bluuebunny/crossref_metadata_2025_split huggingface dataset:
Construction of a quadruple gene-deleted vaccine confers complete protective immunity against emerging PRV variant challenge in piglets
Authors: Sun Leqiang , Tang Yajie , Yan Keji , Zhang Huawei 
Published: January 2022

Abstract
Background
Pseudorabies virus (PRV) causes Aujeszky’s disease or pseudorabies (PR) in pigs worldwide, which leads to heavy economic losses to the swine industry. Pigs are the natural host, meanwhile, animals such as dogs, cats, foxes, rabbits, cattle and sheep are susceptible to infection. In 2011, the emerging PRV variant led to the outbreak of PR in Bartha-K61 vaccinated pigs. The PR outbreaks demonstrated that the Bartha-K61 vaccine did not provide full protection against the emerging PRV variant. It is widely believed that PRV live attenuated vaccine could control PRV infection.

Methods
In this study, we developed a novel PRV live attenuated vaccine by deleting its gI, gE, US9, and US2 genes through CRISPR/Cas9, which was named PRV GDFS-delgI/gE/US9/US2.

Results
Safety experiments confirmed that PRV GDFS-delgI/gE/US9/US2 was safe for 5- to 7-day-old suckling piglets. Piglets immunized with the PRV GDFS-delgI/gE/US9/US2 vaccine did not produce PRV gE-specific antibodies but could generate PRV gB-specific antibodies and high neutralizing titers against the PRV GDFS strain (variant PRV strain) or PRV Ea strain (older PRV strain). After challenge with the emerging PRV GDFS variant, none of the piglets immunized with the PRV GDFS-delgI/gE/US9/US2 vaccine showed any clinical signs, and their rectal temperatures were normal. Moreover, the autopsy and histopathological analyses revealed that the piglets in the PRV GDFS-delgI/gE/US9/US2 vaccine group did not show apparent gross or pathological lesions. Furthermore, the piglets in the PRV GDFS-delgI/gE/US9/US2 vaccine groups did not present weight loss. According to the criteria of the OIE terrestrial manual, the results of the experiment confirmed that the PRV GDFS-delgI/gE/US9/US2 vaccine could provide full protection against the emerging PRV variant strain in piglets.

Conclusions
The PRV GDFS-delgI/gE/US9/US2 strain is a potential new live attenuated vaccine against emerging PRV variant strain infections in China.
Intra‐assessor reliability and measurement error of ultrasound measures for foot muscle morphology in older adults using a tablet‐based ultrasound machine
Authors: Willemse Lydia , Wouters Eveline J. M. , Pisters Martijn F. , Vanwanseele Benedicte 
Published: January 2022

AbstractBackgroundTo gain insight into the role of plantar intrinsic foot muscles in fall‐related gait parameters in older adults, it is fundamental to assess foot muscles separately. Ultrasonography is considered a promising instrument to quantify the strength capacity of individual muscles by assessing their morphology. The main goal of this study was to investigate the intra‐assessor reliability and measurement error for ultrasound measures for the morphology of selected foot muscles and the plantar fascia in older adults using a tablet‐based device. The secondary aim was to compare the measurement error between older and younger adults and between two different ultrasound machines.MethodsUltrasound images of selected foot muscles and the plantar fascia were collected in younger and older adults by a single operator, intensively trained in scanning the foot muscles, on two occasions, 1–8 days apart, using a tablet‐based and a mainframe system. The intra‐assessor reliability and standard error of measurement for the cross‐sectional area and/or thickness were assessed by analysis of variance. The error variance was statistically compared across age groups and machines.ResultsEighteen physically active older adults (mean age 73.8 (SD: 4.9) years) and ten younger adults (mean age 21.9 (SD: 1.8) years) participated in the study. In older adults, the standard error of measurement ranged from 2.8 to 11.9%. The ICC ranged from 0.57 to 0.97, but was excellent in most cases. The error variance for six morphology measures was statistically smaller in younger adults, but was small in older adults as well. When different error variances were observed across machines, overall, the tablet‐based device showed superior repeatability.ConclusionsThis intra‐assessor reliability study showed that a tablet‐based ultrasound machine can be reliably used to assess the morphology of selected foot muscles in older adults, with the exception of plantar fascia thickness. Although the measurement errors were sometimes smaller in younger adults, they seem adequate in older adults to detect group mean hypertrophy as a response to training. A tablet‐based ultrasound device seems to be a reliable alternative to a mainframe system. This advocates its use when foot muscle morphology in older adults is of interest.
The transcriptional landscape and biomarker potential of circular RNAs in prostate cancer
Authors: Hansen Emma Bollmann , Fredsøe Jacob , Okholm Trine Line Hauge , Ulhøi Benedicte Parm , Klingenberg Søren , Jensen Jørgen Bjerggaard , Kjems Jørgen , Bouchelouche Kirsten , Borre Michael , Damgaard Christian Kroun , Pedersen Jakob Skou , Kristensen Lasse Sommer , Sørensen Karina Dalsgaard 
Published: January 2022

Abstract
Background
Circular RNAs (circRNAs) constitute a largely unexplored source for biomarker discovery in prostate cancer (PC). Here, we characterize the biomarker potential of circRNAs in PC, where the need for novel diagnostic and prognostic tools to facilitate more personalized management is pressing.

Methods
We profiled the transcriptomic landscape of circRNAs in PC by total RNA sequencing of 31 adjacent-normal and 143 tumor samples from localized (radical prostatectomy (RP)) and metastatic PC patients (cohort 1, training). Diagnostic and prognostic potential was evaluated in cohort 1, and 39 top circRNA candidates were selected for validation in two additional PC cohorts (cohort 2, n = 111; RP cohort 3, n = 191) by NanoString-based expression analysis. Biochemical recurrence (BCR)-free survival was assessed using Kaplan-Meier, univariate, and multivariate Cox regression analyses. The circRNA candidates were further detected in extracellular vesicle (EV)-enriched plasma samples from PC patients and controls (cohort 4, n = 54).

Results
Expression of circABCC4, circFAT3, circATRNL1, and circITGA7 was highly cancer-specific (area under the curve 0.71–0.86), while low circITGA7 expression was significantly (P < 0.05) associated with BCR in univariate analysis in two RP cohorts. Moreover, we successfully trained and validated a novel 5-circRNA prognostic signature (circKMD1A/circTULP4/circZNF532/circSUMF1/circMKLN1) significantly associated with BCR beyond routine clinicopathological variables (RP cohort 1: P = 0.02, hazard ratio = 2.1; RP cohort 3: P < 0.001, hazard ratio = 2.1). Lastly, we provide proof-of-principle for detection of candidate circRNAs in EV-enriched plasma samples from PC patients.

Conclusions
circRNAs hold great biomarker potential in PC and display both high cancer specificity and association to disease progression.
Closely related Salmonella Derby strains triggered distinct gut microbiota alteration
Authors: Yuan Xiaohui , Xue Han , Xu Xiaomeng , Jiao Xinan , Pan Zhiming , Zhang Yunzeng 
Published: January 2022

Abstract
Background
Salmonella Derby is one of the most predominant Salmonella serotypes that seriously threatens food safety. This bacterium can be further differentiated to sub-populations with different population sizes; however, whether and how the S. Derby–gut microbiota interactions affect epidemic patterns of S. Derby sub-populations remain largely unknown.

Results
We selected two representative strains, 14T and 14C, which represent rarely distributed and prevalent sub-populations of the S. Derby ST40 group, respectively, to address this question using a mouse model. Effects of oral administration of both strains was monitored for 14 days. Alpha diversity of gut microbiota at early stages of infection (4 h post infection) was higher in 14C-treated mice and lower in 14T-treated mice compared with controls. Strain 14T triggered stronger inflammation responses but with lower pathogen titer in spleen compared with strain 14C at 14 days post infection. Certain known probiotic bacteria that can hinder colonization of Salmonella, such as Bifidobacteriaceae and Akkermansiaceae, exhibited increased relative abundance in 14T-treated mice compared with 14C-treated mice. Our results also demonstrated that Ligilactobacillus strains isolated from gut microbiota showed stronger antagonistic activity against strain 14T compared with strain 14C.

Conclusions
We identified how S. Derby infection affected gut microbiota composition, and found that the 14T strain, which represented a rarely distributed S. Derby sub-population, triggered stronger host inflammation responses and gut microbiota disturbance compared with the 14C strain, which represented a prevalent S. Derby sub-population. This study provides novel insights on the impacts of gut microbiota on the epidemic patterns of Salmonella populations.
One-year spatiotemporal database of Emergency Medical Service (EMS) calls in Mashhad, Iran: data on 224,355 EMS calls
Authors: Hashtarkhani Soheil , Kiani Behzad , Mohammadi Alireza , MohammadEbrahimi Shahab , Eslami Saeid , Tara Mahmood , Matthews Stephen A. 
Published: January 2022

Abstract
Objectives
Emergency Medical Services (EMS) is the first point of service for the people who are in critical condition and in need of urgent health care. In Iran, as in other countries, people in need of emergency services often die or are left with a permanent injury due to the poor EMS-related infrastructure. It has been shown that a detailed examination of the response times and the spatiotemporal pattern of EMS calls for service can lead to improvements in time-sensitive patient outcomes. We performed a spatiotemporal study in city of Mashhad, the second-most populous city of Iran, to investigate the pattern of the EMS calls and now wish to release a comprehensive dataset resulting from this study.

Data description
The data include three data files plus a data dictionary file. Data file 1 contains the characteristics of EMS requests including sex, age group, date of call, different time periods of each EMS missions, the census tracts’ ID of callers, the chief complaint, and the EMS mission result. Two spatial data files include the boundaries of the census tracts in Mashhad and the point location of all EMS stations, respectively. A data dictionary file defines all fields and values across the data files.
Domestic violence during the COVID-19 confinement: do victims feel more socially isolated?
Authors: Drieskens Sabine , Braekman Elise , Ridder Karin De , Gisle Lydia , Charafeddine Rana , Hermans Lize , Demarest Stefaan 
Published: January 2022

Abstract
Background
Since March 13th 2020, confinement measures have been introduced in Belgium to curb the spread of the coronavirus (COVID-19). These measures also have an impact on people’s daily life (closure of school/businesses, teleworking, recommendation to stay at home). This can cause stress on social, economic and psychological levels and thereby can trigger domestic violence. Besides, confinement also fosters social isolation, which can complicate help seeking behaviour. The aim of this study is to determine the prevalence of domestic violence during the coronavirus crisis and to assess whether there is an association between domestic violence and social isolation.

Methods
Several online COVID-19 Health Surveys were organised among Belgian residents aged 18+ via snowball sampling. This study is based on the second (April 2020) and the sixth survey (March 2021). After excluding 1-person households and missing data, the sample size was respectively 25,251 and 12,589. Weighted prevalence of domestic violence was evaluated for the two surveys. The association (OR; 95% CI; p-value) between domestic violence and subjective social isolation was assessed with logistic regression stratified by survey and adjusted for covariates.

Results
In April 2020, 4.0% of the adult population reported being a victim of domestic violence (1.2% in the Health Interview Survey 2018); in March 2021, this was 6.2%. In April 2020, victims of domestic violence had higher odds of being unsatisfied with their social contacts (OR = 1.25; 95% CI: 1.08–1.44; p < .05), weak social support (OR = 2.26; 95% CI: 1.97–2.58; p < .0001) and having less confidence in health care services (OR = 1.38; 95% CI: 1.13–1.71; p < .05). In March 2021, victims had higher odds of being unsatisfied with their social contacts (OR = 1.30; 95% CI: 1.08–1.56; p < .05) and weak social support (OR = 2.41; 95% CI: 2.04–2.84; p < .0001), and social (OR = 2.64; 95% CI: 2.23–3.13; p < .0001) and emotional loneliness (OR = 2.22; 95% CI: 1.80–2.73; p < .0001).

Conclusions
More people have reported domestic violence since the start of the coronavirus crisis than did in 2018. An association between domestic violence and social isolation was determined. Although confinement is needed to counteract the virus, it can put people in a dangerous situation since they do not get the help they need. Therefore, adequate support is essential.
Heat and drought impact on carbon exchange in an age-sequence of temperate pine forests
Authors: Arain M. Altaf , Xu Bing , Brodeur Jason J. , Khomik Myroslava , Peichl Matthias , Beamesderfer Eric , Restrepo-Couple Natalia , Thorne Robin 
Published: January 2022

Abstract
Background
Most North American temperate forests are plantation or regrowth forests, which are actively managed. These forests are in different stages of their growth cycles and their ability to sequester atmospheric carbon is affected by extreme weather events. In this study, the impact of heat and drought events on carbon sequestration in an age-sequence (80, 45, and 17 years as of 2019) of eastern white pine (Pinus strobus L.) forests in southern Ontario, Canada was examined using eddy covariance flux measurements from 2003 to 2019.

Results
Over the 17-year study period, the mean annual values of net ecosystem productivity (NEP) were 180 ± 96, 538 ± 177 and 64 ± 165 g C m–2 yr–1 in the 80-, 45- and 17-year-old stands, respectively, with the highest annual carbon sequestration rate observed in the 45-year-old stand. We found that air temperature (Ta) was the dominant control on NEP in all three different-aged stands and drought, which was a limiting factor for both gross ecosystem productivity (GEP) and ecosystems respiration (RE), had a smaller impact on NEP. However, the simultaneous occurrence of heat and drought events during the early growing seasons or over the consecutive years had a significant negative impact on annual NEP in all three forests. We observed a similar trend of NEP decline in all three stands over three consecutive years that experienced extreme weather events, with 2016 being a hot and dry, 2017 being a dry, and 2018 being a hot year. The youngest stand became a net source of carbon for all three of these years and the oldest stand became a small source of carbon for the first time in 2018 since observations started in 2003. However, in 2019, all three stands reverted to annual net carbon sinks.

Conclusions
Our study results indicate that the timing, frequency and concurrent or consecutive occurrence of extreme weather events may have significant implications for carbon sequestration in temperate conifer forests in Eastern North America. This study is one of few globally available to provide long-term observational data on carbon exchanges in different-aged temperate plantation forests. It highlights interannual variability in carbon fluxes and enhances our understanding of the responses of these forest ecosystems to extreme weather events. Study results will help in developing climate resilient and sustainable forestry practices to offset atmospheric greenhouse gas emissions and improving simulation of carbon exchange processes in terrestrial ecosystem models.
Concepturealize™: a new contribution to generate real-needs-focussed, user-centred, lean business models
Authors: Allen Graeme Joseph 
Published: January 2022

AbstractIt is widely accepted that somewhere in the region of 90–95% of startups fail. It is often suggested that the majority of unsuccessful startups either failed to identify a viable idea, or they failed to execute the idea effectively enough to get to market before running out of cash. Two approaches stand out as being particularly well-suited to addressing these problems: Design Thinking and Lean Startup, respectively. This paper presents the Concepturealize™ methodology that cross-applies Design Thinking and Lean Startup as a single iterative process and that enables the entrepreneur to generate real-needs-focussed, user-centred, lean business models. Existing literature reveals a need for further exploration of cross-application of Design Thinking and Lean Startup (and other related methodologies) in the areas of business model development and innovation. This work answers the research question by review of prior attempts to combine Design Thinking and Lean Startup and presenting the Concepturealize™ model that cross-applies Design Thinking and Lean Startup in a single iterative methodology and that enables the practitioner to generate real-needs-focussed, user-centred, lean business models. By following this new process model correctly, a practitioner will be guided to uncover a viable way to create value, develop a deep understanding of the value proposition, the target customers and how to reach and serve them, together with the expected revenue and costs, all needed to properly formulate the business model. Finally, the practitioner may use the Concepturealize™ model to retest the problem–solution fit and understand how the customers perception of value has altered, each time a new product or new features are launched, looking to continually add value at each cycle. Whilst prior research has explored how organisations may make use of both DT and LS, it has failed to demonstrate how they may be used in parallel, throughout the entire business model development process, instead it demonstrates examples of insight into where to transition from one model to the other. This work progresses the state of the art by following Design Science guidelines to present how the true, in-parallel, cross-application of DT and LS, in the context of business model development, is possible.
CT-based radiomic nomogram for predicting the severity of patients with COVID-19
Authors: Shi Hengfeng , Xu Zhihua , Cheng Guohua , Ji Hongli , He Linyang , Zhu Juan , Hu Hanjin , Xie Zongyu , Ao Weiqun , Wang Jian 
Published: January 2022

Abstract
Background
The coronavirus disease 2019 (COVID-19) is a pandemic now, and the severity of COVID-19 determines the management, treatment, and even prognosis. We aim to develop and validate a radiomics nomogram for identifying patients with severe COVID-19.

Methods
There were 156 and 104 patients with COVID-19 enrolled in primary and validation cohorts, respectively. Radiomics features were extracted from chest CT images. Least absolute shrinkage and selection operator (LASSO) method was used for feature selection and radiomics signature building. Multivariable logistic regression analysis was used to develop a predictive model, and the radiomics signature, abnormal WBC counts, and comorbidity were incorporated and presented as a radiomics nomogram. The performance of the nomogram was assessed through its calibration, discrimination, and clinical usefulness.

Results
The radiomics signature consisting of four selected features was significantly associated with clinical condition of patients with COVID-19 in the primary and validation cohorts (P < 0.001). The radiomics nomogram including radiomics signature, comorbidity and abnormal WBC counts showed good discrimination of severe COVID-19, with an AUC of 0.972, and good calibration in the primary cohort. Application of the nomogram in the validation cohort still gave good discrimination with an AUC of 0.978 and good calibration. Decision curve analysis demonstrated that the radiomics nomogram was clinically useful to identify the severe COVID-19.

Conclusion
We present an easy-to-use radiomics nomogram to identify the patients with severe COVID-19 for better guiding a prompt management and treatment.
Excitotoxicity, calcium and mitochondria: a triad in synaptic neurodegeneration
Authors: Verma Manish , Lizama Britney N. , Chu Charleen T. 
Published: January 2022

AbstractGlutamate is the most commonly engaged neurotransmitter in the mammalian central nervous system, acting to mediate excitatory neurotransmission. However, high levels of glutamatergic input elicit excitotoxicity, contributing to neuronal cell death following acute brain injuries such as stroke and trauma. While excitotoxic cell death has also been implicated in some neurodegenerative disease models, the role of acute apoptotic cell death remains controversial in the setting of chronic neurodegeneration. Nevertheless, it is clear that excitatory synaptic dysregulation contributes to neurodegeneration, as evidenced by protective effects of partial N-methyl-D-aspartate receptor antagonists. Here, we review evidence for sublethal excitatory injuries in relation to neurodegeneration associated with Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis and Huntington’s disease. In contrast to classic excitotoxicity, emerging evidence implicates dysregulation of mitochondrial calcium handling in excitatory post-synaptic neurodegeneration. We discuss mechanisms that regulate mitochondrial calcium uptake and release, the impact of LRRK2, PINK1, Parkin, beta-amyloid and glucocerebrosidase on mitochondrial calcium transporters, and the role of autophagic mitochondrial loss in axodendritic shrinkage. Finally, we discuss strategies for normalizing the flux of calcium into and out of the mitochondrial matrix, thereby preventing mitochondrial calcium toxicity and excitotoxic dendritic loss. While the mechanisms that underlie increased uptake or decreased release of mitochondrial calcium vary in different model systems, a common set of strategies to normalize mitochondrial calcium flux can prevent excitatory mitochondrial toxicity and may be neuroprotective in multiple disease contexts.