Febrile infants risk score at triage (FIRST) for the early identification of serious bacterial infections.

We aimed to derive the Febrile Infants Risk Score at Triage (FIRST) to quantify risk for serious bacterial infections (SBIs), defined as bacteremia, meningitis and urinary tract infections. We performed a prospective observational study on febrile infants < 3 months old at a tertiary hospital in Singapore between 2018 and 2021. We utilized machine learning and logistic regression to derive 2 models: FIRST, based on patient demographics, vital signs and history, and FIRST + , adding laboratory results to the same variables. SBIs were diagnosed in 224/1002 (22.4%) infants. Among 994 children with complete data, age (adjusted odds ratio [aOR] 1.01 95%CI 1.01-1.02, p < 0.001), high temperature (aOR 2.22 95%CI 1.69-2.91, p < 0.001), male sex (aOR 2.62 95%CI 1.86-3.70, p < 0.001) and fever of ≥ 2 days (aOR 1.79 95%CI 1.18-2.74, p = 0.007) were independently associated with SBIs. For FIRST + , abnormal urine leukocyte esterase (aOR 16.46 95%CI 10.00-27.11, p < 0.001) and procalcitonin (aOR 1.05 95%CI 1.01-1.09, p = 0.009) were further identified. A FIRST + threshold of ≥ 15% predicted risk had a sensitivity of 81.8% (95%CI 70.5-91.0%) and specificity of 65.6% (95%CI 57.8-72.7%). In the testing dataset, FIRST + had an area under receiver operating characteristic curve of 0.87 (95%CI 0.81-0.94). These scores can potentially guide triage and prioritization of febrile infants.

Microstructures and Mechanical Properties of Al-Zn-Mg-Cu Alloys under Multi-Directional Severe Strain and Aging.

Microstructure is a significant factor that influences the mechanical properties of alloys. The effect of multiaxial forging (MAF) and subsequent aging treatment on the precipitated phases of Al-Zn-Mg-Cu alloy remains unclear. Therefore, an Al-Zn-Mg-Cu alloy was processed by means of solid solution and aging treatment, and MAF and aging treatment in this work, and the composition and distribution of precipitated phases were characterized in detail. The MAF results for dislocation multiplication and grain refinement were found. The high density of dislocation greatly accelerates the nucleation and growth of precipitated phases. Thus, the GP-zones almost transform into precipitated phases during subsequent aging. The MAF and aging alloy has more precipitated phases than the solid solution and aging treated alloy. The precipitates on the grain boundary are coarse and discontinuously distributed due to dislocation and grain boundary promoting the nucleation, growth and coarsening of the precipitates. The hardness, strength, ductility and microstructures of the alloy have been studied. Without compromising the ductility much, the MAF and aging alloy has higher hardness and strength, with values of 202 HV and 606 MPa, respectively, and an appreciable ductility of 16.2%.

Identifying clinical features and blood biomarkers associated with mild cognitive impairment in Parkinson disease using machine learning.

BACKGROUND AND PURPOSE: A broad list of variables associated with mild cognitive impairment (MCI) in Parkinson disease (PD) have been investigated separately. However, there is as yet no study including all of them to assess variable importance. Shapley variable importance cloud (ShapleyVIC) can robustly assess variable importance while accounting for correlation between variables. Objectives of this study were (i) to prioritize the important variables associated with PD-MCI and (ii) to explore new blood biomarkers related to PD-MCI. METHODS: ShapleyVIC-assisted variable selection was used to identify a subset of variables from 41 variables potentially associated with PD-MCI in a cross-sectional study. Backward selection was used to further identify the variables associated with PD-MCI. Relative risk was used to quantify the association of final associated variables and PD-MCI in the final multivariable log-binomial regression model. RESULTS: Among 41 variables analysed, 22 variables were identified as significantly important variables associated with PD-MCI and eight variables were subsequently selected in the final model, indicating fewer years of education, shorter history of hypertension, higher Movement Disorder Society-Unified Parkinson's Disease Rating Scale motor score, higher levels of triglyceride (TG) and apolipoprotein A1 (ApoA1), and SNCA rs6826785 noncarrier status were associated with increased risk of PD-MCI (p < 0.05). CONCLUSIONS: Our study highlighted the strong association between TG, ApoA1, SNCA rs6826785, and PD-MCI by machine learning approach. Screening and management of high TG and ApoA1 levels might help prevent cognitive impairment in early PD patients. SNCA rs6826785 could be a novel therapeutic target for PD-MCI. ShapleyVIC-assisted variable selection is a novel and robust alternative to traditional approaches for future clinical study to prioritize the variables of interest.

Adding heart rate n-variability (HRnV) to clinical assessment potentially improves prediction of serious bacterial infections in young febrile infants at the emergency department: a prospective observational study.

Background: We aim to investigate the utility of heart rate variability (HRV) and heart rate n-variability (HRnV) in addition to vital signs and blood biomarkers, among febrile young infants at risk of serious bacterial infections (SBIs). Methods: We performed a prospective observational study between December 2017 and November 2021 in a tertiary paediatric emergency department (ED). We included febrile infants <90 days old with a temperature ≥38 ℃. We obtained HRV and HRnV parameters via a single lead electrocardiogram. HRV measures beat-to-beat (R-R) oscillation and reflects autonomic nervous system (ANS) regulation. HRnV includes overlapping and non-overlapping R-R intervals and provides additional physiological information. We defined SBIs as meningitis, bacteraemia and urinary tract infections (UTIs). We performed area under curve (AUC) analysis to assess predictive performance. Results: We recruited 330 and analysed 312 infants. The median age was 35.5 days (interquartile range 13.0-61.0); 74/312 infants (23.7%) had SBIs with the most common being UTIs (66/72, 91.7%); 2 infants had co-infections. No patients died and 32/312 (10.3%) received fluid resuscitation. Adding HRV and HRnV to demographics and vital signs at ED triage successively improved the AUC from 0.765 [95% confidence interval (CI): 0.705-0.825] to 0.776 (95% CI: 0.718-0.835) and 0.807 (95% CI: 0.752-0.861) respectively. The final model including demographics, vital signs, HRV, HRnV and blood biomarkers had an AUC of 0.874 (95% CI: 0.828-0.921). Conclusions: Addition of HRV and HRnV to current assessment tools improved the prediction of SBIs among febrile infants at ED triage. We intend to validate our findings and translate them into tools for clinical care in the ED.

Relation of CDC42, Th1, Th2, and Th17 cells with cognitive function decline in Alzheimer's disease.

OBJECTIVE: Cell division cycle 42 (CDC42) regulates neurite outgrowth, neurotransmitter, and T help (Th) cell-mediated neuroinflammation, while its clinical implication in Alzheimer's disease (AD) is not clear. The present study aimed to investigate the correlation of CDC42 with Th1, Th2, and Th17 cells, as well as CDC42' longitudinal change and relation to cognitive function decline in AD patients. METHODS: 150 AD patients were enrolled, then their blood Th1, Th2, and Th17 cells were quantified by flow cytometry at baseline; CDC42 was detected by RT-qPCR and MMSE score was assessed at baseline and during 3-year follow-up. Meanwhile, CDC42, Th1, Th2, and Th17 cells were quantified in 30 Parkinson's disease (PD) patients and 30 healthy controls (HCs). RESULTS: CDC42 (p < 0.001) and Th2 cells (p < 0.001) were lowest in AD patients, followed by PD patients, highest in HCs; but Th1 cells (p = 0.001) and Th17 cells (p < 0.001) showed opposite trends. CDC42 was not related to Th1 cells (p = 0.134), positively correlated with Th2 cells (p = 0.023) and MMSE (p < 0.001), while negatively associated with Th17 cells (p < 0.001) in AD patients. CDC42 was only related to Th17 cells (p = 0.048) and MMSE (p = 0.048) in PD patients; and it was not linked with Th1, Th2, Th17 cells, or MMSE in HCs (all p > 0.05). During a 3-year follow-up, CDC42 was gradually declined in AD patients (p < 0.001), its decline was positively correlated with MMSE decline at 1 year (p = 0.004), 2 years (p = 0.005), and 3 years (p = 0.026). INTERPRETATION: CDC42 might have the potency to serve as a biomarker for estimating AD risk and progression.

Heart rate n-variability (HRnV) measures for prediction of mortality in sepsis patients presenting at the emergency department.

Sepsis is a potentially life-threatening condition that requires prompt recognition and treatment. Recently, heart rate variability (HRV), a measure of the cardiac autonomic regulation derived from short electrocardiogram tracings, has been found to correlate with sepsis mortality. This paper presents using novel heart rate n-variability (HRnV) measures for sepsis mortality risk prediction and comparing against current mortality prediction scores. This study was a retrospective cohort study on patients presenting to the emergency department of a tertiary hospital in Singapore between September 2014 to April 2017. Patients were included if they were above 21 years old and were suspected of having sepsis by their attending physician. The primary outcome was 30-day in-hospital mortality. Stepwise multivariable logistic regression model was built to predict the outcome, and the results based on 10-fold cross-validation were presented using receiver operating curve analysis. The final predictive model comprised 21 variables, including four vital signs, two HRV parameters, and 15 HRnV parameters. The area under the curve of the model was 0.77 (95% confidence interval 0.70-0.84), outperforming several established clinical scores. The HRnV measures may have the potential to allow for a rapid, objective, and accurate means of patient risk stratification for sepsis severity and mortality. Our exploration of the use of wealthy inherent information obtained from novel HRnV measures could also create a new perspective for data scientists to develop innovative approaches for ECG analysis and risk monitoring.

Coronavirus disease 2019 (COVID-19): an evidence map of medical literature.

BACKGROUND: Since the beginning of the COVID-19 outbreak in December 2019, a substantial body of COVID-19 medical literature has been generated. As of June 2020, gaps and longitudinal trends in the COVID-19 medical literature remain unidentified, despite potential benefits for research prioritisation and policy setting in both the COVID-19 pandemic and future large-scale public health crises. METHODS: In this paper, we searched PubMed and Embase for medical literature on COVID-19 between 1 January and 24 March 2020. We characterised the growth of the early COVID-19 medical literature using evidence maps and bibliometric analyses to elicit cross-sectional and longitudinal trends and systematically identify gaps. RESULTS: The early COVID-19 medical literature originated primarily from Asia and focused mainly on clinical features and diagnosis of the disease. Many areas of potential research remain underexplored, such as mental health, the use of novel technologies and artificial intelligence, pathophysiology of COVID-19 within different body systems, and indirect effects of COVID-19 on the care of non-COVID-19 patients. Few articles involved research collaboration at the international level (24.7%). The median submission-to-publication duration was 8 days (interquartile range: 4-16). CONCLUSIONS: Although in its early phase, COVID-19 research has generated a large volume of publications. However, there are still knowledge gaps yet to be filled and areas for improvement for the global research community. Our analysis of early COVID-19 research may be valuable in informing research prioritisation and policy planning both in the current COVID-19 pandemic and similar global health crises.

The correlation of long non-coding RNA intersectin 1-2 with disease risk, disease severity, inflammation, and prognosis of acute ischemic stroke.

BACKGROUND: This study aimed to evaluate the predictive value of long non-coding RNA intersectin 1-2 (lnc-ITSN1-2) for acute ischemic stroke (AIS) risk, and investigate its correlation with disease severity, inflammation, and recurrence-free survival (RFS) in AIS patients. METHODS: Three hundred and twenty AIS patients were recruited, and plasma samples were collected within 24 hours after admission. lnc-ITSN1-2 expression form plasma was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The National Institute of Health Stroke Scale (NIHSS) score was assessed, and RFS was calculated. Meanwhile, 320 controls were enrolled and plasma samples were collected on the enrollment, and lnc-ITSN1-2 expression was detected by RT-qPCR. RESULTS: lnc-ITSN1-2 expression was increased in AIS patients compared to controls (P < .001), and receiver operating characteristic curve revealed its predictive value for AIS risk (area under the curve: 0.804, 95% confidence interval, 0.763-0.845). In AIS patients, lnc-ITSN1-2 expression was positively correlated with NIHSS score (r = 0.464, P < .001). For inflammation, lnc-ITSN1-2 expression was positively correlated with CRP (r = 0.398, P < .001), TNF-α (r = 0.502, P < .001), IL-1ß (r = 0.313, P < .001), IL-6 (r = 0.207, P < .001), IL-8 (r = 0.400, P < .001), IL-17 (r = 0.272, P < .001), and IL-22 (r = 0.222, P < .001). In terms of predicted target microRNAs, lnc-ITSN1-2 expression was negatively correlated with microRNA (miR)-107 (r = -0.467, P < .001), miR-125a (r = -0.494, P < .001), and miR-146a (r = -0.126, P = .025). For prognosis, high lnc-ITSN1-2 expression was correlated with worse RFS in AIS patients. CONCLUSION: lnc-ITSN1-2 exerts a good predictive value for AIS risk; meanwhile, its increased expression is correlated with enhanced disease severity, elevated inflammation, and worse RFS in AIS patients.

Hydrolyzed protein supplementation improves protein content and peroxidation of skeletal muscle by adjusting the plasma amino acid spectrums in rats after exhaustive swimming exercise: a pilot study.

BACKGROUND: This study was designed to evaluate the effects of hydrolyzed protein supplementation upon skeletal muscle total protein and peroxidation in rats following exhaustive swimming exercise. METHODS: Twenty-four rats were randomized to 4 experimental groups (n = 6 per group): control group fed standard diet without exercise (SD), exercise (EX), exercise plus standard diet for 72 hours (EX + SD), and exercise plus standard diet supplemented with hydrolyzed protein (2 g/kg/d) for 72 hours (EX + HP). Immediately following exercise, the EX group was euthanized for collecting plasma and skeletal muscle samples. The EX + SD and EX + HP groups were fed their respective diets for 72 hour still plasma and skeletal muscle collection. Skeletal muscle samples were used to measure levels of total protein (TP), malondialdehyde (MDA), and protein carbonyl (PC). Plasma samples were used to analyze the amino acids spectrum. RESULTS: Compared with the EX + SD, EX + HP presented the significantly increased TP (P = 0.02) and decreased MDA and PC levels (P = 0.035). MDA was negatively correlated with the methionine levels. Moreover, EX + HP maintained higher levels of plasmaleucine, isoleucine, and methionine than EX + SD, which may be associated with the increased skeletal muscle TP levels observed (P < 0.05). CONCLUSIONS: These results collectively suggest that hydrolyzed protein supplementation can improve skeletal muscle TP and ameliorate peroxidation damage in rats subjected to exhaustive exercise stress, which may be, at least in part, related with the maintenance of plasma leucine, isoleucine, and methionine levels.

[Effect of enteral nutrition on liver function and inflammatory response after abdominal operation in patients complicated with liver dysfunction].

OBJECTIVE: To investigate the effect of enteral nutrition(EN) on liver function and inflammatory response after abdominal operation in patients with liver dysfunction. METHODS: A prospective multicenter study was conducted. Patients requiring EN for at least 5 days after abdominal surgery with at least 1 abnormal liver function index were included. After operations, EN suspensions(TPF-FOS) were administered for 5 days after the return of bowel function with targeted content of 125.52 kJ(30 kcal)·kg(-1)·d(-1) maintained for a minimum of 3 days. Levels of serum pre-albumin, C-reaction protein(CRP), and liver function index were measured and the incidence of systemic inflammatory response syndrome(SIRS) was recorded before operation and 6 days after EN. Occurrence of gastrointestinal discomfort was monitored during the treatment. RESULTS: No statistically significant difference was found in pre-albumin between preoperative level and post-EN level[(175.94±71.79) mg/L vs.(192.22±91.26) mg/L, P=0.162]. Patients with abnormal level of γ-glutamyl transpeptidase were less after EN compared to the preoperative period(30 vs. 40, P=0.041), as was total bilirubin (3 vs. 9, P=0.034). No significant differences in other indices of liver function were found. Total bilirubin and direct bilirubin decreased after EN support(P=0.000 and P=0.015, respectively). CRP was notably reduced after EN support [(48.74±65.16) mg/L vs.(25.79±23.63) mg/L, P=0.009] and the incidence of SIRS largely declined after EN support(19.0% vs. 10.3%, P=0.059). The incidence of gastrointestinal discomfort was 22.4% on postoperative day 1 and declined to 19.0% on postoperative day 5. CONCLUSION: For patients with liver dysfunction, enteral nutrition support with TPF-FOS after abdominal operation can reduce inflammatory response, improve liver function, and maintain serum protein level.

Thymosin alpha 1 is associated with improved cellular immunity and reduced infection rate in severe acute pancreatitis patients in a double-blind randomized control study.

The aim of this prospective, double-blinded pilot trial study was to evaluate the effects of Thymosin alpha 1 use in the early phase on immunomodulation and clinical outcomes in patients with severe acute pancreatitis (SAP). A total of 24 patients with SAP were randomized to receive either conventional therapy for SAP or immunomodulatory therapy (TA1 group). The patients in the thymosin group were injected with Talpha1 3.2 mg twice per day for 7 days. The serum level of HLA-DR and CD4/CD8 ratio and other immune parameters were measured on admission, the 8th day and the 28th day. There was a low expression of monocyte HLA-DR in both groups on admission, and more rapid alterations in the HLA-DR were found in the TA1 group. The positive rates of blood and abdominal drainage culture were statistically significant during the 28th follow-up period. The duration of ICU stay was shorter after TA1 treatment. Improves cell-induced immunity and reduces infection rate in severe acute pancreatitis patients.