bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sialic acid-engineered mesoporous polydopamine dual loaded with ferritin gene and SPIO for achieving endogenous and exogenous synergistic T2-weighted magnetic resonance imaging of HCC
Authors: Fan Kai , Lu Chengying , Shu Gaofeng , Lv Xiu-Ling , Qiao Enqi , Zhang Nannan , Chen Minjiang , Song Jingjing , Wu Fazong , Zhao Zhongwei , Xu Xiaoling , Xu Min , Chen Chunmiao , Yang Weibin , Sun Jihong , Du Yongzhong , Ji Jiansong 
Published: March 2021

Abstract
Background
Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. Magnetic resonance imaging (MRI) is one of the most effective imaging methods for the early diagnosis of HCC. However, the current MR contrast agents are still facing challenges in the early diagnosis of HCC due to their relatively low sensitivity and biosafety. Thus, the development of effective MR agents is highly needed for the early diagnosis of HCC.

Results
Herein, we fabricated an HCC-targeted nanocomplexes containing SPIO-loaded mesoporous polydopamine (MPDA@SPIO), sialic acid (SA)-modified polyethyleneimine (SA-PEI), and alpha-fetoprotein regulated ferritin gene (AFP-Fth) which was developed for the early diagnosis of HCC. It was found that the prepared nanocomplexes (MPDA@SPIO/SA-PEI/AFP-Fth) has an excellent biocompatibility towards the liver cells. In vivo and in vivo studies revealed that the transfection of AFP-Fth gene in hepatic cells significantly upregulated the expression level of ferritin, thereby resulting in an enhanced contrast on T2-weighted images via the formed endogenous MR contrast.

Conclusions
The results suggested that MPDA@SPIO/SA-PEI/AFP-Fth had a superior ability to enhance the MR contrast of T2-weighted images of tumor region than the other preparations, which was due to its HCC-targeted ability and the combined T2 contrast effect of endogenous ferritin and exogenous SPIO. Our study proved that MPDA@SPIO/SA-PEI/AFP-Fth nanocomplexes could be used as an effective MR contrast agent to detect HCC in the early stage.
Elevated levels of inflammatory plasma biomarkers are associated with risk of HIV infection
Authors: McInally Samantha , Wall Kristin , Yu Tianwei , Tirouvanziam Rabindra , Kilembe William , Gilmour Jill , Allen Susan A. , Hunter Eric 
Published: March 2021

AbstractBackgroundTo determine if individuals, from HIV-1 serodiscordant couple cohorts from Rwanda and Zambia, who become HIV-positive have a distinct inflammatory biomarker profile compared to individuals who remain HIV-negative, we compared levels of biomarkers in plasma of HIV-negative individuals who either seroconverted (pre-infection) and became HIV-positive or remained HIV-negative (uninfected).ResultsWe observed that individuals in the combined cohort, as well as those in the individual country cohorts, who later became HIV-1 infected had significantly higher baseline levels of multiple inflammatory cytokines/chemokines compared to individuals who remained HIV-negative. Genital inflammation/ulceration or schistosome infections were not associated with this elevated profile. Defined levels of ITAC and IL-7 were significant predictors of later HIV acquisition in ROC predictive analyses, whereas the classical Th1 and Th2 inflammatory cytokines such as IL-12 and interferon-γ or IL-4, IL-5 and Il-13 were not.ConclusionsOverall, the data show a significant association between increased plasma biomarkers linked to inflammation and immune activation and HIV acquisition and suggests that pre-existing conditions that increase systemic biomarkers represent a factor for increased risk of HIV infection.
COVID-19 infection among healthcare workers: a cross-sectional study in southwest Iran
Authors: Sabetian Golnar , Moghadami Mohsen , Hashemizadeh Fard Haghighi Leila , Shahriarirad Reza , Fallahi Mohammad Javad , Asmarian Naeimehossadat , Moeini Yalda Sadat 
Published: March 2021

Abstract
Objective
With the novel coronavirus pandemic, the impact on the healthcare system and workers cannot be overlooked. However, studies on the infection status of medical personnel are still lacking. It is imperative to ensure the safety of health-care workers (HCWs) not only to safeguard continuous patient care but also to ensure they do not transmit the virus, therefore evaluation of infection rates in these groups are indicated.

Methods
Demographic and clinical data regarding infected cases among HCWs of Fars, Iran with positive SARS‐CoV‐2 PCR tests were obtained from 10th March to 17th May 2020.

Results
Our data demonstrated a rate of 5.62% (273 out of 4854 cases) infection among HCW, with a mean age of 35 years and a dominance of female cases (146 cases: 53.5%). The majority of infected cases were among nurses (51.3%), while the most case infection rate (CIR) was among physicians (27 positive cases out of 842 performed test (3.2%)). Also, the highest rate of infection was in the emergency rooms (30.6%). Also, 35.5% of the patients were asymptomatic and the most frequent clinical features among symptomatic patients were myalgia (46%) and cough (45.5%). Although 5.5% were admitted to hospitals, there were no reports of ICU admission. Furthermore, 10.3% of the cases reported transmitting the infection to family and friends. Regarding safety precautions, 1.6% didn't wear masks and 18.7% didn't use gloves in work environments.

Conclusion
HCWs are among the highest groups at risk of infection during the COVID-19 pandemic; therefore, evaluating infection rates and associated features is necessary to improve and adjust protective measures of these vulnerable, yet highly essential group.
Early extubation is associated with improved outcomes after complete surgical repair of pulmonary atresia with ventricular septal defect and hypoplastic pulmonary arteries in pediatric patients
Authors: Li Yinan , Jia Yuan , Wang Hongbai , Wu Xie , Li Shoujun , Yan Fuxia , Yuan Su 
Published: March 2021

Abstract
Background
The aim of this study was to investigate the impact of an early extubation strategy on outcomes following complete repair of pulmonary atresia, ventricular septal defect, and hypoplastic pulmonary artery.

Methods
One hundred thirteen patients undergoing complete repair surgery of pulmonary atresia, ventricular septal defect, and hypoplastic pulmonary artery between 2016 and 2018 were included in our retrospective propensity-score matched study. Propensity score matching was conducted in 1 to 2 ratio to balance the covariables impacting on clinical outcomes between groups. The primary outcomes were defined as length of intensive care unit stay, postoperative length of hospital stay and in-hospital medical cost. The secondary outcomes included postoperative complications such as re-intubation, re-exploration, in-hospital mortality, arrhythmia and etc.. In addition, blood product consumption were also abstracted.

Results
Compared with matched controls, patients in the early extubation group were demonstrated with a significant reduced length of intensive care unit stay (Median: 1.9 d νs. 4.1 d, p = 0.039), postoperative length of hospital stay (Median: 9.0 d νs. 17.0 d, p = 0.007) and in-hospital medical cost (Median: 69.5 × 1000CNY νs. 113.6× 1000CNY, p = 0.041). As for the postoperative complications, the occurrence of re-intubation, re-exploration, in-hospital mortality, arrhythmia and renal replacement therapy was similar between groups. However, pulmonary complications (p = 0.049) were with a significantly lower rate in the early extubation group. In addition, fresh frozen plasma (p = 0.041) transfusion volume were significantly reduced in the early extubation group rather than packed red blood cells and platelets.

Conclusions
Early extubation following complete repair of pulmonary atresia improved clinical outcomes and reduced in-hospital medical cost without increasing any postoperative complications.
Bloodmeal sources and feeding behavior of anopheline mosquitoes in Bure district, northwestern Ethiopia
Authors: Adugna Tilahun , Yewhelew Delensaw , Getu Emana 
Published: March 2021

Abstract
Background
Mosquito bloodmeal sources determine the feeding rates, adult survival, fecundity, hatching rates, and developmental times. Only the female Anopheles mosquito takes bloodmeals from humans, birds, mammals, and other vertebrates for egg development. Studies of the host preference patterns in blood-feeding anopheline mosquitoes are crucial to determine malaria vectors. However, the human blood index, foraging ratio, and host preference index of anopheline mosquitoes are not known so far in Bure district, Ethiopia.

Methods
The origins of bloodmeals from all freshly fed and a few half-gravid exophagic and endophagic females collected using Centers for Disease Control and Prevention light traps were identified as human and bovine using enzyme-linked immunosorbent assay. The human blood index, forage ratio, and host feeding index were calculated.

Results
A total of 617 specimens belonging to An. arabiensis (n = 209), An. funestus (n = 217), An. coustani (n = 123), An. squamosus (n = 54), and An. cinereus (n = 14) were only analyzed using blood ELISA. Five hundred seventy-five of the specimens were positive for blood antigens of the host bloods. All anopheline mosquitoes assayed for a bloodmeal source had mixed- rather than single-source bloodmeals. The FR for humans was slightly > 1.0 compared to bovines for all Anopheles species. HFI for each pair of vertebrate hosts revealed that humans were the slightly preferred bloodmeal source compared to bovines for all species (except An. squamosus), but there was no marked host selection.

Conclusions
All anopheline mosquitoes assayed for bloodmeal ELISA had mixed feeds, which tends to diminish the density of gametocytes in the mosquito stomach, thereby reducing the chance of fertilization of the female gamete and reducing the chances of a malaria vector becoming infected. Moreover, An. coustani was the only species that had only human bloodmeals, meaning that this species has the potential to transmit the disease. Therefore, combination zooprophylaxis should be reinforced as a means of vector control because the study sites are mixed dwellings.

Graphical Abstract
SeqEnhDL: sequence-based classification of cell type-specific enhancers using deep learning models
Authors: Wang Yupeng , Jaime-Lara Rosario B. , Roy Abhrarup , Sun Ying , Liu Xinyue , Joseph Paule V. 
Published: March 2021

Abstract
Objective
To address the challenge of computational identification of cell type-specific regulatory elements on a genome-wide scale.

Results
We propose SeqEnhDL, a deep learning framework for classifying cell type-specific enhancers based on sequence features. DNA sequences of “strong enhancer” chromatin states in nine cell types from the ENCODE project were retrieved to build and test enhancer classifiers. For any DNA sequence, positional k-mer (k = 5, 7, 9 and 11) fold changes relative to randomly selected non-coding sequences across each nucleotide position were used as features for deep learning models. Three deep learning models were implemented, including multi-layer perceptron (MLP), Convolutional Neural Network (CNN) and Recurrent Neural Network (RNN). All models in SeqEnhDL outperform state-of-the-art enhancer classifiers (including gkm-SVM and DanQ) in distinguishing cell type-specific enhancers from randomly selected non-coding sequences. Moreover, SeqEnhDL can directly discriminate enhancers from different cell types, which has not been achieved by other enhancer classifiers. Our analysis suggests that both enhancers and their tissue-specificity can be accurately identified based on their sequence features. SeqEnhDL is publicly available at https://github.com/wyp1125/SeqEnhDL.
Process development and safety evaluation of ABCB5+ limbal stem cells as advanced-therapy medicinal product to treat limbal stem cell deficiency
Authors: Norrick Alexandra , Esterlechner Jasmina , Niebergall-Roth Elke , Dehio Ulf , Sadeghi Samar , Schröder Hannes M. , Ballikaya Seda , Stemler Nicole , Ganss Christoph , Dieter Kathrin , Dachtler Ann-Kathrin , Merz Patrick , Sel Saadettin , Chodosh James , Cursiefen Claus , Frank Natasha Y. , Auffarth Gerd U. , Ksander Bruce , Frank Markus H. , Kluth Mark A. 
Published: March 2021

Abstract
Background
While therapeutic success of the limbal tissue or cell transplantation to treat severe cases of limbal stem cell (LSC) deficiency (LSCD) strongly depends on the percentage of LSCs within the transplanted cells, prospective LSC enrichment has been hampered by the intranuclear localization of the previously reported LSC marker p63. The recent identification of the ATP-binding cassette transporter ABCB5 as a plasma membrane-spanning marker of LSCs that are capable of restoring the cornea and the development of an antibody directed against an extracellular loop of the ABCB5 molecule stimulated us to develop a novel treatment strategy based on the utilization of in vitro expanded allogeneic ABCB5+ LSCs derived from human cadaveric limbal tissue.

Methods
We developed and validated a Good Manufacturing Practice- and European Pharmacopeia-conform production and quality-control process, by which ABCB5+ LSCs are derived from human corneal rims, expanded ex vivo, isolated as homogenous cell population, and manufactured as an advanced-therapy medicinal product (ATMP). This product was tested in a preclinical study program investigating the cells’ engraftment potential, biodistribution behavior, and safety.

Results
ABCB5+ LSCs were reliably expanded and manufactured as an ATMP that contains comparably high percentages of cells expressing transcription factors critical for LSC stemness maintenance (p63) and corneal epithelial differentiation (PAX6). Preclinical studies confirmed local engraftment potential of the cells and gave no signals of toxicity and tumorgenicity. These findings were sufficient for the product to be approved by the German Paul Ehrlich Institute and the U.S. Food & Drug Administration to be tested in an international multicenter phase I/IIa clinical trial (NCT03549299) to evaluate the safety and therapeutic efficacy in patients with LSCD.

Conclusion
Building upon these data in conjunction with the previously shown cornea-restoring capacity of human ABCB5+ LSCs in animal models of LSCD, we provide an advanced allogeneic LSC-based treatment strategy that shows promise for replenishment of the patient’s LSC pool, recreation of a functional barrier against invading conjunctival cells and restoration of a transparent, avascular cornea.
Orchestration an extracellular lipase production from Aspergillus niger MYA 135: biomass morphology and fungal physiology
Authors: Salvatierra Hebe Natalia , Regner Erika Lucía , Baigorí Mario Domingo , Pera Licia María 
Published: March 2021

AbstractThe impact of biomass morphology and culture conditions on fungal fermentation was widely reviewed in the literature. In this work, we presented three independent experiments in order to evaluate the influence of some of those input factors on a lipase production separately by using the Aspergillus niger MYA 135 and the two-stage fermentation technique. Regarding the culture modality, the biomass was pre-grown in a first reactor. Then, the washed mycelium was transferred to a second reactor to continue the study. Firstly, linear effects of fungal morphology and several physiological parameters on a lipase production were explored using the Plackett–Burman design. The dispersed fungal morphology was confirmed as a proper quality characteristic for producing an extracellular lipase activity. Concerning the impact of the carbon source on the biomass pre-growth, the sucrose (E = 9.923, p < 0.001) and the l-arabinose (E = 4.198, p = 0.009) presented positive and significant effects on the enzyme production. On the contrary, the supplementation of 0.05 g/L CaCl2 displayed a highly negative and significant effect on this process (E = − 7.390, p < 0.001). Secondly, the relationship between the enzyme production and the input variables N:C ratio, FeCl3 and olive oil was explored applying the central composite design. Among the model terms, the N:C ratio of the production medium had the most negative and significant influence on the enzyme synthesis. Thus, it was concluded that a low N:C ratio was preferable to increase its production. In addition, the bifunctional role of FeCl3 on this fungus was presented. Thirdly, a prove of concept assay was also discussed.
A study of ethnic, gender and educational differences in attitudes toward COVID-19 vaccines in Israel – implications for vaccination implementation policies
Authors: Green Manfred S. , Abdullah Rania , Vered Shiraz , Nitzan Dorit 
Published: March 2021

Abstract
Background
Vaccines for COVID-19 are currently available for the public in Israel. The compliance with vaccination has differed between sectors in Israel and the uptake has been substantially lower in the Arab compared with the Jewish population.

Aim
To assess ethnic and socio-demographic factors in Israel associated with attitudes towards COVID-19 vaccines prior to their introduction.

Methods
A national cross-sectional survey was carried out In Israel during October 2020 using an internet panel of around 100,000 people, supplemented by snowball sampling. A sample of 957 adults aged 30 and over were recruited of whom 606 were Jews (49% males) and 351 were Arabs (38% males).

Results
The sample of Arabs was younger than for the Jewish respondents. Among the men, 27.3% of the Jewish and 23.1% of the Arab respondents wanted to be vaccinated immediately, compared with only 13.6% of Jewish women and 12.0% of Arab women. An affirmative answer to the question as to whether they would refuse the vaccine at any stage was given by 7.7% of Jewish men and 29.9% of Arab men, and 17.2% of Jewish women and 41.0% of Arab women. Higher education was associated with less vaccine hesitancy. In multiple logistic regression analysis, the ethnic and gender differences persisted after controlling for age and education. Other factors associated with vaccine hesitancy were the belief that the government restrictions were too lenient and the frequency of socializing prior to the pandemic.

Conclusions
The study revealed a relatively high percentage reported would be reluctant to get vaccinated, prior to the introduction of the vaccine. This was more marked so for Arabs then Jews, and more so for women within the ethnic groups. While this was not a true random sample, the findings are consistent with the large ethnic differences in compliance with the vaccine, currently encountered and reinforce the policy implications for developing effective communication to increase vaccine adherence. Government policies directed at controlling the pandemic should include sector-specific information campaigns, which are tailored to ensure community engagement, using targeted messages to the suspected vaccine hesitant groups. Government ministries, health service providers and local authorities should join hands with civil society organizations to promote vaccine promotion campaigns.
External validation of an opioid misuse machine learning classifier in hospitalized adult patients
Authors: Afshar Majid , Sharma Brihat , Bhalla Sameer , Thompson Hale M. , Dligach Dmitriy , Boley Randy A. , Kishen Ekta , Simmons Alan , Perticone Kathryn , Karnik Niranjan S. 
Published: March 2021

Abstract
Background
Opioid misuse screening in hospitals is resource-intensive and rarely done. Many hospitalized patients are never offered opioid treatment. An automated approach leveraging routinely captured electronic health record (EHR) data may be easier for hospitals to institute. We previously derived and internally validated an opioid classifier in a separate hospital setting. The aim is to externally validate our previously published and open-source machine-learning classifier at a different hospital for identifying cases of opioid misuse.

Methods
An observational cohort of 56,227 adult hospitalizations was examined between October 2017 and December 2019 during a hospital-wide substance use screening program with manual screening. Manually completed Drug Abuse Screening Test served as the reference standard to validate a convolutional neural network (CNN) classifier with coded word embedding features from the clinical notes of the EHR. The opioid classifier utilized all notes in the EHR and sensitivity analysis was also performed on the first 24 h of notes. Calibration was performed to account for the lower prevalence than in the original cohort.

Results
Manual screening for substance misuse was completed in 67.8% (n = 56,227) with 1.1% (n = 628) identified with opioid misuse. The data for external validation included 2,482,900 notes with 67,969 unique clinical concept features. The opioid classifier had an AUC of 0.99 (95% CI 0.99–0.99) across the encounter and 0.98 (95% CI 0.98–0.99) using only the first 24 h of notes. In the calibrated classifier, the sensitivity and positive predictive value were 0.81 (95% CI 0.77–0.84) and 0.72 (95% CI 0.68–0.75). For the first 24 h, they were 0.75 (95% CI 0.71–0.78) and 0.61 (95% CI 0.57–0.64).

Conclusions
Our opioid misuse classifier had good discrimination during external validation. Our model may provide a comprehensive and automated approach to opioid misuse identification that augments current workflows and overcomes manual screening barriers.
What is the impact of human wastewater biosolids (sewage sludge) application on long-term soil carbon sequestration rates? A systematic review protocol
Authors: Badzmierowski Mike J. , Evanylo Gregory K. , Daniels W. Lee , Haering Kathryn C. 
Published: March 2021

Abstract
Background
Human wastewater biosolids, hereafter referred to as biosolids, are produced in significant quantities around the world and often applied to an extensive land mass including agricultural fields, forests, mine lands, and urban areas. Land-application of biosolids has been reported in peer-reviewed and non-peer-reviewed work to change soil organic carbon stocks in varying amounts. Determining the potential of soil organic carbon (SOC) stock change and sequestration from biosolids land application is critical for biosolids producers and users to gain access to carbon credit markets. Our review question is, "what is the impact of biosolids application on long-term soil carbon sequestration rates?” We look to explore this main question with the follow-up, "does biosolids processing methods and characteristics, application method, soil properties, land management and other modifiers affect rates of carbon accumulation from land-applied biosolids?"

Methods
Searches will be conducted using online databases (i.e., Web of Science Core Collection, CAB Abstracts, Scopus, ProQuest Dissertations & Theses Global), search engines (Google Scholar and Microsoft Academic), and specialist websites to find primary field studies and grey literature of biosolids land-application effects on soil organic carbon stocks. We will use English search terms and predefined inclusion criteria of: (1) a field study of at least 24 months that reports soil organic carbon/matter (SOC/SOM) concentrations/stocks; (2) has two types of treatments: (i) a control (non-intervention AND/OR synthetic fertilizer) AND (ii) a biosolids-based amendment; and (3) information of amendment properties and application dates and rates to estimate the relative contribution of the applied materials to SOC changes. We will screen results in two stages: (1) title and abstract and (2) full text. A 10% subset will be screened by two reviewers for inclusion at the title and abstract level and use a kappa analysis to ensure agreement of at least 0.61. All results in the full text stage will be dual screened. Data will be extracted by one person and reviewed by a second person. Critical appraisal will be used to assess studies’ potential bias and done by two reviewers. A meta-analysis using random effects models will be conducted if sufficient data of high enough quality are extracted.