Overcoming the Size Limit of First Principles Molecular Dynamics Simulations with an In-Distribution Substructure Embedding Active Learner

Large-scale first principles molecular dynamics are crucial for simulating complex processes in chemical, biomedical, and materials sciences. However, the unfavorable time complexity with respect to system sizes leads to prohibitive computational costs when the simulation contains over a few hundred atoms in practice. We present an In-Distribution substructure Embedding Active Learner (IDEAL) to enable efficient simulation of large complex systems with quantum accuracy by maintaining a machine learning force field (MLFF) as an accurate surrogate to the first principles methods. By extracting high-uncertainty substructures into low-uncertainty atom environments, the active learner is allowed to concentrate on and learn from small substructures of interest rather than carrying out intractable quantum chemical computations on large structures. IDEAL is benchmarked on various systems and shows sub-linear complexity, accelerating the simulation thousands of times compared with conventional active learning and millions of times compared with pure first principles simulations. To demonstrate the capability of IDEAL in practical applications, we simulated a polycrystalline lithium system composed of one million atoms and the full ammonia formation process in a Haber-Bosch reaction on a 3-nm Iridium nanoparticle catalyst on a computing node comprising one single A100 GPU and 24 CPU cores

Impact of stress hyperglycemia ratio on mortality in patients with critical acute myocardial infarction: insight from American MIMIC-IV and the Chinese CIN-II study

Background: Among patients with acute coronary syndrome and percutaneous coronary intervention, stress hyperglycemia ratio (SHR) is primarily associated with short-term unfavorable outcomes. However, the relationship between SHR and long-term worsen prognosis in acute myocardial infarction (AMI) patients admitted in intensive care unit (ICU) are not fully investigated, especially in those with different ethnicity. This study aimed to clarify the association of SHR with all-cause mortality in critical AMI patients from American and Chinese cohorts. Methods: Overall 4,337 AMI patients with their first ICU admission from the American Medical Information Mart for Intensive Care (MIMIC)-IV database (n = 2,166) and Chinese multicenter registry cohort Cardiorenal ImprovemeNt II (CIN-II, n = 2,171) were included in this study. The patients were divided into 4 groups based on quantiles of SHR in both two cohorts. Results: The total mortality was 23.8% (maximum follow-up time: 12.1 years) in American MIMIC-IV and 29.1% (maximum follow-up time: 14.1 years) in Chinese CIN-II. In MIMIC-IV cohort, patients with SHR of quartile 4 had higher risk of 1-year (adjusted hazard radio [aHR] = 1.87; 95% CI: 1.40–2.50) and long-term (aHR = 1.63; 95% CI: 1.27–2.09) all-cause mortality than quartile 2 (as reference). Similar results were observed in CIN-II cohort (1-year mortality: aHR = 1.44; 95%CI: 1.03–2.02; long-term mortality: aHR = 1.32; 95%CI: 1.05–1.66). In both two group, restricted cubic splines indicated a J-shaped correlation between SHR and all-cause mortality. In subgroup analysis, SHR was significantly associated with higher 1-year and long-term all-cause mortality among patients without diabetes in both MIMIC-IV and CIN-II cohort. Conclusion: Among critical AMI patients, elevated SHR is significantly associated with and 1-year and long-term all-cause mortality, especially in those without diabetes, and the results are consistently in both American and Chinese cohorts

Altered spontaneous brain activity in patients with acute spinal cord injury revealed by resting-state functional MRI.

Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI). However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo) analysis based on resting-state functional magnetic resonance imaging.A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity.Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores.Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as potential biomarkers for assessment of neuronal damage and the prediction of clinical outcomes in acute SCI

Altered Activation in Cerebellum Contralateral to Unilateral Thalamotomy May Mediate Tremor Suppression in Parkinson's Disease: A Short-Term Regional Homogeneity fMRI Study.

BACKGROUND:Ventral intermediate nucleus thalamotomy is an effective treatment for Parkinson's disease tremor. However, its mechanism is still unclear. PURPOSE:We used resting-state fMRI to investigate short-term ReHo changes after unilateral thalamotomy in tremor-dominant PD, and to speculate about its possible mechanism on tremor suppression. METHODS:26 patients and 31 healthy subjects (HS) were recruited. Patients were divided into two groups according to right- (rPD) and left-side (lPD) thalamotomy. Tremor was assessed using the 7-item scale from the Unified Parkinson's disease rating scale motor score (mUPDRS). Patients were scanned using resting state fMRI after 12h withdrawal of medication, both preoperatively (PDpre) and 7- day postoperatively (PDpost), whereas healthy subjects were scanned once. The regions associated with tremor and altered ReHo due to thalamic ablation were examined. RESULTS:The impact of unilateral VIM thalamotomy was characterized in the frontal, parietal, temporal regions, basal ganglia, thalamus, and cerebellum. Compared with PDpre, significantly reduced ReHo was found in the left cerebellum in patients with rPDpost, and slightly decreased ReHo in the cerebellum vermis in patients with lPDpost, which was significantly higher than HS. We demonstrated a positive correlation between the ReHo values in the cerebellum (in rPD, peak coordinate [-12, -54, -21], R = 0.64, P = 0.0025, and peak coordinate [-9, -54, -18], R = 0.71, P = 0.0025; in lPD, peak coordinate [3, -45, -15], R = 0.71, P = 0.004) in the pre-surgical condition, changes of ReHo induced by thalamotomy (in rPD, R = 0.63, P = 0.021, R = 0.6, P = 0.009; in lPD, R = 0.58, P = 0.028) and tremor scores contralateral to the surgical side, respectively. CONCLUSION:The specific area that may be associated with PD tremor and altered ReHo due to thalamic ablation is the cerebellum. The neural basis underlying thalamotomy is complex; cerebellum involvement is far beyond cerebello-thalamic tract breakage

Analysis of the Expression of Cell Division Cycle-Associated Genes and Its Prognostic Significance in Human Lung Carcinoma: A Review of the Literature Databases

Background. Lung cancer (LC) has become the top cause responsible for cancer-related deaths. Cell division cycle-associated (CDCA) genes exert an important role in the life process. Dysregulation in the process of cell division may lead to malignancy. Methods. Transcriptional data on CDCA gene family and patient survival data were examined for lung cancer (LC) patients from the GEPIA, Oncomine, cBioPortal, and Kaplan–Meier Plotter databases. Results. CDCA1/2/3/4/5/7/8 expression levels were higher in lung adenocarcinoma tissues, and the CDCA1/2/3/4/5/6/7/8 expression levels were increased in squamous cell LC tissues compared with those in noncarcinoma lung tissues. The expression levels of CDCA1/2/3/4/5/8 showed correlation with tumor classification. The Kaplan–Meier Plotter database was employed to carry out survival analysis, indicating that increased CDCA1/2/3/4/5/6/7/8 expression levels were obviously related to poor overall survival (OS) and progression-free survival (PFS) (P<0.05). Only LC patients with increased CDCA3/4/5/8 expression were significantly related to lower post-progression survival (PPS) (P<0.05). The following processes were affected by CDCA genes’ alteration: R-HAS-2500257: resolution of sister chromatid cohesion; GO:0051301: cell division; CORUM: 1118: chromosomal passenger complex (CPC, including CDCA8, INCENP, AURKB, and BIRC5); CORUM: 127: NDC80 kinetochore complex; M129: the PID PLK1 pathway; and GO: 0007080: mitotic metaphase plate congression, all of which were remarkably modulated since the alterations affected CDCA genes. Conclusions. Upregulated CDCA genes’ expression levels in LC tissues probably play a crucial part in LC oncogenesis. The upregulated CDCA genes’ expression levels are used as the potential prognostic markers to improve patient survival and the LC prognostic accuracy. CDCA genes probably exert their functions in tumorigenesis through the PLK1 pathway

Brain areas with altered ReHo compared with healthy controls (Alphasim corrected, <i>p</i>_alpha<0.05).

<p>The blue areas showed decreased ReHo in acute SCI patients relative to healthy controls. The regions are the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/ dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate. The red areas showed increased ReHo in acute SCI patients. The regions include bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The left side of the image corresponds to the right hemisphere of the brain. The underlying structure image is Ch2 image.</p

Demographic and clinical information of patients with acute spinal cord injury.

<p>RTA, road traffic accident; AIS, American Spinal Injury Association Impairment Scale; grade A, complete, no motor or sensory function is preserved in the sacral segments S4 and S5; grade B, incomplete, sensory but not motor function is preserved below the neurological level and extends through the sacral segment S4-S5; grade C, incomplete, motor function is preserved below the neurological level, and more than half of key muscles below the neurological level have a muscle grade less than 3; grade D, incomplete, motor function is preserved below the neurological level and at least half of key muscles below the neurological level have a muscle grade of 3 or more; NLI, neurological level of injury; ISNCSCI, international standards for the neurological classification of spinal cord injury.</p><p>Demographic and clinical information of patients with acute spinal cord injury.</p

Clinical details of healthy subjects and patients with Parkinson’s disease.

<p>Clinical details of healthy subjects and patients with Parkinson’s disease.</p

Recombinant Lactococcus Expressing a Novel Variant of Infectious Bursal Disease Virus VP2 Protein Can Induce Unique Specific Neutralizing Antibodies in Chickens and Provide Complete Protection

Recent reports of infectious bursal disease virus (IBDV) infections in China, Japan, and North America have indicated the presence of variant, and the current conventional IBDV vaccine cannot completely protect against variant IBDV. In this study, we constructed recombinant Lactococcus lactis (r-L. lactis) expressing a novel variant of IBDV VP2 (avVP2) protein along with the Salmonella resistance to complement killing (RCK) protein, and Western blotting analysis confirmed that r-L. lactis successfully expressed avVP2-RCK fusion protein. We immunized chickens with this vaccine and subsequently challenged them with the very virulent IBDV (vvIBDV) and a novel variant wild IBDV (avIBDV) to evaluate the immune effect of the vaccine. The results show that the r-L. lactis-avVP2-RCK-immunized group exhibited a 100% protection rate when challenged with avIBDV and 100% survival rate to vvIBDV. Furthermore, this immunization resulted in the production of unique neutralizing antibodies that cannot be detected by conventional ELISA. These results indicate that r-L. lactis-avVP2-RCK is a promising candidate vaccine against IBDV infections, which can produce unique neutralizing antibodies that cannot be produced by other vaccines and protect against IBDV infection, especially against the variant strain