bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic models for fever of unknown origin based on 18F-FDG PET/CT: a prospective study in China
Authors: Chen Jia , Xing MingYou , Xu Dong , Xie NaNa , Zhang WenCong , Ruan QiuRong , Song JianXin 
Published: October 2022

Abstract
Background
This study aims to analyze the 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) characteristics of different causes of fever of unknown origin (FUO) and identify independent predictors to develop a suitable diagnostic model for distinguishing between these causes. A total of 524 patients with classical FUO who underwent standard diagnostic procedures and PET/CT were prospectively studied. The diagnostic performance of PET/CT imaging was analyzed, and relevant clinical parameters that could improve diagnostic efficacy were identified. The model was established using the data of 369 patients and the other 155 patients comprised the validation cohort for verifying the diagnostic performance of the model.

Results
The metabolic characteristics of the “hottest” lesion, the spleen, bone marrow, and lymph nodes varied for various causes. PET/CT combined with clinical parameters achieved better discrimination in the differential diagnosis of FUO. The etiological diagnostic models included the following factors: multisite metabolic characteristics, blood cell counts, inflammatory indicators (erythrocyte sedimentation rate, C-reactive protein, serum ferritin, and lactate dehydrogenase), immunological indicators (interferon gamma release assay, antinuclear antibody, and anti-neutrophil cytoplasm antibody), specific signs (weight loss, rash, and splenomegaly), and age. In the testing cohort, the AUCs of the infection prediction model, the malignancy diagnostic model, and the noninfectious inflammatory disease prediction model were 0.89 (95% CI 0.86–0.92), 0.94 (95% CI 0.92–0.97), and 0.95 (95% CI 0.93–0.97), respectively. The corresponding AUCs for the validation cohort were 0.88 (95% CI 0.82–0.93), 0.93 (95% CI 0.89–0.98), and 0.95 (95% CI 0.92–0.99), respectively.

Conclusions
18F-FDG PET/CT has a certain level of sensitivity and accuracy in diagnosing FUO, which can be further improved by combining it with clinical parameters. Diagnostic models based on PET/CT show excellent performance and can be used as reliable tools to discriminate the cause of FUO.
Trial registration This study (a two-step method apparently improved the physicians’ level of diagnosis decision-making for adult patients with FUO) was registered on the website http://www.clinical-trials.gov on January 14, 2014, with registration number NCT02035670.
Radioimmunotherapy study of 131I-labeled Atezolizumab in preclinical models of colorectal cancer
Authors: Zhang Linhan , Zhao Sheng , Jiang Huijie , Zhang Rongjun , Zhang Mingyu , Pan Wenbin , Sun Zhongqi , Wang Dandan , Li Jinping 
Published: October 2022

Abstract
Background
Programmed cell death 1 ligand 1(PD-L1) is overexpressed in many tumors. The radionuclide-labeled anti-PD-L1 monoclonal antibody can be used for imaging and therapy of PD-L1 overexpressing cancer. Here, we described 131I-labeled Atezolizumab (131I-Atezolizumab, targeting PD-L1) as a therapeutic agent for colorectal cancer with PD-L1 overexpression.

Methods
131I-Atezolizumab was prepared by the Iodogen method. The expression levels of PD-L1 in different human colorectal cells were determined by flow cytometry, western blot and cell binding assay. The immunoreactivity of 131I-Atezolizumab to PD-L1 high-expressing cells was determined by immunoreactive fraction. The killing abilities of different concentrations of 131I-Atezolizumab on cells with high and low expression of PD-L1 were detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Cerenkov luminescence imaging (CLI) and radioimmunotherapy (RIT) of 131I-Atezolizumab were performed on two human colorectal cancer models. The distribution and tumor targeting of 131I-Atezolizumab were evaluated by imaging. Tumor volume and survival time were used as indicators to evaluate the anti-tumor effect of 131I-Atezolizumab.

Results
The expression level of PD-L1 in vitro determined by the cell binding assay was related to the data of flow cytometry and western blot. 131I-Atezolizumab can specifically bind to PD-L1 high-expressing cells in vitro to reflect the expression level of PD-L1. Immunoreactive fraction of PD-L1 high-expressing RKO cells with 131I-Atezolizumab was 52.2%. The killing ability of 131I-Atezolizumab on PD-L1 high-expressing cells was higher than that of low-expressing cells. CLI proved that the specific uptake level of tumors depends on the expression level of PD-L1. Effect of 131I-Atezolizumab RIT showed an activity-dependent tumor suppressor effect on RKO tumor-bearing mice with high PD-L1 expression. 131I-Atezolizumab (37 MBq) can improve the median survival time of mice (34 days), compared to untreated mice (27 days) (P = 0.027). Although a single activity(37 MBq) of 131I-Atezolizumab also inhibited the tumors of HCT8 tumor-bearing mice with low PD-L1 expression (P < 0.05), it could not prolong the survival of mice(P = 0.29).

Conclusion
131I-Atezolizumab can be used as a CLI agent for screening PD-L1 expression levels. It may be used as a radioimmunotherapy drug target for PD- L1 overexpressing tumors.
Etoposide treatment in secondary hemophagocytic syndrome: impact on healthcare-associated infections and survival
Authors: Dupont Thibault , Darmon Michael , Mariotte Eric , Lemiale Virginie , Fadlallah Jehane , Mirouse Adrien , Zafrani Lara , Azoulay Elie , Valade Sandrine 
Published: October 2022

Abstract
Background
Etoposide remains the cornerstone of symptomatic management of critically ill patients with secondary hemophagocytic syndrome (sHS). Risk of healthcare-associated infections (HAIs) in this setting with etoposide has never been assessed. We sought to evaluate the association between etoposide administration, HAIs occurrence and survival in critically ill adult patients with sHS. In this retrospective single-center study conducted in a university hospital ICU between January 2007 and March 2020, all consecutive patients with sHS were included. HAIs were defined as any microbiologically documented infection throughout ICU stay. Competing risk survival analysis was performed to determine factors associated with HAIs. Propensity score-based overlap weighting was performed to adjust for factors associated with etoposide use.

Results
168 patients with a median age of 49 [38, 59] were included. Forty-three (25.6%) patients presented with at least 1 microbiologically documented HAI throughout ICU stay. After adjustment, cumulative incidence of HAI was higher in patients receiving etoposide (p = 0.007), while survival was unaffected by etoposide status (p = 0.824). By multivariable analysis, etoposide treatment was associated with a higher incidence of HAIs (sHR 3.75 [1.05, 6.67]), whereas no association with survival (sHR 0.53 [0.20, 1.98]) was found. Other factors associated with increased mortality after adjustment included age, immunodepression, male sex, SOFA score > 13, and occurrence of HAI.

Conclusions
In patients with sHS, etoposide treatment is independently associated with increased occurrence of HAIs, whereas no association with survival was found. Intensivists should be aware of increased infectious risk, to promptly detect and treat infections in this specific setting. Studies to assess benefits from prophylactic anti-infectious agents in this setting are warranted and the lack of benefit of etoposide on survival needs to be interpreted cautiously.
Distributed reinforcement learning-based memory allocation for edge-PLCs in industrial IoT
Authors: Fu Tingting , Peng Yanjun , Liu Peng , Lao Haksrun , Wan Shaohua 
Published: October 2022

AbstractThe exponential device growth in industrial Internet of things (IIoT) has a noticeable impact on the volume of data generated. Edge-cloud computing cooperation has been introduced to the IIoT to lessen the computational load on cloud servers and shorten the processing time for data. General programmable logic controllers (PLCs), which have been playing important roles in industrial control systems, start to gain the ability to process a large amount of industrial data and share the workload of cloud servers. This transforms them into edge-PLCs. However, the continuous influx of multiple types of concurrent production data streams against the limited capacity of built-in memory in PLCs brings a huge challenge. Therefore, the ability to reasonably allocate memory resources in edge-PLCs to ensure data utilization and real-time processing has become one of the core means of improving the efficiency of industrial processes. In this paper, to tackle dynamic changes in arrival data rate over time at each edge-PLC, we propose to optimize memory allocation with Q-learning distributedly. The simulation experiments verify that the method can effectively reduce the data loss probability while improving the system performance.
LPCAT1 acts as an independent prognostic biomarker correlated with immune infiltration in hepatocellular carcinoma
Authors: Li Lan , Wang Xiao , Ding Yanni , Hui Nini , Su Bingjie , Yang Min 
Published: October 2022

Abstract
Background
Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is overexpressed in multiple human tumors. However, the role of LPCAT1 in hepatocellular carcinoma (HCC) has not been understood. We aim to explore the relationships between LPCAT1 expression and prognosis, clinicopathological features, tumor microenvironment (TME), immune cell infiltration, immune checkpoint gene expression, and related signaling pathways in HCC. Furthermore, we also explored the relationship between LPCAT1 expression and drug sensitivity to HCC treatment.

Methods
The expression profiles were acquired from the Cancer Genome Atlas (TCGA) and the Human Protein Atlas (THPA). Immune status and infiltration in cancer tissues were explored using the single sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithm.

Results
LPCAT1 was overexpressed in HCC, and its expression was related to poor prognosis, LPCAT1 was an independent prognostic biomarker in HCC. Expression of LPCAT1 increased statistically with the increase of clinical stage and grade of HCC patients. GO and KEGG network analysis revealed that LPCAT1 positively associated molecules were mostly enriched in functions related to cell adhesion. The TME score of high-LPCAT1 group was significantly higher than that of low-LPCAT1 group. Immune infiltrating cells positively correlated with LPCAT1 expression were Macrophages M0, B cells memory, Dendritic cells activated, T cells regulatory and T cells gamma delta in HCC. We found a positive correlation between LPCAT1 and most immune checkpoint gene expression. The IC50 of 5-Fluorouracil, Gemcitabine, Mitomycin C, Sorafenib and Cabozantinib in patients with high-LPCAT1 expression was lower than that in patients with low-LPCAT1 expression. Our findings provide a wealth of information for further understanding of the biological functions and signaling pathways of LPCAT1 in HCC.

Conclusions
LPCAT1 is an independent prognostic biomarker and associated with tumor microenvironment, immune cell infiltration, immune checkpoint expression and drug sensitivity in hepatocellular carcinoma.
Neuroprotective effects of donepezil against Aβ25-35-induced neurotoxicity
Authors: Gao Bu-Lang , Che Ning-Ning , Li Xue , Ren Chun-Feng 
Published: October 2022

Abstract
Purpose
The purpose of this study was to investigate the neuroprotective effect of donepezil against β-amyloid25-35 (Aβ25-35)-induced neurotoxicity and the possible mechanism.

Methods
PC12 cells were conventionally cultured. Serial concentrations of Aβ25-35 and donepezil (0, 0.5, 1, 5, 10, 20 and 50 μmol/L) were added to the PC12 cells, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) staining was performed to detect the effects of these treatments on PC 12 viability. The PC 12 cells were pretreated with 1, 5, 10, 20 or 50 μmol/L donepezil two hours before 20 μmol/L Aβ25-35 was added to pretreatment groups A, B, C, D and E. Normal control group I and the 20 μmol/L Aβ25-35-treated group were selected. An MTT assay was used to detect PC12 cell viability, and the level of lactate dehydrogenase (LDH) was determined. PC12 cells were pretreated with 10 μmol/L GF109203X (a protein kinase C [PKC] antagonist) 30 min before 10 μmol/L donepezil was added to pretreatment group F, and normal control group II, the 10 μmol/L GF109203X-treated group and the 10 μmol/L donepezil-treated group were chosen. The expression of phosphorylation-PKC (P-PKC) and its major substrate phosphorylated myristoylated alanine-rich protein C kinase substrate (P-MARCKS) was measured by Western blotting. The effects of donepezil on the subcellular distribution of the PKCα and PKCε isoforms were detected by immunofluorescence staining.

Results
Treatment with Aβ25-35 (5, 10, 20 or 50 μmol/L) for 24 h significantly (P < 0.05) decreased PC 12 cell viability in a dose-dependent manner. Compared with the PC12 cells in the control group, those in the 20 μmol/L Aβ25-35-treated group exhibited lower viability but higher LDH release. Compared with the 20 μmol/L Aβ25–35-treated group, pretreatment groups B, C, D and E exhibited significantly (P < 0.05) increased cell viability but significantly (P < 0.05) decreased LDH release. Western blotting demonstrated that compared with control, 10 μmol/L donepezil promoted PKC and MARCKS phosphorylation and that the expression of P-PKC and P-MARCKS in pretreatment group F was significantly (P < 0.05) lower than that in the donepezil-treated group. Immunofluorescence staining revealed that the PKCα and PKCε isoforms were located mainly in the cytoplasm of PC12 control cells, whereas donepezil increased the expression of the PKCα and PKCε isoforms in the membrane fraction. The Western blot results showed that donepezil altered the subcellular distribution of the PKCα and PKCε isoforms by decreasing their expression in the cytosolic fraction but increasing their expression in the membrane fraction.

Conclusion
Donepezil can antagonize Aβ25–350-induced neurotoxicity in PC 12 cells, and PKC activation may account for the neuroprotective effect of donepezil.
The Pseudo-Direct Numerical Simulation Method considered as a Reduced Order Model
Authors: Idelsohn Sergio R. , Gimenez Juan M. , Nigro Norberto M. 
Published: October 2022

AbstractThe multiscale method called Pseudo-Direct Numerical Simulation (P-DNS) is presented as a Reduced Order Model (ROM) aiming to solve problems obtaining similar accuracy to a solution with many degrees of freedom (DOF). The theoretical basis of P-DNS is other than any standard ROM. However, from a methodological point of view, P-DNS shares the idea of an offline computation, as ROM does, providing the set of coefficients, as a database or table, needed to solve the main problem. This work highlights the advantages and disadvantages of both methodologies. In particular, the drawback of the standard ROM concerning problems where space and time are not separated variables is discussed. The so-called Idelsohn’s benchmark is possibly the most elemental test that can be proposed to point out this drawback. This one-dimensional heat transfer problem with a moving heat source shows that, unlike ROMs, P-DNS can solve it by reducing the number of degrees of freedom as much as needed.
Dual-probe fluorescence spectroscopy for sensitive quantitation of Alzheimer’s amyloid pathology
Authors: Stepanchuk Anastasiia A. , Morgan Megan L. , Joseph Jeffrey T. , Stys Peter K. 
Published: October 2022

AbstractProtein misfolding is a prominent pathological hallmark of neurodegenerative disorders, including Alzheimer’s disease (AD). Studies have shown that the diversity of β sheet-rich protein deposits (such as amyloid β plaques and neurofibrillary tangles), present across different brain regions, might underlie different disease phenotypes and only certain types of aggregates might be associated with cognitive decline. Conformationally sensitive fluorescent amyloid probes have the ability to report different structures of protein aggregates by virtue of their shifting emission spectra. Here we defined the binding affinity of the fluorescent amyloid probes BSB and MCAAD to disease-relevant protein aggregates, and combined the two probes to examine formalin-fixed paraffin-embedded mouse and human brain samples. Coupled with quantitative spectral phasor analysis, the dual-probe staining approach revealed remarkable heterogeneity of protein aggregates across the samples. Distinct emission spectra were consistent with certain types of deposits present in the mouse and human brain sections. The sensitivity of this staining, imaging and analysis approach outperformed conventional immunohistochemistry with the detected spectral differences between the greater parenchyma of cognitively normal and AD cases indicating a subtle yet widespread proteopathy associated with disease. Our method offers more sensitive, objective, and quantitative examination of protein misfolding pathology using conventional tissue sections.
Effect of biodegradable poly-3-hydroxybutyrate amendment on the soil biochemical properties and fertility under varying sand loads
Authors: Brtnicky M. , Pecina V. , Holatko J. , Hammerschmiedt T. , Mustafa A. , Kintl A. , Fojt J. , Baltazar T. , Kucerik J. 
Published: October 2022

AbstractBackgroundPoly-3-hydroxybutyrate (P3HB) is a bacterial intracellular carbon and energy storage polymer, used as a thermoplastic polyester in a wide array of industrial and agricultural applications. However, how the soil microbiome and fertility are altered by exogenously applied P3HB has been relatively unexplored. This study aimed to assess the effects of P3HB addition to nutrient restricted soil: its biological properties and lettuce (Lactuca sativaL. var.capitataL.) biomass production. The experiment was designed to evaluate impacts of spatial arrangement of the relatively organic-rich (soil organic matter, P3HB particles) versus poor fractions of the matrix with confounding factors such as variable microbial biomass, inherent nutrient/energy status, different water relations (due to variable hydrophysical properties of soil augmented by sand at different ratios).ResultsThe results revealed that P3HB in soils induced inconsistent to contradictory changes in the microbial abundance as well as in most enzymatic activities. The differences were conditioned by the sand content both under P3HB presence or absence. On the other hand, dehydrogenase, urease activities, basal and substrate-induced soil respirations were mostly enhanced by P3HB addition, directly with increasing sand content (several respiration types). Nevertheless, P3HB significantly inhibited lettuce biomass production.ConclusionsP3HB introduction to soil boosts the microbial activity owing to the preferential utilization of P3HB as C source, which depletes soil N and strongly inhibits the plant growth. Enhanced microbial activity in P3HB-amended soils with high sand content (60–80%) suggested that in nutrient-impoverished soil P3HB can temporarily replace SOM as a C source for microbial communities due to the shift of their structure to preferentially P3HB-degrading microbiome.Graphical Abstract
Terminalia chebula: a novel natural product colorimetric sensor for Fe2+ and Fe3+ ions
Authors: Sen Subhadeep , Singh Tejinder , Im Jungkyun , Debnath Dilip , Biswas Goutam 
Published: October 2022

AbstractNatural product like Terminalia chebula as Fe2+ and Fe3+ ions sensor was not reported in the literature till now. Herein, we first reported Terminalia chebula (T. chebula), a natural product used in Ayurveda, as a highly sensitive, simple, and cost-effective colorimetric sensor for the detection of Fe2+ and Fe3+ ions. Terminalia chebula showed a selective colorimetric sensing ability for iron (2+/3+) by changing color from green and pale yellow to blue, having limit of detection level of 43.7 μM and 60.8 μM for Fe2+ and Fe3+ ions, respectively. The concentration-dependent colorimetric determination of iron (2+/3+) was carried out, and the color change to distinguish between different concentrations was excellent. Using High Performance Liquid Chromatography, the fraction having sensing ability was isolated and purified. From the mass spectra of the purified fraction, it was concluded that, the major component responsible for the sensing ability was tri-O-galloyl-β-D-glucose. This chemosensor could be used to detect and quantify Fe2+ and Fe3+ in water samples, which is particularly a useful tool.
Robot-assisted total knee arthroplasty improves mechanical alignment and accuracy of component positioning compared to the conventional technique
Authors: Nam Chang Hyun , Lee Su Chan , Kim Jin-Hong , Ahn Hye Sun , Baek Ji-Hoon 
Published: October 2022

Abstract
Purpose
The purpose of this study was to compare the mechanical axis, accuracy of component positioning, and polyethylene liner thickness between robot-assisted total knee arthroplasty (TKA) and conventional TKA.

Methods
From July 2020 to December 2020, 154 TKAs were performed in 110 patients with Kellgren-Lawrence grade IV varus knees using a robot-assisted system (MAKO group). Additionally, 110 propensity score-matched patients who had undergone primary conventional TKA were chosen in a one-to-one ratio for the conventional group. Post-operative radiographs were used to evaluate mechanical axis and component coronal and sagittal positioning. The polyethylene liner thickness was investigated. The respective mean error values and outliers were obtained for the two study groups and were compared to determine the mechanical axis and the accuracy of the postoperative component positioning.

Results
Patients in the MAKO group achieved better accuracy than those in the conventional group in terms of postoperative mean mechanical axis (1.9˚ vs. 2.8˚, p < 0.05), femur coronal inclination (91.2˚ vs. 91.8˚, p < 0.05), tibia coronal inclination (90.8˚ vs. 91.1˚, p < 0.05), and tibia sagittal inclination (90.7˚ vs. 91.7˚, p < 0.05). However, there was no difference between the two groups in polyethylene liner thickness.

Conclusions
Robot-assisted TKA showed improved mechanical axis and higher accuracy of component positioning compared to the conventional TKA technique, with no significant difference in polyethylene liner thickness between the two groups. Long-term follow-up studies are needed to compare the clinical outcomes of robot-assisted TKA.

Level of evidence
IV.