bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi‐omics atlas of combinatorial abiotic stress responses in wheat
Authors: Da Ros Letitia , Bollina Venkatesh , Soolanayakanahally Raju , Pahari Shankar , Elferjani Raed , Kulkarni Manoj , Vaid Neha , Risseuw Eddy , Cram Dustin , Pasha Asher , Esteban Eddi , Konkin David , Provart Nicholas , Nambara Eiji , Kagale Sateesh 
Published: May 2023

SUMMARYField‐grown crops rarely experience growth conditions in which yield can be maximized. Environmental stresses occur in combination, with advancements in crop tolerance further complicated by its polygenic nature. Strategic targeting of causal genes is required to meet future crop production needs. Here, we employed a systems biology approach in wheat (Triticum aestivum L.) to investigate physio‐metabolic adjustments and transcriptome reprogramming involved in acclimations to heat, drought, salinity and all combinations therein. A significant shift in magnitude and complexity of plant response was evident across stress scenarios based on the agronomic losses, increased proline concentrations and 8.7‐fold increase in unique differentially expressed transcripts (DETs) observed under the triple stress condition. Transcriptome data from all stress treatments were assembled into an online, open access eFP browser for visualizing gene expression during abiotic stress. Weighted gene co‐expression network analysis revealed 152 hub genes of which 32% contained the ethylene‐responsive element binding factor‐associated amphiphilic repression (EAR) transcriptional repression motif. Cross‐referencing against the 31 DETs common to all stress treatments isolated TaWRKY33 as a leading candidate for greater plant tolerance to combinatorial stresses. Integration of our findings with available literature on gene functional characterization allowed us to further suggest flexible gene combinations for future adaptive gene stacking in wheat. Our approach demonstrates the strength of robust multi‐omics‐based data resources for gene discovery in complex environmental conditions. Accessibility of such datasets will promote cross‐validation of candidate genes across studies and aid in accelerating causal gene validation for crop resiliency.
Auxin biosynthesis gene FveYUC4 is critical for leaf and flower morphogenesis in woodland strawberry
Authors: Lu Rui , Pi Mengting , Liu Zhongchi , Kang Chunying 
Published: May 2023

SUMMARYAuxin plays an essential role in plant growth and development, particularly in fruit development. The YUCCA (YUC) genes encode flavin monooxygenases that catalyze a rate‐limiting step in auxin biosynthesis. Mutations that disrupt YUC gene function provide useful tools for dissecting general and specific functions of auxin during plant development. In woodland strawberry (Fragaria vesca), two ethyl methanesulfonate mutants, Y422 and Y1011, have been identified that exhibit severe defects in leaves and flowers. In particular, the width of the leaf blade is greatly reduced, and each leaflet in the mutants has fewer and deeper serrations. In addition, the number and shape of the floral organs are altered, resulting in smaller fruits. Mapping by sequencing revealed that both mutations reside in the FveYUC4 gene, and were therefore renamed as yuc4‐1 and yuc4‐2. Consistent with a role for FveYUC4 in auxin synthesis, free auxin and its metabolites are significantly reduced in the yuc4 leaves and flowers. This role of FveYUC4 in leaf and flower development is supported by its high and specific expression in young leaves and flower buds using GUS reporters. Furthermore, germline transformation of pYUC4::YUC4, which resulted in elevated expression of FveYUC4 in yuc4 mutants, not only rescued the leaf and flower defects but also produced parthenocarpic fruits. Taken together, our data demonstrate that FveYUC4 is essential for leaf and flower morphogenesis in woodland strawberry by providing auxin hormone at the proper time and in the right tissues.
Novel computational methods on electronic health record yields new estimates of transfusion‐associated circulatory overload in populations enriched with high‐risk patients
Authors: Wang Michelle , Goldgof Gregory M. , Patel Ayan , Whitaker Barbee , Belov Artur , Chan Brian , Phelps Evan , Rubin Benjamin , Anderson Steven , Butte Atul J. 
Published: May 2023

AbstractBackgroundTransfusion‐associated circulatory overload (TACO) is a severe adverse reaction (AR) contributing to the leading cause of mortality associated with transfusions. As strategies to mitigate TACO have been increasingly adopted, an update of prevalence rates and risk factors associated with TACO using the growing sources of electronic health record (EHR) data can help understand transfusion safety.Study Design and MethodsThis retrospective study aimed to provide a timely and reproducible assessment of prevalence rates and risk factors associated with TACO. Novel natural language processing methods, now made publicly available on GitHub, were developed to extract ARs from 3178 transfusion reaction reports. Other patient‐level data were extracted computationally from UCSF EHR between 2012 and 2022. The odds ratio estimates of risk factors were calculated using a multivariate logistic regression analysis with case‐to‐control matched on sex and age at a ratio of 1:5.ResultsA total of 56,208 patients received transfusions (total 573,533 units) at UCSF during the study period and 102 patients developed TACO. The prevalence of TACO was estimated to be 0.2% per patient (102/total 56,208). Patients with a history of coagulopathy (OR, 1.36; 95% CI, 1.04–1.79) and transplant (OR, 1.99; 95% CI, 1.48–2.68) were associated with increased odds of TACO.DiscussionWhile TACO is a serious AR, events remained rare, even in populations enriched with high‐risk patients. Novel computational methods can be used to find and continually surveil for transfusion ARs. Results suggest that patients with history or presence of coagulopathy and organ transplant should be carefully monitored to mitigate potential risks of TACO.
Standing in the canine precision medicine knowledge gap: Improving annotation of canine cancer genomic biomarkers through systematic comparative analysis of human cancer mutations in COSMIC
Authors: Sakthikumar Sharadha , Facista Salvatore , Whitley Derick , Byron Sara A. , Ahmed Zeeshan , Warrier Manisha , Zhu Zhanyang , Chon Esther , Banovich Kathryn , Haworth David , Hendricks William P. D. , Wang Guannan 
Published: May 2023

AbstractThe accrual of cancer mutation data and related functional and clinical associations have revolutionised human oncology, enabling the advancement of precision medicine and biomarker‐guided clinical management. The catalogue of cancer mutations is also growing in canine cancers. However, without direct high‐powered functional data in dogs, it remains challenging to interpret and utilise them in research and clinical settings. It is well‐recognised that canine and human cancers share genetic, molecular and phenotypic similarities. Therefore, leveraging the massive wealth of human mutation data may help advance canine oncology. Here, we present a structured analysis of sequence conservation and conversion of human mutations to the canine genome through a ‘caninisation’ process. We applied this analysis to COSMIC, the Catalogue of Somatic Mutations in Cancer, the most prominent human cancer mutation database. For the project's initial phase, we focused on the subset of the COSMIC data corresponding to Cancer Gene Census (CGC) genes. A total of 670 canine orthologs were found for 721 CGC genes. In these genes, 365 K unique mutations across 160 tumour types were converted successfully to canine coordinates. We identified shared putative cancer‐driving mutations, including pathogenic and hotspot mutations and mutations bearing similar biomarker associations with diagnostic, prognostic and therapeutic utility. Thus, this structured caninisation of human cancer mutations facilitates the interpretation and annotation of canine mutations and helps bridge the knowledge gap to enable canine precision medicine.
Revealing cryptic diversity and population divergence in subtropical aphids throughDNAbarcoding
Authors: Li Qiang , Liu Qian , Yu Yuhua , Lin Xiaolan , He Xueyou , Huang Xiaolei 
Published: May 2023

AbstractAphids are worldwide distributed pests, which feed on plant sap and cause serious losses to agricultural and forestry industries. Relatively few comprehensive studies have been conducted on aphid diversity in subtropics, although these regions may harbour hidden aphid diversity due to high plant diversity. In this study, we conducted DNA barcoding analysis for aphids in subtropical regions based on a comprehensive DNA barcode reference library including 5821 sequences and related ecological information (e.g. geography, host plant) of 379 morphospecies. In the reference library, 2140 sequences and related data of 151 morphospecies belonging to 77 genera and 11 subfamilies were newly produced by the current study. The average Kimura 2‐parameter distances within species, genera and subfamilies were 0.92%, 3.55% and 8.3%, respectively. The minimum interspecific distances were greater than the maximum intraspecific distances in 79.8% species, suggesting that barcode gaps existed in most aphid species. Automatic barcode gap discovery, Barcode Index Number, Bayesian Poisson tree processes and generalized mixed Yule‐coalescent revealed 419, 401, 462 and 455 single species‐representing clusters, respectively. A total of 32 morphospecies were assigned to more than one subclade respectively, suggesting geography or host plant‐mediated divergences and the existence of cryptic diversity. This study demonstrates that subtropical regions should have a higher species diversity of aphids, and cryptic species in certain morphospecies indicated in this study need to be investigated based on integrative taxonomic practices in the future. The DNA barcode reference library constructed herein provides a robust baseline data set to support future research in taxonomy, phylogenetics, ecology and evolution of aphids.
The Dynamic Energy-Momentum Tensor and the Logarithmic Singularity of a Generally Accelerating Edge Dislocation
Authors: Ni Luqun , Markenscoff Xanthippi 
Published: May 2023

Abstract
The near-field logarithmic singularities in the field quantities associated with the acceleration of an arbitrarily moving edge dislocation are calculated based on a conservation law involving the dynamic energy-momentum tensor integrated over a domain enclosed by a multi-scale contour (an annulus of inner radius ϵ02 and outer radius ϵ0). The existence of the logarithmic singularities is obtained solely from the conservation law and the leading 1/r terms in the near fields of the stress and the velocity (which are those of the steady-state motion with velocity the instantaneous velocity in the accelerating motion). From the equations of motion and the symmetry in the second partial derivatives of the displacements for y≠0 we obtain that all six logarithmic terms of the near-field expansions are independent of the angle in the polar coordinates. All logarithmic terms in the near-field expansion of the strains and velocity in an arbitrarily moving edge dislocation (subsonically) are evaluated.
Stable tungsten isotopic composition of seawater over the past 80 million years
Authors: Yang Ruiyu , Stubbs Daniel , Elliott Tim , Li Tao , Chen Tianyu , Paytan Adina , Kemp David B. , Ling Hongfei , Chen Jun , Hein James R. , Coath Christopher D. , Li Gaojun 
Published: May 2023

Abstract
The isotopic composition of seawater provides valuable information on how the Earth system has evolved. Here we present the stable tungsten isotopic composition (δ186/184W) of seawater recorded in three ferromanganese (Fe-Mn) crusts spanning the past 80 million years in the Pacific. The δ186/184W of Fe-Mn crusts displays a pronounced decrease of ∼0.2‰ from 60 Ma to 40 Ma followed by a stable value of ∼0‰ since ca. 40 Ma. Multiple lines of evidence indicate an invariable equilibrium isotopic fractionation between Fe-Mn crusts and seawater. The consistent variations in δ186/184W in the three Fe-Mn crusts also indicate limited alteration by deposition regime or diagenetic overprinting. Thus, the δ186/184W of Fe-Mn crusts reflects mainly that of seawater. A simple mass-balance calculation and comparison to other proxies suggest that the early Cenozoic decrease of seawater δ186/184W was most likely caused by decreased W isotopic fractionation between seawater and W sinks linked to shifting sedimentation regimes. We propose that increased burial of organics and decreased Fe-Mn oxide (FMO) sedimentation may result in a smaller isotopic fractionation associated with W sinks by limiting the adsorption of W from the water column onto FMOs in openocean sediments. Our results demonstrate the potential of δ186/184W as a novel paleo-proxy for global biogeochemical cycling.
Risk stratified monitoring for methotrexate toxicity in immune mediated inflammatory diseases: prognostic model development and validation using primary care data from the UK
Authors: Nakafero Georgina , Grainge Matthew J , Williams Hywel C , Card Tim , Taal Maarten W , Aithal Guruprasad P , Fox Christopher P , Mallen Christian D , van der Windt Danielle A , Stevenson Matthew D , Riley Richard D , Abhishek Abhishek 
Published: May 2023

AbstractObjectiveTo develop and validate a prognostic model to inform risk stratified decisions on frequency of monitoring blood tests during long term methotrexate treatment.DesignRetrospective cohort study.SettingElectronic health records within the UK’s Clinical Practice Research Datalink (CPRD) Gold and CPRD Aurum.ParticipantsAdults (≥18 years) with a diagnosis of an immune mediated inflammatory disease who were prescribed methotrexate by their general practitioner for six months or more during 2007-19.Main outcome measureDiscontinuation of methotrexate owing to abnormal monitoring blood test result. Patients were followed-up from six months after their first prescription for methotrexate in primary care to the earliest of outcome, drug discontinuation for any other reason, leaving the practice, last data collection from the practice, death, five years, or 31 December 2019. Cox regression was performed to develop the risk equation, with bootstrapping used to shrink predictor effects for optimism. Multiple imputation handled missing predictor data. Model performance was assessed in terms of calibration and discrimination.ResultsData from 13 110 (854 events) and 23 999 (1486 events) participants were included in the development and validation cohorts, respectively. 11 candidate predictors (17 parameters) were included. In the development dataset, the optimism adjusted R2was 0.13 and the optimism adjusted Royston D statistic was 0.79. The calibration slope and Royston D statistic in the validation dataset for the entire follow-up period was 0.94 (95% confidence interval 0.85 to 1.02) and 0.75 (95% confidence interval 0.67 to 0.83), respectively. The prognostic model performed well in predicting outcomes in clinically relevant subgroups defined by age group, type of immune mediated inflammatory disease, and methotrexate dose.ConclusionA prognostic model was developed and validated that uses information collected during routine clinical care and may be used to risk stratify the frequency of monitoring blood test during long term methotrexate treatment.
Fecal microbiota transplantation ameliorates type 2 diabetes via metabolic remodeling of the gut microbiota in db/db mice
Authors: Chen Lijuan , Guo Lin , Feng Susu , Wang Congcong , Cui Zhicheng , Wang Sijing , Lu Qingmiao , Chang Hang , Hang Bo , Snijders Antoine M , Mao Jian-Hua , Lu Yibing , Ding Dafa 
Published: May 2023

IntroductionGut microbiome (GM) deregulation has been implicated in major conditions such as obesity and type 2 diabetes (T2DM). Our previous prospective study indicated that fecal microbiota transplantation (FMT) successfully improved patients with T2DM. We hypothesized that FMT may be a potential therapeutic method for T2DM, but its precise mechanisms in T2DM remains to be elucidated.Research design and methodsEight db/m mice were FMT donors and control mice, and 16 genetically diabetic db/db mice were equally divided into two groups (db/db+phosphate-buffered saline (PBS) group, db/db+FMT group). The db/db+FMT group was administered fresh fecal suspension (0.2 mL/mice) daily for 4 weeks. Analysis of the GM and serum metabolome was carried out by 16S ribosomal RNA sequencing and liquid chromatogram-mass spectrometry, respectively. Effects of FMT on the gut barrier and pancreas were assessed using protein assays, messenger RNA, immunohistology and clinical indicators testing.ResultsOur results showed that FMT treatment of db/db mice relieves a series of clinical indicators, including fasting plasma glucose, serum insulin and oral glucose tolerance test among others. Compared with non-diabetic control mice, db/db+PBS mice exhibited decreased abundance of Ruminococaceae, Porphyromonadaceae and increased abundance of Rikenellaceae and Lactobacillaceae. FMT treatment reversed this effect on the microbiome. Eleven metabolites were changed between the db/db+PBS and db/db+FMT groups. Correlation analysis showed that the structural changes of the GM were correlated with host metabolite levels. We further showed that FMT treatment of db/db mice improved intestinal barrier function, reduced inflammation and caused an alteration in the number of circulating immune cells.ConclusionsFMT-mediated changes in the GM, serum metabolites, intestinal epithelial barrier, inflammation and circulating immune cells play an important role in the efficacy of FMT on T2DM disease progression.
Obstacles to the deceased donor transplantation in Pakistan
Authors: Ullah Kaleem , Dogar Abdul Wahab , Ochani Sidhant , Shoaib Azam , Shah Hussain Haider , Ur Rehman Mohammad Ebad 
Published: May 2023

IntroductionTransplantation in many Asian countries is moulded by socioeconomic, religious, cultural and health indicators. In most Asian countries, the living-related donation is the common most organ donation. Due to the limited deceased organ donation, live donor programmes flourished in many Asian countries. Another apparent reason for this tremendous growth of living-related programmes in Asian countries is their larger serving population. Several centres from Asia, including Pakistan and India from Southeast Asia and Egypt in Middle East Asia, on the one hand, have recently emerged as leading living donor transplant programmes. On the other hand, a few Asian countries, including Iran and China, have established some of the world’s largest deceased donor programmes.DiscussionIn Pakistan, thousands of patients die from end-stage organ failure annually, seeking organ transplants for survival. The exact statics are not available, but over 50 000 people are estimated to die each year as a result of end-stage organ failure without getting a transplant, about 15 000–18 000 from kidney failure, and 10 000 from liver failure and the National Centre for Health Statistics labelled organ failure as a leading cause of death. Despite all these efforts, the knowledge of organ donation among Pakistani people was determined to be around 60%. In Pakistan, the lack of deceased organ donation programmes and the unwillingness of people to deceased organ donation contributes to an increased demand for living organ donation and patients continue to rely on living donors. We discuss various obstacles to deceased organ donation comprising various challenges that form a unique combination, including religious, economic, social, demographic and political factors.Conclusion:Every single effort should be made to initiate and establish multiple deceased donor programmes in Pakistan. Developing the deceased donor programmes in the country will be vital to counter the countrywide increasing organ shortage. The mainstay transplant activities like organ procurement and distribution systems need to be adequately developed. It will help achieve national self-sufficiency and decrease living donors’ burden. With education, the behaviour of healthcare professionals and common people can be changed and a positive attitude toward deceased organ donation can be obtained. As healthcare professionals, we should come forward and take responsibility by enrolling ourselves in deceased donors’ registration. Public awareness, medical community interest and government support are essential in initiating and establishing deceased donor programmes in Pakistan.
Cluster analysis of dietary patterns associated with colorectal cancer derived from a Moroccan case–control study
Authors: Qarmiche Noura , El Kinany Khaoula , Otmani Nada , El Rhazi Karima , Chaoui Nour El Houda 
Published: May 2023

IntroductionColorectal cancer (CRC) is a global public health problem. There is strong indication that nutrition could be an important component of primary prevention. Dietary patterns are a powerful technique for understanding the relationship between diet and cancer varying across populations.ObjectiveWe used an unsupervised machine learning approach to cluster Moroccan dietary patterns associated with CRC.MethodsThe study was conducted based on the reported nutrition of CRC matched cases and controls including 1483 pairs. Baseline dietary intake was measured using a validated food-frequency questionnaire adapted to the Moroccan context. Food items were consolidated into 30 food groups reduced on 6 dimensions by principal component analysis (PCA).ResultsK-means method, applied in the PCA-subspace, identified two patterns: ‘prudent pattern’ (moderate consumption of almost all foods with a slight increase in fruits and vegetables) and a ‘dangerous pattern’ (vegetable oil, cake, chocolate, cheese, red meat, sugar and butter) with small variation between components and clusters. The student test showed a significant relationship between clusters and all food consumption except poultry. The simple logistic regression test showed that people who belong to the ‘dangerous pattern’ have a higher risk to develop CRC with an OR 1.59, 95% CI (1.37 to 1.38).ConclusionThe proposed algorithm applied to the CCR Nutrition database identified two dietary profiles associated with CRC: the ‘dangerous pattern’ and the ‘prudent pattern’. The results of this study could contribute to recommendations for CRC preventive diet in the Moroccan population.