Score Method Research Articles

Research on Radiation Monitoring Strategy for Spent Fuel Reprocessing Plant Based on Coordination of Nuclear Security Risk and Facility Importance Evaluation

This paper examines a method and scheme for optimizing the allocation of nuclear radiation monitoring resources, based on the analysis of the risk of nuclear security events and the importance of facilities in a spent fuel reprocessing plant. By constructing a nuclear security radiation accident tree for a plant, the importance of different security events was calculated using fuzzy mathematics and expert scoring methods. The importance of each facility was determined by establishing a fuzzy comprehensive decision model, and a resource allocation scheme for nuclear radiation monitoring was proposed based on the importance level of facilities. The research findings demonstrated that the extraction process plant in the main process area, and the centralized control room in the front area of the plant, were of highest importance. Accordingly, three levels of nuclear radiation monitoring programs were established based on the importance of each facility. This study offers theoretical and technical support for the safety management and operation of a spent fuel reprocessing plant. Additionally, the analysis results can serve as a reference for allocating nuclear radiation monitoring resources in various facilities in a reasonable manner.

520 - Evaluating the expression of OX40 and OX40 ligand in lesional skin versus non-lesional skin in volunteers with atopic dermatitis and in healthy control skin

Abstract Introduction/Background Growing evidence suggests that blocking the OX40 ligand (OX40L)/OX40 costimulatory pathway could have therapeutic effects in inflammatory diseases such as atopic dermatitis (AD). Amlitelimab (SAR445229; KY1005) is a potential first-in-class, fully human, non-depleting anti-OX40L monoclonal antibody that blocks OX40L-OX40 interactions. We report OX40L and OX40 expression from skin biopsies collected in two studies: an amlitelimab Phase 2a (Ph2a) study in patients with moderate-to-severe AD, and a small-scale study of patients with mild AD and healthy volunteers. Objectives Assess OX40L and OX40 expression in AD skin (lesional and non-lesional) and healthy control skin. Methods As part of a Ph2a randomized, double-blind, placebo-controlled study (NCT03754309) of amlitelimab in moderate-to-severe AD, 174 baseline-paired lesional/non-lesional skin biopsies were collected from all patients (n=87). In a separate small-scale study, 24 skin biopsies were collected, including healthy control skin from healthy volunteers (n=6) and paired lesional/non-lesional skin from patients with mild AD (n=9). Each biopsy underwent immunohistochemical (IHC; formalin-fixed paraffin-embedded) analyses using various antibodies (OX40L: rabbit IgG antibody from Cell Signaling Technology for Ph2a biopsies, proprietary mouse IgG2a KY1005 for small-scale study biopsies; OX40: clone Ber-ACT35 from BioLegend for all biopsies). A trained pathologist assessed IHC staining in the dermis and/or epidermis using semi-quantitative scoring (0 [no stained cells] to 10 [all cells stained]) or quantitative methods (cells/mm2, Tissue Studio 4.0, and HALO link image analysis software). Wilcoxon matched-pairs signed-rank test was used to assess IHC staining of Ph2a biopsies. Ph2a biopsies also underwent transcriptomic analyses (stored in RNALater) for OX40L (TNFSF4) and OX40 (TNFRSF4) on sequenced RNA using a linear mixed model with Benjamini-Hochberg adjustment. Results In baseline Ph2a biopsies, IHC analysis revealed elevated OX40L and OX40 staining in lesional versus non-lesional AD skin (P <0.0001 for both markers). For OX40L, the median score was 3 (lesional) versus 1 (non-lesional) and the Wilcoxon matched-pairs signed-rank test found P<0.0001. For OX40+ cells, the median expression was 179.8 cells/mm2 in lesional AD skin versus 54.45 cells/mm2 in non-­lesional AD skin (P<0.0001 using the Wilcoxon matched-pairs signed-rank test). These findings were confirmed by RNA sequencing analysis, with TNFSF4 (OX40L) and TNFRSF4 (OX40) differentially expressed in lesional and non-lesional AD skin (P<0.01 and P<0.0001, respectively). A larger scale study is ongoing that may further support this finding. In the small-scale study including patients with mild AD and healthy volunteers, there was a trend for an increase of mean OX40L+ and OX40+ cells/mm2 in lesional skin versus non-lesional skin and healthy control skin in the dermis and epidermis (OX40L+ dermal lesional, non-lesional, healthy, respectively: 17.6, 11.2, 11.5; OX40L+ epidermal: 5.8, 2.1, 1.9; OX40+ dermal: 5.7, 2.1, 0.4; OX40+ epidermal: 10.9, 9.0, 1.8); the increase was significant for lesional versus healthy control skin for dermal OX40+ cells/mm2 (P<0.001). Conclusions We confirm with IHC and RNA sequencing that OX40L and OX40 expression is elevated in skin lesions of patients with moderate-to-severe AD. We also demonstrate a trend to elevated OX40L and elevated OX40 in mild AD skin versus healthy volunteers. A potential explanation for the lower levels of OX40L and OX40 in patients with mild AD in this study may be their lower disease severity versus Ph2a study patients. These findings support the OX40L/OX40 pathway as a relevant target in T cell immune dysregulation; its blockade may represent a novel treatment approach for moderate-to-severe AD.

Risk factors and an early predictive model for Kawasaki disease shock syndrome in Chinese children

BackgroundKawasaki disease shock syndrome (KDSS), though rare, has increased risk for cardiovascular complications. Early diagnosis is crucial to improve the prognosis of KDSS patients. Our study aimed to identify risk factors and construct a predictive model for KDSS.MethodsThis case-control study was conducted from June, 2015 to July, 2023 in two children’s hospitals in China. Children initially diagnosed with KDSS and children with Kawasaki disease (KD) without shock were matched at a ratio of 1:4 by using the propensity score method. Laboratory results obtained prior to shock syndrome and treatment with intravenous immunoglobulin were recorded to predict the onset of KDSS. Univariable logistic regression and forward stepwise logistic regression were used to select significant and independent risk factors associated with KDSS.ResultsAfter matching by age and gender, 73 KDSS and 292 KD patients without shock formed the development dataset; 40 KDSS and 160 KD patients without shock formed the validation dataset. Interleukin-10 (IL-10) > reference value, platelet counts (PLT) < 260 × 109/L, C-reactive protein (CRP) > 80 mg/ml, procalcitonin (PCT) > 1ng/ml, and albumin (Alb) < 35 g/L were independent risk factors for KDSS. The nomogram model including the above five indicators had area under the curves (AUCs) of 0.91(95% CI: 0.87–0.94) and 0.90 (95% CI: 0.71–0.86) in the development and validation datasets, with a specificity and sensitivity of 80% and 86%, 66% and 77%, respectively. Calibration curves showed good predictive accuracy of the nomogram. Decision curve analyses revealed the predictive model has application value.ConclusionsThis study identified IL-10, PLT, CRP, PCT and Alb as risk factors for KDSS. The nomogram model can effectively predict the occurrence of KDSS in Chinese children. It will facilitate pediatricians in early diagnosis, which is essential to the prevention of cardiovascular complications.

Quantitative analysis of risk assessment indicators for re-introduction of imported malaria in China

To quantitatively analyze the risk indicators of re-introduction of imported malaria in China and their weighting coefficients, so as to investigate the difference in the contribution of risk indicators included in the current risk assessment framework for re-introduction of imported malaria in China to the risk assessment of re-introduction of imported malaria. Publications pertaining to the risk assessment framework for re-introduction of imported malaria in China that reported the risk indicators and their weighting coefficients were retrieved in PubMed, Web of Science, CNKI, Wanfang Data, and VIP with terms of "malaria", "re-introduction/re-transmission/re-establishment", "risk assessment/risk evaluation/risk prediction" from the inception of the database through 3 August 2023, and literature search was performed in Google Scholar to ensure the comprehensiveness of the retrieval. Basic characteristics of included studies were extracted using pre-designed information extraction forms by two investigators, and data pertaining to risk indicators of re-introduction of imported malaria were cross-checked by these two investigators. The risk indicators included in the risk assessment framework for re-introduction of imported malaria in China and their weighting coefficients were visualized with the Nightingale's rose diagrams using the software R 4.2.1, and the importance of risk indictors was evaluated with the frequency of risk indicators included in the risk assessment framework and the ranking of weighting coefficients of risk indicators. In addition, the capability of risk indicators screened by different weighting methods was compared by calculating the ratio of the maximum to the minimum of the weighting coefficients of the risk indicators screened by different weighting methods. A total of 2 138 publications were retrieved, and following removal of duplications and screening, a total of 8 publications were included in the final analysis. In these 8 studies, 8 risk assessment frameworks for re-introduction of imported malaria in China and 52 risk indicators of re-introduction of imported malaria were reported, in which number of imported malaria cases (n = 8) and species of malaria vectors were more frequently included in the risk assessment frameworks (n = 8), followed by species of imported malaria parasites (n = 6) and population density of local malaria vectors (n = 6), and species of local malaria vectors (n = 6), number of imported malaria cases (n = 5) and species of imported malaria parasites had the three highest weighting coefficients (n = 4). The weighting methods included expert scoring method, combination of expert scoring method and analytic hierarchy process, and combination of expert scoring method and entropy weight method in these 8 studies, and the ratios of the maximum to the minimum of the weighting coefficients of the risk indicators screened by the expert scoring method were 1.143 to 2.241, while the ratios of the maximum to the minimum of the weighting coefficients of the risk indicators screened by combination of the expert scoring method and analytic hierarchy process were 34.970 to 162.000. Number of imported malaria cases, species of imported malaria parasites, species of local malaria vectors and population density of local malaria vectors are core indicators in the current risk assessment framework for re-introduction of imported malaria in China. Combination of the expert scoring method and analytic hierarchy process is superior to the expert scoring method alone for weighting the risk indicators.

PD-L1 Expression in HPV-associated Versus HPV-independent Invasive Vulvar Squamous Cell Carcinoma.

Two etiological pathways have been implicated in the pathogenesis of vulvar squamous cell carcinoma (VSCC): a high-risk human papillomavirus (HPV)-associated route and an HPV-independent pathway characterized by TP53 mutations. Programmed cell death ligand 1 (PD-L1) has become increasingly useful in predicting the response to checkpoint inhibitor therapy in squamous cell carcinomas at various anatomical sites. This study aimed to assess the association between PD-L1 expression and the VSCC subtype to evaluate the utility of PD-L1 in prognostication and therapeutic selection based on HPV status. PD-L1 status was assessed using 3 separate metrics for the extent of PD-L1 staining in various cell types: immune cell score, tumor proportion score (TPS), and combined positive score. The study group consisted of 25 HPV-associated and 28 HPV-independent VSCCs. PD-L1 expression was positive in the majority of VSCCs according to all 3 scoring metrics (84.9% by immune cell score, 77.3% by TPS, and 90.6% by combined positive score). PD-L1 expression was observed in the majority of cases in both groups (60%-96.4%). PD-L1 expression using the TPS method was greater in HPV-independent tumors than in HPV-associated tumors ( P = 0.004), and high PD-L1 expression was also more common in the HPV-independent subtype ( P = 0.016 using the TPS method and P = 0.013 using the combined positive score method). Our findings contribute to the growing evidence that PD-L1 is expressed in the majority of invasive VSCCs, and thus may serve as an attractive therapeutic target. PD-L1 expression is higher in HPV-independent tumors, suggesting that this subtype may be more responsive to PD-L1 inhibitor therapy.

A deep learning and radiomics based Alberta stroke program early CT score method on CTA to evaluate acute ischemic stroke.

Alberta stroke program early CT score (ASPECTS) is a semi-quantitative evaluation method used to evaluate early ischemic changes in patients with acute ischemic stroke, which can guide physicians in treatment decisions and prognostic judgments. We propose a method combining deep learning and radiomics to alleviate the problem of large inter-observer variance in ASPECTS faced by physicians and assist them to improve the accuracy and comprehensiveness of the ASPECTS. Our study used a brain region segmentation method based on an improved encoding-decoding network. Through the deep convolutional neural network, 10 regions defined for ASPECTS will be obtained. Then, we used Pyradiomics to extract features associated with cerebral infarction and select those significantly associated with stroke to train machine learning classifiers to determine the presence of cerebral infarction in each scored brain region. The experimental results show that the Dice coefficient for brain region segmentation reaches 0.79. Three radioactive features are selected to identify cerebral infarction in brain regions, and the 5-fold cross-validation experiment proves that these 3 features are reliable. The classifier trained based on 3 features reaches prediction performance of AUC = 0.95. Moreover, the intraclass correlation coefficient of ASPECTS between those obtained by the automated ASPECTS method and physicians is 0.86 (95% confidence interval, 0.56-0.96). This study demonstrates advantages of using a deep learning network to replace the traditional template registration for brain region segmentation, which can determine the shape and location of each brain region more precisely. In addition, a new brain region classifier based on radiomics features has potential to assist physicians in clinical stroke detection and improve the consistency of ASPECTS.

Abstract TP73: Outcomes in Mexican American Informal Stroke Caregivers and Differences by Ethnicity

Background: Informal home care is the most prevalent type of post-acute care (PAC) in Mexican American (MA) stroke survivors, but data on the impact on caregivers is not available. The objective was to investigate strain, positive aspects of caregiving, familial obligations/support, and depression in stroke caregivers and ethnic differences in a population-based study. Methods: Data are from Brain Attack Surveillance in Corpus Christi PAC Study. Community-dwelling stroke survivors and their caregivers were recruited (n=307). Caregiver eligibility included: 1) residence in study county, 2) not cognitively impaired, 3) not providing care pre-stroke. Caregiver interviews at ~90 days included sociodemographics, dyad characteristics, Modified Caregiver Strain Index (MCSI range 0-26, higher more), PAC scale by Tarlow et al (range 5-45, higher more), familial obligations/support scales by Sabogal et al (range 1-5, higher greater), and PHQ-8 (range 0-30, higher worse). Patient data were from interviews and medical records. Propensity score (PS) methods were used to balance caregiver and patient factors among MA and non-Hispanic white (NHW) caregivers by fitting a model with ethnicity of caregiver as the outcome and predictors being caregiver sociodemographics, patient-caregiver dyad characteristics, and patient sociodemographics and disability. PS were then included as a covariate in regression models considering the association between ethnicity and outcomes. Results: MA caregivers were younger, more likely female, and more likely a child than NHWs. Median MCSI, PAC scale, PHQ-8 were 11 (IQR:6-17), 36 (IQR:30-40), and 11 (IQR:9-15) in MAs and 13.5 (IQR:9-18.3), 30 (IQR:25-36.3) and 13 (IQR:10-16) in NHWS. MA ethnicity was associated with less caregiver strain (β=-2.22, 95% CI:-4.19, -0.26) and depression (β=-2.05, 95% CI:-3.48, -0.63) and more positive aspects of caregiving (β=2.96, 95% CI:0.91, 5.01), but not associated with familial obligations/support. Conclusions: Informal stroke caregivers report moderate levels of strain and depressive symptoms, with NHW caregivers reporting higher levels. MA caregivers report greater positive aspects of caregiving suggesting a possible intervention target to improve outcomes in MAs.

Performance evaluation system of key energy-saving technologies in public institutions based on heat pump system in cold regions

The energy systems of public institutions experience unsatisfactory actual operation and improper operation management, and the level of building energy consumption is increasing annually. Research on the application of key energy-saving technologies in public institutions is an effective method to improve building energy efficiency and reduce energy wastage. In this study, the aperformance of key energy-saving technologies in public institutions were considered as the research object. Combined with the characteristics of different energy-saving technologies and relevant national standards, the evaluation indices were selected from four aspects: comprehensive energy efficiency, economy, environment, and operation management. According to the results of expert investigations and measured data, the index weight was determined using the artificial neural network and expert scoring methods, and a complete evaluation system of indices was built. There were 4 first-level, 10 second-level, and 11 third-level evaluation indices in the evaluation system. The evaluation indices of each level with the largest weights were the comprehensive energy efficiency of the buildings (0.532), technical energy efficiency (0.331), and water pump power consumption to heat (cold) transmission ratio (0.167). The evaluation system for key energy-saving technologies in public institutions is useful for operation managers to identify the weak points of system operations and formulate timely optimisation schemes. This evaluation system can be used as a valuable reference for improving the energy-saving levels of public institutions.

Evaluation of tobacco-planting soil quality using multiple distinct scoring methods and soil quality indices

The economic significance of flue-cured tobacco in China relies heavily on soil quality, directly affecting yield and sustainability. However, human activities and climate change have led to soil quality deterioration. Therefore, assessing soil quality in tobacco-planting soil has become imperative. Herein, a total of 177 soil samples were collected from the representative tobacco-growing areas in Qiannan, Guizhou. Twenty-four soil physical, chemical, and biochemical indicators were determined and compiled as the total data set (TDS). The minimum data set (MDS) was formed through the principal component analysis (PCA) and norm value. These two data sets were applied to calculate the soil quality of this region by combining multiple approaches, including three scoring methods and three soil quality indices (SQIs). Linear analysis between MDS and TDS showed that R2 values ranged from 0.617 to 0.762, suggesting the MDS can represent the TDS. Likewise, the MDS, integrated with the non-linear method (NL) and weighed addictive soil quality (SQIw) (SQIw-NL-MDS) and the TDS, integrated with NL and SQIw (SQIw-NL-TDS) exhibited the highest R2 value. The SQIw-NL-MDS model was the best approach to assess soil quality in subsequent analysis. According to the SQIw-NL-MDS model, this region exhibited moderate soil quality. This study preliminarily developed a soil quality assessment model for the tobacco-growing soil in Qiannan region, which might provide theoretical guidance for other key tobacco-growing areas.

Efficacy and safety of Chinese herbal medicine as adjunctive therapy in sepsis patients with bloodstream infection: a propensity-matched analysis.

To investigate the efficacy and safety of Chinese herbal medicine in treating sepsis patients with bloodstream infection. A 6-year retrospective study was carried out at a university hospital in China. Adult sepsis patients with bloodstream infection were included. The primary outcome was 28-day mortality after admission. Propensity score method was used to adjust for possible confounding. 28-day mortality was estimated by Kaplan-Meier analysis and compared using the log-rank test. Cox regression analysis was carried out to identify factors impacting in-hospital mortality outcomes. Following the application of the propensity score method, a total of 176 patients were included. The all-cause 28-day mortality in the control group and Chinese herbal medicine group was 21.6% and 14.8%, respectively. Kaplan-Meier survival analysis showed that Chinese herbal medicine was associated with a lower hazard ratio (HR) in all-cause 28-day death compared with the control group [HR = 0.44, 95% CI(0.22, 0.90), P < 0.05]. The complications were similar between the two groups (P >0.05). Blood-activating and stasis-eliminating herb administration was associated with reduced in-hospital mortality among sepsis patients with bloodstream infection [HR = 0.54, 95% CI(0.34, 0.94), P < 0.05]. Chinese herbal medicine, especially the blood-activating and stasis-eliminating herb, might have certain efficacy and safety in treating sepsis patients with bloodstream infection. Clinicians should prescribe blood-activating and stasis-eliminating herb in treating these two coalescent critical diseases as long as no contraindications exist. However, further studies are needed to validate our results.

Abstract WP70: Novel Weighted FANG-D Scale Scoring to Detect Large Vessel Occlusion

Objective: To determine if a novel weighted FANG-D scoring scale (NWFSS) increases sensitivity and specificity rates of large vessel occlusion (LVO) as compared to those reported with the original FANG-D scale scoring. Methodology: The present study used an observational, descriptive design to identify the important variables (field cut, aphasia, neglect, gaze preference, and dense hemiparesis) associated with the likelihood of detecting LVO. We used the FANG-D scale in patients admitted through the emergency department (ED) of a comprehensive stroke center (CSC), from December 2022 through April 2023. The NIHSS was performed and compared with the NWFSS for analysis. Each component was required to have a score ≥ 2(moderate to severe deficits) except dense hemiparesis which required a score ≥3 (significant weakness) to receive one point on the FANG-D scale. A total score of 2 or higher on FANG-D indicated a positive result suggesting LVO. If aphasia or neglect were present with a NIHSS of≥2, it was considered a positive FANG-D score. Results: A total of 311 patients were included in the study for analysis with a mean age of 67 ±16.4 years of whom 56.6% were female. The sensitivity and specificity rates were 85.7% (Confidence Interval (CI) =72.8%-94.1%) and 90.5% (CI= 86.2%-93.7%) respectively for positive predictive value of NWFSS to identify LVO. The sensitivity and specificity of the NIHSS has been reported as 86% and 60% respectively for LVO detection. The previous FANG-D study group used lower values in calculating the FANG-D scores and reported a sensitivity rate of 98% and specificity of 76.7%. Conclusion: The NWFSS has high specificity and is reliable for LVO prediction. While the NIHSS assesses eleven items sensitive for stroke diagnosis, it may take up to 10 minutes to complete and is not specific for LVO, whereas the FANG-D assesses 5items critical to LVO detection and is simple and fast with completion in &lt;1 minute, minimizing time to intervention. Our study occurred in the ED, but this scale scoring method could be tested in the prehospital setting. The use of a scale with higher specificity for LVO could improve patient outcomes and resource utilization by faster routing of patients to CSCs capable of performing mechanical thrombectomy.

Optimal filters for ERP research I: A general approach for selecting filter settings.

Filtering plays an essential role in event-related potential (ERP) research, but filter settings are usually chosen on the basis of historical precedent, lab lore, or informal analyses. This reflects, in part, the lack of a well-reasoned, easily implemented method for identifying the optimal filter settings for a given type of ERP data. To fill this gap, we developed an approach that involves finding the filter settings that maximize the signal-to-noise ratio for a specific amplitude score (or minimizes the noise for a latency score) while minimizing waveform distortion. The signal is estimated by obtaining the amplitude score from the grand average ERP waveform (usually a difference waveform). The noise is estimated using the standardized measurement error of the single-subject scores. Waveform distortion is estimated by passing noise-free simulated data through the filters. This approach allows researchers to determine the most appropriate filter settings for their specific scoring methods, experimental designs, subject populations, recording setups, and scientific questions. We have provided a set of tools in ERPLAB Toolbox to make it easy for researchers to implement this approach with their own data.

Gesture imitation performance in community-dwelling older people: assessment of a gesture imitation task in the screening and diagnosis of mild cognitive impairment and dementia.

Gesture imitation, a simple tool for assessing visuospatial/visuoconstructive functions, is reportedly useful for screening and diagnosing dementia. However, gesture imitation performance in healthy older adults is largely unknown, as are the factors associated with lower performance. To address these unknowns, we examined the gesture imitation performance of a large number of community-dwelling older adults aged ≥65 years in Arao City, Kumamoto Prefecture (southern Japan). The examiner presented the participants with eight gesture patterns and considered it a success if they could imitate them within 10 s. The success rate of each gesture imitation was calculated for three diagnostic groups: cognitively normal (CN) (n = 1184), mild cognitive impairment (MCI) (n = 237), and dementia (n = 47). Next, we reorganised the original gesture imitation battery by combining six selected gestures with the following scoring method: if the participants successfully imitated the gestures, immediately or within 5 s, two points were assigned. If they succeeded within 5-10 s, one point was assigned. The sensitivity and specificity of the battery were investigated to detect the dementia and MCI groups. Factors associated with gesture imitation battery scores were examined. Except one complex gesture, the success rate of imitation in the CN group was high, approximately 90%. The sensitivity and specificity of the gesture imitation battery for discriminating between the dementia and CN groups and between the MCI and CN groups were 70%/88%, and 45%/75%, respectively. Ageing, male sex, and a diagnosis of dementia or MCI were associated with lower scores on the gesture imitation battery. Gesture imitation tasks alone may not be sufficient to detect MCI. However, by combining gestures with set time limits, gesture imitation tasks can be a low-burden and effective method for detecting dementia, even in community medicine, such as during health check-ups.

Impact of children's age on parental HIV disclosure: a parental HIV disclosure intervention among parents living with HIV in China

ABSTRACT Parental HIV disclosure, where parents living with HIV (PLH) communicate their diagnosis to their children, is crucial for family communication. This study assessed intervention effects of a parental HIV disclosure intervention on psychosocial factors, focusing on child's age impact. Data from a randomized controlled trial involving 791 PLH in China were analyzed at baseline (W1), 6-month (W2), and 12-month follow-ups (W3). The study measured effects on psychosocial factors (HIV disclosure knowledge, outcome expectancy, action self-efficacy, and action planning) using the proportional latent change score method. Among PLH with children aged 6–9, the intervention yielded significant intervention effects on knowledge (β = 0.190, p = .004), action self-efficacy (β = 0.342, p = .001), and action planning (β = 0.389, p < .001) from W1 to W2. For PLH with children aged 10-12, the intervention significantly enhanced action self-efficacy (β = 0.162, p = .003) and action planning (β = 0.367, p = .001) from W1 to W2, but there was a reduction in perceived benefits (β = −0.175, p = 0.024) from W2 to W3. For PLH with children aged 13–15, significant intervention effects were observed on action planning, both from W1 to W2 (β = 0.251, p = .045) and from W2 to W3 (β = 0.321, p < .001). These findings highlight the importance of tailoring interventions to consider psychosocial factors and children's developmental stages to enhance HIV disclosure practices.

Can the FIB-4 score predict the severity of acute pancreatitis in NAFLD?

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a liver pathology. NAFLD’s prevalence is increasing in the world and because of the increase non-invasive methods are gaining importance in diagnosis. The Fibrosis 4 (FIB-4) score is one of the most commonly used non-invasive scoring methods for diagnosing NAFLD today. Acute pancreatitis is a disease with inflammation and high morbidity. There are studies indicating that acute pancreatitis progresses more severely in patients with NAFLD. In our study, it was aimed to define the possible relationship between the FIB-4 score and the severity of acute pancreatitis, which has not been investigated before and contribute to the literature.MethodsOur study was conducted by retrospectively scanning 124 patients diagnosed with acute pancreatitis between 2018 and 2020. The patients were compared with the presence of NAFLD and the FIB-4 score results in those with NAFLD.ResultsThe 48th-hour Ranson score was found to be statistically significantly higher in patients with NAFLD compared to those without NAFLD. In patients with NAFLD, the total billurbin, direct billurbin, AST, ALT, ALP, GGT, and Ranson scores were found to be statistically significantly higher in those with FIB-4 score ≥ 2.67.ConclusıonAs liver fibrosis increases in patients with NAFLD, it is suggested that liver damage accompanying acute pancreatitis increases, and the prognosis of acute pancreatitis worsens. There is a need for further studies to be conducted while centering more on this subject, which has not been investigated before in the literature.

MAPPING OF LANDSLIDE-PRONE AREAS ON ENDE-WOLOWARU ROAD SECTION ENDE REGENCY BASED ON GEOGRAPHIC INFORMATION SYSTEM

&lt;p&gt;&lt;span&gt;Landslides on the Ende - Wolowaru road, Ende Regency often occur every year, especially in the rainy season. Therefore, research was carried out to determine the level of vulnerability to landslides on the Ende - Wolowaru road section, Ende Regency, using an estimation model referring to Puslittanak research in 2004. Mapping of landslide-prone areas was carried out at a radius of 250 meters along the Ende - Wolowaru road section, Ende Regency with area 2,514 ha. The analysis used GIS analysis, such as: scoring and overlay methods based on 2004 Puslittanak Department of Agriculture estimation model. The parameters used are rainfall, rock type, slope, land cover and soil type. The results of the analysis in this study show that the level of vulnerability to landslides at the research location consists of a non-prone class covering an area of 13.38 ha, a vulnerable class covering an area of 1,620.38 ha and a very vulnerable class covering an area of 880.65 ha and (2) the level of validation mapping results that is equal to 88%.&lt;/span&gt;&lt;/p&gt;

Structure-based drug design and molecular dynamics studies of an allosteric modulator targeting the protein-protein interaction site of PDK1.

Protein-protein interaction interfaces play a major role in cell signaling pathways. There is always agreat interest in developing protein-protein interaction (PPI) inhibitors of kinases, as they are challenging due to their hydrophobicity, flat surface, specificity, potency, etc. 3 Phosphoinositide-dependent kinase-1 (PDK1), which is involved in the PI3K/PDK1/AKT pathway, is a cancer target that has gained insight for the past two decades. PDK1 possesses a protein interaction fragment (PIF) pocket, which is a well-known PPI that targets allosteric modulators. This work focusses on energy-based pharmacophore model development which on virtual screening could yield novel scaffolds towards the drug designing objective for the kind of PDK1 modulators. A novel pyrazolo pyridine molecule was identified as an allosteric modulator that binds to the PPI site. The metadynamics simulations with free energy profiles further revealed the conformational allosteric changes stimulated on the protein structure upon ligand binding. The cytotoxic activity (IC50-20 μM) of the identified compound against five different cancer cell lines and cell cycle analysis supported the anticancer activity of the identified compound. All the computational works were carried out by the most commonly used Schrodinger Suite software. The pharmacophore was validated by Receiver Operation Characteristics (ROC) and screening against allosteric Enamine database library. The Optimized Potential Liquid Simulations (OPLS-2005) was used to minimize the structures for molecular docking calculations, and inbuilt scoring method of ranking the compounds based on docking score and Glide energy was used. Molecular dynamics simulations were conducted by Desmond implemented in Maestro. The hit compound was purchased from Enamine and tested against different cancer cell lines by MTT assay, apoptosis by western blotting technique, and by flow cytometry analysis.

A nomogram for predicting mortality risk within 30 days in sepsis patients admitted in the emergency department: A retrospective analysis.

To establish and validate an individualized nomogram to predict mortality risk within 30 days in patients with sepsis from the emergency department. Data of 1205 sepsis patients who were admitted to the emergency department in a tertiary hospital between Jun 2013 and Sep 2021 were collected and divided into a training group and a validation group at a ratio of 7:3. The independent risk factors related to 30-day mortality were identified by univariate and multivariate analysis in the training group and used to construct the nomogram. The model was evaluated by receiver operating characteristic (ROC) curve, calibration chart and decision curve analysis. The model was validated in patients of the validation group and its performance was confirmed by comparing to other models based on SOFA score and machine learning methods. The independent risk factors of 30-day mortality of sepsis patients included pro-brain natriuretic peptide, lactic acid, oxygenation index (PaO2/FiO2), mean arterial pressure, and hematocrit. The AUCs of the nomogram in the training and verification groups were 0.820 (95% CI: 0.780-0.860) and 0.849 (95% CI: 0.783-0.915), respectively, and the respective P-values of the calibration chart were 0.996 and 0.955. The DCA curves of both groups were above the two extreme curves, indicating high clinical efficacy. The AUC values were 0.847 for the model established by the random forest method and 0.835 for the model established by the stacking method. The AUCs of SOFA model in the model and validation groups were 0.761 and 0.753, respectively. The sepsis nomogram can predict the risk of death within 30 days in sepsis patients with high accuracy, which will be helpful for clinical decision-making.

Platelet Transfusion and Death or Neurodevelopmental Impairment in Children Born Extremely Preterm

Infants born extremely preterm receive transfusions at higher platelet count thresholds than older children and adults due to concerns for intracranial hemorrhage. A recent randomized trial comparing 2 platelet transfusion thresholds showed the higher threshold was associated with increased risk of long-term adverse neurodevelopmental outcomes. To evaluate the association of platelet transfusion exposure with death and severe neurodevelopmental impairment (NDI) at 2 years' corrected age in a cohort of infants born extremely preterm. An observational cohort study and secondary analysis of the Preterm Erythropoietin Neuroprotection Trial, a randomized, placebo-controlled clinical trial of erythropoietin neuroprotection in neonates born extremely preterm, was conducted in 30 neonatal intensive care units in the US from December 1, 2013, to September 31, 2016. This analysis included 819 infants born extremely preterm at 24 to 27 completed weeks of gestation who had a documented outcome (death or neurodevelopmental assessment). Analysis was performed in April 2023. Any platelet transfusion during neonatal intensive care unit hospitalization. The primary composite outcome was death or severe NDI evaluated at 2 years' corrected age using the Bayley Scales of Infant Development-Third Edition (BSID-III) and the Gross Motor Function Classification System and was defined as the presence of severe cerebral palsy or a BSID-III composite motor or cognitive score 2 SDs below the mean. Confounding by indication for platelet transfusion was addressed with covariate adjustment and propensity score methods. Of the 819 infants included in the analysis (429 [52.4%] male; mean [SD] gestational age, 25.5 [1.1] weeks), 245 (30.0%) received at least 1 platelet transfusion during their initial hospitalization. The primary outcome occurred in 46.5% (114 of 245) of infants exposed to a platelet transfusion and 13.9% (80 of 574) of nonexposed infants with a corresponding odds ratio of 2.43 (95% CI, 1.24-4.76), adjusted for propensity score, gestational age at birth, and trial treatment group. The individual components of death and severe NDI were directionally consistent with the overall composite outcome. The findings of this study suggest that platelet transfusion in infants born extremely preterm may be associated with an increased risk of death or severe NDI at 2 years' corrected age, although the possibility of residual confounding by indication cannot be excluded.

Identification and assessment of new PIM2 inhibitors for treating hematologic cancers: A combined approach of energy-based virtual screening and machine learning evaluation.

PIM2, part of the PIM kinase family along with PIM1 and PIM3, is often overexpressed in hematologic cancers, fueling tumor growth. Despite its significance, there are no approved drugs targeting it. In response to this challenge, we devised a thorough virtual screening workflow for discovering novel PIM2 inhibitors. Our process includes molecular docking and diverse scoring methods likemolecular mechanics generalized born surface area, XGBOOST, and DeepDock to rank potential inhibitors by binding affinities and interaction potential. Ten compounds were selected and subjected to an adequate evaluation of their biological activity. Compound 2 emerged as the most potent inhibitor with an IC50 of approximately 135.7 nM. It also displayed significant activity against various hematological cancers, including acute myeloid leukemia, mantle cell lymphoma, and anaplastic large cell lymphoma (ALCL). Molecular dynamics simulations elucidated the binding mode of compound 2 with PIM2, offering insights for drug development. These results highlight the reliability and efficacy of our virtual screening workflow, promising new drugs for hematologic cancers, notably ALCL.