bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pretransplant Screening for Prevention of Hyperacute Graft Loss in Pig-to-primate Kidney Xenotransplantation
Authors: Hisadome Yu , Eisenson Daniel L. , Santillan Michelle R. , Iwase Hayato , Yamada Kazuhiko 
Published: March 2024

Background.
Xenotransplantation using pig organs is now a clinical reality. However, the process for xenograft recipient screening lacks clarity and scientific rigor: no established thresholds exist to determine which levels of preformed antipig natural antibodies (Nabs) will be safe for clinical xenograft transplantation, and hyperacute rejection (HAR) or acute humoral xenograft rejection (AHXR), which still impacts pig-to-primate kidney xenograft survivals, may impede broader application of pig-to-human clinical xenograft transplantation.

Methods.
We retrospectively examined 28 cases of pig-to-baboon kidney xenotransplantation using GalTKO±human complement regulatory protein (hCRP)-transgenic (Tg) pig donors, as well as 6 cases of triple-KO multi-Tg (10GE) pig donors, and developed screening algorithms to predict risk of HAR/AHXR based on recipient antipig Nab levels. Preformed Nabs were evaluated using both complement-dependent cytotoxicity and antibody (IgM and IgG) binding flow-cytometry assays.

Results.
High complement-dependent cytotoxicity was associated with HAR/AHXR as expected. However, we also found that high levels of IgG were independently associated with HAR/AHXR, and we developed 2 indices to interpret and predict the risk of IgG-mediated HAR/AHXR.

Conclusions.
Based on the data in this study, we have established a new 2-step screening, which will be used for future clinical kidney xenotransplantation trials.
Long-term Kidney Transplant Survival Across the Globe
Authors: Hariharan Sundaram , Rogers Natasha , Naesens Maarten , Pestana J. Medina , Ferreira Gustavo F. , Requião-Moura Lucio R. , Foresto Renato D. , Kim S. Joseph , Sullivan Katrina , Helanterä Ilkka , Goutaudier Valentin , Loupy Alexandre , Kute Vivek B. , Cardillo Massimo , Tanabe Kazunari , Åsberg Anders , Jensen Trond , Mahillo Beatriz , Jeong Jong Cheol , Anantharaman Vathsala , Callaghan Chris , Ravanan Rommel , Manas Derek , Israni Ajay K. , Mehta Rajil B. 
Published: March 2024

Background.
The outcomes after kidney transplantation (KT), including access, wait time, and other issues around the globe, have been studied. However, issues do vary from one country to another.

Methods.
We obtained data from several countries from North America, South America, Europe, Asia, and Australia, including the number of patients awaiting KT from 2015, transplant rate per million population (pmp), proportion of living donor and deceased donor (LD/DD) KT, and posttransplant survival. We also sought opinions on key difficulties faced by each of these countries with respect to KT and long-term survival.

Results.
Variation in access to KT across the globe was noted. Countries with the highest rates of KT pmp included the United States (79%) and Spain (71%). A higher proportion of LD transplants was noted in Japan (93%), India (85%), Singapore (63%), and South Korea (63%). A higher proportion of DD KTs was noted in Spain (90%), Brazil (90%), France (85%), Italy (85%), Finland (85%), Australia–New Zealand (80%), and the United States (77%). The 5-y graft survival for LD was highest in South Korea (95%), Singapore (94%), Italy (93%), Finland (93%), and Japan (93%), whereas for DD, it was South Korea (93%), Italy (88%), Japan (86%), and Singapore (86%). The common issues surrounding KTs are access and a limited number of LDs and DDs. Key issues identified for long-term survival were increasing age of donors and recipients, higher recipient comorbidity, and posttransplant events, such as alloimmune injury to the kidney, infection, cancer, and suboptimal adherence to therapy.

Conclusions.
A unified approach is necessary to improve issues surrounding KT as the demand continues to increase.
Prognostic Value of Mitral Annular Calcification in Liver Transplant Patients: Implication in Posttransplant Outcomes
Authors: Jang Hwa-Young , Han Sang-Bin , Jeong Jun-Hyeop , Kwon Hye-Mee , Kim Kyoung-Sun , Kim Jae-Hwan , Kim Sung-Hoon , Jun In-Gu , Song Jun-Gol , Hwang Gyu-Sam 
Published: March 2024

Background.
With the rise of metabolic diseases and aging in liver transplant (LT) candidates, mitral annular calcification (MAC) is more recognizable. Despite cardiovascular risk becoming a leading cause of mortality in LT recipients, the influence of MAC remains unexamined. This study investigates the prevalence, related factors, and impact of MAC on LT outcomes.

Methods.
We explored 4148 consecutive LT patients who underwent routine pretransplant echocardiography from 2008 to 2019. Multivariate logistic analysis and the tree-based Shapley additive explanation scores in machine learning were used to evaluate the significant and important related factors. The primary outcome was 30-d major adverse cardiac events (MACE), and the secondary outcome was a median of 5-y cumulative all-cause mortality.

Results.
MAC was found in 123 (3.0%) patients. Significant and important related factors included age, alcoholic liver disease, chronic kidney disease, hyperuricemia, hypertension, and coronary artery disease. The MACE rate was higher in patients with MAC compared with those without MAC at 30 d (P < 0.001, adjusted hazard ratio 1.67; 95% confidence interval, 1.08-2.57). Patients with MAC had poorer cumulative overall survival probability compared with those without MAC (P = 0.0016; adjusted hazard ratio 1.47; 95% confidence interval, 1.01-2.15). Specifically, women with MAC had a poorer survival probability compared with men without MAC (65.0% versus 80.7%, P < 0.001) >10 y post-LT.

Conclusions.
The presence of MAC before LT was linked to increased 30-d MACE and lower long-term survival rates, especially in women. Identification and management of MAC and potential risk factors are crucial for improving post-LT survival.
Taurine Deficiency Is a Hallmark of Injured Kidney Allografts
Authors: Rinaldi Anna , Cippà Pietro E. , Nemazanyy Ivan , Anglicheau Dany , Pallet Nicolas 
Published: March 2024

Background.
Taurine is one of the most abundant amino acids in humans. Low taurine levels are associated with cellular senescence, mitochondrial dysfunction, DNA damage, and inflammation in mouse, all of which can be reversed by supplementation. It is unknown whether taurine metabolism is associated with kidney allograft function and survival.

Methods.
We performed urine metabolomic profiling of kidney transplant recipients in the early and late phases after transplantation combined with transcriptomic analysis of human kidney allografts. Single-nucleus RNA sequencing data sets of mouse kidneys after ischemia–reperfusion injury were analyzed. We analyzed the association of urinary taurine levels and taurine metabolism genes with kidney function, histology, and graft survival.

Results.
Urine taurine concentrations were significantly lower in kidney transplant recipients who experienced delayed graft function. In a mouse model of ischemia–reperfusion injury, the taurine biosynthesis gene, CSAD, but not the taurine transporter SLC6A6, was repressed. In the late stage of transplantation, low level of taurine in urine was associated with impaired kidney function and chronic structural changes. Urine taurine level in the lowest tertile was predictive of graft loss. Expression of the taurine transporter SLC6A6 in the upper median, but not CSAD, was associated with chronic kidney injury and was predictive of graft loss.

Conclusions.
Low urine taurine level is a marker of injury in the kidney allograft, is associated with poor kidney function, is associated with chronic histological changes, and is predictive of graft survival. The differential expression of CSAD and SLC6A6, depending on the time after transplantation and marks of injury, highlights different mechanisms affecting taurine metabolism.
Concurrent JCPyV-DNAemia Is Correlated With Poor Graft Outcome in Kidney Transplant Recipients With Polyomavirus-associated Nephropathy
Authors: Zhang Hui , Luo Jin-Quan , Zhao Guo-Dong , Huang Yang , Yang Shi-Cong , Chen Pei-Song , Li Jun , Wu Cheng-Lin , Qiu Jiang , Chen Xu-Tao , Huang Gang 
Published: March 2024

Background.
Co-infection of JC polyomavirus (JCPyV) and BK polyomavirus (BKPyV) is uncommon in kidney transplant recipients, and the prognosis is unclear. This study aimed to investigate the effect of concurrent JCPyV-DNAemia on graft outcomes in BKPyV-infected kidney transplant recipients with polyomavirus-associated nephropathy (PyVAN).

Methods.
A total of 140 kidney transplant recipients with BKPyV replication and PyVAN, 122 without concurrent JCPyV-DNAemia and 18 with JCPyV-DNAemia were included in the analysis. Least absolute shrinkage and selection operator regression analysis and multivariate Cox regression analysis were used to identify prognostic factors for graft survival. A nomogram for predicting graft survival was created and evaluated.

Results.
The median tubulitis score in the JCPyV-DNAemia-positive group was higher than in JCPyV-DNAemia-negative group (P = 0.048). At last follow-up, the graft loss rate in the JCPyV-DNAemia-positive group was higher than in the JCPyV-DNAemia-negative group (50% versus 25.4%; P = 0.031). Kaplan–Meier analysis showed that the graft survival rate in the JCPyV-DNAemia-positive group was lower than in the JCPyV-DNAemia-negative group (P = 0.003). Least absolute shrinkage and selection operator regression and multivariate Cox regression analysis demonstrated that concurrent JCPyV-DNAemia was an independent risk factor for graft survival (hazard ratio = 4.808; 95% confidence interval: 2.096-11.03; P < 0.001). The nomogram displayed favorable discrimination (C-index = 0.839), concordance, and clinical applicability in predicting graft survival.

Conclusions.
Concurrent JCPyV-DNAemia is associated with a worse graft outcome in BKPyV-infected kidney transplant recipients with PyVAN.
Development of a Tremor Detection Algorithm for use in an Academic Movement Disorders Center
Authors: Saad Mark , Hefner Sofia , Donovan Suzann , Bernhard Doug , Tripathi Richa , Factor Stewart A. , Powell Jeanne , Kwon Hyeokhyen , Sameni Reza , Esper Christine D. , McKay J. Lucas 
Published: March 2024

AbstractTremor, defined as an “involuntary, rhythmic, oscillatory movement of a body part,” is a key feature of many neurological conditions, but is still clinically assessed by visual observation. Methodologies for objectively quantifying tremor are promising but remain non-standardized across centers. Our center performs full-body behavioral testing with 3D motion capture for clinical and research purposes for patients with Parkinson’s disease, essential tremor, and other conditions. The objective of this study was to assess the ability of several candidate processing pipelines to identify the presence or absence of tremor in kinematic data from movement disorders patients compared to expert ratings from movement disorders specialists. We curated a database of 2,272 separate kinematic data recordings from our center, each of which was contemporaneously annotated as tremor present or absent by a clinical provider. We compared the ability of six separate processing pipelines to recreate clinician ratings based on F1 score, in addition to accuracy, precision, and recall. We found generally comparable performance across algorithms. The averageF1 score was 0.84±0.02 (Mean±SD; range 0.81−0.87), with allF1 confidence intervals overlapping. The highest performing algorithm (cross-validatedF1 = 0.87) was a hybrid that used engineered features adapted from an algorithm in longstanding clinical use with a modern Support Vector Machine classifier. Taken together, our results suggest the potential to update legacy clinical decision support systems to incorporate modern machine learning classifiers in order to create better performing tools.
Large-scale plasma proteomics in the UK Biobank modestly improves prediction of major cardiovascular events in a population without previous cardiovascular disease
Authors: Royer Patrick , Björnson Elias , Adiels Martin , Josefson Rebecca , Hagberg Eva , Gummesson Anders , Bergström Göran 
Published: March 2024

AbstractBackground and AimsImproved identification of individuals at high risk of developing cardiovascular disease would enable targeted interventions and potentially lead to reductions in mortality and morbidity. Our aim was to determine whether use of large-scale proteomics improves prediction of cardiovascular events beyond traditional risk factors (TRFs).MethodsUsing proximity extension assays, 2919 plasma proteins were measured in 38 380 participants of the UK Biobank. Both data- and hypothesis-driven feature selection and trained models using extreme gradient boosting machine learning were used to predict risk of major cardiovascular events (MACE: fatal and non-fatal myocardial infarction, stroke and coronary artery revascularisation) during a 10-year follow-up. Area under the curve (AUC) and net reclassification index (NRI) were used to evaluate the additive value of selected protein panels to MACE prediction by Systematic COronary Risk Evaluation 2 (SCORE2) or the 10 TRFs used in SCORE2.ResultsSCORE2 and SCORE2 refitted to UK Biobank data predicted MACE with AUCs of 0.740 and 0.749, respectively. Data-driven selection identified 114 proteins of greatest relevance for prediction. Prediction of MACE was not improved by using these proteins alone (AUC of 0.758) but was significantly improved by combining these proteins with SCORE2 or the 10 TRFs (AUC=0.771, p<001, NRI=0.140, and AUC=0.767, p=0.03, NRI 0.053, respectively). Hypothesis-driven protein selection (113 proteins from five previous studies) also improved risk prediction beyond TRFs while a random selection of 114 proteins did not.ConclusionsLarge-scale plasma proteomics with data- and hypothesis-driven protein selection modestly improves prediction of future MACE beyond TRFs.Structured Graphical Abstract legend.
CD1c Dendritic Cells are depleted and accompanied by new HLA-DRhiPhenotypes in Rheumatoid Arthritis Blood
Authors: Geier Christian , Qudsi Haani , Gabr Jihad Ben , Winchester Robert , Perl Andras 
Published: March 2024

ABSTRACTRheumatoid arthritis (RA) in an autoimmune disease that leads to inflammation of synovial joints and other organs. Many RA patients ‘share’ a common peptide sequence within the HLA-DR (DR) molecule expressed on antigen-presenting cells (APC), suggesting that DRhicells are important in RA. Here, we use DRhito broadly define and immunophenotype RA APC, including potential APC not meeting standard definitions for lymphocytes, monocytes, dendritic cells (DC) from RA patients and healthy controls (HC). We measured mean fluorescence intensities (MFI) of molecules associated with DC (CD141, CD1c, CD11c, CD123, CD303), monocytes (CD14, CD16); granulocytic markers (CD15, CCR3), co-stimulatory molecules and chemokine receptors. DC2 (CD1c+) showed higher CD56, CD86, CD275, and CCR7 in RA. DC2 frequencies were much lower in RA: 3.2% of DRhi[IQR 2.41 to 4.46] in RA vs. 6.9% [IQR 3.96 to 9.08] in HC; p=0.005. CD15 was increased in all RA APC subsets (p<0.01). A distinct CD15+CD16+population appeared in RA, representing 1.5% of leukocytes [IQR 0.68 to 3.32] (vs 0.1% in HC [IQR 0.08 to 0.46]; p<0.001) and contributed a mean of 2.34% to overall DRhi. The CD15+CD16+subset was CD303+, CD83+and CD275+with much less CD123 relative to reference plasmacytoid DC (p<0.01). In conclusion, APC alterations in RA include depletion of DC2 and increased CD15. Moreover, the APC (DRhi) compartment in RA contains cells with shared dendritic cell and granulocytic features; this phenotype suggests these apparent APC may participate in the pathophysiology of rheumatoid arthritis via the presentation of self-antigen(s) to CD4+T lymphocytes.
Look-alike modelling in violence-related research: a missing data approach
Authors: Barbosa Estela Capelas , Blom Niels , Bunce Annie 
Published: March 2024

AbstractViolence as a phenomena has been analysed in silo due to difficulties in accessing data and concerns for the safety of those exposed. While there is some literature on violence and its associations using individual datasets, analyses using combined sources of data are very limited. Ideally data from the same individuals would enable linkage and a longitudinal understanding of experiences of violence and their (health) impacts and consequences. However, in the absence of directly linked data, look-alike modelling may provide an innovative and cost-effective approach to exploring patterns and associations in violence-related research in a multi-sectorial setting.We approached the problem of data integration as a missing data problem to create a synthetic combined dataset. We combined data from the Crime Survey of England and Wales with administrative data from Rape Crisis, focussing on victim-survivors of sexual violence in adulthood. Multiple imputation with chained equations were employed to collate/impute data from different sources. To test whether this procedure was effective, we compared regressions analyses for the individual and combined synthetic datasets on a binary, continuous and categorical variables. Our results show that the effect sizes for the combined dataset reflect those from the dataset used for imputation. The variance is higher, resulting in fewer statistically significant estimates. We extended our testing to an outcome measures and finally applied the technique to a variable fully missing in one data source. Our approach reinforces the possibility to combine administrative with survey datasets using look-alike methods to overcome existing barriers to data linkage.
A framework for conducting time-varying genome-wide association studies: An application to body mass index across childhood in six multiethnic cohorts
Authors: Burrows Kimberley , Heiskala Anni , Bradfield Jonathan P. , Balkhiyarova Zhanna , Ning Lijiao , Boissel Mathilde , Chan Yee-Ming , Froguel Philippe , Bonnefond Amelie , Hakonarson Hakon , Alves Alessander Couto , Lawlor Deborah A , Kaakinen Marika , Järvelin Marjo-Riitta , Grant Struan F.A. , Tilling Kate , Prokopenko Inga , Sebert Sylvain , Canouil Mickaël , Warrington Nicole M ,   Early Growth Genetics (EGG) Consortium
Published: March 2024

AbstractGenetic effects on changes in human traits over time are understudied and may have important pathophysiological impact. We propose a framework that enables data quality control, implements mixed models to evaluate trajectories of change in traits, and estimates phenotypes to identify age-varying genetic effects in genome-wide association studies (GWASs). Using childhood body mass index (BMI) as an example, we included 71,336 participants from six cohorts and estimated the slope and area under the BMI curve within four time periods (infancy, early childhood, late childhood and adolescence) for each participant, in addition to the age and BMI at the adiposity peak and the adiposity rebound. GWAS on each of the estimated phenotypes identified 28 genome-wide significant variants at 13 loci across the 12 estimated phenotypes, one of which was novel (inDAOA)and had not been previously associated with childhood or adult BMI. Genetic studies of changes in human traits over time could uncover novel biological mechanisms influencing quantitative traits.
Divergent effects of C4a, C4adesArg, and thrombin on platelet aggregation and phosphorylation of ERK and Akt in human endothelial cells
Authors: Liu Mengyao , Tran Luu Vy K. , Wang Hongbin 
Published: March 2024

AbstractPrior studies have established C4a as an untethered ligand for protease-activated receptors (PAR)1 and PAR4, which can increase ERK phosphorylation and [Ca2+]iinflux in human endothelial cells (ECs). C4adesArgis a stable metabolite produced from C4a through cleavage of an arginine at the carboxyl terminus by plasma carboxypeptidases B/N. PAR1 and PAR4 are typical receptors for thrombin and transduce cellular responses to the serine protease generated by the activation of coagulation pathways. Here, we aim to address whether C4adesArgcan induce the same effects as C4a through PAR1 and PAR4, and whether C4a and C4adesArgcan activate the same downstream signaling effectors as thrombin through PAR1 and PAR4.We demonstrated that C4adesArginduces ERK phosphorylation and [Ca2+]iinflux with the reduced efficacy as compared to C4a in human ECs. Distinct from C4a, C4adesArg-induced ERK phosphorylation was only inhibited by the PAR4 antagonist tcY-NH2, indicating that C4adesArg-mediated ERK phosphorylation is PAR4-dependent. Both C4a and C4adesArgat a concentration of 3 μM failed to induce platelet aggregation. Moreover, both C4a and C4adesArginduce significant Akt phosphorylation, whereas thrombin causes Akt dephosphorylation in human ECs.Our study revealed that the absence of the C-terminal arginine in C4a decreases its efficacy and changes its preference for receptor of ERK and Akt activations in human ECs, suggesting that the C-terminal arginine of C4a might govern its binding specificity and/or affinity to PAR1 and/or PAR4. Unlike thrombin, both C4a and C4adesArgfail to induce platelet aggregation at supraphysiological concentrations. Contrary to thrombin, both C4a and C4adesArginduce significant Akt phosphorylation, indicating a unique role of C4a and C4adesArgin inflammation and coagulation through their association with PAR1 and/or PAR4.
A rapid and efficientin vivoinoculation method for introducing tree stem canker pathogens onto leaves: Suitable for large-scale assessment of resistance in poplar breeding progeny
Authors: Li Zheng , Zhang Bingyu , Fu Yuchen , Suo Yutian , Zhang Yinan , Feng Jinxia , Pan Long , Shen Wanna , Liu Huixiang , Su Xiaohua , Zhao Jiaping 
Published: March 2024

AbstractHybrid breeding, a direct and efficient strategy for disease control and management in tree species, is currently limited by the selection method of resist clones: the “in vitrostem segment inoculation method.” This method, constrained by the availability of inoculating materials, cannot rapidly, efficiently, and cost-effectively screen the resistance of all hybrid clones. To overcome these limitations, we introduce a novel pathogen inoculation method for the resistance assessment of hybrid clones in the poplar-Valsa sordidapathosystem. This method involves inoculating the stem canker pathogen on the host leaf, a unique and promising approach we have successfully validated.Results showed that stem canker pathogenV. sordidainduced the extended necrotic lesion and even induced the formation of pycnidium structure and conidia on the leaf surface five days after mycelium inoculation; 1) the upper 5-7thleaves exhibited higher resistance than the middle 18-20thleaves; 2) the shading conditions induced more severe symptoms on the leaves than lighting conditions; 3) the juvenile mycelium inoculums (4-day-cultured) were more susceptible to poplar leaves than the old ones (7-day-cultured). Our results demonstrate the robustness of the “in vivoleaf inoculation method” in revealing the resistance differentiation in poplar hybrid clones. According to the leaf necrotic area disease index, we divided these poplar clones into seven different resistance groups. The resistance assessed by leaf assessment was validated in 15 selected poplar clones using the “in vitrostem segment inoculation method.” Results showed that the effectiveness of these two methods was consistent. Moreover, the leaf inoculation method can be used to detect the pathogenicity diversity of the pathogen population of tree species. Compared to the conventional “in vitrostem segment inoculation method,” the leaf method has the advantages of abundant inoculation materials, easy operation, rapid disease onset, and almost no adverse effect on the host. It is particularly suitable for the resistance screening of all progeny and the early (seedling) phenotypic selection of resistant poplar clones in poplar stem disease resistance breeding. The “in vivoleaf inoculation method” holds significant promise in poplar breeding, tree pathology, and molecular biology research on tree stem diseases.