bluuebunny/crossref_metadata_2025_split huggingface dataset:
Value-based evidence across health care sectors: a push for transparent real-world studies, data, and evidence dissemination
Authors: van den Broek Remon W. M. , Matheis Robert J. , Bright Jennifer L. , Hartog Tessa E. , Perfetto Eleanor M. 
Published: April 2022

Abstract
There is currently a heightened need for transparency in pharmaceutical sectors. The inclusion of real-world (RW) evidence, in addition to clinical trial evidence, in decision-making processes, was an important step forward toward a more inclusive established value proposition. This advance has introduced new transparency challenges. Increasing transparency is a critical step toward accelerating improvement in type, quality, and access to data, regardless of whether these originate from clinical trials or from RW studies. However, so far, advances in transparency have been relatively restricted to clinical trials, and there remains a lack of similar expectations or standards of transparency concerning the generation and reporting of RW data. This perspective paper aims to highlight the need for transparency concerning RW studies, data, and evidence across health care sectors, to identify areas for improvement, and provide concrete recommendations and practices for the future. Specific issues are discussed from different stakeholder perspectives, culminating in recommended actions, from individual stakeholder perspectives, for improved RW study, data, and evidence transparency. Furthermore, a list of potential guidelines for consideration by stakeholders is proposed. While recommendations from different stakeholder perspectives are made, true transparency in the processes involved in the generation, reporting, and use of RW evidence will require a concerted effort from all stakeholders across health care sectors.
In or against the state? Hospitality and hostility in homelessness charities and deportation practice
Authors: Dobson Rachael , Turnbull Sarah 
Published: April 2022

AbstractThis paper examines how deportation became a solution to rough sleeping in pre-Brexit England. It identifies relationships between the social regulation of vulnerable and marginalised adults, contemporary governance arrangements and bordering practices characteristic of Britain's ‘hostile environment’. Drawing on media reports and grey organisational literature, the focus of discussion is events across 2015–2018 in which three London-based charities were criticised for working with the Home Office to deport homeless migrants under its European Economic Area Administrative Removal policy. The overall tenor of criticism was that collaboration with the government compromised the organisations’ independence and charitable missions and aims. This diminished their capacity to both advocate for vulnerable adults and effectively challenge oppressive state practices. The paper observes how state and nonprofit relations structure institutional and socio-legal responses to marginalised and ‘othered’ adults through commissioning and contracting mechanisms. It demonstrates that the social and legal control of homeless migrants may be differently constituted by institutions delivering services in relation to citizenship, vulnerability and marginalisation. This analysis incorporates a broader appraisal of institutional motivations, values and beliefs in social welfare delivery, including the historic role of charitable agencies in the criminalisation of social welfare users. Taken together, the paper offers an interdisciplinary critique of the relationships between border control, neoliberal governance and the sociocultural and historic construction of homeless migrants.
Understanding the molecular basis of anorexia and tissue wasting in cancer cachexia
Authors: Yeom Eunbyul , Yu Kweon 
Published: April 2022

AbstractCancer cachexia syndrome is a major cause of morbidity and mortality in cancer patients in the advanced stage. It is a devastating disorder characterized by nutritional impairment, weakness, and wasting, and it affects treatment success and quality of life. Two major symptoms of cancer cachexia are anorexia and weight loss. Weight loss in cachexia is not reversed through increased food intake, suggesting that anorexia and weight loss in cancer patients are regulated by independent molecular mechanisms. Although the wasting phenotype mostly occurs in skeletal muscle and adipose tissue, other organs, such as the brain, liver, pancreas, heart, and gut, are also involved in cachexia. Thus, cachexia is a multiorgan syndrome. Although the molecular basis of cancer cachexia-induced weight loss is known, the mechanism underlying anorexia is poorly understood. Here, we highlight our recent discovery of a new anorexia mechanism by which a tumor-derived humoral factor induces cancer anorexia by regulating feeding-related neuropeptide hormones in the brain. Furthermore, we elucidated the process through which anorexia precedes tissue wasting in cachexia. This review article aims to provide an overview of the key molecular mechanisms of anorexia and tissue wasting caused by cancer cachexia.
A recurrent SHANK1 mutation implicated in autism spectrum disorder causes autistic-like core behaviors in mice via downregulation of mGluR1-IP3R1-calcium signaling
Authors: Qin Yue , Du Yasong , Chen Liqiang , Liu Yanyan , Xu Wenjing , Liu Ying , Li Ying , Leng Jing , Wang Yalan , Zhang Xiao-Yong , Feng Jianfeng , Zhang Feng , Jin Li , Qiu Zilong , Gong Xiaohong , Wang Hongyan 
Published: April 2022

AbstractThe genetic etiology and underlying mechanism of autism spectrum disorder (ASD) remain elusive. SHANK family genes (SHANK1/2/3) are well known ASD-related genes. However, little is known about how SHANK missense mutations contribute to ASD. Here, we aimed to clarify the molecular mechanism of and the multilevel neuropathological features induced by Shank1 mutations in knock-in (KI) mice. In this study, by sequencing the SHANK1 gene in a cohort of 615 ASD patients and 503 controls, we identified an ASD-specific recurrent missense mutation, c.2621 G > A (p.R874H). This mutation demonstrated strong pathogenic potential in in vitro experiments, and we generated the corresponding Shank1 R882H-KI mice. Shank1 R882H-KI mice displayed core symptoms of ASD, namely, social disability and repetitive behaviors, without confounding comorbidities of abnormal motor function and heightened anxiety. Brain structural changes in the frontal cortex, hippocampus and cerebellar cortex were observed in Shank1 R882H-KI mice via structural magnetic resonance imaging. These key brain regions also showed severe and consistent downregulation of mGluR1-IP3R1-calcium signaling, which subsequently affected the release of intracellular calcium. Corresponding cellular structural and functional changes were present in Shank1 R882H-KI mice, including decreased spine size, reduced spine density, abnormal morphology of postsynaptic densities, and impaired hippocampal long-term potentiation and basal excitatory transmission. These findings demonstrate the causative role of SHANK1 in ASD and elucidate the underlying biological mechanism of core symptoms of ASD. We also provide a reliable model of ASD with core symptoms for future studies, such as biomarker identification and therapeutic intervention studies.
Engineering strategies to enhance oncolytic viruses in cancer immunotherapy
Authors: Tian Yaomei , Xie Daoyuan , Yang Li 
Published: April 2022

AbstractOncolytic viruses (OVs) are emerging as potentially useful platforms in treatment methods for patients with tumors. They preferentially target and kill tumor cells, leaving healthy cells unharmed. In addition to direct oncolysis, the essential and attractive aspect of oncolytic virotherapy is based on the intrinsic induction of both innate and adaptive immune responses. To further augment this efficacious response, OVs have been genetically engineered to express immune regulators that enhance or restore antitumor immunity. Recently, combinations of OVs with other immunotherapies, such as immune checkpoint inhibitors (ICIs), chimeric antigen receptors (CARs), antigen-specific T-cell receptors (TCRs) and autologous tumor-infiltrating lymphocytes (TILs), have led to promising progress in cancer treatment. This review summarizes the intrinsic mechanisms of OVs, describes the optimization strategies for using armed OVs to enhance the effects of antitumor immunity and highlights rational combinations of OVs with other immunotherapies in recent preclinical and clinical studies.
LncRNA HOXC-AS3 promotes non-small-cell lung cancer growth and metastasis through upregulation of YBX1
Authors: Su HongBo , Fan GuanZhi , Huang Jin , Qiu XueShan 
Published: April 2022

AbstractNSCLC is common and is the primary cause of cancer-related deaths due to a lack of early diagnosis and its propensity for metastasis. The pathogenesis of NSCLC is still unclear. Here, we explored the molecular mechanisms underlying NSCLC development, focusing on the HOXC-AS3/YBX1/HOXC8 axis. Human NSCLC specimens and cell lines were used. qRT-PCR and western blotting were utilised to examine the levels of HOXC-AS3/YBX1/HOXC8. CCK-8, colony formation, scratch wound healing and Transwell assays were performed to evaluate cancer cell proliferation, migration and invasion. A nude mouse xenograft model was used to examine tumour growth and metastasis in vivo. RNA pull-down, chromatin immunoprecipitation, coimmunoprecipitation and dual-luciferase assays were applied to validate the interactions of HOXC-AS3/YBX1, MDM2/YBX1 and the YBX1/HOXC8 promoter. The levels of HOXC-AS3 and HOXC8 were increased in human NSCLC specimens and cells. Knockdown of HOXC-AS3 suppressed NSCLC cell proliferation, migration and invasion, as well as tumour growth and metastasis in vivo. HOXC-AS3 directly bound to YBX1 to suppress its ubiquitination mediated by MDM2. YBX1 bound to the HOXC8 promoter and enhanced its transcription. Knockdown of HOXC8 inhibited the effects of HOXC-AS3 overexpression on NSCLC. HOXC-AS3 promotes NSCLC growth and metastasis by stabilising YBX1 and thus increasing HOXC8 transcription. Our study indicates that the HOXC-AS3/YBX1/HOXC8 axis could serve as a biomarker for NSCLC diagnosis or as a target for therapy development.
Stabilization of parameter estimates from multiexponential decay through extension into higher dimensions
Authors: Bi Chuan , Fishbein Kenneth , Bouhrara Mustapha , Spencer Richard G. 
Published: April 2022

AbstractAnalysis of multiexponential decay has remained a topic of active research for over 200 years. This attests to the widespread importance of this problem and to the profound difficulties in characterizing the underlying monoexponential decays. Here, we demonstrate the fundamental improvement in stability and conditioning of this classic problem through extension to a second dimension; we present statistical analysis, Monte-Carlo simulations, and experimental magnetic resonance relaxometry data to support this remarkable fact. Our results are readily generalizable to higher dimensions and provide a potential means of circumventing conventional limits on multiexponential parameter estimation.
An ambient air quality evaluation model based on improved evidence theory
Authors: Sun Qiao , Zhang Tong , Wang Xinyang , Lin Weiwei , Fong Simon , Chen Zhibo , Xu Fu , Wu Ling 
Published: April 2022

AbstractIt is significant to evaluate the air quality scientifically for the management of air pollution. As an air quality comprehensive evaluation problem, its uncertainty can be effectively addressed by the Dempster–Shafer (D–S) evidence theory. However, there is not enough research on air quality comprehensive assessment using D–S theory. Aiming at the counterintuitive fusion results of the D–S combination rule in the field of comprehensive decision, an improved evidence theory with evidence weight and evidence decision credibility (here namely DCre-Weight method) is proposed, and it is used to comprehensively evaluate air quality. First, this method determines the weights of evidence by the entropy weight method and introduces the decision credibility by calculating the dispersion of different evidence decisions. An algorithm case shows that the credibility of fusion results is improved and the uncertainty is well expressed. It can make reasonable fusion results and solve the problems of D–S. Then, the air quality evaluation model based on improved evidence theory (here namely the DCreWeight model) is proposed. Finally, according to the hourly air pollution data in Xi’an from June 1, 2014, to May 1, 2016, comparisons are made with the D–S, other improved methods of evidence theory, and a recent fuzzy synthetic evaluation method to validate the effectiveness of the model. Under the national AQCI standard, the MAE and RMSE of the DCreWeight model are 1.02 and 1.17. Under the national AQI standard, the DCreWeight model has the minimal MAE, RMSE, and maximal index of agreement, which validated the superiority of the DCreWeight model. Therefore, the DCreWeight model can comprehensively evaluate air quality. It can provide a scientific basis for relevant departments to prevent and control air pollution.
Low molecular weight polysialic acid binds to properdin and reduces the activity of the alternative complement pathway
Authors: Shahraz Anahita , Lin Yuchen , Mbroh Joshua , Winkler Jonas , Liao Huan , Lackmann Marie , Bungartz Annemarie , Zipfel Peter F. , Skerka Christine , Neumann Harald 
Published: April 2022

AbstractSialic acids as the terminal caps of the cellular glycocalyx play an essential role in self-recognition and were shown to modulate complement processes via interaction between α2,3-linked sialic acids and complement factor H. Previously, it was suggested that low molecular weight α2,8-linked polysialic acid (polySia avDP20) interferes with complement activation, but the exact molecular mechanism is still unclear. Here, we show that soluble polySia avDP20 (molecular weight of ~ 6 kDa) reduced the binding of serum-derived alternative pathway complement activator properdin to the cell surface of lesioned Hepa-1c1c7 and PC-12 neuroblastoma cells. Furthermore, polySia avDP20 added to human serum blocked the alternative complement pathway triggered by plate-bound lipopolysaccharides. Interestingly, no inhibitory effect was observed with monosialic acid or oligosialic acid with a chain length of DP3 and DP5. In addition, polySia avDP20 directly bound properdin, but not complement factor H. These data show that soluble polySia avDP20 binds properdin and reduces the alternative complement pathway activity. Results strengthen the previously described concept of self-recognition of sialylation as check-point control of complement activation in innate immunity.
Naturally occurring combinations of receptors from single cell transcriptomics in endothelial cells
Authors: Domanskyi Sergii , Hakansson Alex , Meng Michelle , Pham Benjamin K. , Graff Zivin Joshua S. , Piermarocchi Carlo , Paternostro Giovanni , Ferrara Napoleone 
Published: April 2022

AbstractVEGF inhibitor drugs are part of standard care in oncology and ophthalmology, but not all patients respond to them. Combinations of drugs are likely to be needed for more effective therapies of angiogenesis-related diseases. In this paper we describe naturally occurring combinations of receptors in endothelial cells that might help to understand how cells communicate and to identify targets for drug combinations. We also develop and share a new software tool called DECNEO to identify them. Single-cell gene expression data are used to identify a set of co-expressed endothelial cell receptors, conserved among species (mice and humans) and enriched, within a network, of connections to up-regulated genes. This set includes several receptors previously shown to play a role in angiogenesis. Multiple statistical tests from large datasets, including an independent validation set, support the reproducibility, evolutionary conservation and role in angiogenesis of these naturally occurring combinations of receptors. We also show tissue-specific combinations and, in the case of choroid endothelial cells, consistency with both well-established and recent experimental findings, presented in a separate paper. The results and methods presented here advance the understanding of signaling to endothelial cells. The methods are generally applicable to the decoding of intercellular combinations of signals.
An analysis of student essays on medical leadership and its educational implications in South Korea
Authors: Lee I Re , Jung Hanna , Lee Yewon , Shin Jae Il , An Shinki 
Published: April 2022

AbstractTo examine medical students’ perceptions of leadership and explore their implications for medical leadership education. We conducted a qualitative analysis of the essays submitted by students in the medical leadership course from 2015 to 2019. We categorised the essays by the characteristics of the selected model leaders (N = 563) and types of leadership (N = 605). A statistically significant proportion of students selected leaders who were of the same gender as themselves (P < 0.001), graduate track students chose leaders in science (P = 0.005), while; military track students chose leaders in the military (P < 0.001). Although the highest proportion of students chose politicians as their model leaders (22.7%), this number decreased over time (P < 0.001), and a wider range of occupational groups were represented between 2015 and 2019. Charismatic leadership was the most frequently selected (31.9%), and over time there was a statistically significant (P = 0.004) increase in the selection of transformational leadership. Students tended to choose individuals whose acts of leadership could be seen and applied. Medical leadership education should account for students’ changing perceptions and present a feasible leadership model, introducing specific examples to illustrate these leadership skills.
Hierarchical multi-label classification based on LSTM network and Bayesian decision theory for LncRNA function prediction
Authors: Feng Shou , Li Huiying , Qiao Jiaqing 
Published: April 2022

AbstractGrowing evidence shows that long noncoding RNAs (lncRNAs) play an important role in cellular biological processes at multiple levels, such as gene imprinting, immune response, and genetic regulation, and are closely related to diseases because of their complex and precise control. However, most functions of lncRNAs remain undiscovered. Current computational methods for exploring lncRNA functions can avoid high-throughput experiments, but they usually focus on the construction of similarity networks and ignore the certain directed acyclic graph (DAG) formed by gene ontology annotations. In this paper, we view the function annotation work as a hierarchical multilabel classification problem and design a method HLSTMBD for classification with DAG-structured labels. With the help of a mathematical model based on Bayesian decision theory, the HLSTMBD algorithm is implemented with the long-short term memory network and a hierarchical constraint method DAGLabel. Compared with other state-of-the-art algorithms, the results on GOA-lncRNA datasets show that the proposed method can efficiently and accurately complete the label prediction work.
Monitoring of SARS-CoV-2 antibodies using dried blood spot for at-home collection
Authors: Miesse Peyton K. , Collier Bradley B. , Grant Russell P. 
Published: April 2022

AbstractThe utilization of vaccines to fight the spread of SARS-CoV-2 has led to a growing need for expansive serological testing. To address this, an EUA approved immunoassay for detection of antibodies to SARS-CoV-2 in venous serum samples was investigated for use with dried blood spot (DBS) samples. Results from self-collected DBS samples demonstrated a 98.1% categorical agreement to venous serum with a correlation (R) of 0.9600 while professionally collected DBS samples demonstrated a categorical agreement of 100.0% with a correlation of 0.9888 to venous serum. Additional studies were performed to stress different aspects of at-home DBS collection, including shipping stability, effects of interferences, and other sample-specific robustness studies. These studies demonstrated a categorical agreement of at least 95.0% and a mean bias less than ± 20.0%. Furthermore, the ability to track antibody levels following vaccination with the BioNTech/Pfizer vaccine was demonstrated with serial self-collected DBS samples from pre-dose (Day 0) out to 19 weeks.
Mapping the wildland-urban interface in California using remote sensing data
Authors: Li Shu , Dao Vu , Kumar Mukesh , Nguyen Phu , Banerjee Tirtha 
Published: April 2022

AbstractDue to the mixed distribution of buildings and vegetation, wildland-urban interface (WUI) areas are characterized by complex fuel distributions and geographical environments. The behavior of wildfires occurring in the WUI often leads to severe hazards and significant damage to man-made structures. Therefore, WUI areas warrant more attention during the wildfire season. Due to the ever-changing dynamic nature of California’s population and housing, the update frequency and resolution of WUI maps that are currently used can no longer meet the needs and challenges of wildfire management and resource allocation for suppression and mitigation efforts. Recent developments in remote sensing technology and data analysis algorithms pose new opportunities for improving WUI mapping methods. WUI areas in California were directly mapped using building footprints extracted from remote sensing data by Microsoft along with the fuel vegetation cover from the LANDFIRE dataset in this study. To accommodate the new type of datasets, we developed a threshold criteria for mapping WUI based on statistical analysis, as opposed to using more ad-hoc criteria as used in previous mapping approaches. This method removes the reliance on census data in WUI mapping, and does not require the calculation of housing density. Moreover, this approach designates the adjacent areas of each building with large and dense parcels of vegetation as WUI, which can not only refine the scope and resolution of the WUI areas to individual buildings, but also avoids zoning issues and uncertainties in housing density calculation. Besides, the new method has the capability of updating the WUI map in real-time according to the operational needs. Therefore, this method is suitable for local governments to map local WUI areas, as well as formulating detailed wildfire emergency plans, evacuation routes, and management measures.
Extensive epigenetic modification with large-scale chromosomal and plasmid recombination characterise the Legionella longbeachae serogroup 1 genome
Authors: Slow Sandy , Anderson Trevor , Murdoch David R. , Bloomfield Samuel , Winter David , Biggs Patrick J. 
Published: April 2022

AbstractLegionella longbeachae is an environmental bacterium that is the most clinically significant Legionella species in New Zealand (NZ), causing around two-thirds of all notified cases of Legionnaires’ disease. Here we report the sequencing and analysis of the geo-temporal genetic diversity of 54 L. longbeachae serogroup 1 (sg1) clinical isolates, derived from cases from around NZ over a 22-year period, including one complete genome and its associated methylome. The 54 sg1 isolates belonged to two main clades that last shared a common ancestor between 95 BCE and 1694 CE. There was diversity at the genome-structural level, with large-scale arrangements occurring in some regions of the chromosome and evidence of extensive chromosomal and plasmid recombination. This includes the presence of plasmids derived from recombination and horizontal gene transfer between various Legionella species, indicating there has been both intra- and inter-species gene flow. However, because similar plasmids were found among isolates within each clade, plasmid recombination events may pre-empt the emergence of new L. longbeachae strains. Our complete NZ reference genome consisted of a 4.1 Mb chromosome and a 108 kb plasmid. The genome was highly methylated with two known epigenetic modifications, m4C and m6A, occurring in particular sequence motifs within the genome.