bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parental Age and Childhood Lymphoma and Solid Tumor Risk: A Literature Review and Meta-Analysis
Authors: Domingues Allison , Moore Kristin J , Sample Jeannette , Kharoud Harmeet , Marcotte Erin L , Spector Logan G 
Published: May 2022

Abstract

Background
Although advanced parental age has been definitively linked to pediatric acute lymphoblastic leukemia, studies of parental age and pediatric solid tumors have not reached firm conclusions. This analysis aimed to elucidate the relationship between parental age and pediatric solid tumors through meta-analysis of existing studies based in population registries.

Methods
We searched Medline (PubMed) and Embase for registry-based studies of parental age and solid tumors through March 2022. We performed random-effects meta-analysis to estimate pooled effects and 95% confidence intervals (CIs). All statistical tests were 2-sided.

Results
A total of 15 studies covering 10 childhood solid tumor types (30 323 cases and 3 499 934 controls) were included in this analysis. A 5-year increase in maternal age was associated with an increased risk of combined central nervous system tumors (odds ratio [OR] = 1.07, 95% CI = 1.04 to 1.10), ependymoma (OR = 1.19, 95% CI = 1.09 to 1.31), astrocytoma (OR = 1.10, 95% CI = 1.05 to 1.15), rhabdomyosarcoma (OR = 1.14, 95% CI = 1.03 to 1.25), and germ cell tumors (OR = 1.06, 95% CI = 1.00 to 1.12). A 5-year increase in paternal age was associated with an increased risk of non-Hodgkin lymphoma (OR = 1.06, 95% CI = 1.00 to 1.12).

Conclusions
This meta-analysis of registry-based analyses of parental age and childhood cancer supports the association between older maternal age and certain childhood solid cancers. There is also some evidence that paternal age may be associated with certain cancers such as non-Hodgkin lymphoma. However, as maternal and paternal age are highly correlated, disentangling potential independent causal effects of either factor will require large studies with extensive data on potential confounders.
Current situation survey for establishing personally acceptable radiation dose limits for nuclear disaster responders
Authors: Iyama Keita , Kakamu Takeyasu , Yamashita Kazunori , Shimada Jiro , Tasaki Osamu , Hasegawa Arifumi 
Published: May 2022

Abstract
When responding to disasters, emergency preparedness is essential to ensure that disaster activities are performed smoothly, safely and efficiently. Investigations on the Fukushima accident revealed that lack of preparedness, poor communication and unsuitable emergency measures contributed to an inadequate emergency response to the nuclear disaster. In this study, we conducted a questionnaire survey on the establishment of a personal radiation exposure dose among Disaster Medical Assistance Team (DMAT) members in Japan who might be involved in the initial response to a nuclear disaster. Establishing personal exposure doses for personnel can encourage emergency preparedness and inform decisions on appropriate role assignments during nuclear response activities. Valid responses were obtained from 178 participants, and the response distribution was as follows: ‘Already have own acceptable dose standard,’ 16 (9%); ‘Follow own institution’s standard (and know its value),’ 30 (17%); ‘Follow own institution’s standard (but do not know its value),’ 59 (33%); ‘Haven’t decided,’ 63 (35%) and ‘Don’t understand question meaning,’ 10 (6%). We also assessed intention to engage in nuclear disaster activities among respondents via engagement intent scores (EIS) and found that participants who had established personal exposure standards had significantly higher EIS scores than those who had not decided or who did not understand the question. Thus, educating potential nuclear disaster responders on personal exposure doses may contribute to a higher intention to engage in emergency responses and improve preparedness and response efficiency.
Ancestral Sequence Reconstruction of a Cytochrome P450 Family Involved in Chemical Defense Reveals the Functional Evolution of a Promiscuous, Xenobiotic-Metabolizing Enzyme in Vertebrates
Authors: Harris Kurt L. , Thomson Raine E.S. , Gumulya Yosephine , Foley Gabriel , Carrera-Pacheco Saskya E. , Syed Parnayan , Janosik Tomasz , Sandinge Ann-Sofie , Andersson Shalini , Jurva Ulrik , Bodén Mikael , Gillam Elizabeth M.J. 
Published: May 2022

AbstractThe cytochrome P450 family 1 enzymes (CYP1s) are a diverse family of hemoprotein monooxygenases, which metabolize many xenobiotics including numerous environmental carcinogens. However, their historical function and evolution remain largely unstudied. Here we investigate CYP1 evolution via the reconstruction and characterization of the vertebrate CYP1 ancestors. Younger ancestors and extant forms generally demonstrated higher activity toward typical CYP1 xenobiotic and steroid substrates than older ancestors, suggesting significant diversification away from the original CYP1 function. Caffeine metabolism appears to be a recently evolved trait of the CYP1A subfamily, observed in the mammalian CYP1A lineage, and may parallel the recent evolution of caffeine synthesis in multiple separate plant species. Likewise, the aryl hydrocarbon receptor agonist, 6-formylindolo[3,2-b]carbazole (FICZ) was metabolized to a greater extent by certain younger ancestors and extant forms, suggesting that activity toward FICZ increased in specific CYP1 evolutionary branches, a process that may have occurred in parallel to the exploitation of land where UV-exposure was higher than in aquatic environments. As observed with previous reconstructions of P450 enzymes, thermostability correlated with evolutionary age; the oldest ancestor was up to 35 °C more thermostable than the extant forms, with a 10T50 (temperature at which 50% of the hemoprotein remains intact after 10 min) of 71 °C. This robustness may have facilitated evolutionary diversification of the CYP1s by buffering the destabilizing effects of mutations that conferred novel functions, a phenomenon which may also be useful in exploiting the catalytic versatility of these ancestral enzymes for commercial application as biocatalysts.
Detecting critical transition signals from single-cell transcriptomes to infer lineage-determining transcription factors
Authors: Yang Xinan H , Goldstein Andrew , Sun Yuxi , Wang Zhezhen , Wei Megan , Moskowitz Ivan P , Cunningham John M 
Published: May 2022

AbstractAnalyzing single-cell transcriptomes promises to decipher the plasticity, heterogeneity, and rapid switches in developmental cellular state transitions. Such analyses require the identification of gene markers for semi-stable transition states. However, there are nontrivial challenges such as unexplainable stochasticity, variable population sizes, and alternative trajectory constructions. By advancing current tipping-point theory-based models with feature selection, network decomposition, accurate estimation of correlations, and optimization, we developed BioTIP to overcome these challenges. BioTIP identifies a small group of genes, called critical transition signal (CTS), to characterize regulated stochasticity during semi-stable transitions. Although methods rooted in different theories converged at the same transition events in two benchmark datasets, BioTIP is unique in inferring lineage-determining transcription factors governing critical transition. Applying BioTIP to mouse gastrulation data, we identify multiple CTSs from one dataset and validated their significance in another independent dataset. We detect the established regulator Etv2 whose expression change drives the haemato-endothelial bifurcation, and its targets together in CTS across three datasets. After comparing to three current methods using six datasets, we show that BioTIP is accurate, user-friendly, independent of pseudo-temporal trajectory, and captures significantly interconnected and reproducible CTSs. We expect BioTIP to provide great insight into dynamic regulations of lineage-determining factors.
Molecular Regulation and Evolution of Cytokinin Signaling in Plant Abiotic Stresses
Authors: Li Lijun , Zheng Qingfeng , Jiang Wei , Xiao Nayun , Zeng Fanrong , Chen Guang , Mak Michelle , Chen Zhong-Hua , Deng Fenglin 
Published: May 2022

AbstractThe sustainable production of crops faces increasing challenges from global climate change and human activities, which leads to increasing instances of many abiotic stressors to plants. Among the abiotic stressors, drought, salinity and excessive levels of toxic metals cause reductions in global agricultural productivity and serious health risks for humans. Cytokinins (CKs) are key phytohormones functioning in both normal development and stress responses in plants. Here, we summarize the molecular mechanisms on the biosynthesis, metabolism, transport and signaling transduction pathways of CKs. CKs act as negative regulators of both root system architecture plasticity and root sodium exclusion in response to salt stress. The functions of CKs in mineral-toxicity tolerance and their detoxification in plants are reviewed. Comparative genomic analyses were performed to trace the origin, evolution and diversification of the critical regulatory networks linking CK signaling and abiotic stress. We found that the production of CKs and their derivatives, pathways of signal transduction and drought-response root growth regulation are evolutionarily conserved in land plants. In addition, the mechanisms of CK-mediated sodium exclusion under salt stress are suggested for further investigations. In summary, we propose that the manipulation of CK levels and their signaling pathways is important for plant abiotic stress and is, therefore, a potential strategy for meeting the increasing demand for global food production under changing climatic conditions.
Prospects of Feral Crop De Novo Redomestication
Authors: Pisias Michael T , Bakala Harmeet Singh , McAlvay Alex C , Mabry Makenzie E , Birchler James A , Yang Bing , Pires J Chris 
Published: May 2022

Abstract
Modern agriculture depends on a narrow variety of crop species, leaving global food and nutritional security highly vulnerable to the adverse effects of climate change and population expansion. Crop improvement using conventional and molecular breeding approaches leveraging plant genetic diversity using crop wild relatives (CWRs) has been one approach to address these issues. However, the rapid pace of the global change requires additional innovative solutions to adapt agriculture to meet global needs. Neodomestication—the rapid and targeted introduction of domestication traits using introgression or genome editing of CWRs—is being explored as a supplementary approach. These methods show promise; however, they have so far been limited in efficiency and applicability. We propose expanding the scope of neodomestication beyond truly wild CWRs to include feral crops as a source of genetic diversity for novel crop development, in this case ‘redomestication’. Feral crops are plants that have escaped cultivation and evolved independently, typically adapting to their local environments. Thus, feral crops potentially contain valuable adaptive features while retaining some domestication traits. Due to their genetic proximity to crop species, feral crops may be easier targets for de novo domestication (i.e. neodomestication via genome editing techniques). In this review, we explore the potential of de novo redomestication as an application for novel crop development by genome editing of feral crops. This approach to efficiently exploit plant genetic diversity would access an underutilized reservoir of genetic diversity that could prove important in support of global food insecurity in the face of the climate change.
Alternative splicing of REGULATOR OF LEAF INCLINATION 1 modulates phosphate starvation signaling and growth in plants
Authors: Guo Meina , Zhang Yuxin , Jia Xianqing , Wang Xueqing , Zhang Yibo , Liu Jifeng , Yang Qingshen , Ruan Wenyuan , Yi Keke 
Published: May 2022

Abstract
Phosphate (Pi) limitation represents a primary constraint on crop production. To better cope with Pi deficiency stress, plants have evolved multiple adaptive mechanisms for phosphorus acquisition and utilization, including the alteration of growth and the activation of Pi starvation signaling. However, how these strategies are coordinated remains largely unknown. Here, we found that the alternative splicing (AS) of REGULATOR OF LEAF INCLINATION 1 (RLI1) in rice (Oryza sativa) produces two protein isoforms: RLI1a, containing MYB DNA binding domain and RLI1b, containing both MYB and coiled-coil (CC) domains. The absence of a CC domain in RLI1a enables it to activate broader target genes than RLI1b. RLI1a, but not RLI1b, regulates both brassinolide (BL) biosynthesis and signaling by directly activating BL-biosynthesis and signaling genes. Both RLI1a and RLI1b modulate Pi starvation signaling. RLI1 and PHOSPHATE STARVATION RESPONSE 2 function redundantly to regulate Pi starvation signaling and growth in response to Pi deficiency. Furthermore, the AS of RLI1-related genes to produce two isoforms for growth and Pi signaling is widely present in both dicots and monocots. Together, these findings indicate that the AS of RLI1 is an important and functionally conserved strategy to orchestrate Pi starvation signaling and growth to help plants adapt to Pi-limitation stress.
Spatially specific mechanisms and functions of the plant circadian clock
Authors: Davis William , Endo Motomu , Locke James C W 
Published: May 2022

AbstractLike many organisms, plants have evolved a genetic network, the circadian clock, to coordinate processes with day/night cycles. In plants, the clock is a pervasive regulator of development and modulates many aspects of physiology. Clock-regulated processes range from the correct timing of growth and cell division to interactions with the root microbiome. Recently developed techniques, such as single-cell time-lapse microscopy and single-cell RNA-seq, are beginning to revolutionize our understanding of this clock regulation, revealing a surprising degree of organ, tissue, and cell-type specificity. In this review, we highlight recent advances in our spatial view of the clock across the plant, both in terms of how it is regulated and how it regulates a diversity of output processes. We outline how understanding these spatially specific functions will help reveal the range of ways that the clock provides a fitness benefit for the plant.
Phosphate transporter PHT1;1 is a key determinant of phosphorus acquisition in Arabidopsis natural accessions
Authors: Chien Pei-Shan , Chao Ya-Ting , Chou Chia-Hui , Hsu Yu-Ying , Chiang Su-Fen , Tung Chih-Wei , Chiou Tzyy-Jen 
Published: May 2022

Abstract
Phosphorus (P) is a mineral nutrient essential for plant growth and development, but most P in the soil is unavailable for plants. To understand the genetic basis of P acquisition regulation, we performed genome-wide association studies (GWASs) on a diversity panel of Arabidopsis (Arabidopsis thaliana). Two primary determinants of P acquisition were considered, namely, phosphate (Pi)-uptake activity and PHOSPHATE TRANSPORTER 1 (PHT1) protein abundance. Association mapping revealed a shared significant peak on chromosome 5 (Chr5) where the PHT1;1/2/3 genes reside, suggesting a connection between the regulation of Pi-uptake activity and PHT1 protein abundance. Genes encoding transcription factors, kinases, and a metalloprotease associated with both traits were also identified. Conditional GWAS followed by statistical analysis of genotype-dependent PHT1;1 expression and transcriptional activity assays revealed an epistatic interaction between PHT1;1 and MYB DOMAIN PROTEIN 52 (MYB52) on Chr1. Further, analyses of F1 hybrids generated by crossing two subgroups of natural accessions carrying specific PHT1;1- and MYB52-associated single nucleotide polymorphisms (SNPs) revealed strong effects of these variants on PHT1;1 expression and Pi uptake activity. Notably, the soil P contents in Arabidopsis habitats coincided with PHT1;1 haplotype, emphasizing how fine-tuned P acquisition activity through natural variants allows environmental adaptation. This study sheds light on the complex regulation of P acquisition and offers a framework to systematically assess the effectiveness of GWAS approaches in the study of quantitative traits.
Liquid flow in scaffold derived from natural source: experimental observations and biological outcome
Authors: Salerno Elisabetta , Orlandi Giulia , Ongaro Claudio , d’Adamo Alessandro , Ruffini Andrea , Carnevale Gianluca , Zardin Barbara , Bertacchini Jessika , Angeli Diego 
Published: May 2022

AbstractThis study investigates the biological effects on a 3D scaffold based on hydroxyapatite cultured with MC3T3 osteoblasts in response to flow-induced shear stress (FSS). The scaffold adopted here (B-HA) derives from the biomorphic transformation of natural wood and its peculiar channel geometry mimics the porous structure of the bone. From the point of view of fluid dynamics, B-HA can be considered a network of micro-channels, intrinsically offering the advantages of a microfluidic system. This work, for the first time, offers a description of the fluid dynamic properties of the B-HA scaffold, which are strongly connected to its morphology. These features are necessary to determine the FSS ranges to be applied during in vitro studies to get physiologically relevant conditions. The selected ranges of FSS promoted the elongation of the attached cells along the flow direction and early osteogenic cell differentiation. These data confirmed the ability of B-HA to promote the differentiation process along osteogenic lineage. Hence, such a bioactive and naturally derived scaffold can be considered as a promising tool for bone regeneration applications.
Development and psychometric evaluation of the PMR-Impact Scale: a new patient reported outcome measure for polymyalgia rheumatica
Authors: Twohig Helen , Mitchell Caroline , Mallen Christian D , Muller Sara 
Published: May 2022

Abstract

Objectives
PMR causes pain, stiffness and disability in older adults. Measuring the impact of the condition from the patient’s perspective is vital to high-quality research and patient-centred care, yet there are no validated patient-reported outcome measures (PROMs) for PMR. We set out to develop and psychometrically evaluate a PMR-specific PROM.

Methods
Two cross-sectional postal surveys of people with a confirmed diagnosis of PMR were used to provide data for field testing and psychometric evaluation. A total of 256 participants completed the draft PROM. Distribution of item responses was examined, and exploratory factor analysis and Rasch analysis were used to inform item reduction, formation of dimension structure and scoring system development. Some 179 participants completed the PROM at two time points, along with comparator questionnaires and anchor questions. Test–retest reliability, construct validity and responsiveness were evaluated.

Results
Results from the field-testing study led to the formation of the PMR-Impact Scale (PMR-IS), comprising four domains (symptoms, function, psychological and emotional well-being, and steroid side effects). Construct validity and test–retest reliability met accepted quality criteria for each domain. There was insufficient evidence from this study to determine its ability to detect flares/deterioration, but the PMR-IS was responsive to improvements in the condition.

Conclusion
The PMR-IS offers researchers a new way to assess patient-reported outcomes in clinical studies of PMR. It has been developed robustly, with patient input at every stage. It has good construct validity and test–retest reliability. Further work is needed to fully establish its responsiveness and interpretability parameters, and to assess its real-world clinical utility.
Low incidence and transient elevation of autoantibodies post mRNA COVID-19 vaccination in inflammatory arthritis
Authors: Blank Rebecca B , Haberman Rebecca H , Qian Kun , Samanovic Marie , Castillo Rochelle , Jimenez Hernandez Anthony , Vasudevapillai Girija Parvathy , Catron Sydney , Uddin Zakwan , Rackoff Paula , Solomon Gary , Azar Natalie , Rosenthal Pamela , Izmirly Peter , Samuels Jonathan , Golden Brian , Reddy Soumya , Mulligan Mark J , Hu Jiyuan , Scher Jose U 
Published: May 2022

Abstract

Objectives
Autoantibody seroconversion has been extensively studied in the context of COVID-19 infection but data regarding post-vaccination autoantibody production is lacking. Here we aimed to determine the incidence of common autoantibody formation following mRNA COVID-19 vaccines in patients with inflammatory arthritis (IA) and in healthy controls.

Methods
Autoantibody seroconversion was measured by serum ELISA in a longitudinal cohort of IA participants and healthy controls before and after COVID-19 mRNA-based immunization.

Results
Overall, there was a significantly lower incidence of ANA seroconversion in participants who did not contract COVID-19 prior to vaccination compared with those who been previously infected (7.4% vs 24.1%, P = 0.014). Incidence of de novo anti-CCP seroconversion in all participants was low at 4.9%. Autoantibody levels were typically of low titre, transient, and not associated with increase in IA flares.

Conclusions
In both health and inflammatory arthritis, the risk of autoantibody seroconversion is lower following mRNA-based immunization than following natural SARS-CoV-2 infection. Importantly, seroconversion does not correlate with self-reported IA disease flare risk, further supporting the encouragement of mRNA-based COVID-19 immunization in the IA population.
0007 Temporal Associations Between Actigraphy-Measured Daytime Movement Behaviors and Daytime Sleep in Early Childhood
Authors: Laurent Christine St , Holmes Jennifer , Spencer Rebecca 
Published: May 2022

Abstract

Introduction
Although napping in early childhood is associated with some cognitive and behavioral outcomes, less is known about relations with physical health measures. Lower levels of sedentary behavior and higher levels of physical activity have been beneficially associated with sleep measures in adults. Studies exploring sleep and daytime movement behaviors (sedentary time and physical activity) in young children have had inconsistent results and primarily focused on overnight sleep. The purpose of this micro-longitudinal analysis was to determine if: 1) daytime movement behaviors predicted the likelihood of napping the next day, 2) daytime movement behaviors predicted next-day nap duration, and 3) the occurrence of a nap predicted next-day movement behaviors.

Methods
In 240 children (age=50.8±9.8 months, 49.2% female) sedentary time (% of wake time), total physical activity (counts/min), and nap duration (min) were derived from wrist-based actigraphy (mean = 9.7 days), and occurrence of a nap was recorded daily. Multilevel logistic and linear models with lagged effects were used to examine temporal within-person relations between wake behaviors and nap sleep, and adjusted for night’s sleep duration of nights between days of interest (min), age (months), sex (male or female), and socioeconomic status (index). Preliminary models included interactions with nap habituality (rarely, sometimes, or frequent).

Results
Occurrence of a nap was not associated with next-day wake behaviors and previous-day wake behaviors did not predict nap duration. However, on days children napped, they were less sedentary (B=-2.09, p&lt;0.001) and more active (B=25.8, p&lt;0.001) the following day. Nap habituality did not moderate these associations.

Conclusion
Bidirectional associations between nap sleep and daytime wake behaviors were not evident. While daytime movement behaviors were not predictive of nap sleep, napping was beneficially associated with subsequent-day movement behaviors in preschool children. Further studies could explore specific nap sleep metrics in samples with more diverse sleep health, as well as consider the reason for daytime napping.

Support (If Any)
NIH R01 HL111695