bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and validation of cellular senescence patterns to predict clinical outcomes and immunotherapeutic responses in lung adenocarcinoma
Authors: Lin Weihao , Wang Xin , Xu Zhenyi , Wang Zhen , Liu Tiejun , Cao Zheng , Feng Xiaoli , Gao Yibo , He Jie 
Published: December 2021

Abstract
Background
Aging and senescence can alter immune cell fitness and influence the efficacy of lung cancer treatments, especially immunotherapy. However, the correlations between cellular senescence and tumor microenvironment are still not clearly clarified and the value of cellular senescence-related genes in evaluating the immune infiltration and clinical outcomes of lung adenocarcinoma (LUAD) need further investigated.

Methods
We identified three cellular senescence clusters by NMF algorithm and correlated the cellular senescence clusters with the immune landscape in LUAD patients. A prognostic scoring system was established using random survival forest algorithm and validated in 4 external cohorts. Multivariate Cox regression analysis was performed to evaluate the prognostic value of the scoring system. Expression of LYPD3 was evaluated by immunohistochemistry in LUAD samples.

Results
Based on the mRNA expression profiles of 278 cellular senescence-related genes, three cellular senescence clusters with distinct prognosis were identified. We characterized three cellular senescence clusters by differences in biological processes, EMT score, expression of immunomodulatory genes, extent of intratumor heterogeneity and response to immunotherapy. Meanwhile, a cellular senescence-related scoring system (CSS) was established and validated as an independent prognostic factor and immunotherapy predictor of LUAD. Patients with low CSS was characterized by prolonged survival time. In response to anti-cancer drugs, patients with low CSS exhibited higher sensitivities to molecular drugs, such as Roscovitine (CDKs inhibitor), Lenaidornide (TNF-α inhibitor), MK2206 (Akt 1/2/3 inhibitor), and especially increased response to anti-PD-1/L1 immunotherapy.

Conclusions
This study demonstrated the correlations between cellular senescence patterns and tumor immune landscape in LUAD, which enhanced our understanding of the tumor immune microenvironment and provided new insights for improving the outcome of immunotherapy for LUAD patients.
Camera-based heart rate estimation for hospitalized newborns in the presence of motion artifacts
Authors: Chen Qiong , Wang Yalin , Liu Xiangyu , Long Xi , Yin Bin , Chen Chen , Chen Wei 
Published: December 2021

AbstractBackgroundHeart rate (HR) is an importantvital signfor evaluating the physiological condition of a newborn infant. Recently, for measuring HR, novel RGB camera-based non-contact techniques have demonstrated their specific superiority compared with other techniques, such as dopplers and thermal cameras. However, they still suffered poor robustness in infants’ HR measurements due to frequent body movement.MethodsThis paper introduces a framework to improve the robustness of infants’ HR measurements by solving motion artifact problems. Our solution is based on the following steps: morphology-based filtering, region-of-interest (ROI) dividing, Eulerian video magnification and majority voting. In particular, ROI dividing improves ROI information utilization. The majority voting scheme improves the statistical robustness by choosing the HR with the highest probability. Additionally, we determined the dividing parameter that leads to the most accurate HR measurements. In order to examine the performance of the proposed method, we collected 4 hours of videos and recorded the corresponding electrocardiogram (ECG) of 9 hospitalized neonates under two different conditions—rest stillandvisible movements.ResultsExperimental results indicate a promising performance: the mean absolute error duringrest stillandvisible movementsare 3.39 beats per minute (BPM) and 4.34 BPM, respectively, which improves at least 2.00 and 1.88 BPM compared with previous works. The Bland-Altman plots also show the remarkable consistency of our results and the HR derived from the ground-truth ECG.ConclusionsTo the best of our knowledge, this is the first study aimed at improving the robustness of neonatal HR measurement under motion artifacts using an RGB camera. The preliminary results have shown the promising prospects of the proposed method, which hopefully reduce neonatal mortality in hospitals.
Tumor antigens and immune subtypes guided mRNA vaccine development for kidney renal clear cell carcinoma
Authors: Xu Hang , Zheng Xiaonan , Zhang Shiyu , Yi Xianyanling , Zhang Tianyi , Wei Qiang , Li Hong , Ai Jianzhong 
Published: December 2021

AbstractCurrent treatment strategy for kidney renal clear cell carcinoma (KIRC) is limited. Tumor-associated antigens, especially neoantigen-based personalized mRNA vaccines represent new strategies and manifest clinical benefits in solid tumors, but only a small proportion of patients could benefit from them, which prompts us to identify effective antigens and suitable populations to facilitate mRNA vaccines application in cancer therapy. Through performing expression, mutation, survival and correlation analyses in TCGA-KIRC dataset, we identified four genes including DNA topoisomerase II alpha (TOP2A), neutrophil cytosol factor 4 (NCF4), formin-like protein 1 (FMNL1) and docking protein 3 (DOK3) as potential KIRC-specific neoantigen candidates. These four genes were upregulated, mutated and positively associated with survival and antigen-presenting cells in TCGA-KIRC. Furthermore, we identified two immune subtypes, named renal cell carcinoma immune subtype 1 (RIS1) and RIS2, of KIRC. Distinct clinical, molecular and immune-related signatures were observed between RIS1 and RIS2. Patients of RIS2 had better survival outcomes than those of RIS1. Further comprehensive immune-related analyses indicated that RIS1 is immunologically “hot” and represent an immunosuppressive phenotype, whereas RIS2 represents an immunologically “cold” phenotype. RIS1 and RIS2 also showed differential features with regard to tumor infiltrating immune cells and immune checkpoint-related genes. Moreover, the immune landscape construction identified the immune cell components of each KIRC patient, predicted their survival outcomes, and assisted the development of personalized mRNA vaccines. In summary, our study identified TOP2A, NCF4, FMNL1 and DOK3 as potential effective neoantigens for KIRC mRNA vaccine development, and patients with RIS2 tumor might benefit more from mRNA vaccination.
Recent advances of fluorescent biosensors based on cyclic signal amplification technology in biomedical detection
Authors: Qu Hongke , Fan Chunmei , Chen Mingjian , Zhang Xiangyan , Yan Qijia , Wang Yumin , Zhang Shanshan , Gong Zhaojian , Shi Lei , Li Xiayu , Liao Qianjin , Xiang Bo , Zhou Ming , Guo Can , Li Guiyuan , Zeng Zhaoyang , Wu Xu , Xiong Wei 
Published: December 2021

AbstractThe cyclic signal amplification technology has been widely applied for the ultrasensitive detection of many important biomolecules, such as nucleic acids, proteins, enzymes, adenosine triphosphate (ATP), metal ions, exosome, etc. Due to their low content in the complex biological samples, traditional detection methods are insufficient to satisfy the requirements for monitoring those biomolecules. Therefore, effective and sensitive biosensors based on cyclic signal amplification technology are of great significance for the quick and simple diagnosis and treatment of diseases. Fluorescent biosensor based on cyclic signal amplification technology has become a research hotspot due to its simple operation, low cost, short time, high sensitivity and high specificity. This paper introduces several cyclic amplification methods, such as rolling circle amplification (RCA), strand displacement reactions (SDR) and enzyme-assisted amplification (EAA), and summarizes the research progress of using this technology in the detection of different biomolecules in recent years, in order to provide help for the research of more efficient and sensitive detection methods.
Graphical Abstract
Assessing the impact of knowledge communication and dissemination strategies targeted at health policy-makers and managers: an overview of systematic reviews
Authors: Chapman Evelina , Pantoja Tomas , Kuchenmüller Tanja , Sharma Tarang , Terry Robert F. 
Published: December 2021

Abstract
Background
The use of research evidence as an input for health decision-making is a need for most health systems. There are a number of approaches for promoting evidence use at different levels of the health system, but knowledge of their effectiveness is still scarce. The objective of this overview was to evaluate the effectiveness of knowledge communication and dissemination interventions, strategies or approaches targeting policy-makers and health managers.

Methods
This overview of systematic reviews used systematic review methods and was conducted according to a predefined and published protocol. A comprehensive electronic search of 13 databases and a manual search in four websites were conducted. Both published and unpublished reviews in English, Spanish or Portuguese were included. A narrative synthesis was undertaken, and effectiveness statements were developed, informed by the evidence identified.

Results
We included 27 systematic reviews. Three studies included only a communication strategy, while eight only included dissemination strategies, and the remaining 16 included both. None of the selected reviews provided “sufficient evidence” for any of the strategies, while four provided some evidence for three communication and four dissemination strategies. Regarding communication strategies, the use of tailored and targeted messages seemed to successfully lead to changes in the decision-making practices of the target audience. Regarding dissemination strategies, interventions that aimed at improving only the reach of evidence did not have an impact on its use in decisions, while interventions aimed at enhancing users’ ability to use and apply evidence had a positive effect on decision-making processes. Multifaceted dissemination strategies also demonstrated the potential for changing knowledge about evidence but not its implementation in decision-making.

Conclusions
There is limited evidence regarding the effectiveness of interventions targeting health managers and policy-makers, as well as the mechanisms required for achieving impact. More studies are needed that are informed by theoretical frameworks or specific tools and using robust methods, standardized outcome measures and clear descriptions of the interventions. We found that passive communication increased access to evidence but had no effect on uptake. Some evidence indicated that the use of targeted messages, knowledge-brokering and user training was effective in promoting evidence use by managers and policy-makers.
The use of food swaps to encourage healthier online food choices: a randomized controlled trial
Authors: Jansen Laura , van Kleef Ellen , Van Loo Ellen J. 
Published: December 2021

Abstract
Background
Online grocery stores offer opportunities to encourage healthier food choices at the moment that consumers place a product of their choice in their basket. This study assessed the effect of a swap offer, Nutri-Score labeling, and a descriptive norm message on the nutrient profiling (NP) score of food choices in an online food basket. Additionally explored was whether these interventions made it more motivating and easier for consumers to select healthier foods and whether potential effects were moderated by consumer health interest.

Methods
Hypotheses were tested with a randomized controlled trial (RCT) in a simulated online supermarket. Dutch participants (n = 550) chose their preferred product out of six product options for four different categories (breakfast cereals, crackers, pizza, and muesli bars). Participants were randomly allocated to one of eight groups based on the interventions in a 2 (Nutri-Score: present, not present) X 2 (swap offer: present, not present) X 2 (norm message: present, not present) between subject design. The primary outcome was the difference in combined NP score of product choices, for which a lower score represented a healthier product.

Results
Swap offer (B = − 9.58, 95% CI: [− 12.026; − 7.132], Ƞ2 = 0.098) and Nutri-Score labeling (B = − 3.28, 95% CI: [− 5.724; −.829], Ƞ2 = 0.013) significantly improved the combined NP score compared to the control condition (NP score M = 18.03, SD = 14.02), whereas a norm message did not have a significant effect (B = − 1.378, 95% CI [− 3.825; 1.070], Ƞ2 = 0.002). No evidence was found that interventions made it more motivating or easier for consumers to select healthier food, but situational motivation significantly influenced the healthiness score of food choices for both swap offer (b = − 3.40, p < .001) and Nutri-Score (b = − 3.25, p < .001). Consumer health interest only significantly moderated the influence of Nutri-Score on ease of identifying the healthy food option (b = .23, p = .04).

Conclusions
Swap offer and Nutri-Score labeling were effective in enhancing healthy purchase behavior in the online store environment.

Trial registration
This study was retrospectively registered in the ISRCTN database on 02-09-2021 (ISRCTN80519674).
The maintained attention assessment in patients affected by Myalgic encephalomyelitis/chronic fatigue syndrome: a reliable biomarker?
Authors: Murga Iñigo , Aranburu Larraitz , Gargiulo Pascual A. , Gómez-Esteban Juan-Carlos , Lafuente José-Vicente 
Published: December 2021

AbstractThe maintained attention is the cause of great functional limitations in CFS/ME, a disease that mainly affects women in the central period of life. Cognitive function is explored using the Montreal Cognitive Assessment, the maintained attention using the Toulouse-Piéron test with which the Global Index of Attention and Perception (GIAP) is obtained, the fatigue using the visual analog scale and the perception of effort using the modified Borg scale. The final sample were 84 patients (66 women/18 men) who met diagnostic criteria (Fukuda-1994, Carruthers-2011) and 22 healthy controls (14 women/8 men). Most of patients maintain normal cognitive function, showing low or very low attention score in the 70% of patients with a marked cognitive fatigue compared to the control group (p < 0.05). There were no significant differences between genders in GIAP or fatigue for CFS/ME; however, sick women perceive cognitive effort higher than men. Deficits in sustained attention and the perception of fatigue, so effort after performing the proposed test are a sensitive and reliable indicator that allows us to substantiate a clinical suspicion and refer patients for further studies in order to confirm or rule out CFS/ME.
Automated and accurate assessment for postural abnormalities in patients with Parkinson’s disease based on Kinect and machine learning
Authors: Zhang Zhuoyu , Hong Ronghua , Lin Ao , Su Xiaoyun , Jin Yue , Gao Yichen , Peng Kangwen , Li Yudi , Zhang Tianyu , Zhi Hongping , Guan Qiang , Jin LingJing 
Published: December 2021

Abstract
Background
Automated and accurate assessment for postural abnormalities is necessary to monitor the clinical progress of Parkinson’s disease (PD). The combination of depth camera and machine learning makes this purpose possible.

Methods
Kinect was used to collect the postural images from 70 PD patients. The collected images were processed to extract three-dimensional body joints, which were then converted to two-dimensional body joints to obtain eight quantified coronal and sagittal features (F1-F8) of the trunk. The decision tree classifier was carried out over a data set established by the collected features and the corresponding doctors’ MDS-UPDRS-III 3.13 (the 13th item of the third part of Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale) scores. An objective function was implanted to further improve the human–machine consistency.

Results
The automated grading of postural abnormalities for PD patients was realized with only six selected features. The intraclass correlation coefficient (ICC) between the machine’s and doctors’ score was 0.940 (95%CI, 0.905–0.962), meaning the machine was highly consistent with the doctors’ judgement. Besides, the decision tree classifier performed outstandingly, reaching 90.0% of accuracy, 95.7% of specificity and 89.1% of sensitivity in rating postural severity.

Conclusions
We developed an intelligent evaluation system to provide accurate and automated assessment of trunk postural abnormalities in PD patients. This study demonstrates the practicability of our proposed method in the clinical scenario to help making the medical decision about PD.
Multiple novel filamentous phages detected in the cloacal swab samples of birds using viral metagenomics approach
Authors: Zeng Jian , Wang Yan , Zhang Ju , Yang Shixing , Zhang Wen 
Published: December 2021

AbstractMembers of the family Inoviridae (inoviruses) are characterized by their unique filamentous morphology and infection cycle. The viral genome of inovirus is able to integrate into the host genome and continuously releases virions without lysing the host, establishing chronic infection. A large number of inoviruses have been obtained from microbial genomes and metagenomes recently, but putative novel inoviruses remaining to be identified. Here, using viral metagenomics, we identified four novel inoviruses from cloacal swab samples of wild and breeding birds. The circular genome of those four inoviruses are 6732 to 7709 nt in length with 51.4% to 56.5% GC content and encodes 9 to 13 open reading frames, respectively. The zonula occludens toxin gene implicated in the virulence of pathogenic host bacteria were identified in all four inoviruses and shared the highest amino acid sequences identity (< 37.3%) to other reference strains belonging to different genera of the family Inoviridae and among themselves. Phylogenetic analysis indicated that all the four inoviruses were genetically far away from other strains belonging to the family Inoviridae and formed an independent clade. According to the genetic distance-based criteria, all the four inoviruses identified in the present study respectively belong to four novel putative genera in the family Inoviridae.
Capsule-dependent impact of MAPK signalling on host cell invasion and immune response during infection of the choroid plexus epithelium by Neisseria meningitidis
Authors: Herold Rosanna , Scholtysik René , Moroniak Selina , Weiss Christel , Ishikawa Hiroshi , Schroten Horst , Schwerk Christian 
Published: December 2021

Abstract
Background
The Gram-negative bacterium Neisseria meningitidis (Nm) can cause meningitis in humans, but the host signalling pathways manipulated by Nm during central nervous system (CNS) entry are not completely understood.

Methods
We investigate the role of the mitogen-activated protein kinases (MAPK) Erk1/2 and p38 in an in vitro model of the blood-cerebrospinal fluid barrier (BCSFB) based on human epithelial choroid plexus (CP) papilloma (HIBCPP) cells during infection with Nm serogroup B (NmB) and serogroup C (NmC) strains. A transcriptome analysis of HIBCPP cells following infection with Nm by massive analysis of cDNA ends (MACE) was done to further characterize the cellular response to infection of the barrier.

Results
Interestingly, whereas NmB and NmC wild type strains required active Erk1/2 and p38 pathways for infection, invasion by capsule-deficient mutants was independent of Erk1/2 and, in case of the NmB strain, of p38 activity. The transcriptome analysis of HIBCPP cells following infection with Nm demonstrated specific regulation of genes involved in the immune response dependent on Erk1/2 signalling. Gene ontology (GO) analysis confirmed loss of MAPK signalling after Erk1/2 inhibition and revealed an additional reduction of cellular responses including NFκB and JAK-STAT signalling. Interestingly, GO terms related to TNF signalling and production of IL6 were lost specifically following Erk1/2 inhibition during infection with wild type Nm, which correlated with the reduced infection rates by the wild type in absence of Erk1/2 signalling.

Conclusion
Our data point towards a role of MAPK signalling during infection of the CP epithelium by Nm, which is strongly influenced by capsule expression, and affects infection rates as well as the host cell response.
In search of traces of the mandrake myth: the historical, and ethnobotanical roots of its vernacular names
Authors: Dafni Amots , Blanché Cesar , Khatib Salekh Aqil , Petanidou Theodora , Aytaç Bedrettin , Pacini Ettore , Kozuharova Ekaterina , Geva-Kleinberger Aharon , Shahvar Soli , Dajic Zora , Klug Helmut W. , Benítez Guillermo 
Published: December 2021

AbstractBackgroundMandrake (Mandragoraspp.) is one of the most famous medicinal plant in western cultures since Biblical times and throughout written history. In many cultures, mandrake is related to magic and witchcraft, which is said to have a psychosomatic effect (especially when mandrake contains narcotic compounds) in addition to the pharmacological influence, as occurs with other narcotic magical plants. Due to its unique properties and related myths, it is not surprising that this plant has many names in many languages.MethodsThis paper presents an attempt to reconstruct the historical, ethnobotanical, and folkloristic roots of 292 vernacular names ofMandragoraspp. in forty-one languages. We used the plant’s morphological data, philology, myths and legends, medicinal properties and uses, as well as historical evidence and folkloric data, to explain meaning, origin, migration, and history of the plant’s names.ResultsThe names were classified into the following main categories: Derivatives ofmandragora(19 languages),alraun(7) and ofyabroukh(5). The salient groups of the plant’s vernacular names are related to: Anthropomorphism (33 names in 13 languages); Similarity to other plants (28/9); Supernatural agents (28/9); Narcotic effects (21/8); Leaves, fruits, and seeds (21/8); Aphrodisiac properties (17/10); Use of a dog (15/9); Gallows (14/5); Black magic, sorcery, witchcraft (13/8), and Medicinal use (11/7).ConclusionsThis frequency distribution of the mandrake’s vernacular names reflects its widespread reputation as related to the doctrine of signatures, beliefs in its supernatural, natural, and mythic powers, and to a lesser extent, its uses in magic and medicine. A spatiotemporal analysis of the mandrake’s names supports the old idea that the pulling ceremonies for this plant originated in the Near East and that various other myths related to this plant may have originated in different places and periods.
A simpler linear-time algorithm for the common refinement of rooted phylogenetic trees on a common leaf set
Authors: Schaller David , Hellmuth Marc , Stadler Peter F. 
Published: December 2021

AbstractBackgroundThe supertree problem, i.e., the task of finding a common refinement of a set of rooted trees is an important topic in mathematical phylogenetics. The special case of a common leaf setLis known to be solvable in linear time. Existing approaches refine one input tree using information of the others and then test whether the results are isomorphic.ResultsAnO(k|L|) algorithm, , for constructing the common refinementTofkinput trees with a common leaf setLis proposed that explicitly computes the parent function ofTin a bottom-up approach.Conclusionis simpler to implement than other asymptotically optimal algorithms for the problem and outperforms the alternatives in empirical comparisons.AvailabilityAn implementation of in Python is freely available athttps://github.com/david-schaller/tralda.