis and provide insights into the treatment of other liver diseases and fibrosis in other organs.