bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical immunogenicity and protective efficacy of a SARS-CoV-2 RBD based vaccine produced with the thermophilic filamentous fungal expression system Thermothelomyces heterothallica, C1.
Authors: Osterhaus Albert , Gonzalez-Hernandez Mariana , Kaiser Franziska , Steffen Imke , Ciurkiewicz Malgorzata , Amerongen Geert van , Tchelet Ronen , Emalfarb Mark , Saloheimo Markku , Wiebe Marilyn , Vitikainen Marika , Albulescu Irina , Bosch Berend-Jan , Baumgärtner Wolfgang , Haagmans Bart 
Published: March 2023

Abstract
The emergency use of vaccines has been the most efficient way to control the ongoing COVID-19 pandemic. However, the emergence of SARS-CoV-2 variants of concern has reduced the efficacy of currently used vaccines. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein is the main target for virus neutralizing (VN) antibodies. Here, we evaluated the immunogenicity and efficacy of a SARS-CoV-2 RBD vaccine candidate produced in the Thermothelomyces heterothallica (formerly Myceliophthora thermophila), C1 protein expression system, in a Syrian golden hamster (Mesocricetus auratus) infection model. One dose of 10 µg RBD vaccine based on SARS-CoV-2 Wuhan strain, coupled to a nanoparticle in combination with aluminum hydroxide as adjuvant, efficiently induced VN antibodies and reduced viral load and lung damage upon SARS-CoV-2 challenge infection. The VN antibodies, neutralized SARS-CoV-2 variants of concern D614G, Alpha, Beta and Gamma. Our results support the use of the Thermothelomyces heterothallica, C1 protein expression system to produce recombinant vaccines against SARS-CoV-2 and other virus infections, in order to help overcome limitations associated with the use of mammalian expression systems.
Assessment of suppliers through the resiliency and sustainability paradigms using a new MCDM model under interval type-2 fuzzy sets
Authors: Nemati Elyas , Mohamadzadeh Saeid 
Published: March 2023

Abstract
Today, improvement and development must occur in all parts of the supply chain, and supplier selection as the starting point of the chain must be considered one of the most critical parts of planning. In the current competitive and unstable environment, in selecting the best suppliers, common approaches such as resilience and sustainability can be helpful for organizations in terms of sustainability and competitive advantage. Therefore, designing a sustainable and resilient supply chain model and considering all these parameters can effectively provide products and services. Also, to consider real-world uncertainties, interval type-2 trapezoidal fuzzy sets (IT2TFSs) are used because these sets are more powerful than classical fuzzy sets and better reflect uncertainties. Then, a new version of the MULTIMOORA model called MULTIMOOSRA is extended. In this model, the importance of the criteria is specified using the best-worst method. The importance of experts is defined using a new version of the MABAC approach developed by the average concept. Then the rank of each supplier is determined by the developed MULTIMOOSRA method. Notably, the proposed approach is developed in the IT2TF environment to consider the uncertainties of real issues and the ambiguity caused by experts' opinions in the decision-making process. Eventually, a case study is solved utilizing the proposed approach, and the best supplier is determined under resilient and sustainable paradigms.
ETDA as a legacy soil chelatant; a comparative study to a more environmentally-sensitive alternative for metal removal by Pistia stratiotes L.
Authors: Lebrun Manhattan , Szakova Jirina , Drabek Ondrej , Tejnecky Vaclav , Hough Rupert Lloyd , Beesley Luke , Wang Hailong , Trakal Lukas 
Published: March 2023

Abstract
The accuracy of environmental risk assessment depends upon selecting appropriate matrices to extract the most risk-relevant portion of contaminant(s) from the soil. Here we applied the chelatants Na-EDTA and tartaric acid to extract a metal-contaminated soil. Pistia stratiotes was applied as an indicator plant to measure accumulation from the metal-laden bulk solutions generated, in a hydroponic experiment lasting 15 days. Speciation modelling was used to elucidate key geo-chemical mechanisms impacting matrix and metal-specific uptake revealed by experimental work. The highest concentrations of soil-borne metals were extracted from soil by Na-EDTA (7.4% for Cd), but their uptake and translocation to the plant were restricted due to the formation of stable metal complexes predominantly with DOC. Tartaric acid solubilized metals to a lesser extent (4.6% for Cd), but a higher proportion was plant-available due to its presence mainly in the form of bivalent metal cations. The water extraction showed the lowest metal extraction (e.g., 3.9% for Cd) but the metal species behaved similarly to those extracted by tartaric acid. This study demonstrates that not all extractions are equal and that metal-specific speciation will impact accurate risk assessment in soil (water)-plant systems. In the case of EDTA, a deleterious impact on DOC leaching is an obvious drawback. As such, further work should now determine soil, and not only metal, specific impacts of chelatants on the extraction of environmentally relevant portions of metal(loid)s.
Predictors of Frequent Emergency Department Visits among Hospitalized Cancer Patients: A Comparative Cohort Study Using Integrated Clinical and Administrative Data to Improve Care Delivery
Authors: Kurteva Siyana , Tamblyn Robyn , Meguerditchian Ari N. 
Published: March 2023

Abstract
Background
Frequent emergency department (FED) visits by cancer patients represent a significant burden to the health system. This study identified determinants of FED in recently hospitalized cancer patients, with a particular focus on opioid use.
Methods
A prospective cohort discharged from surgical/medical units of the McGill University Health Centre was assembled. The outcome was FED use (≥ 4 ED visits) within one year of discharge. Data retrieved from the universal health insurance system was analyzed using Cox Proportional Hazards (PH) model, adopting the Lunn-McNeil approach for competing risk of death.
Results
Of 1253 patients, 14.5% became FED users. FED use was associated with chemotherapy one-year pre-admission (adjusted hazard ratio (aHR) 2.60, 95% CI: 1.80–3.70), ≥1 ED visit in the previous year (aHR: 1.80, 95% CI 1.20–2.80), ≥15 pre-admission ambulatory visits (aHR 1.54, 95% CI 1.06–2.34), previous opioid and benzodiazepine use (aHR: 1.40, 95% CI: 1.10–1.90 and aHR: 1.70, 95% CI: 1.10–2.40), Charlson Comorbidity Index ≥ 3 (aHR: 2.0, 95% CI: 1.2–3.4), diabetes (aHR: 1.60, 95% CI: 1.10–2.20), heart disease (aHR: 1.50, 95% CI: 1.10–2.20) and lung cancer (aHR: 1.70, 95% CI: 1.10–2.40). Surgery (cardiac (aHR: 0.33, 95% CI: 0.16–0.66), gastrointestinal (aHR: 0.34, 95% CI: 0.14–0.82) and thoracic (aHR: 0.45, 95% CI: 0.30–0.67) led to a decreased risk of FED use.
Conclusions
Cancer patients with higher co-morbidity, frequent use of the healthcare system, and opioid use were at increased risk of FED use. High-risk patients should be flagged for preventive intervention.
Optical and Rogue type electrical soliton solutions of the (2+1) dimensional nonlinear Heisenberg ferromagnetic spin chains equation
Authors: Islam Shariful , Halder Bishnupada , Ali Ahmed Refaie 
Published: March 2023

Abstract
In this study, the uses of unified method for finding solutions of a nonlinear Schrodinger equation that describes the nonlinear spin dynamics of (2+1) dimensional Heisenberg ferromagnetic spin chains equation. We successfully construct solutions to these equations. For each of the derived solutions, we provide the parametric requirements for the existence of a valid soliton. In order to visualize some of the discovered solutions, we plot the 2D and 3D graphics. The results of this investigation, which have been presented, might be useful in elucidating the model's physical significance. These are a highly useful tool for studying how electrical solitons, which travel as voltage waves in nonlinear dispersive media, spread out, as well as for doing various physical calculations. The study's findings, which have been disclosed, might be useful in illuminating the models under consideration's physical significance and electrical field.
Explainable Automated Pain Recognition in Cats
Authors: Feighelstein Marcelo , Henze Lea , Meller Sebastian , Shimshoni Ilan , Hermoni Ben , Berko Michael , Twele Friederike , Schutter Alexandra , Dorn Nora , Kastner Sabine , Finka Lauren , Luna Stelio P. , Mills Daniel S. , Volk Holger A. , Zamansky Anna 
Published: March 2023

Abstract
Manual tools for pain assessment from facial expressions have been suggested and validated for several animal species. However, facial expression analysis performed by humans is prone to subjectivity and bias, and in many cases also requires special expertise and training. This has led to an increasing body of work on automated pain recognition, which has been addressed for several species, including cats. Even for experts, cats are a notoriously challenging species for pain assessment. A previous study compared two approaches to automated ‘pain’/‘no pain’ classification from cat facial images: a deep learning approach, and an approach based on manually annotated geometric landmarks, reaching comparable accuracy results. However, the study included a very homogeneous dataset of cats and thus further research to study generalizability of pain recognition to more realistic settings is required. This study addresses the question of whether AI models can classify ‘pain’/‘no pain’ in cats in a more realistic (multi-breed, multi-sex) setting using a more heterogenous and thus potentially ‘noisy’ dataset of 84 client-owned cats. Cats were a convenience sample presented to the Department of Small Animal Medicine and Surgery of the University of Veterinary Medicine Hannover and included individuals of different breeds, ages, sex, and with varying medical conditions/medical histories. Cats were scored by veterinary experts using the Glasgow composite measure pain scale; the scoring was then used for training AI models using two different approaches. We show that in this context the landmark-based approach performs better, reaching accuracy above 77% in pain detection as opposed to only above 65% reached by the deep learning approach. Furthermore, we investigated the explainability of such machine recognition in terms of identifying facial features that are important for the machine, revealing that the region of nose and mouth seems more important for machine pain classification, while the region of ears is less important, with these findings being consistent across the models and techniques studied here.
A systematic literature review of Real-World Evidence (RWE) on post-market assessment of medical devices
Authors: Manetti Stefania , Guidotti Elisa , Vola Federico Vola , Vainieri Milena 
Published: March 2023

Abstract

The increasing use of real-world evidence (RWE) and real-world data (RWD) to assess post-market Medical Devices (MDs) might satisfy the urgent need for data sharing and traceability. This study sought to i) get an overview of current practice in post-market assessments of MDs reporting on RWE/RWD; ii) draw policy recommendations for governments and health organizations and identify a research agenda for scholars. A systematic review was undertaken until July 2020 following the PRISMA guidelines. Original peer-reviewed articles in English and incorporating RWE/RWD into any sort of post-market assessment strategy for an MD were included and their reference lists manually checked. A narrative synthesis was employed to describe evidence retrieved. Totally, 103 research articles were identified. Administrative databases were mostly utilised; clinical and/or economic evidence gathered in a short/medium time horizon the most frequently reported; other evidence types (e.g., organizational) underreported; patient perspectives rarely incorporated; the innovation complexity of MDs relatively low. To our knowledge, this study is the first in its kind to provide a comprehensive picture of how non-randomized evidence has been used when assessing MDs working in real-life conditions. The implications of this review might help policy-makers to better understand the risks and benefits of medium and long-term use of MDs alongside clinical practice and make more informed decisions about adoption and use.
LCVD resistance breeding in heat tolerant bell pepper: Combined phenotypic &amp; marker-assisted backcrossing for introgression of LCVD resistance from hot pepper
Authors: S Tejpal Singh , Jindal Salesh Kumar , Sharma Abhishek , Bhatia Dharminder 
Published: March 2023

Abstract
Hot pepper (Capsicum annuum var. annuum) and bell pepper (C. annuum var. grossum) are the important crops of the Solanaceae family. In the present study, marker-assisted selection (MAS) was employed for interspecific leaf curl virus disease (LCVD) resistant gene introgression from hot pepper (S-343) to heat-tolerant bell pepper lines. Segregating populations were developed using resistant (S-343) and susceptible (bell pepper) genotypes for understanding the genetics of LCVD resistance. The micro-cage artificial screening technique was used for the phenotypic selection of LCVD resistant plants from progenies of each population. The F1 of all crosses were resistant to LCVD, while F2­ and BC1F2­ generations of all the crosses were segregated into 3:1 (resistant: susceptible) and BC1F1 generations of all crosses were a good fit to ratio 1:1 (resistant:susceptible) suggesting monogenic dominant control of LCVD resistance. In addition to phenotypic selection for LCVD resistance, MAS for non-pungency was done using ‘BF7’ and ‘BR9’-SCAR primers along with the very stringent phenotyping (background selection) in backcrossed populations for most important fruit traits. The background selection was performed for the recovery of recurrent parent phenome (RPP) and it was measured as shift in means of these important fruit traits. To the best of our knowledge, it is a novel experiment of introgression of LCVD resistance in heat tolerant bell pepper lines that led to the successful development of six improved LCVD resistant, heat-tolerant and non-pungent BC2F1 populations (LCVRS3SM-1, LCVRS3SM-2, LCVRS3SM-8, LCVRS3SM-4, LCVRS3SM-17, and LCVRS3SM-58) that will help in future bell pepper resistant breeding programs.
From the three-dimensional perspective of college students' school, family and themselves, explore the mechanism of the influence of proactive personality on career exploration
Authors: Zhang Caizhi , Lu Lei , Xiao Yan , Zheng Zhou , Jia Qiuhong , Luo Yuanxin , Luo Jun 
Published: March 2023

Abstract
Career exploration, as the antecedent variable of college student's career choice and employment, guides for the construction of their career. Based on the theory of social cognitive career, this study explores the formation mechanism of career exploration from three aspects: personality, family and university. Through a multi-stage investigation of 980 college students from 16 colleges and universities on Chinese mainland, it is found that: (1) Proactive personality positively affects career exploration; (2) College students' self-efficacy plays a mediating role between proactive personality and career exploration; (3) Teacher support and parental support strengthen the positive effect between self-efficacy and career exploration; (4) Both teacher support and parental support positively moderate the indirect influence of proactive personality on career exploration through self-efficacy. This study tries to provide practical guidance for college students to engage in career exploration and career construction from a pluralistic perspective.
Spatial-temporal evolution patterns and drivers of PM2.5 chemical fraction concentrations in China over the past 20 years
Authors: he chao , Li Bin , Gong Xusheng , Liu Lijun , Li Haiyan , Zhang Lu , Jin Jiming 
Published: March 2023

Abstract
The quantitative assessment of the spatial and temporal variability and drivers of fine particulate matter (PM2.5) fraction concentrations is important for pollution control and public health preservation in China. In this study, we investigated the spatial temporal variation of PM2.5 chemical component based on the PM2.5 chemical component datasets from 2000 to 2019 and revealed the driving forces of the differences in the spatial distribution using a spatial regression model and a two-step clustering approach. The results show that: the PM2.5 chemical fraction concentrations show a trend of first increasing (2000–2007) and then decreasing (2007–2019). From 2000 to 2019, the change rates of PM2.5, organic matter (OM), black carbon (BC), sulfates (SO2– 4), ammonium(NH + 4), and nitrates ༈NO– 3༉ were − 0.59, − 0.23, − 0.07, − 0.15, − 0.02, and 0.04µg/m3/yr in the entirety of China. The secondary aerosol (i.e., SO2– 4, NO– 3, and NH + 4; SNA) had the highest fraction in PM2.5 concentrations (55.6–68.1% in different provinces), followed by OM and BC. Spatially, North, Central, and East China are the regions with the highest PM2.5 chemical component concentrations in China, meanwhile, they are also the regions with the most significant decrease in PM2.5 chemical fraction concentrations. The regression results show that among all variables, the number of enterprises, disposable income, private car ownership, and the share of secondary industry non-linearly enhance the differences in the spatial distribution of PM2.5 component concentrations. Electricity consumption has the strongest influence on NH + 4 emissions in Northwest China and BC and OM emissions in Northeast China.
Low-Dose Intranasal Dexmedetomidine Premedication Improves Epidural Labor Analgesia Onset and Reduces Procedural Distress on Epidural Puncture: A Prospective Randomized Double-blind Clinical Study
Authors: Sun Hao , Ma Xiang , Wang Shengyou , Li Zhenzhen , Lu Yao , Zhu Haijuan 
Published: March 2023

Abstract
Background Epidural labor analgesia is a safe and effective method of pain management during labor with the drawbacks of delayed onset and the maternal distress on the epidural puncture. This study aimed to determine whether pretreatment with intranasal low-dose dexmedetomidine (IND) effectively shortens the onset of analgesia and reduces procedural pain.
Methods In this prospective randomized double-blind trial, nulliparous patients were randomly assigned to either the IND or the control group (CON). The IND group received 0.5 µg/kg dexmedetomidine intranasally, and the CON group received an equal volume of normal saline also intranasally. Two groups were maintained with a programmed intermittent epidural bolus (PIEB). The primary outcome was the onset time of analgesia and procedural pain scores caused by the epidural puncture.
Results 79 patients were enrolled, 60 completed the study and were included in analysis. The time to adequate analgesia was significantly shorter in the IND group than that in the CON group (Hazard ratio=2.069; 95% CI, 2.187 to 3.606; P=0.010). The visual analogue scale (VAS) scores during epidural puncture in the IND group were also significantly lower than those in the CON group [2.0 (1.8-2.5) vs. 3.5 (3.3-4.5) , P≤0.001, Table2]. IND in combination with PIEB was associated with improved VAS and Ramsay scores, fewer consumption of analgesics and PCEA boluses, and higher maternal satisfaction (P<0.05). No differences were shown in labor and neonatal outcomes and incidence of adverse effects between the two groups.
Conclusions IND yielded a faster onset of analgesia, and decreased epidural puncture pain without increasing adverse effects. Pretreatment with IND may be a useful adjunct on initiation of epidural analgesia, and further investigation should be encouraged to better determine its utility.
Trial Registration: This trial was prospectively registered at Chictr.org.cn on 29/05/2020 with the registration number of ChiCTR2000033356 (http://www.chictr.org.cn/ listbycreater.aspx).
Mdm2/p53 levels in bone marrow mesenchymal stromal cells is essential for maintaining the hematopoietic niche in response to DNA damage
Authors: Pourebrahim Rasoul , Montoya Rafael Heinz , Alaniz Zoe , Ostermann Lauren , Lin Patrick P. , Liu Bin , Ayoub Edward , Burks Jared K. , Andreeff Michael 
Published: March 2023

Abstract
Mesenchymal stromal cells (MSCs) are a key component of the bone marrow (BM) niche, providing essential support required for maintenance of hematopoietic stem cells. To advance our understanding of physiological functions of p53 and Mdm2 in BM-MSCs, we developed traceable conditional mouse models targeting Mdm2 and/or Trp53 in vivo. We demonstrate that Mdm2 is essential for the emergence, maintenance and hematopoietic support of BM-MSCs. Mdm2 haploinsufficiency in BM-MSCs resulted in genotoxic stress–associated thrombocytopenia, suggesting a functional role for Mdm2 in hematopoiesis. In a syngeneic mouse model of acute myeloid leukemia (AML), Trp53 deletion in BM-MSCs improved survival, and protected BM against hematopoietic toxicity from a murine Mdm2i, DS-5272. The transcriptional changes were associated with dysregulation of glycolysis, gluconeogenesis, and Hif-1α in BM-MSCs. Our results reveal a physiologic function of Mdm2 in BM-MSC, identify a previously unknown role of p53 pathway in BM-MSC–mediated support in AML and expand our understanding of the mechanism of hematopoietic toxicity of MDM2is.
Huangqi Decoction ameliorates kidney injury in db/db mice by regulating the BMP/Smad signaling pathway.
Authors: Chen Ying , Rui Rong , Wang Li , Wang Hao , Zhu Bingbing , Cao Aili 
Published: March 2023

Abstract

Purpose Our study clarifies the mechanism of Huangqi decoction (HQD) against DKD in diabetic db/db mice. Methods Eight-week-old male diabetic db/db mice were randomly divided into four groups: Model (1% CMC), HQD-L (0.12 g/kg), HQD-M (0.36 g/kg), and HQD-H (1.08 g/kg) groups. Non-diabetic db/m mice were used as a control group. These mice received HQD treatment for 8 weeks continuously. After 8 weeks of feeding, kidneys were harvested to observe the kidney function, pathological changes, micro-assay study, and the protein expression levels. Results HQD treatment improved the albumin/creatine ratio (ACR) and 24 h urinary albumin, prevented the pathological phenotypes of increased glomerular volume, widened mesangial areas, the proliferation of mesangial matrix, the disappearance of foot processes, the decreased expression of nephrin and the number of podocytes. The expression profile chips were assessed to reveal the global transcriptional response and predict related functions, diseases and pathways. To verify this, we found that HQD treatment activated the protein expressions of BMP1, BMP7, BMPR2, and active-Rap1 and inhibited Smad1 and phospho-ERK. In addition, HQD could improve lipid deposition in the kidneys of db/db mice. Conclusion HQD prevents the progression of DKD in db/db mice by regulating the transcription of BMPs and their downstream target genes, inhibiting the phosphorylation of ERK and Smad1 by promoting the binding of Rap1 to GTP and regulating the lipid metabolism dysfunction. These provide a new idea for the treatment of DKD.