A novel prognostic signature based on smoking-associated genes for predicting prognosis and immune microenvironment in NSCLC smokers.

BACKGROUND: As a highly heterogeneous tumor, non-small cell lung cancer (NSCLC) is famous for its high incidence and mortality worldwide. Smoking can cause genetic changes, which leading to the occurrence and progress of NSCLC. Nevertheless, the function of smoking-related genes in NSCLC needs more research. METHODS: We downloaded transcriptome data and clinicopathological parameters from Gene Expression Omnibus (GEO) databases, and screened smoking-related genes. Lasso regression were applied to establish the 7-gene signature. The associations between the 7-gene signature and immune microenvironment analysis, survival analysis, drug sensitivity analysis and enriched molecular pathways were studied. Ultimately, cell function experiments were conducted to research the function of FCGBP in NSCLC. RESULTS: Through 7-gene signature, NSCLC samples were classified into high-risk group (HRG) and low-risk group (LRG). Significant difference in overall survival (OS) between HRG and LRG was found. Nomograms and ROC curves indicated that the 7-gene signature has a stable ability in predicting prognosis. Through the analysis of immune microenvironment, we found that LRG patients had better tumor immune activation. FCGBP showed the highest mutation frequency among the seven prognostic smoking related genes (LRRC31, HPGD, FCGBP, SPINK5, CYP24A1, S100P and FGG), and was notable down-regulated in NSCLC smokers compared with non-smoking NSCLC patients. The cell experiments confirmed that FCGBP knockdown promoting proliferation, migration, and invasion in NSCLC cells. CONCLUSION: This smoking-related prognostic signature represents a promising tool for assessing prognosis and tumor microenvironment in smokers with NSCLC. The role of FCGBP in NSCLC was found by cell experiments, which can be served as diagnostic biomarker and immunotherapy target for NSCLC.

Prevalence, genetic and clinical characteristics in first-degree relatives of patients with familial cerebral cavernous malformations in China.

OBJECTIVE: This study aims to investigate the prevalence of familial cerebral cavernous malformations (FCCMs) in first-degree relatives (FDRs) using familial screening, to describe the distribution of initial symptoms, lesion count on cranial MRI and pathogenic gene in patients. METHODS: Patients with multiple CCMs who enrolled from the Treatments and Outcomes of Untreated Cerebral Cavernous Malformations in China database were considered as probands and FDRs were recruited. Cranial MRI was performed to screen the CCMs lesions, and whole-exome sequencing was performed to identify CCM mutations. MRI and genetic screening were combined to diagnose FCCM in FDRs, and the results were presented as prevalence and 95% CIs. The Kaplan-Meier (KM) method was used to calculate the cumulative incidence of FCCM. RESULTS: 33 (76.74%) of the 43 families (110 FDRs) were identified as FCCM (85 FDRs). Receiver operating characteristic analysis revealed three lesions on T2-weighted imaging (T2WI) were the strong indicator for distinguishing probands with FCCM (sensitivity, 87.10%; specificity, 87.50%). Of the 85 FDRs, 31 were diagnosed with FCCM, resulting in a prevalence of 36.5% (26.2%-46.7%). In families with FCCMs, the mutation rates for CCM1, CCM2 and CCM3 were 45.45%, 21.21% and 9.09%, respectively. Furthermore, 53.13% of patients were asymptomatic, 17.19% were intracranial haemorrhage and 9.38% were epilepsy. The mean age of symptom onset analysed by KM was 46.67 (40.56-52.78) years. CONCLUSION: Based on MRI and genetic analysis, the prevalence of CCMs in the FDRs of families with FCCMs in China was 36.5%. Genetic counselling and MRI screening are recommended for FDRs in patients with more than three CCM lesions on T2WI.

Identification of Plasma hsa_circ_0001230 and hsa_circ_0023879 as Potential Novel Biomarkers for Focal Segmental Glomerulosclerosis and circRNA-miRNA-mRNA network analysis.

Introduction Focal segmental glomerulosclerosis (FSGS) is a common glomerulopathy with unclear mechanism. The demand for FSGS clinical diagnostic biomarkers has not yet been met. Circular RNA (circRNA) is a novel non-coding RNA with multiple functions, but its diagnostic value for FSGS remains unexplored. This study aimed to identify circRNAs that could aid in early clinical diagnosis and to investigate their mechanisms in podocyte injury. Methods The signature of plasma circRNAs for FSGS was identified by circRNA microarray. The existence of circRNAs was confirmed by qRT-PCR, RNase R assay, and DNA sequencing. Plasma levels of circRNAs were evaluated by qRT-PCR. The diagnostic value was appraised by receiver operating characteristic curve. The circRNA-miRNA-mRNA network was built with Cytoscape 7.3.2. Statistically significant differences were calculated by the Mann-Whitney U-test. Results A total of 493 circRNAs (165 upregulated, 328 downregulated) were differentially expressed in the plasma of FSGS patients (n = 3) and normal controls (n = 3). Eight candidate circRNAs were demonstrated to be circular and stable transcripts. Among them, hsa_circ_0001230 and hsa_circ_0023879 were significantly upregulated in FSGS patients (n = 29) compared to normal controls (n = 51). The areas under the curve value of hsa_circ_0001230 and hsa_circ_0023879 were 0.668 and 0.753, respectively, while that of two-circRNAs panel was 0.763. The RNA pull-down analysis revealed that hsa_circ_0001230 and hsa_circ_0023879 could sponge hsa-miR-106a. Additionally, hsa_circ_0001230 and hsa_circ_0023879 positively regulated hsa-miR-106a target genes phosphatase and tensin homolog (PTEN) and Bcl-2-like protein 11 (BCL2L11) in podocytes. Conclusion Hsa_circ_0001230 and hsa_circ_0023879 are novel blood biomarkers for FSGS. They may regulate podocyte apoptosis by competitively binding to hsa-miR-106a.

Dual-Function Electrolyte Additive Design for Long Life Alkaline Zinc Flow Batteries.

Alkaline zinc-based flow batteries (AZFBs) have emerged as a promising electrochemical energy storage technology owing to Zn abundance, high safety, and low cost. However, zinc dendrite growth and the formation of dead zinc greatly impede the development of AZFBs. Herein, a dual-function electrolyte additive strategy is proposed to regulate zinc nucleation and mitigate the hydroxide corrosion of zinc depositions for stable AZFBs. This strategy, as exemplified by urea, introduces an electrolyte additive to coordinate with Zn2+/Zn with proper strength, slowing zinc deposition kinetics to induce uniform nucleation and protecting the deposited zinc surface from attack by hydroxide ions through preferable adsorption. The zincate complexes with urea are identified to be Zn(OH)2(urea)(H2O)2 and Zn2(OH)4(H2O)4(urea), which exhibit slow zinc deposition kinetics, allowing instantaneous nucleation. Calculation results reveal an additional energy barrier of 1.29 eV for the subsequent adsorption of an OH- group when a urea molecule absorbs on the zinc cluster, significantly mitigating the formation of dead zinc. Consequently, prolonged cell cycling of the prototype alkaline zinc-iron flow battery demonstrates stable operation for over 130 h and an average coulombic efficiency of 98.5%. It is anticipated that this electrolyte additive strategy will pave the way for developing highly stable AZFBs.

Cause of Concussion With Persisting Symptoms Is Associated With Long-Term Recovery and Symptom Type, Duration, and Number in a Longitudinal Cohort of 600 Patients.

It is important for patients and clinicians to know the potential for recovery from concussion as soon as possible after injury, especially in patients who do not recover completely in the first month and have concussion with persisting concussion symptoms (C+PCS). We assessed the association between the causes of concussion and recovery from C+PCS in a consecutive retrospective and prospective cohort of 600 patients referred to the Canadian Concussion Center (CCC) at Toronto Western Hospital. Data were obtained from clinical records and follow-up questionnaires and not from a standardized database. A novel method was used to assess long-term recovery, and multi-variable Cox proportional hazards models were used to assess relationships between cause of concussion and time to recovery. We examined the subsequent recovery of patients who had not recovered after at least one month from the time of concussion. Patients were grouped into the following four causes: sports and recreation (S&R, n = 312, 52%); motor vehicle collisions (MVC, n = 103, 17%); falls (n = 100, 17%); and being struck by an object including violence (SBOV, n = 85, 14%). The MVC group had the highest percentage of females (75.7%), the oldest participants (median: 40.0 [interquartile range (IQR):30.5-49.0] years), the most symptoms (median:11.0 [IQR:8.5-15.0]), and the longest symptom duration (median: 28.0 [IQR:12.0-56.00] months). In contrast, the S&R group had the highest percentage of males (58.1%), the youngest participants (median:20.0 [IQR:17.0-30.0] years), the best recovery outcome, and shortest symptom duration (median:22.0 [IQR:8.0-49.5] months). Significant differences among the four causes included age (p < 0.001), sex (p < 0.001), number of previous concussions (p < 0.001), history of psychiatric disorders (p = 0.002), and migraine (p = 0.001). Recovery from concussion was categorized into three groups: (1) Complete Recovery occurred in only 60 (10%) patients with median time 8.0 (IQR:3.5-18.0) months and included 42 S&R, 7 MVC, 8 falls, and 3 SBOV; (2) Incomplete Recovery occurred in 408 (68.0%) patients with persisting median symptom time of 5.0 (IQR:2.0-12.0) months; and (3) Unknown Recovery occurred in 132 (22.0%) patients and was because of lack of follow-up. In summary, the cause of C+PCS was associated with the type, number, and duration of symptoms and time required for recovery, although all causes of C+PCS produced prolonged symptoms in a large percentage of patients, which emphasizes the importance of concussions as a public health concern necessitating improved prevention and treatment strategies.

Recurrence of locally invasive retroperitoneal dedifferentiated liposarcoma shortly after surgery: A case report and literature review.

RATIONALE: Retroperitoneal dedifferentiated liposarcoma (RPDDL) is an uncommon malignancy, which often remains undetected for many years due to having adequate space in the retroperitoneal cavity and lacking clinical manifestations in the early stage of the disease. Surgical procedure is usually used as the first choice for treatment. However, it is prone to local recurrence after the operation, resulting in an unfavorable prognosis. Our aim is to draw useful lessons from the new case and provide some experience for management of the disease. PATIENT CONCERNS: We describe a 55-year-old male patient who was admitted for a 3-week history of persistent dull ache of the left waist. A large mass of the left upper abdomen was palpated in physical examination. Moreover, the imaging examination revealed that the diameter of the mass was about 21 cm, and some adjacent vital organs were invaded, which brought great challenges to complete surgical resection. DIAGNOSIS: The postoperative pathological results confirmed that the mass was RPDDL with invasion of the surrounding vital structures including pancreas, spleen, left adrenal gland, left kidney, and vasculature with tumor emboli. INTERVENTIONS: Surgical resection of the mass was performed by our multidisciplinary team. The patient received chemotherapy 1 month after surgery. OUTCOMES: The effect of chemotherapy seemed to be unsatisfactory. Local multifocal recurrence of the tumor was considered about 2 months after surgery. Finally, he gave up any treatments and died of the disease. LESSONS: Regular physical examination and ultrasound screening may detect the disease as early as possible, especially for high-risk group aged 60 to 70, which should be popularized. Incomplete resection, vascular invasion, and interruption of postoperative treatment may lead to an unfavorable prognosis. Therefore, we think that patients with the disease may benefit from complete surgical resection and uninterrupted adjuvant therapy.

Identification of L11L and L7L as virulence-related genes in the African swine fever virus genome.

Introduction: African swine fever (ASF) is an infectious disease that causes considerable economic losses in pig farming. The agent of this disease, African swine fever virus (ASFV), is a double-stranded DNA virus with a capsid membrane and a genome that is 170-194 kb in length encoding over 150 proteins. In recent years, several live attenuated strains of ASFV have been studied as vaccine candidates, including the SY18ΔL7-11. This strain features deletion of L7L, L8L, L9R, L10L and L11L genes and was found to exhibit significantly reduced pathogenicity in pigs, suggesting that these five genes play key roles in virulence. Methods: Here, we constructed and evaluated the virulence of ASFV mutations with SY18ΔL7, SY18ΔL8, SY18ΔL9, SY18ΔL10, and SY18ΔL11L. Results: Our findings did not reveal any significant differences in replication efficiency between the single-gene deletion strains and the parental strains. Pigs inoculated with SY18ΔL8L, SY18ΔL9R and SY18ΔL10L exhibited clinical signs similar to those inoculated with the parental strains. Survival rate of pigs inoculated with 103.0TCID50 of SY18ΔL7L was 25%, while all pigs inoculated with 103.0TCID50 of SY18ΔL11L survived, and 50% inoculated with 106.0TCID50 SY18ΔL11L survived. Discussion: The results indicate that L8L, L9R and L10L do not affect ASFV SY18 virulence, while the L7L and L11L are associated with virulence.

Deleting the C84L Gene from the Virulent African Swine Fever Virus SY18 Does Not Affect Its Replication in Porcine Primary Macrophages but Reduces Its Virulence in Swine.

(1) Background: African swine fever (ASF) is a highly contagious disease that causes high pig mortality. Due to the absence of vaccines, prevention and control are relatively challenging. The pathogenic African swine fever virus (ASFV) has a complex structure and encodes over 160 proteins, many of which still need to be studied and verified for their functions. In this study, we identified one of the unknown functional genes, C84L. (2) Methods: A gene deficient strain was obtained through homologous recombination and several rounds of purification, and its replication characteristics and virulence were studied through in vitro and in vivo experiments, respectively. (3) Results: Deleting this gene from the wild-type virulent strain SY18 did not affect its replication in porcine primary macrophages but reduced its virulence in pigs. In animal experiments, we injected pigs with a 102 TCID50, 105 TCID50 deletion virus, and a 102 TCID50 wild-type strain SY18 intramuscularly. The control group pigs reached the humane endpoint on the ninth day (0/5) and were euthanized. Two pigs in the 102 TCID50(2/5) deletion virus group survived on the twenty-first day, and one in the 105 TCID50(1/5) deletion virus group survived. On the twenty-first day, the surviving pigs were euthanized, which was the end of the experiment. The necropsies of the survival group and control groups' necropsies showed that the surviving pigs' liver, spleen, lungs, kidneys, and submaxillary lymph nodes did not show significant lesions associated with the ASFV. ASFV-specific antibodies were first detected on the seventh day after immunization; (4) Conclusions: This is the first study to complete the replication and virulence functional exploration of the C84L gene of SY18. In this study, C84L gene was preliminarily found not a necessary gene for replication, gene deletion strain SY18ΔC84L has similar growth characteristics to SY18 in porcine primary alveolar macrophages. The C84L gene affects the virulence of the SY18 strain.

A cuproptosis score model and prognostic score model can evaluate clinical characteristics and immune microenvironment in NSCLC.

BACKGROUND: Cuproptosis-related genes (CRGs) are associated with lung adenocarcinoma. However, the links between CRGs and non-small-cell lung cancer (NSCLC) are not clear. In this study, we aimed to develop two cuproptosis models and investigate their correlation with NSCLC in terms of clinical features and tumor microenvironment. METHODS: CRG expression profiles and clinical data from NSCLC and normal tissues was obtained from GEO (GSE42127) and TCGA datasets. Molecular clusters were classified into three patterns based on CRGs and cuproptosis cluster-related specific differentially expressed genes (CRDEGs). Then, two clinical models were established. First, a prognostic score model based on CRDEGs was established using univariate/multivariate Cox analysis. Then, through principal component analysis, a cuproptosis score model was established based on prognosis-related genes acquired via univariate analysis of CRDEGs. NSCLC patients were divided into high/low risk groups. RESULTS: Eighteen CRGs were acquired, all upregulated in tumor tissues, 15 of which significantly (P < 0.05). Among the three CRG clusters, cluster B had the best prognosis. In the CRDEG clusters, cluster C had the best survival. In the prognostic score model, the high-risk group had worse prognosis, higher tumor mutation load, and lower immune infiltration while in the cuproptosis score model, a high score represented better survival, lower tumor mutation load, and high-level immune infiltration. CONCLUSIONS: The cuproptosis score model and prognostic score model may be associated with NSCLC prognosis and immune microenvironment. These novel findings on the progression and immune landscape of NSCLC may facilitate the provision of more personalized immunotherapy interventions for NSCLC patients.

Deletion of the B125R gene in the African swine fever virus SY18 strain leads to an A104R frameshift mutation slightly attenuating virulence in domestic pigs.

African swine fever (ASF), caused by the ASF virus (ASFV), is a hemorrhagic and fatal viral disease that affects Eurasian wild boars and domestic pigs, posing a substantial threat to the global pig breeding industry. ASFV, a double-stranded DNA virus, possesses a large genome containing up to 160 open reading frames, most of which exhibit unknown functions. The B125R gene of ASFV, located at the 105595-105972 bp site in the ASFV-SY18 genome, remains unexplored. In this study, we discovered that B125R deletion did not affect recombinant virus rescue, nor did it hinder viral replication during the intermediate growth phase. Although the virulence of the recombinant strain harboring this deletion was attenuated, intramuscular inoculation of the recombinant virus in pigs at doses of 102 or 104 TCID50 resulted in mortality. Moreover, sequencing analysis of six recombinant strains obtained from three independent experiments consistently revealed an adenine insertion at the 47367-47375 bp site in the A104R gene due to the B125R deletion, leading to premature termination of this gene. Intriguingly, this insertion did not influence the transcription of the A104R gene between the recombinant and parental strains. Consequently, we postulate that the deletion of the B125R gene in ASFV-SY18 or other genotype II strains may marginally attenuate virulence in domestic pigs.

Bioinformatics analysis and experimental validation reveal the anti-ferroptosis effect of FZD7 in acute kidney injury.

BACKGROUND: Ferroptosis plays an important role in acute kidney injury (AKI), but the specific regulatory mechanism of ferroptosis in AKI remains unclear. This study is expected to analyze ferroptosis-related genes (FRGs) in AKI and explore their underlying mechanisms. RESULTS: A total of 479 differentially expressed genes (DEGs), including 196 up-regulated genes and 283 down-regulated genes were identified in the AKI chip GSE30718. 341 FRGs were obtained from the Genecard, OMIM and NCBI database. Totally 11 ferroptosis-related DEGs in AKI were found, in which 7 genes (CD44, TIGAR, RB1, LCN2, JUN, ARNTL, ACSL4) were up-regulated and 4 genes (FZD7, EP300, FOXC1, DLST) were down-regulated. Three core genes (FZD7, JUN, EP300) were obtained by PPI and KEGG analysis, among which the function of FZD7 in AKI is unclear. The WGCNA analysis found that FZD7 belongs to a module that was negatively correlated with AKI. Further basic experiments confirmed that FZD7 is down-regulated in mouse model of ischemia-reperfusion-AKI and cellular model of hypoxia-reoxygenation(H/R). In addition, knockdown of FZD7 could further aggravate the down-regulation of cell viability induced by H/R and Erastin, while overexpression of FZD7 can rescue its down-regulation to some extent. Furthermore, we verified that knockdown of FZD7 decreased the expression of GPX4 and overexpression of FZD7 increased the expression of GPX4, suggesting that FZD7 may inhibit ferroptosis by regulating the expression of GPX4 and plays a vital role in the onset and development of AKI. CONCLUSIONS: This article revealed the anti-ferroptosis effect of FZD7 in acute kidney injury through bioinformatics analysis and experimental validation, suggesting that FZD7 is a promising target for AKI and provided more evidence about the vital role of ferroptosis in AKI.

Efficacy of Telitacicept in a systemic lupus erythematosus patient with suboptimal response to Belimumab: A case report.

As a therapeutic treatment for systemic lupus erythematosus (SLE), Belimumab reduces disease relapses and minimizes organ damage. Clinical practice, however, shows that the treatment is ineffective for a number of patients. Treatments for such cases are still lacking. As a biologic agent that targets both BLys and APRIL, Telitacicept inhibits both B cells and plasma cells. This case report describes a 35-year-old female with lupus nephritis (LN) who had previously undergone 10 cycles of Belimumab treatment but remained poorly controlled. Despite this, her condition improved significantly after switching to Telitacicept. This is the first report on the efficacy of Telitacicept in an SLE patient with suboptimal response to Belimumab. Telitacicept's role in this scenario needs more investigation and attention.

Center variability in the prognostic value of a cumulative acute cellular rejection "A-score" for long-term lung transplant outcomes.

The acute rejection score (A-score) in lung transplant recipients, calculated as the average of acute cellular rejection A-grades across transbronchial biopsies, summarizes the cumulative burden of rejection over time. We assessed the association between A-score and transplant outcomes in 2 geographically distinct cohorts. The primary cohort included 772 double lung transplant recipients. The analysis was repeated in 300 patients from an independent comparison cohort. Time-dependent multivariable Cox models were constructed to evaluate the association between A-score and chronic lung allograft dysfunction or graft failure. Landmark analyses were performed with A-score calculated at 6 and 12 months posttransplant. In the primary cohort, no association was found between A-score and graft outcome. However, in the comparison cohort, time-dependent A-score was associated with chronic lung allograft dysfunction both as a time-dependent variable (hazard ratio, 1.51; P < .01) and when calculated at 6 months posttransplant (hazard ratio, 1.355; P = .031). The A-score can be a useful predictor of lung transplant outcomes in some settings but is not generalizable across all centers; its utility as a prognostication tool is therefore limited.

Cost-Utility Analysis of Geriatric Assessment and Management in Older Adults With Cancer: Economic Evaluation Within 5C Trial.

PURPOSE: Geriatric assessment (GA) is a guideline-recommended approach to optimize cancer management in older adults. We conducted a cost-utility analysis alongside the 5C randomized controlled trial to compare GA and management (GAM) plus usual care (UC) against UC alone in older adults with cancer. METHODS: The economic evaluation, conducted from societal and health care payer perspectives, used a 12-month time horizon. The Canadian 5C study randomly assigned patients to receive GAM or UC. Quality-adjusted life-years (QALYs) were measured using the EuroQol five dimension-5L questionnaire and health care utilization using cost diaries and chart reviews. We evaluated the incremental net monetary benefit (INMB) for the full sample and preselected subgroups. RESULTS: A total of 350 patients were included, of whom 173 received GAM and 177 UC. At 12 months, the average QALYs per patient were 0.728 and 0.751 for GAM and UC, respectively (ΔQALY, -0.023 [95% CI, -0.076 to 0.028]). Considering a societal perspective, the total average costs (in 2021 Canadian dollars) per patient were $46,739 and $45,177 for GAM and UC, respectively (ΔCost, $1,563 [95% CI, -$6,583 to $10,403]). At a cost-effectiveness threshold of $50,000/QALY, GAM was not cost-effective compared with UC (INMB, -$2,713 [95% CI, -$11,767 to $5,801]). The INMB was positive ($2,984 [95% CI, -$7,050 to $14,179]; probability of being cost-effective, 72%) for patients treated with curative intent, but remained negative for patients treated with palliative intent (INMB, -$9,909 [95% CI, -$24,436 to $4,153]). Findings were similar considering a health care payer perspective. CONCLUSION: To our knowledge, this is the first cost-utility analysis of GAM in cancer. GAM was cost-effective for patients with cancer treated with curative but not with palliative intent. The study provides further considerations for future adoption of GAM in practice.

Validation of a novel point-of-care ultrasound method to assess diaphragmatic excursion.

INTRODUCTION: Point-of-care ultrasound can assess diaphragmatic function and rule in or rule out paresis of the diaphragm. While this is a useful bedside tool, established methods have significant limitations. This study explores a new method to assess diaphragmatic motion by measuring the excursion of the uppermost point of the zone of apposition (ZOA) at the mid-axillary line using a high-frequency linear ultrasound probe and compares it with two previously established methods: the assessment of the excursion of the dome of the diaphragm (DOD) and the thickening ratio at the ZOA. METHODS: This is a single-centre, prospective comparative study on elective surgical patients with normal diaphragmatic function. Following research ethics board approval and patient written consent, 75 elective surgical patients with normal diaphragmatic function were evaluated preoperatively. Three ultrasound methods were compared: (1) assessment of the excursion of the DOD using a curvilinear probe through an abdominal window; (2) assessment of the thickening fraction of the ZOA; and (3) assessment of the excursion of the ZOA. The last two methods performed with a linear probe on the lateral aspect of the chest. RESULTS: Seventy-five patients were studied. We found that the evaluation of the excursion of the ZOA was more consistently successful (100% bilaterally) than the evaluation of the excursion of the DOD (98.7% and 34.7% on the right and left sides, respectively). The absolute values of the excursion of the ZOA were greater than and well correlated with the values of the DOD. CONCLUSION: Our preliminary data from this exploratory study suggest that the evaluation of the excursion of the ZOA on the lateral aspect of the chest using a linear probe is consistently successful on both right and left sides. Future studies are needed to establish the distribution of normal values and suggest diagnostic criteria for diaphragmatic paresis or paralysis. TRIAL REGISTRATION NUMBER: NCT03225508.

High Plasma Fibrinogen Level Elevates the Risk of Cardiac Complications Following Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Cardiac complications are related to poor prognosis after spontaneous intracerebral hemorrhage (ICH). This study aims to predict the cardiac complications arising from small intracranial hematoma at ultraearly stage. METHODS: The data of this work were derived from the Risk Stratification and Minimally Invasive Surgery in Acute ICH Patients study (ClinicalTrials.gov Identifier: NCT03862729). This work included patients with ICH but without brain herniation, as confirmed by a brain computed tomography scan within 48 hours of symptom onset. Every Patient's information recorded at the emergent department, including clinical, laboratory, electrocardiogram, and medical records, was derived from the electronic data capture. Cardiac complications were defined as the occurrence of myocardial damage, arrhythmias, and ischemic electrocardiogram changes during hospitalization. Variables associated with cardiac complications were filtrated by univariate and multivariate regression analyses. Independent risk factors were used to form the early predictive model. The restricted cubic splines were employed to investigate the nonlinear associations in a more sophisticated and scholarly manner. RESULTS: A total of 587 ICH patients were enrolled in this work, including 72 patients who suffered from cardiac complications after ICH. Out of the 78 variables, 24 were found to be statistically significant in the univariate logistic regression analysis. These significant variables were then subjected to multivariate logistic regression analysis and utilized for constructing risk models. Multivariate logistic regression analysis showed high plasma fibrinogen (FIB) level [odds ratio (OR) per standard deviation (SD) 1.327, 95% confidence intervals (CI) 1.037-1.697; P = 0. 024)] and older age (OR per SD 1.777, 95% CI 1.344-2.349; P ＜0.001) were associated with a higher incidence of cardiac complications after ICH. High admission pulse rate (OR 0.620, 95% CI 0.451-0.853; P = 0. 003) was considered a protective factor for cardiac complications after ICH. In the restricted cubic spline regression model, FIB and cardiac complications following ICH were positively correlated and almost linearly (P for nonlinearity = 0.073). The reference point for FIB in predicting cardiac complications after ICH was 2.64 g/L. CONCLUSIONS: Emergent factors, including plasma FIB level, age, and pulse rate, might be independently associated with cardiac complications after ICH, which warrants attention in the context of treatment.

Effectiveness of geriatric assessment and management in older cancer patients: a systematic review and meta-analysis.

BACKGROUND: Frailty and multimorbidity among older cancer patients affect treatment tolerance and efficacy. Comprehensive geriatric assessment and management is recommended to optimize cancer treatment, but its effect on various outcomes remains uncertain. OBJECTIVE: Our objective was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) and cost-effectiveness studies comparing comprehensive geriatric assessment (with or without implementation of recommendations) to usual care in older cancer patients. METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane trials from inception to January 27, 2023, for RCTs and cost-effectiveness studies. Pooled estimates for outcomes were calculated using random-effects models. RESULTS: A total of 19 full-text articles representing 17 RCTs were included. Average participant age was 72-80 years, and 31%-62% were female. Comprehensive geriatric assessment type, mode of delivery, and evaluated outcomes varied across studies. Meta-analysis revealed no difference in risk of mortality (risk ratio [RR] = 1.08. 95% confidence interval [CI] = 0.91 to 1.29), hospitalization (RR = 0.92, 95% CI = 0.77 to 1.10), early treatment discontinuation (RR = 0.89, 95% CI = 0.67 to 1.19), initial dose reduction (RR = 0.99, 95% CI = 0.99 to 1.26), and subsequent dose reduction (RR = 0.87, 95% CI = 0.70 to 1.09). However, the risk of treatment toxicity was statistically significantly lower in the comprehensive geriatric assessment group (RR = 0.78, 95% CI = 0.70 to 0.86). No cost-effectiveness studies were identified. CONCLUSION: Compared with usual care, comprehensive geriatric assessment was not associated with a difference in risk of mortality, hospitalization, treatment discontinuation, and dose reduction but was associated with a lower risk of treatment toxicity indicating its potential to optimize cancer treatment in this population. Further research is needed to evaluate cost-effectiveness.

Application of Deep Learning in Cancer Prognosis Prediction Model.

As an important branch of artificial intelligence and machine learning, deep learning (DL) has been widely used in various aspects of cancer auxiliary diagnosis, among which cancer prognosis is the most important part. High-accuracy cancer prognosis is beneficial to the clinical management of patients with cancer. Compared with other methods, DL models can significantly improve the accuracy of prediction. Therefore, this article is a systematic review of the latest research on DL in cancer prognosis prediction. First, the data type, construction process, and performance evaluation index of the DL model are introduced in detail. Then, the current mainstream baseline DL cancer prognosis prediction models, namely, deep neural networks, convolutional neural networks, deep belief networks, deep residual networks, and vision transformers, including network architectures, the latest application in cancer prognosis, and their respective characteristics, are discussed. Next, some key factors that affect the predictive performance of the model and common performance enhancement techniques are listed. Finally, the limitations of the DL cancer prognosis prediction model in clinical practice are summarized, and the future research direction is prospected. This article could provide relevant researchers with a comprehensive understanding of DL cancer prognostic models and is expected to promote the research progress of cancer prognosis prediction.

Nondeformed Ultrasound Image Production Method for Ultrasound-Guided Radiotherapy.

Purpose: During ultrasound (US)-guided radiotherapy, the tissue is deformed by probe pressure, and the US image is limited by changes in tissue and organ position and geometry when the US image is aligned with computed tomography (CT) image, leading to poor alignment. Accordingly, a pixel displacement-based nondeformed US image production method is proposed. Methods: The correction of US image deformation is achieved by calculating the pixel displacement of an image. The positioning CT image (CTstd) is used as the gold standard. The deformed US image (USdef) is inputted into the Harris algorithm to extract corner points for selecting feature points, and the displacement of adjacent pixels of feature points in the US video stream is calculated using the Lucas-Kanade optical flow algorithm. The moving least squares algorithm is used to correct USdef globally and locally in accordance with image pixel displacement to generate a nondeformed US image (USrev). In addition, USdef and USrev were separately aligned with CTstd to evaluate the improvement of alignment accuracy through deformation correction. Results: In the phantom experiment, the overall and local average correction errors of the US image under the optimal probe pressure were 1.0944 and 0.7388 mm, respectively, and the registration accuracy of USdef and USrev with CTstd was 0.6764 and 0.9016, respectively. During the volunteer experiment, the correction error of all 12 patients' data ranged from -1.7525 to 1.5685 mm, with a mean absolute error of 0.8612 mm. The improvement range of US and CT registration accuracy, before and after image deformation correction in the 12 patients evaluated by a normalized correlation coefficient, was 0.1232 to 0.2476. Conclusion: The pixel displacement-based deformation correction method can solve the limitation imposed by image deformation on image alignment in US-guided radiotherapy. Compared with USdef, the alignment results of USrev with CT were better.

SY18ΔL60L: a new recombinant live attenuated African swine fever virus with protection against homologous challenge.

Introduction: African swine fever (ASF) is an acute and highly contagious disease and its pathogen, the African swine fever virus (ASFV), threatens the global pig industry. At present, management of ASF epidemic mainly relies on biological prevention and control methods. Moreover, due to the large genome of ASFV, only half of its genes have been characterized in terms of function. Methods: Here, we evaluated a previously uncharacterized viral gene, L60L. To assess the function of this gene, we constructed a deletion strain (SY18ΔL60L) by knocking out the L60L gene of the SY18 strain. To evaluate the growth characteristics and safety of the SY18ΔL60L, experiments were conducted on primary macrophages and pigs, respectively. Results: The results revealed that the growth trend of the recombinant strain was slower than that of the parent strain in vitro. Additionally, 3/5 (60%) pigs intramuscularly immunized with a 105 50% tissue culture infectious dose (TCID50) of SY18ΔL60L survived the 21-day observation period. The surviving pigs were able to protect against the homologous lethal strain SY18 and survive. Importantly, there were no obvious clinical symptoms or viremia. Discussion: These results suggest that L60L could serve as a virulence- and replication-related gene. Moreover, the SY18ΔL60L strain represents a new recombinant live-attenuated ASFV that can be employed in the development of additional candidate vaccine strains and in the elucidation of the mechanisms associated with ASF infection.