A Segmented Iterative Learning Scheme-Based Distributed Fault Estimation for Switched Interconnected Nonlinear Systems.

In this article, a distributed fault estimation (DFE) approach for switched interconnected nonlinear systems (SINSs) with time delays and external disturbances is proposed using a novel segmented iterative learning scheme (SILS). First, through the utilization of interrelated information among subsystems, a distributed iterative learning observer is developed to enhance the accuracy of fault estimation results, which can realize the fault estimation of all subsystems under time delays and external disturbances. Simultaneously, to facilitate rapid fault information tracking and significantly reduce sensitivity to interference, a new SILS-based fault estimation law is constructed by combining the idea of segmented design with the method of variable gain. Then, an assessment of the convergence of the established fault estimation methodology is conducted, and the configurations of observer gain matrices and iterative learning gain matrices are duly accomplished. Finally, simulation results are showcased to demonstrate the superiority and feasibility of the developed fault estimation approach.

Parvalbumin Regulates GAD Expression through Calcium Ion Concentration to Affect the Balance of Glu-GABA and Improve KA-Induced Status Epilepticus in PV-Cre Transgenic Mice.

Aims: the study aimed to (i) use adeno-associated virus technology to modulate parvalbumin (PV) gene expression, both through overexpression and silencing, within the hippocampus of male mice and (ii) assess the impact of PV on the metabolic pathway of glutamate and γ-aminobutyric acid (GABA). Methods: a status epilepticus (SE) mouse model was established by injecting kainic acid into the hippocampus of transgenic mice. When the seizures of mice reached SE, the mice were killed at that time point and 30 min after the onset of SE. Hippocampal tissues were extracted and the mRNA and protein levels of PV and the 65 kDa (GAD65) and 67 kDa (GAD67) isoforms of glutamate decarboxylase were assessed using real-time quantitative polymerase chain reaction and Western blot, respectively. The concentrations of glutamate and GABA were detected with high-performance liquid chromatography (HPLC), and the intracellular calcium concentration was detected using flow cytometry. Results: we demonstrate that the expression of PV is associated with GAD65 and GAD67 and that PV regulates the levels of GAD65 and GAD67. PV was correlated with calcium concentration and GAD expression. Interestingly, PV overexpression resulted in a reduction in calcium ion concentration, upregulation of GAD65 and GAD67, elevation of GABA concentration, reduction in glutamate concentration, and an extension of seizure latency. Conversely, PV silencing induced the opposite effects. Conclusion: parvalbumin may affect the expression of GAD65 and GAD67 by regulating calcium ion concentration, thereby affecting the metabolic pathways associated with glutamate and GABA. In turn, this contributes to the regulation of seizure activity.

Significance of atherosclerotic plaque location in recanalizing non-acute long-segment occlusion of the internal carotid artery.

To investigate the significance of atherosclerotic plaque location in hybrid surgery comprising both endovascular recanalization approaches and carotid endarterectomy for symptomatic atherosclerotic non-acute long-segment occlusion of the internal carotid artery (ICA), 162 patients were enrolled, including 120 (74.1%) patients in the proximal plaque group and 42 (25.9%) in the distal plaque group. Surgical recanalization was performed in all patients, with successful recanalization in 119 (99.2%) patients in the proximal and 39 (92.9%) in the distal plaque group. The total successful recanalization rate was 97.5% (158/162) with a failure rate of 2.5% (4/162). Periprocedural complications occurred in 5 (4.2% or 5/120) patients in the proximal plaque group, including neck infection in two (1.7%), recurrent nerve injury in 1 (0.8%), and laryngeal edema in 2 (1.7%), and 2 (4.8%) in the distal plaque group, including femoral puncture infection in 2 (4.8%). No severe complications occurred in either group. Univariate analysis showed plaque location was a significant (P = 0.018) risk factor for successful recanalization, and multivariate analysis indicated that the plaque location remained a significant independent risk factor for recanalization success (P = 0.017). In follow-up 6-48 months after the recanalization surgery, reocclusion occurred in two (2.8%) patients in the proximal plaque group and 4 (13.3%) in the distal plaque group. In conclusion, although hybrid surgery achieves similar outcomes in patients with ICA occlusion caused by either proximal or distal atherosclerotic plaques, plaque location may be a significant risk factor for successful recanalization of symptomatic non-acute long-segment ICA occlusion.

No genetic causal association between circulating alpha-tocopherol levels and osteoarthritis, a two-sample Mendelian randomization analysis.

The causal association between vitamin E status and osteoarthritis (OA) remains controversial in previous epidemiological studies. We employed a Mendelian randomization (MR) analysis to explore the causal relationship between circulating alpha-tocopherol levels (main forms of vitamin E in our body) and OA. The instrumental variables (IVs) of circulating alpha-tocopherol levels were obtained from a Genome-wide association study (GWAS) dataset of 7781 individuals of European descent. The outcome of OA was derived from the UK biobank. Two-sample MR analysis was used to estimate the causal relationship between circulating alpha-tocopherol levels and OA. The inverse-variance weighted (IVW) method was the primary analysis in this analysis. We used the MR-Egger method to determine horizontal pleiotropic in this work. The heterogeneity effect of instrumental IVs was detected by MR-Egger and IVW analyses. Sensitivity analysis was performed by removing single nucleotide polymorphism (SNP) one by one. Three SNPs (rs964184, rs2108622, and rs11057830) (P < 5E-8) strongly associated with circulating alpha-tocopherol levels were used in this analysis. The IVW-random effect indicated no causal relationship between circulating alpha-tocopherol levels and clinically diagnosed OA (OR = 0.880, 95% CI 0.626, 1.236, P = 0.461). Similarly, IVW analysis showed no causal association between circulating alpha-tocopherol levels and self-reported OA (OR = 0.980, 95% CI 0.954, 1.006, P = 0.139). Other methods of MR analyses and sensitivity analyses revealed consistent findings. MR-Egger and IVW methods indicated no significant heterogeneity between IVs. The MR-Egger intercept showed no horizontal pleiotropic. The results of this linear Mendelian randomization study indicate no causal association between genetically predicted alpha-tocopherol levels and the progression of OA. Alpha-tocopherol may not provide beneficial and more favorable outcomes for the progression of OA. Further MR analysis based on updated GWASs with more IVs is required to verify the results of our study.

Third-generation sequencing identified a novel complex variant in a patient with rare alpha-thalassemia.

BACKGROUND: Thalassemias represent some of the most common monogenic diseases worldwide and are caused by variations in human hemoglobin genes which disrupt the balance of synthesis between the alpha and beta globin chains. Thalassemia gene detection technology is the gold standard to achieve accurate detection of thalassemia, but in clinical practice, most of the tests are only for common genotypes, which can easily lead to missing or misdiagnosis of rare thalassemia genotypes. CASE PRESENTATION: We present the case of an 18-year-old Chinese female with abnormal values of routine hematological indices who was admitted for genetic screening for thalassemia. Genomic DNA was extracted and used for the genetic assays. Gap polymerase chain reaction and agarose gel electrophoresis were performed to detect HBA gene deletions, while PCR-reverse dot blot hybridization was used to detect point mutations in the HBA and HBB genes. Next-generation sequencing and third-generation sequencing (TGS) were used to identify known and potentially novel genotypes of thalassemia. We identified a novel complex variant αHb WestmeadαHb Westmeadαanti3.7/-α3.7 in a patient with rare alpha-thalassemia. CONCLUSIONS: Our study identified a novel complex variant that expands the thalassemia gene variants spectrum. Meanwhile, the study suggests that TGS could effectively improve the specificity of thalassemia gene detection, and has promising potential for the discovery of novel thalassemia genotypes, which could also improve the accuracy of genetic counseling. Couples who are thalassemia carriers have the opportunity to reduce their risk of having a child with thalassemia.

Revolutionizing aquatic eco-environmental monitoring: Utilizing the RPA-Cas-FQ detection platform for zooplankton.

The integration of recombinase polymerase amplification (RPA) with CRISPR/Cas technology has revolutionized molecular diagnostics and pathogen detection due to its unparalleled sensitivity and trans-cleavage ability. However, its potential in the ecological and environmental monitoring scenarios for aquatic ecosystems remains largely unexplored, particularly in accurate qualitative/quantitative detection, and its actual performance in handling complex real environmental samples. Using zooplankton as a model, we have successfully optimized the RPA-CRISPR/Cas12a fluorescence detection platform (RPA-Cas-FQ), providing several crucial "technical tips". Our findings indicate the sensitivity of CRISPR/Cas12a alone is 5 × 109 copies/reaction, which can be dramatically increased to 5 copies/reaction when combined with RPA. The optimized RPA-Cas-FQ enables reliable qualitative and semi-quantitative detection within 50 min, and exhibits a good linear relationship between fluorescence intensity and DNA concentration (R2 = 0.956-0.974***). Additionally, we developed a rapid and straightforward identification procedure for single zooplankton by incorporating heat-lysis and DNA-barcode techniques. We evaluated the platform's effectiveness using real environmental DNA (eDNA) samples from the Three Gorges Reservoir, confirming its practicality. The eDNA-RPA-Cas-FQ demonstrated strong consistency (Kappa = 0.43***) with eDNA-Metabarcoding in detecting species presence/absence in the reservoir. Furthermore, the two semi-quantitative eDNA technologies showed a strong positive correlation (R2 = 0.58-0.87***). This platform also has the potential to monitor environmental pollutants by selecting appropriate indicator species. The novel insights and methodologies presented in this study represent a significant advancement in meeting the complex needs of aquatic ecosystem protection and monitoring.

Multidisciplinary management and surgical resection of a rare posterior mediastinal haemangioma.

Mediastinal haemangiomas pose diagnostic and therapeutic challenges owing to their rarity and complex anatomy. A 36-year-old man, with a history of smoking and drinking, presented with a posterior mediastinal mass with back pain. Initial investigations suggested a lymphangioma. However, owing to persistent symptoms and complex pathology, we performed surgical intervention involving open resection of the tumour, which was closely associated with the descending aorta and extended into the right posterior mediastinum. The surgical approach was influenced by the proximity of the tumour to vital structures, necessitating an open procedure. Postoperative complications included chylothorax, managed with a fat-free diet. The final pathological diagnosis was consistent with a benign vascular tumour with a low proliferative rate. Two months post-surgery, computed tomography revealed no complications, and the patient's pain had decreased. A multidisciplinary approach and surgical intervention played important roles in the diagnosis and treatment of this posterior mediastinal haemangioma.

Feasibility and Preliminary Efficacy of American Elderberry Juice for Improving Cognition and Inflammation in Patients with Mild Cognitive Impairment.

Despite data showing that nutritional interventions high in antioxidant/anti-inflammatory properties (anthocyanin-rich foods, such as blueberries/elderberries) may decrease risk of memory loss and cognitive decline, evidence for such effects in mild cognitive impairment (MCI) is limited. This study examined preliminary effects of American elderberry (Sambucus nigra subsp. canadensis) juice on cognition and inflammatory markers in patients with MCI. In a randomized, double-blind, placebo-controlled trial, patients with MCI (n = 24, Mage = 76.33 ± 6.95) received American elderberry (n = 11) or placebo (n = 13) juice (5 mL orally 3 times a day) for 6 months. At baseline, 3 months, and 6 months, patients completed tasks measuring global cognition, verbal memory, language, visuospatial cognitive flexibility/problem solving, and memory. A subsample (n = 12, 7 elderberry/5 placebo) provided blood samples to measure serum inflammatory markers. Multilevel models examined effects of the condition (elderberry/placebo), time (baseline/3 months/6 months), and condition by time interactions on cognition/inflammation outcomes. Attrition rates for elderberry (18%) and placebo (15%) conditions were fairly low. The dosage compliance (elderberry-97%; placebo-97%) and completion of cognitive (elderberry-88%; placebo-87%) and blood-based (elderberry-100%; placebo-100%) assessments was high. Elderberry (not placebo) trended (p = 0.09) towards faster visuospatial problem solving performance from baseline to 6 months. For the elderberry condition, there were significant or significantly trending decreases over time across several markers of low-grade peripheral inflammation, including vasorin, prenylcysteine oxidase 1, and complement Factor D. Only one inflammatory marker showed an increase over time (alpha-2-macroglobin). In contrast, for the placebo, several inflammatory marker levels increased across time (L-lactate dehydrogenase B chain, complement Factor D), with one showing deceased levels over time (L-lactate dehydrogenase A chain). Daily elderberry juice consumption in patients with MCI is feasible and well tolerated and may provide some benefit to visuospatial cognitive flexibility. Preliminary findings suggest elderberry juice may reduce low-grade inflammation compared to a placebo-control. These promising findings support the need for larger, more definitive prospective studies with longer follow-ups to better understand mechanisms of action and the clinical utility of elderberries for potentially mitigating cognitive decline.

Bilateral intertrochanteric fractures in an elderly patient following high-energy trauma: a case report.

BACKGROUND: Cases of bilateral hip fractures are rare, and even more so are cases of bilateral intertrochanteric fractures. Common causes include trauma, internal diseases, and primary or secondary bone diseases. We report a case of bilateral intertrochanteric fractures in an elderly patient following a severe car accident, a scenario not extensively reported in existing literature. CASE PRESENTATION: We report on an 84-year-old male who suffered severe trauma from a car accident, resulting in multiple injuries and shock state, with pain and limited mobility in both hip joints. After examination and imaging studies, the patient was diagnosed with multiple injuries and bilateral intertrochanteric fractures. Following emergency resuscitation, he was admitted to the orthopedic ward. A pre-surgical multidisciplinary team (MDT) consultation was convened to optimize surgical conditions. The patient underwent successful one-stage bilateral intramedullary nailing. The patient was assisted to stand with a walker on the third day after surgery. Six months post-surgery, the patient resumed outdoor activities. CONCLUSION: Managing bilateral intertrochanteric fractures, particularly in the elderly with severe trauma, is notably challenging due to their rarity. However, a coordinated multidisciplinary approach and one-stage bilateral internal fixation can lead to effective treatment outcomes and favorable prognoses.

Comparison of early patient-reported outcomes between uniportal thoracoscopic segmentectomy and wedge resection for peripheral small-sized non-small-cell lung cancer.

BACKGROUND: Analysis of patient-reported outcomes (PROs) offers valuable insights into distinguishing the effects of closely related medical procedures from the patient's perspective. In this study we compared symptom burden in patients undergoing uniportal thoracoscopic segmentectomy and wedge resection for peripheral small-sized non-small cell lung cancer (NSCLC). METHODS: This study included patients with peripheral NSCLC from an ongoing longitudinal prospective cohort study (CN-PRO-Lung 3) who underwent segmentectomy or wedge resection with tumor diameter ≤ 2 cm and consolidation tumor ratio (CTR) ≤ 0.5. PROs data were collected using the Perioperative Symptom Assessment for Lung Surgery questionnaire pre-operatively, daily post-surgery up to the fourth hospitalization day, and weekly post-discharge up to the fourth week. Propensity score matching and a generalized estimation equation model were employed to compare symptom severity. In addition, short-term clinical outcomes were compared. RESULTS: In total, data of 286 patients (82.4%) undergoing segmentectomy and 61 patients (17.6%) undergoing wedge resection were extracted from the cohort. No statistically significant differences were found in the proportion of moderate-to-severe symptoms and mean scores for pain, cough, shortness of breath, disturbed sleep, fatigue, drowsiness, and distress during the 4-day postoperative hospitalization or the 4-week post-discharge period before or after matching (all p > 0.05). Compared with segmentectomy, wedge resection showed better short-term clinical outcomes, including shorter operative time (p = 0.001), less intraoperative bleeding (p = 0.046), and lower total hospital costs (p = 0.002). CONCLUSIONS: The study findings indicate that uniportal thoracoscopic segmentectomy and wedge resection exert similar early postoperative symptom burden in patients with peripheral NSCLC (tumor diameter ≤ 2 cm and CTR ≤ 0.5). CLINICAL TRIAL REGISTRATION: Not applicable.

Pan-Cancer Analysis of the Prognostic and Immunological Role of TOMM40 to Identify Its Function in Breast Cancer.

Breast cancer (BRCA) is currently the most commonly diagnosed malignancy in women worldwide. Previous studies have demonstrated that mitophagy is important for the prevention and treatment of BRCA. However, few studies have focused on the individual mitochondrial autophagy-related genes (MARG) in human cancers. Based on bioinformatics analyses, TOMM40 was identified as a prognostic DEMARG (PDEMARGs); Kaplan-Meier (KM) survival analysis also indicates that TOMM40 can be useful as a prognostic indicator in BRCAs, with patients in the high expression group having a poorer prognosis. For 20 distinct cancer kinds, there were appreciable differences in the expression of TOMM40 between tumor and normal tissues; in addition, in 21 different cancer types, there were associations between the expression profile of TOMM40 and patient prognosis. Gene Set Enrichment Analysis (GSEA), functional enrichment analysis, and immunological and drug sensitivity analyses of TOMM40 have indicated its biological significance in pan-cancers. Knockdown of TOMM40 in MDA-MB-231 cells inhibited their proliferation, migration, and invasiveness. In conclusion, we found that TOMM40 has prognostic value in 21 cancers, including breast cancer, by bioinformatics analysis. Based on immune correlation analysis, TOMM40 may also be a potential immunotherapeutic target for the treatment of BRCA. Therefore, our results may provide researchers to further explore the role of MARGs, especially TOMM40, in the developmental process of breast cancer, which may provide new directions and targets for the improvement of prognosis of breast cancer patients and their treatment.

B(C6F5)3/CPA-Catalyzed Aza-Diels-Alder Reaction of 3,3-Difluoro-2-Aryl-3H-indoles and Unactivated Dienes.

Here we report B(C6F5)3/CPA-catalyzed enantioselective aza-Diels-Alder reaction of 3,3-difluoro-2-Aryl-3H-indoles with unactivated dienes to access chiral 10,10-difluoro-tetrahydropyrido[1,2-a]indoles. This protocol allows the formation of pyrazole-based C2-quaternary indolin-3-ones with high enantioselectivities and regioselectivities. Moreover, gram-scale synthesis of the 10,10-difluoro-tetrahydropyrido[1,2-a]indole skeleton was successfully achieved without any reduction in both yield and enantioselectivity.

Electronic Patient-Reported Outcome-Based Symptom Management Versus Usual Care After Lung Cancer Surgery: Long-Term Results of a Multicenter, Randomized, Controlled Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.We previously reported superior symptom control of electronic patient-reported outcome (ePRO)-based symptom management after lung cancer surgery for up to 1 month postdischarge. Here, we present the long-term results (1-12 months) of this multicenter, randomized trial, where patients were assigned 1:1 to receive postoperative ePRO-based symptom management or usual care daily postsurgery, twice weekly postdischarge until 1 month, and at 3, 6, 9, and 12 months postdischarge. Long-term patient-reported outcomes were assessed with MD Anderson Symptom Inventory-Lung Cancer module. Per-protocol analyses were performed with 55 patients in the ePRO group and 57 in the usual care group. At 12 months postdischarge, the ePRO group reported significantly fewer symptom threshold events (any of the five target symptom scored ≥4; median [IQR], 0 [0-0] v 0 [0-1]; P = .040) than the usual care group. From 1 to 12 months postdischarge, the ePRO group consistently reported significantly lower composite scores for physical interference (estimate, -0.86 [95% CI, -1.32 to -0.39]) and affective interference (estimate, -0.70 [95% CI, -1.14 to -0.26]). Early intensive ePRO-based symptom management after lung cancer surgery reduced symptom burden and improved functional status for up to 1 year postdischarge, supporting its integration into standard care.

B-Myb deficiency boosts bortezomib-induced immunogenic cell death in colorectal cancer.

B-Myb has received considerable attention for its critical tumorigenic function of supporting DNA repair. However, its modulatory effects on chemotherapy and immunotherapy have rarely been reported in colorectal cancer. Bortezomib (BTZ) is a novel compound with chemotherapeutic and immunotherapeutic effects, but it fails to work in colorectal cancer with high B-Myb expression. The present study was designed to investigate whether B-Myb deletion in colorectal cancer could potentiate the immune efficacy of BTZ against colorectal cancer and to clarify the underlying mechanism. Stable B-Myb knockdown was induced in colorectal cancer cells, which increased apoptosis of the cancer cells relative to the control group in vitro and in vivo. We found that BTZ exhibited more favourable efficacy in B-Myb-defective colorectal cancer cells and tumor-bearing mice. BTZ treatment led to differential expression of genes enriched in the p53 signaling pathway promoted more powerful downstream DNA damage, and arrested cell cycle in B-Myb-defective colorectal cancer. In contrast, recovery of B-Myb in B-Myb-defective colorectal cancer cells abated BTZ-related DNA damage, cell cycle arrest, and anticancer efficacy. Moreover, BTZ promoted DNA damage-associated enhancement of immunogenicity, as indicated by potentiated expression of HMGB1 and HSP90 in B-Myb-defective cells, thereby driving M1 polarization of macrophages. Collectively, B-Myb deletion in colorectal cancer facilitates the immunogenic death of cancer cells, thereby further promoting the immune efficacy of BTZ by amplifying DNA damage. The present work provides an effective molecular target for colorectal cancer immunotherapy with BTZ.

Learning mapping by curve iteration estimation For real-time underwater image enhancement.

The degradation and attenuation of light in underwater images impose constraints on underwater vision tasks. However, the complexity and the low real-time performance of most current image enhancement algorithms make them challenging in practical applications. To address the above issues, we propose a new lightweight framework for underwater image enhancement. We adopt the curve estimation to learn the mapping between images rather than end-to-end networks, which greatly reduces the requirement for computing resources. Firstly, a designed iterative curve with parameters is used to simulate the mapping from the raw to the enhanced image. Then, the parameters of this curve are learned with a parameter estimation network called CieNet and a set of loss functions. Experimental results demonstrate that our proposed method is superior to existing algorithms in terms of evaluating indexes and visual perception quality. Furthermore, our highly lightweight network enables it to be easily integrated into small devices, making it highly applicable. The extremely short running-time of our method facilitates real-time underwater image enhancement.

Tumor-selective activity of RAS-GTP inhibition in pancreatic cancer.

Broad-spectrum RAS inhibition holds the potential to benefit roughly a quarter of human cancer patients whose tumors are driven by RAS mutations1,2. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS, and NRAS, with affinity for both mutant and wild type (WT) variants (RAS(ON) multi-selective)3. As >90% of human pancreatic ductal adenocarcinoma (PDAC) cases are driven by activating mutations in KRAS4, we assessed the therapeutic potential of the RAS(ON) multi-selective inhibitor RMC-7977 in a comprehensive range of PDAC models. We observed broad and pronounced anti-tumor activity across models following direct RAS inhibition at exposures that were well-tolerated in vivo. Pharmacological analyses revealed divergent responses to RMC-7977 in tumor versus normal tissues. Treated tumors exhibited waves of apoptosis along with sustained proliferative arrest whereas normal tissues underwent only transient decreases in proliferation, with no evidence of apoptosis. In the autochthonous KPC model, RMC-7977 treatment resulted in a profound extension of survival followed by on-treatment relapse. Analysis of relapsed tumors identified Myc copy number gain as a prevalent candidate resistance mechanism, which could be overcome by combinatorial TEAD inhibition in vitro. Together, these data establish a strong preclinical rationale for the use of broad-spectrum RAS-GTP inhibition in the setting of PDAC and identify a promising candidate combination therapeutic regimen to overcome monotherapy resistance.

Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers.

RAS-driven cancers comprise up to 30% of human cancers. RMC-6236 is a RAS(ON) multi-selective noncovalent inhibitor of the active, GTP-bound state of both mutant and wild-type variants of canonical RAS isoforms with broad therapeutic potential for the aforementioned unmet medical need. RMC-6236 exhibited potent anticancer activity across RAS-addicted cell lines, particularly those harboring mutations at codon 12 of KRAS. Notably, oral administration of RMC-6236 was tolerated in vivo and drove profound tumor regressions across multiple tumor types in a mouse clinical trial with KRASG12X xenograft models. Translational PK/efficacy and PK/PD modeling predicted that daily doses of 100 mg and 300 mg would achieve tumor control and objective responses, respectively, in patients with RAS-driven tumors. Consistent with this, we describe here objective responses in two patients (at 300 mg daily) with advanced KRASG12X lung and pancreatic adenocarcinoma, respectively, demonstrating the initial activity of RMC-6236 in an ongoing phase I/Ib clinical trial (NCT05379985). SIGNIFICANCE: The discovery of RMC-6236 enables the first-ever therapeutic evaluation of targeted and concurrent inhibition of canonical mutant and wild-type RAS-GTP in RAS-driven cancers. We demonstrate that broad-spectrum RAS-GTP inhibition is tolerable at exposures that induce profound tumor regressions in preclinical models of, and in patients with, such tumors.

Relationship Between Heart Rate Variability Parameters and Short-Term Prognosis of Patients with Acute Myocardial Infarction.

OBJECTIVE: To determine the link between heart rate variability (HRV) and short-term adverse outcomes (re-hospitalisation or death due to cardiac arrhythmia, recurrent myocardial infarction, heart failure, all-cause death) in acute myocardial infarction (AMI). STUDY DESIGN: A descriptive study. Place and Duration of the Study: Department of Cardiovascular Medicine, The First Affiliated Hospital of Anhui Medical University, China, from January 2018 to December 2021. METHODOLOGY: Clinical data of 245 patients diagnosed with AMI were retrospectively analysed. After discharge from the hospital, patients were followed for a year and categorised into two groups based on the occurrence of adverse events: the adverse event group (n=82) and the no adverse event group (n=163). Differences in clinical characteristics were compared, independent factors influencing adverse events were analysed, and diagnostic efficacy was assessed. RESULTS: Univariate analysis showed age, hyperlipidaemia, specific HRV parameters (SDNN, SDANN, RMSSD, PNN50, LF/HF), and myocardial injury markers (CK-MB, cTnI, NT-proBNP) as associated with these events (all p < 0.05). Multivariable analysis revealed decreased SDNN, decreased SDANN, increased LF/HF, and elevated levels of CK-MB, cTnI, and NT-proBNP as independent influences. Both HRV parameters and myocardial injury markers were reliable predictors on ROC curve analysis. The highest diagnostic efficacy was achieved by combining these predictors. CONCLUSION: AMI patients frequently experience short-term adverse events. Both HRV parameters and myocardial injury markers, which demonstrate significant predictive efficacy, independently influence these outcomes. KEY WORDS: Acute myocardial infarction, Coronary angiography, Heart rate variability, Myocardial injury, Risk factors.

[Corrigendum] miR­27a promotes proliferation, migration, and invasion of colorectal cancer by targeting FAM172A and acts as a diagnostic and prognostic biomarker.

Following the publication of this article, an interested reader drew to the authors' attention that the western blots in Fig. 4B on p. 3560 and Fig. 6B on p. 3562 shared remarkably similar data (including both the GAPDH and the FAM172A blots in Fig. 4B), such that these data were likely to have been derived from the same original source. Upon asking the authors to provide an explanation, the authors realized that these errors inadvertently arose during the process of assembling these figures. Due to a mislabelling of the files, representative blots for FAM172A and GAPDH were chosen incorrectly for Fig. 4B. The authors had retained their original data, however, and were also able to present to the Editorial Office for our perusal the uncropped versions of their western blots, which resolved any other potential issues of anomalies associated with the data. The revised version of Fig. 4, now showing alternative data for Fig. 4B, is shown on the next page (note that, in the repeated experiment, relative to the original version of this figure the miR­27a, miR27a­inhibitor and negative control experiments were run on different lanes of the gel). Also note that the errors made in terms of assembling the data in Fig. 4 did not greatly affect either the results or the conclusions reported in this paper, and all the authors agree to the publication of this corrigendum. The authors regret that these errors went unnoticed prior to the publication of their article, are grateful to the Editor of Oncology Reports for granting them this opportunity to publish a corrigendum, and apologize to the readership for any inconvenience caused. [Oncology Reports 37: 3554­3564, 2017; DOI: 10.3892/or.2017.5592].