bluuebunny/crossref_metadata_2025_split huggingface dataset:
LncRNA model predicts liver cancer drug resistance and validate in vitro experiments
Authors: Yin Qiushi , Huang Xiaolong , Yang Qiuxi , Lin Shibu , Song Qifeng , Fan Weiqiang , Li Wang , Li Zhongyi , Gao Lianghui 
Published: April 2023

Introduction: Hepatocellular carcinoma (HCC) patients may benefit from chemotherapy, but drug resistance is an important obstacle to favorable prognoses. Overcoming drug resistance is an urgent problem to be solved.Methods: Differential expression analysis was used to identify long non-coding RNAs (LncRNAs) that differed in chemotherapy-sensitive and chemotherapy-resistant patients. Machine learning algorithms including random forest (RF), lasso regression (LR), and support vector machines (SVMs) were used to identify important chemotherapy-related LncRNAs. A back propagation (BP) network was then used to validate the predictive capacity of important LncRNAs. The molecular functions of hub LncRNAs were investigated via qRT-PCR and cell proliferation assay. Molecular-docking technique was used to explore candidate drug of targets of hub LncRNA in the model.Results: A total of 125 differentially expressed LncRNAs between sensitive and resistant patients. Seventeen important LncRNAs were identified via RF, and seven factors were identified via LR. With respect to SVM, the top 15 LncRNAs of AvgRank were selected. Five merge chemotherapy-related LncRNAs were used to predict chemotherapy resistance with high accuracy. CAHM was a hub LncRNA of model and expression high in sorafenib resistance cell lines. In addition, the results of CCK8 showed that the sensitivity of HepG2-sorafenib cells to sorafenib was significantly lower than that of HepG2; and the sensitivity of HepG2-sorafenib cells transfected with sh-CAHM was significantly higher than that of Sorafenib. In the non-transfection group, the results of clone formation experiments showed that the number of clones formed by HepG2-sorafenib cells treated with sorafenib was significantly more than that of HepG2; after HepG2-sorafenib cells were transfected with sh-CAHM, the number of clones formed by Sorafenib treatment was significantly higher than that of HepG2 cells. The number was significantly less than that of HepG2-s + sh-NC group. Molecular Docking results indicate that Moschus was candidate drug for target protein of CAHM.Conclusion: Five chemotherapy-related LncRNAs could predict drug resistance in HCC with high accuracy, and the hub LncRNA CAHM has potential as a new biomarker for HCC chemotherapy resistance.
Gene dysregulation in acute HIV-1 infection – early transcriptomic analysis reveals the crucial biological functions affected
Authors: Parker Erica , Judge Melinda A. , Pastor Lucia , Fuente-Soro Laura , Jairoce Chenjerai , Carter Kim W. , Anderson Denise , Mandomando Inácio , Clifford Holly D. , Naniche Denise , Le Souëf Peter Neils 
Published: April 2023

IntroductionTranscriptomic analyses from early human immunodeficiency virus (HIV) infection have the potential to reveal how HIV causes widespread and lasting damage to biological functions, especially in the immune system. Previous studies have been limited by difficulties in obtaining early specimens.MethodsA hospital symptom-based screening approach was applied in a rural Mozambican setting to enrol patients with suspected acute HIV infection (Fiebig stage I-IV). Blood samples were collected from all those recruited, so that acute cases and contemporaneously recruited, uninfected controls were included. PBMC were isolated and sequenced using RNA-seq. Sample cellular composition was estimated from gene expression data. Differential gene expression analysis was completed, and correlations were determined between viral load and differential gene expression. Biological implications were examined using Cytoscape, gene set enrichment analysis, and enrichment mapping.ResultsTwenty-nine HIV infected subjects one month from presentation and 46 uninfected controls were included in this study. Subjects with acute HIV infection demonstrated profound gene dysregulation, with 6131 (almost 13% of the genome mapped in this study) significantly differentially expressed. Viral load was correlated with 1.6% of dysregulated genes, in particular, highly upregulated genes involved in key cell cycle functions, were correlated with viremia. The most profoundly upregulated biological functions related to cell cycle regulation, in particular, CDCA7 may drive aberrant cell division, promoted by overexpressed E2F family proteins. Also upregulated were DNA repair and replication, microtubule and spindle organization, and immune activation and response. The interferome of acute HIV was characterized by broad activation of interferon-stimulated genes with antiviral functions, most notably IFI27 and OTOF. BCL2 downregulation alongside upregulation of several apoptotic trigger genes and downstream effectors may contribute to cycle arrest and apoptosis. Transmembrane protein 155 (TMEM155) was consistently highly overexpressed during acute infection, with roles hitherto unknown.DiscussionOur study contributes to a better understanding of the mechanisms of early HIV-induced immune damage. These findings have the potential to lead to new earlier interventions that improve outcomes.
Targeted proteomics links virulence factor expression with clinical severity in staphylococcal pneumonia
Authors: Pivard Mariane , Bastien Sylvère , Macavei Iulia , Mouton Nicolas , Rasigade Jean-Philippe , Couzon Florence , Youenou Benjamin , Tristan Anne , Carrière Romain , Moreau Karen , Lemoine Jérôme , Vandenesch François 
Published: April 2023

IntroductionThe bacterial pathogen Staphylococcus aureus harbors numerous virulence factors that impact infection severity. Beyond virulence gene presence or absence, the expression level of virulence proteins is known to vary across S. aureus lineages and isolates. However, the impact of expression level on severity is poorly understood due to the lack of high-throughput quantification methods of virulence proteins.MethodsWe present a targeted proteomic approach able to monitor 42 staphylococcal proteins in a single experiment. Using this approach, we compared the quantitative virulomes of 136 S. aureus isolates from a nationwide cohort of French patients with severe community-acquired staphylococcal pneumonia, all requiring intensive care. We used multivariable regression models adjusted for patient baseline health (Charlson comorbidity score) to identify the virulence factors whose in vitro expression level predicted pneumonia severity markers, namely leukopenia and hemoptysis, as well as patient survival.ResultsWe found that leukopenia was predicted by higher expression of HlgB, Nuc, and Tsst-1 and lower expression of BlaI and HlgC, while hemoptysis was predicted by higher expression of BlaZ and HlgB and lower expression of HlgC. Strikingly, mortality was independently predicted in a dose-dependent fashion by a single phage-encoded virulence factor, the Panton-Valentine leucocidin (PVL), both in logistic (OR 1.28; 95%CI[1.02;1.60]) and survival (HR 1.15; 95%CI[1.02;1.30]) regression models.DiscussionThese findings demonstrate that the in vitro expression level of virulence factors can be correlated with infection severity using targeted proteomics, a method that may be adapted to other bacterial pathogens.
Atrial fibrillation as a contributor to the mortality in patients with dementia: A nationwide cohort study
Authors: Chen Yun-Yu , Lin Yenn-Jiang , Hsieh Yu-Cheng , Chien Kuo-Liong , Lin Ching-Heng , Chung Fa-Po , Chen Shih-Ann 
Published: April 2023

BackgroundKnowledge of the risk of death in patients with dementia is essential for planning preventive strategies. This study aimed to evaluate the effect of atrial fibrillation (AF) on death risks and other factors associated with death in patients with dementia and AF.MethodsWe conducted a nationwide cohort study using Taiwan's National Health Insurance Research Database. We identified subjects with dementia diagnosed for the first time and AF diagnosed concomitantly between 2013 and 2014. Subjects under the age of 18 years were excluded. Age, sex, and CHA2DS2-VASc scores were 1: 4 matched for AF patients (N = 1,679) and non-AF controls (N = 6,176) using the propensity score technique. The conditional Cox regression model and competing risk analysis were applied. The risk of mortality was tracked till 2019.ResultsAF history was associated with higher risks of all-cause death (hazard ratio [HR]: 1.208; 95% confidence interval [CI]: 1.142–1.277) and cardiovascular death (subdistribution HR: 1.210; 95% CI: 1.077–1.359) in dementia patients than patients without a diagnosis of AF. For patients with both dementia and AF, they had a higher risk of death due to higher age, diabetes mellitus, congestive heart failure, chronic kidney disease, and prior stroke. Anti-arrhythmic drugs and novel oral anticoagulants significantly reduced the risk of death in patients with AF and dementia.ConclusionThis study found that AF is a risk factor for mortality in patients with dementia and explored several risk factors for AF-related mortality. This study highlights the importance of controlling AF especially in patients with dementia.
Machine learning-based in-hospital mortality risk prediction tool for intensive care unit patients with heart failure
Authors: Chen Zijun , Li Tingming , Guo Sheng , Zeng Deli , Wang Kai 
Published: April 2023

ObjectiveRisk stratification of patients with congestive heart failure (HF) is vital in clinical practice. The aim of this study was to construct a machine learning model to predict the in-hospital all-cause mortality for intensive care unit (ICU) patients with HF.MethodseXtreme Gradient Boosting algorithm (XGBoost) was used to construct a new prediction model (XGBoost model) from the Medical Information Mart for Intensive Care IV database (MIMIC-IV) (training set). The eICU Collaborative Research Database dataset (eICU-CRD) was used for the external validation (test set). The XGBoost model performance was compared with a logistic regression model and an existing model (Get with the guideline-Heart Failure model) for mortality in the test set. Area under the receiver operating characteristic cure and Brier score were employed to evaluate the discrimination and the calibration of the three models. The SHapley Additive exPlanations (SHAP) value was applied to explain XGBoost model and calculate the importance of its features.ResultsThe total of 11,156 and 9,837 patients with congestive HF from the training set and test set, respectively, were included in the study. In-hospital all-cause mortality occurred in 13.3% (1,484/11,156) and 13.4% (1,319/9,837) of patients, respectively. In the training set, of 17 features with the highest predictive value were selected into the models with LASSO regression. Acute Physiology Score III (APS III), age and Sequential Organ Failure Assessment (SOFA) were strongest predictors in SHAP. In the external validation, the XGBoost model performance was superior to that of conventional risk predictive methods, with an area under the curve of 0.771 (95% confidence interval, 0.757–0.784) and a Brier score of 0.100. In the evaluation of clinical effectiveness, the machine learning model brought a positive net benefit in the threshold probability of 0%–90%, prompting evident competitiveness compare to the other two models. This model has been translated into an online calculator which is accessible freely to the public (https://nkuwangkai-app-for-mortality-prediction-app-a8mhkf.streamlit.app).ConclusionThis study developed a valuable machine learning risk stratification tool to accurately assess and stratify the risk of in-hospital all-cause mortality in ICU patients with congestive HF. This model was translated into a web-based calculator which access freely.
Longitudinal changes in blood pressure and fasting plasma glucose among 5,398 primary care patients with concomitant hypertension and diabetes: An observational study and implications for community-based cardiovascular prevention
Authors: Yu Xiao , Li Yu Ting , Cheng Hui , Zhu Sufen , Hu Xiu-Jing , Wang Jia Ji , Mohammed Bedru H. , Xie Yao Jie , Hernandez Jose , Wu Hua-Feng , Wang Harry H. X. 
Published: April 2023

AimsTo assess longitudinal changes in blood pressure (BP) and fasting plasma glucose (FPG) in primary care patients with concomitant hypertension and type 2 diabetes mellitus (T2DM), and to explore factors associated with patients' inability to improve BP and FPG at follow-up.MethodsWe constructed a closed cohort in the context of the national basic public health (BPH) service provision in an urbanised township in southern China. Primary care patients who had concomitant hypertension and T2DM were retrospectively followed up from 2016 to 2019. Data were retrieved electronically from the computerised BPH platform. Patient-level risk factors were explored using multivariable logistic regression analysis.ResultsWe included 5,398 patients (mean age 66 years; range 28.9 to 96.1 years). At baseline, almost half [48.3% (2,608/5,398)] of patients had uncontrolled BP or FPG. During follow-up, more than one-fourth [27.2% (1,467/5,398)] of patients had no improvement in both BP and FPG. Among all patients, we observed significant increases in systolic BP [2.31 mmHg, 95% confidence interval (CI): 2.04 to 2.59, p &lt; 0.001], diastolic BP (0.73 mmHg, 0.54 to 0.92, p &lt; 0.001), and FPG (0.12 mmol/l, 0.09 to 0.15, p &lt; 0.001) at follow-up compared to baseline. In addition to changes in body mass index [adjusted odds ratio (aOR)=1.045, 1.003 to 1.089, p = 0.037], poor adherence to lifestyle advice (aOR = 1.548, 1.356 to 1.766, p &lt; 0.001), and unwillingness to actively enrol in health-care plans managed by the family doctor team (aOR = 1.379, 1.128 to 1.685, p = 0.001) were factors associated with no improvement in BP and FPG at follow-up.ConclusionA suboptimal control of BP and FPG remains an ongoing challenge to primary care patients with concomitant hypertension and T2DM in real-world community settings. Tailored actions aiming to improve patients' adherence to healthy lifestyles, expand the delivery of team-based care, and encourage weight control should be incorporated into routine healthcare planning for community-based cardiovascular prevention.
3D morphological variability in foraminifera unravel environmental changes in the Baltic Sea entrance over the last 200 years
Authors: Choquel Constance , Müter Dirk , Ni Sha , Pirzamanbein Behnaz , Charrieau Laurie M. , Hirose Kotaro , Seto Yusuke , Schmiedl Gerhard , Filipsson Helena L. 
Published: April 2023

Human activities in coastal areas have intensified over the last 200 years, impacting also high-latitude regions such as the Baltic Sea. Benthic foraminifera, protists often with calcite shells (tests), are typically well preserved in marine sediments and known to record past bottom-water conditions. Morphological analyses of marine shells acquired by microcomputed tomography (µCT) have made significant progress toward a better understanding of recent environmental changes. However, limited access to data processing and a lack of guidelines persist when using open-source software adaptable to different microfossil shapes. This study provides a post-data routine to analyze the entire test parameters: average thickness, calcite volume, calcite surface area, number of pores, pore density, and calcite surface area/volume ratio. A case study was used to illustrate this method: 3D time series (i.e., 4D) of Elphidium clavatum specimens recording environmental conditions in the Baltic Sea entrance from the period early industrial (the 1800s) to present-day (the 2010 s). Long-term morphological trends in the foraminiferal record revealed that modern specimens have ∼28% thinner tests and ∼91% more pores than their historic counterparts. However, morphological variability between specimens and the BFAR (specimens cm−2 yr−1) in E. clavatum were not always synchronous. While the BFAR remained unchanged, morphological variability was linked to natural environmental fluctuations in the early industrial period and the consequences of anthropogenic climate change in the 21st century. During the period 1940–2000 s, the variations in BFAR were synchronous with morphological variability, revealing both the effects of the increase in human activities and major hydrographic changes. Finally, our interpretations, based on E. clavatum morphological variations, highlight environmental changes in the Baltic Sea area, supporting those documented by the foraminiferal assemblages.
Relationship between stress hyperglycemia ratio and allcause mortality in critically ill patients: Results from the MIMIC-IV database
Authors: Zhang Chong , Shen He-Chen , Liang Wei-Ru , Ning Meng , Wang Zi-Xuan , Chen Yi , Su Wei , Guo Ting-Ting , Hu Kun , Liu Ying-Wu 
Published: April 2023

BackgroundStress hyperglycemia ratio (SHR) was developed to reduce the impact of long-term chronic glycemic factors on stress hyperglycemia levels, which have been linked to clinical adverse events. However, the relationship between SHR and the short- and long-term prognoses of intensive care unit (ICU) patients remains unclear.MethodsWe retrospectively analyzed 3,887 ICU patients (cohort 1) whose initial fasting blood glucose and hemoglobin A1c data within 24 hours of admission were available and 3,636 ICU patients (cohort 2) who were followed-up for 1-year using the Medical Information Mart for Intensive Care IV v2.0 database. Patients were divided into two groups based on the optimal cutoff value of SHR, which was determined using the receiver operating characteristic (ROC) curve.ResultsThere were 176 ICU deaths in cohort 1 and 378 patients experienced all-cause mortality during 1 year of follow-up in cohort 2. The results of logistic regression revealed that SHR was associated with ICU death (odds ratio 2.92 [95% confidence interval 2.14–3.97] P &lt; 0.001), and non-diabetic patients rather than diabetic patients showed an increased risk of ICU death. As per the Cox proportional hazards model, the high SHR group experienced a higher incidence of 1-year all-cause mortality (hazard ratio 1.55 [95% confidence interval 1.26–1.90] P &lt; 0.001). Moreover, SHR had an incremental effect on various illness scores in predicting ICU all-cause mortality.ConclusionSHR is linked to ICU death and 1-year all-cause mortality in critically ill patients, and it has an incremental predictive value in different illness scores. Moreover, we found that non-diabetic patients, rather than diabetic patients, showed an increased risk of all-cause mortality.
Association between systemic iron status and β-cell function and insulin sensitivity in patients with newly diagnosed type 2 diabetes
Authors: Qin Yao , Huang Yiting , Li Yuxiao , Qin Lu , Wei Qianying , Chen Xin , Yang Chuanhui , Zhang Mei 
Published: April 2023

ObjectiveAbnormal iron metabolism is related to the risk of diabetes, but the underlying mechanism of this association remains uncertain. This study was conducted to evaluate the contributions of systemic iron status to β-cell function and insulin sensitivity of patients with newly diagnosed T2DM.MethodsA total of 162 patients with newly diagnosed T2DM and 162 healthy controls were enrolled in the study. Basic characteristics, biochemical indicators, and iron metabolism biomarkers, including serum iron (SI), ferritin (SF), transferrin (Trf), and transferrin saturation (TS), were collected. All patients underwent a 75 g oral glucose tolerance test. A series of parameters for assessing β-cell function and insulin sensitivity were calculated. The multivariate stepwise linear regression model was used to investigate the contributions of iron metabolism to β-cell function and insulin sensitivity.ResultsCompared with healthy controls, patients with newly diagnosed T2DM had significantly higher levels of SF. Among the diabetic patients, the SI and TS levels were higher, and the percentage of Trf levels below normal values was lower in men than in women. In all diabetic patients, SF was the independent risk factor associated with impaired β-cell function. Further stratification analysis showed that Trf was an independent protective factor for β-cell function in male patients, while SF was an independent risk factor for impaired β-cell function in female patients. However, systemic iron status did not affect insulin sensitivity.ConclusionElevated SF levels and decreased Trf levels had a profound effect on impaired β-cell function in Chinese patients with newly diagnosed T2DM.
Performance of crossbred pigs with indigenous and Hampshire inheritance under a smallholder production system in the Eastern Himalayan hill region
Authors: Kadirvel Govindasamy , Devi Yumkhaibam Sovarani , Naskar Syamal , Bujarbaruah K. M. , Khargariah Gutum , Banik Santanu , Singh Ningthoujam Suraj , Gonmei Chamniugongliu 
Published: April 2023

Pig productivity is very low in the Eastern Himalayan hill region due to the poor performance of local pigs. To improve pig productivity, it was decided to develop a crossbred pig of Niang Megha indigenous and Hampshire as an exotic germplasm. The performance of crossbred pigs with different levels of Hampshire and indigenous inheritance—H-50 × NM-50 (HN-50), H-75 × NM-25 (HN-75), and H-87.5 × NM-12.5 (HN-87.5)—was compared for their performance to find a suitable level of genetic inheritance. Among the crossbreds, HN-75 performed better in terms of production, reproduction performance, and adaptability. Inter se mating and selection were carried out on six generations of HN-75 pigs, and genetic gain and trait stability were evaluated and released as a crossbred. These crossbred pigs attained body weights of 77.5–90.7 kg by 10 months of age, with FCR of 4.3:1. Age at puberty was 276.66 ± 2.25 days, and average birth weight was 0.92 ± 0.06 kg. Litter size at birth and weaning were 9.12 ± 0.55 and 8.52 ± 0.81. These pigs have good mothering abilities with a weaning percentage of 89.32 ± 2.52%, good carcass quality, and consumer preference. The lifetime productivity for an average of six farrowings/sow showed a total litter size at birth of 51.83 ± 1.61 and total litter size at weaning of 47.17 ± 2.69. In a smallholder production system, the crossbred pigs showed a better growth rate and a higher litter size at birth and at weaning than average local pigs. Hence, the popularization of this crossbreed would enhance the production, productivity, livelihood, and income of the regionʼs farmers.
Parameters for the depth of the ocean’s productive layer
Authors: Marra John F. , Chamberlin W. Sean , Knudson Carol A. , Rhea W. Joseph , Ho Cheng 
Published: April 2023

Here we compare various parameters that are used to define the depth of the ocean’s productive layer, the euphotic zone, during the initiation of the spring phytoplankton bloom in the North Atlantic (47°N/20°W). These are (1) the compensation depth (Zc, where gross photosynthesis balances autotrophic respiration), (2) the depth horizon of 1% of surface photosynthetic active irradiance (Ed(0-,PAR), (3) depth horizon of 1% of surface Ed(488), and (4) the depth of the bottom of the fluorescence maximum. We also use two related parameters, the depth of the mixed layer and the ratio of integral gross production to integral respiration as a scaling factor for a proxy for the critical depth. Over the course of the observational period (25 April - 7 May, 1989), the mixed layer decreased from 162 to 20 m, and Zc decreased from 64 to 35 m. The depth of 1%Ed(0-,PAR) followed the trajectory of Zc, while Ed(488) and the depth of the bottom of the fluorescence maximum were about 10 m deeper, on average. These data support the criterion of the depth of “1%PAR” to describe the productive layer for more productive areas of the ocean. However, 1% of Ed(488) or the bottom of the fluorescence maximum could be used over a broader range of trophic conditions.