bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of clinical factors related to prediction of alcohol use disorder from electronic health records using feature selection methods
Authors: Ebrahimi Ali , Wiil Uffe Kock , Naemi Amin , Mansourvar Marjan , Andersen Kjeld , Nielsen Anette Søgaard 
Published: November 2022

Abstract
Background
High dimensionality in electronic health records (EHR) causes a significant computational problem for any systematic search for predictive, diagnostic, or prognostic patterns. Feature selection (FS) methods have been indicated to be effective in feature reduction as well as in identifying risk factors related to prediction of clinical disorders. This paper examines the prediction of patients with alcohol use disorder (AUD) using machine learning (ML) and attempts to identify risk factors related to the diagnosis of AUD.

Methods
A FS framework consisting of two operational levels, base selectors and ensemble selectors. The first level consists of five FS methods: three filter methods, one wrapper method, and one embedded method. Base selector outputs are aggregated to develop four ensemble FS methods. The outputs of FS method were then fed into three ML algorithms: support vector machine (SVM), K-nearest neighbor (KNN), and random forest (RF) to compare and identify the best feature subset for the prediction of AUD from EHRs.

Results
In terms of feature reduction, the embedded FS method could significantly reduce the number of features from 361 to 131. In terms of classification performance, RF based on 272 features selected by our proposed ensemble method (Union FS) with the highest accuracy in predicting patients with AUD, 96%, outperformed all other models in terms of AUROC, AUPRC, Precision, Recall, and F1-Score. Considering the limitations of embedded and wrapper methods, the best overall performance was achieved by our proposed Union Filter FS, which reduced the number of features to 223 and improved Precision, Recall, and F1-Score in RF from 0.77, 0.65, and 0.71 to 0.87, 0.81, and 0.84, respectively. Our findings indicate that, besides gender, age, and length of stay at the hospital, diagnosis related to digestive organs, bones, muscles and connective tissue, and the nervous systems are important clinical factors related to the prediction of patients with AUD.

Conclusion
Our proposed FS method could improve the classification performance significantly. It could identify clinical factors related to prediction of AUD from EHRs, thereby effectively helping clinical staff to identify and treat AUD patients and improving medical knowledge of the AUD condition. Moreover, the diversity of features among female and male patients as well as gender disparity were investigated using FS methods and ML techniques.
Economic evaluation of COVID-19 rapid antigen screening programs in the workplace
Authors: Vilches Thomas N. , Rafferty Ellen , Wells Chad R. , Galvani Alison P. , Moghadas Seyed M. 
Published: November 2022

AbstractBackgroundDiagnostic testing has been pivotal in detecting SARS-CoV-2 infections and reducing transmission through the isolation of positive cases. We quantified the value of implementing frequent, rapid antigen (RA) testing in the workplace to identify screening programs that are cost-effective.MethodsTo project the number of cases, hospitalizations, and deaths under alternative screening programs, we adapted an agent-based model of COVID-19 transmission and parameterized it with the demographics of Ontario, Canada, incorporating vaccination and waning of immunity. Taking into account healthcare costs and productivity losses associated with each program, we calculated the incremental cost-effectiveness ratio (ICER) with quality-adjusted life year (QALY) as the measure of effect. Considering RT-PCR testing of only severe cases as the baseline scenario, we estimated the incremental net monetary benefits (iNMB) of the screening programs with varying durations and initiation times, as well as different booster coverages of working adults.ResultsAssuming a willingness-to-pay threshold of CDN$30,000 per QALY loss averted, twice weekly workplace screening was cost-effective only if the program started early during a surge. In most scenarios, the iNMB of RA screening without a confirmatory RT-PCR or RA test was comparable or higher than the iNMB for programs with a confirmatory test for RA-positive cases. When the program started early with a duration of at least 16 weeks and no confirmatory testing, the iNMB exceeded CDN$1.1 million per 100,000 population. Increasing booster coverage of working adults improved the iNMB of RA screening.ConclusionsOur findings indicate that frequent RA testing starting very early in a surge, without a confirmatory test, is a preferred screening program for the detection of asymptomatic infections in workplaces.
Prognostic models for COVID-19 needed updating to warrant transportability over time and space
Authors: van Klaveren David , Zanos Theodoros P. , Nelson Jason , Levy Todd J. , Park Jinny G. , Retel Helmrich Isabel R. A. , Rietjens Judith A. C. , Basile Melissa J. , Hajizadeh Negin , Lingsma Hester F. , Kent David M. 
Published: November 2022

Abstract
Background
Supporting decisions for patients who present to the emergency department (ED) with COVID-19 requires accurate prognostication. We aimed to evaluate prognostic models for predicting outcomes in hospitalized patients with COVID-19, in different locations and across time.

Methods
We included patients who presented to the ED with suspected COVID-19 and were admitted to 12 hospitals in the New York City (NYC) area and 4 large Dutch hospitals. We used second-wave patients who presented between September and December 2020 (2137 and 3252 in NYC and the Netherlands, respectively) to evaluate models that were developed on first-wave patients who presented between March and August 2020 (12,163 and 5831). We evaluated two prognostic models for in-hospital death: The Northwell COVID-19 Survival (NOCOS) model was developed on NYC data and the COVID Outcome Prediction in the Emergency Department (COPE) model was developed on Dutch data. These models were validated on subsequent second-wave data at the same site (temporal validation) and at the other site (geographic validation). We assessed model performance by the Area Under the receiver operating characteristic Curve (AUC), by the E-statistic, and by net benefit.

Results
Twenty-eight-day mortality was considerably higher in the NYC first-wave data (21.0%), compared to the second-wave (10.1%) and the Dutch data (first wave 10.8%; second wave 10.0%). COPE discriminated well at temporal validation (AUC 0.82), with excellent calibration (E-statistic 0.8%). At geographic validation, discrimination was satisfactory (AUC 0.78), but with moderate over-prediction of mortality risk, particularly in higher-risk patients (E-statistic 2.9%). While discrimination was adequate when NOCOS was tested on second-wave NYC data (AUC 0.77), NOCOS systematically overestimated the mortality risk (E-statistic 5.1%). Discrimination in the Dutch data was good (AUC 0.81), but with over-prediction of risk, particularly in lower-risk patients (E-statistic 4.0%). Recalibration of COPE and NOCOS led to limited net benefit improvement in Dutch data, but to substantial net benefit improvement in NYC data.

Conclusions
NOCOS performed moderately worse than COPE, probably reflecting unique aspects of the early pandemic in NYC. Frequent updating of prognostic models is likely to be required for transportability over time and space during a dynamic pandemic.
Identifying susceptibility of children and adolescents to the Omicron variant (B.1.1.529)
Authors: Chun June Young , Jeong Hwichang , Kim Yongdai 
Published: November 2022

Abstract
Background
The Omicron variant (B.1.1.529) is estimated to be more transmissible than previous strains of SARS-CoV-2 especially among children, potentially resulting in croup which is a characteristic disease in children. Current coronavirus disease 2019 (COVID-19) cases among children might be higher because (i) school-aged children have higher contact rates and (ii) the COVID-19 vaccination strategy prioritizes the elderly in most countries. However, there have been no reports confirming the age-varying susceptibility to the Omicron variant to date.

Methods
We developed an age-structured compartmental model, combining age-specific contact matrix in South Korea and observed distribution of periods between each stage of infection in the national epidemiological investigation. A Bayesian inference method was used to estimate the age-specific force of infection and, accordingly, age-specific susceptibility, given epidemic data during the third (pre-Delta), fourth (Delta driven), and fifth (Omicron driven) waves in South Korea. As vaccine uptake increased, individuals who were vaccinated were excluded from the susceptible population in accordance with vaccine effectiveness against the Delta and Omicron variants, respectively.

Results
A significant difference between the age-specific susceptibility to the Omicron and that to the pre-Omicron variants was found in the younger age group. The rise in susceptibility to the Omicron/pre-Delta variant was highest in the 10–15 years age group (5.28 times [95% CI, 4.94–5.60]), and the rise in susceptibility to the Omicron/Delta variant was highest in the 15–19 years age group (3.21 times [95% CI, 3.12–3.31]), whereas in those aged 50 years or more, the susceptibility to the Omicron/pre-Omicron remained stable at approximately twofold.

Conclusions
Even after adjusting for contact pattern, vaccination status, and waning of vaccine effectiveness, the Omicron variant of SARS-CoV-2 tends to propagate more easily among children than the pre-Omicron strains.
Optimization of l-malic acid production from acetate with Aspergillus oryzae DSM 1863 using a pH-coupled feeding strategy
Authors: Kövilein Aline , Aschmann Vera , Zadravec Lena , Ochsenreither Katrin 
Published: November 2022

Abstract
Background
Malic acid, a dicarboxylic acid mainly used in the food industry, is currently produced from fossil resources. The utilization of low-cost substrates derived from biomass could render microbial processes economic. Such feedstocks, like lignocellulosic hydrolysates or condensates of fast pyrolysis, can contain high concentrations of acetic acid. Acetate is a suitable substrate for l-malic acid production with the filamentous fungus Aspergillus oryzae DSM 1863, but concentrations obtained so far are low. An advantage of this carbon source is that it can be used for pH control and simultaneous substrate supply in the form of acetic acid. In this study, we therefore aimed to enhance l-malate production from acetate with A. oryzae by applying a pH-coupled feeding strategy.

Results
In 2.5-L bioreactor fermentations, several feeding strategies were evaluated. Using a pH-coupled feed consisting of 10 M acetic acid, the malic acid concentration was increased about 5.3-fold compared to the batch process without pH control, resulting in a maximum titer of 29.53 ± 1.82 g/L after 264 h. However, it was not possible to keep both the pH and the substrate concentration constant during this fermentation. By using 10 M acetic acid set to a pH of 4.5, or with the repeated addition of NaOH, the substrate concentration could be maintained within a constant range, but these strategies did not prove beneficial as lower maximum titers and yields were obtained. Since cessation of malic acid production was observed in later fermentation stages despite carbon availability, a possible product inhibition was evaluated in shake flask cultivations. In these experiments, malate and succinate, which is a major by-product during malic acid production, were added at concentrations of up to 50 g/L, and it was found that A. oryzae is capable of organic acid production even at high product concentrations.

Conclusions
This study demonstrates that a suitable feeding strategy is necessary for efficient malic acid production from acetate. It illustrates the potential of acetate as carbon source for microbial production of the organic acid and provides useful insights which can serve as basis for further optimization.
A novel co-production of cadaverine and succinic acid based on a thermal switch system in recombinant Escherichia coli
Authors: Gao Siyuan , Lu Jiachen , Wang Tongtao , Xu Sheng , Wang Xin , Chen Kequan , Ouyang Pingkai 
Published: November 2022

Abstract
Background
Polyamide (nylon) is an important material, which has aroused plenty of attention from all aspects. PA 5.4 is one kind of nylon with excellent property, which consists of cadaverine and succinic acid. Due to the environmental pollution, bio-production of cadaverine and succinic acid has been more attractive due to the less pollution and environmental friendliness. Microbes, like Escherichia coli, has been employed as cell factory to produce cadaverine and succinic acid. However, the accumulation of cadaverine will cause severe damage on cells resulting in inhibition on cell growth and cadaverine production. Herein, a novel two stage co-production of succinic acid and cadaverine was designed based on an efficient thermos-regulated switch to avoid the inhibitory brought by cadaverine.

Results
The fermentation process was divided into two phase, one for cell growth and lysine production and the other for cadaverine and succinic acid synthesis. The genes of ldhA and ackA were deleted to construct succinic acid pathway in cadaverine producer strain. Then, a thermal switch system based on pR/pL promoter and CI857 was established and optimized. The fermentation conditions were investigated that the optimal temperature for the first stage was determined as 33 ℃ and the optimal temperature for the second stage was 39 ℃. Additionally, the time to shifting temperature was identified as the fermentation anaphase. For further enhance cadaverine and succinic acid production, a scale-up fermentation in 5 L bioreactor was operated. As a result, the titer, yield and productivity of cadaverine was 55.58 g/L, 0.38 g/g glucose and 1.74 g/(L·h), respectively. 28.39 g/L of succinic acid was also obtained with yield of 0.19 g/g glucose.

Conclusion
The succinic acid metabolic pathway was constructed into cadaverine producer strain to realize the co-production of succinic acid and cadaverine. This study provided a novel craft for industrial co-production of cadaverine and succinic acid.
Modifying oncolytic virotherapy to overcome the barrier of the hypoxic tumor microenvironment. Where do we stand?
Authors: Shayan Sara , Arashkia Arash , Azadmanesh Kayhan 
Published: November 2022

AbstractViruses are completely dependent on host cell machinery for their reproduction. As a result, factors that influence the state of cells, such as signaling pathways and gene expression, could determine the outcome of viral pathogenicity. One of the important factors influencing cells or the outcome of viral infection is the level of oxygen. Recently, oncolytic virotherapy has attracted attention as a promising approach to improving cancer treatment. However, it was shown that tumor cells are mostly less oxygenated compared with their normal counterparts, which might affect the outcome of oncolytic virotherapy. Therefore, knowing how oncolytic viruses could cope with stressful environments, particularly hypoxic environments, might be essential for improving oncolytic virotherapy.
The role of bone marrow on the mechanical properties of trabecular bone: a systematic review
Authors: Wang Fangxing , Metzner Florian , Osterhoff Georg , Zheng Leyu , Schleifenbaum Stefan 
Published: November 2022

Abstract
Background
Accurate evaluation of the mechanical properties of trabecular bone is important, in which the internal bone marrow plays an important role. The aim of this systematic review is to investigate the roles of bone marrow on the mechanical properties of trabecular bone to better support clinical work and laboratory research.

Methods
A systematic review of the literature published up to June 2022 regarding the role of bone marrow on the mechanical properties of trabecular bone was performed, using PubMed and Web of Science databases. The journal language was limited to English. A total of 431 articles were selected from PubMed (n = 186), Web of Science (n = 244) databases, and other sources (n = 1).

Results
After checking, 38 articles were finally included in this study. Among them, 27 articles discussed the subject regarding the hydraulic stiffening of trabecular bone due to the presence of bone marrow. Nine of them investigated the effects of bone marrow on compression tests with different settings, i.e., in vitro experiments under unconfined and confined conditions, and computer model simulations. Relatively few controlled studies reported the influence of bone marrow on the shear properties of trabecular bone.

Conclusion
Bone marrow plays a non-neglectable role in the mechanical properties of trabecular bone, its contribution varies depending on the different loading types and test settings. To obtain the mechanical properties of trabecular bone comprehensively and accurately, the solid matrix (trabeculae) and fluid-like component (bone marrow) should be considered in parallel rather than tested separately.
Ultrasensitive dopamine detection with graphene aptasensor multitransistor arrays
Authors: Abrantes Mafalda , Rodrigues Diana , Domingues Telma , Nemala Siva S. , Monteiro Patricia , Borme Jérôme , Alpuim Pedro , Jacinto Luis 
Published: November 2022

AbstractDetecting physiological levels of neurotransmitters in biological samples can advance our understanding of brain disorders and lead to improved diagnostics and therapeutics. However, neurotransmitter sensors for real-world applications must reliably detect low concentrations of target analytes from small volume working samples. Herein, a platform for robust and ultrasensitive detection of dopamine, an essential neurotransmitter that underlies several brain disorders, based on graphene multitransistor arrays (gMTAs) functionalized with a selective DNA aptamer is presented. High-yield scalable methodologies optimized at the wafer level were employed to integrate multiple graphene transistors on small-size chips (4.5 × 4.5 mm). The multiple sensor array configuration permits independent and simultaneous replicate measurements of the same sample that produce robust average data, reducing sources of measurement variability. This procedure allowed sensitive and reproducible dopamine detection in ultra-low concentrations from small volume samples across physiological buffers and high ionic strength complex biological samples. The obtained limit-of-detection was 1 aM (10–18) with dynamic detection ranges spanning 10 orders of magnitude up to 100 µM (10–8), and a 22 mV/decade peak sensitivity in artificial cerebral spinal fluid. Dopamine detection in dopamine-depleted brain homogenates spiked with dopamine was also possible with a LOD of 1 aM, overcoming sensitivity losses typically observed in ion-sensitive sensors in complex biological samples. Furthermore, we show that our gMTAs platform can detect minimal changes in dopamine concentrations in small working volume samples (2 µL) of cerebral spinal fluid samples obtained from a mouse model of Parkinson’s Disease. The platform presented in this work can lead the way to graphene-based neurotransmitter sensors suitable for real-world academic and pre-clinical pharmaceutical research as well as clinical diagnosis.
The roles of metabolic profiles and intracellular signaling pathways of tumor microenvironment cells in angiogenesis of solid tumors
Authors: Zalpoor Hamidreza , Aziziyan Fatemeh , Liaghat Mahsa , Bakhtiyari Maryam , Akbari Abdullatif , Nabi-Afjadi Mohsen , Forghaniesfidvajani Razieh , Rezaei Nima 
Published: November 2022

AbstractInnate and adaptive immune cells patrol and survey throughout the human body and sometimes reside in the tumor microenvironment (TME) with a variety of cell types and nutrients that may differ from those in which they developed. The metabolic pathways and metabolites of immune cells are rooted in cell physiology, and not only provide nutrients and energy for cell growth and survival but also influencing cell differentiation and effector functions. Nowadays, there is a growing awareness that metabolic processes occurring in cancer cells can affect immune cell function and lead to tumor immune evasion and angiogenesis. In order to safely treat cancer patients and prevent immune checkpoint blockade-induced toxicities and autoimmunity, we suggest using anti-angiogenic drugs solely or combined with Immune checkpoint blockers (ICBs) to boost the safety and effectiveness of cancer therapy. As a consequence, there is significant and escalating attention to discovering techniques that target metabolism as a new method of cancer therapy. In this review, a summary of immune-metabolic processes and their potential role in the stimulation of intracellular signaling in TME cells that lead to tumor angiogenesis, and therapeutic applications is provided.
A high-throughput neutralizing assay for antibodies and sera evaluation against Epstein-Barr virus
Authors: Zhong Ling , Krummenacher Claude , Zhang Wanlin , Hong Junping , Feng Qisheng , Zhao Qinjian , Chen Yixin , Zeng Mu-Sheng , Zeng Yi-Xin , Xu Miao , Zhang Xiao 
Published: November 2022

Abstract
Background
Epstein-Barr virus (EBV) is a wide-spread human herpesvirus that is highly associated with infectious mononucleosis and several malignancies. Evaluation of EBV neutralizing antibody titers is important for serological studies, vaccine development and monoclonal antibody screening. The traditional method based on antibody inhibition of EBV transformation of B cells is very time-consuming. A more practical flow cytometry-based (FCM) approach to evaluate neutralizing titers is not amenable to achieving high-throughput evaluation of large-scale samples. A high-throughput approach is urgently needed.

Results
Here, we present a rapid and high-throughput method based on high content imaging system (HCIS) analysis. EBV titers determined by the HCIS-based assay were similar to those obtained by the FCM-based assay. Neutralizing titers of sera and monoclonal antibodies measured by the HCIS-based assay strongly correlated with titers measured by the FCM-based assay. HCIS assays showed a strong correlation between B cell infection neutralizing titers and the anti-gp350 IgG titers in healthy EBV carriers and monkey sera. Finally, anti-gHgL IgG titers from sera of healthy EBV carriers significantly correlated with epithelial cell infection neutralizing titers.

Conclusions
This HCIS-based assay is a high-throughput assay to determine viral titers and evaluate neutralizing potentials of sera and monoclonal antibodies. This HCIS-based assay will aid the development of vaccines and therapeutic monoclonal antibody against EBV.