bluuebunny/crossref_metadata_2025_split huggingface dataset:
A system-level analysis of patient disease trajectories based on clinical, phenotypic and molecular similarities
Authors: Giannoula Alexia , Centeno Emilio , Mayer Miguel-Angel , Sanz Ferran , Furlong Laura I 
Published: November 2020

Abstract

Motivation
Incorporating the temporal dimension into multimorbidity studies has shown to be crucial for achieving a better understanding of the disease associations. Furthermore, due to the multifactorial nature of human disease, exploring disease associations from different perspectives can provide a holistic view to support the study of their aetiology.

Results
In this work, a temporal systems-medicine approach is proposed for identifying time-dependent multimorbidity patterns from patient disease trajectories, by integrating data from electronic health records with genetic and phenotypic information. Specifically, the disease trajectories are clustered using an unsupervised algorithm based on dynamic time warping and three disease similarity metrics: clinical, genetic and phenotypic. An evaluation method is also presented for quantitatively assessing, in the different disease spaces, both the cluster homogeneity and the respective similarities between the associated diseases within individual trajectories. The latter can facilitate exploring the origin(s) in the identified disease patterns. The proposed integrative methodology can be applied to any longitudinal cohort and disease of interest. In this article, prostate cancer is selected as a use case of medical interest to demonstrate, for the first time, the identification of temporal disease multimorbidities in different disease spaces.

Availability and implementation
https://gitlab.com/agiannoula/diseasetrajectories.

Supplementary information
Supplementary data are available at Bioinformatics online.
Belatacept-based immunosuppressive regimen in HIV-positive kidney transplant recipients
Authors: El Sakhawi Karim , Melica Giovanna , Scemla Anne , Bertrand Dominique , Garrouste Cyril , Malvezzi Paolo , Rémy Philippe , Moktefi Anissa , Ingels Alexandre , Champy Cécile , Lelièvre Jean-Daniel , Kheav David , Morel Antoine , Mokrani David , Attias Philippe , Grimbert Philippe , Matignon Marie 
Published: November 2020

Abstract

Background
Kidney allograft survival in human immunodeficiency virus (HIV)-positive patients is lower than that in the general population. Belatacept increases long-term patient and allograft survival rates when compared with calcineurin inhibitors (CNIs). Its use in HIV-positive recipients remains poorly documented.

Methods
We retrospectively report a French cohort of HIV-positive kidney allograft recipients who were switched from CNI to belatacept, between June 2012 and December 2018. Patient and allograft survival rates, HIV immunovirological and clinical outcomes, acute rejection, opportunistic infections (OIs) and HLA donor-specific antibodies (DSAs) were analysed at 3 and 12 months, and at the end of follow-up (last clinical visit attended after transplantation). Results were compared with HIV-positive recipients group treated with CNI.

Results
Twelve patients were switched to belatacept 10 (2–25) months after transplantation. One year after belatacept therapy, patient and allograft survival rates scored 92% for both, two (17%) HIV virological rebounds occurred due to antiretroviral therapy non-compliance, and CD4+ and CD8+ T-cell counts remained stable over time. Serious adverse events included two (17%) acute steroid-resistant T-cell-mediated rejections and three (25%) OIs. Kidney allograft function significantly increased over the 12 post-switch months (P = 0.009), and DSAs remained stable at 12 months after treatment. The control group showed similar results in terms of patient and kidney allograft survival rates, DSA characteristics and proteinuria

Conclusions
Switch from CNI to belatacept can be considered safe and may increase long-term kidney allograft survival in HIV-positive kidney allograft recipients. These results need to be confirmed in a larger cohort.
Survival with low- and high-flux dialysis
Authors: Sánchez-Álvarez Emilio , Rodríguez-García Minerva , Locatelli Francesco , Zoccali Carmine , Martín-Malo Alejandro , Floege Jürgen , Ketteler Markus , London Gerard , Górriz José L , Rutkowski Boleslaw , Ferreira Anibal , Pavlovic Drasko , Cannata-Andía Jorge B , Fernández-Martín José L ,   the COSMOS group, Motellón José Luis , Turner Matthew , Chaussy Julien , Molemans Bart , Zani Wal , Rosser Dylan , Dehmel Bastian , Fouqueray Bruno , Bradbury Brian , Acquavella John , Hollowell Jennifer , Carter Dave , Holland Phil , Baños Ana , Mattin Caroline , Critchlow Cathy , Kim Joseph , Lewis Charlotte , Panayi Antonia , Hemetsberger Margit , Croft Stephen , Jaeger Philippe , Muehlebach Prisca , Blackburn Jane , Zumsteg Esther , Gurevich Andrey , Rodríguez Silvia , Pérez Angel , Faner Pau , Izco Irantzu , Traseira Susana , Castro Carmen , Moreno Javier , Calle David , Pieraccini Francesca 
Published: November 2020

Abstract

Background
Besides advances in haemodialysis (HD), mortality rates are still high. The effect of the different types of HD membranes on survival is still a controversial issue. The aim of this COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) analysis was to survey, in HD patients, the relationship between the use of conventional low- or high-flux membranes and all-cause and cardiovascular mortality.

Methods
COSMOS is a multicentre, open-cohort, 3-year prospective study, designed to evaluate mineral and bone disorders in the European HD population. The present analysis included 5138 HD patients from 20 European countries, 3502 randomly selected at baseline (68.2%), plus 1636 new patients with &lt;1 year on HD (31.8%) recruited to replace patients who died, were transplanted, switched to peritoneal dialysis or lost to follow-up by other reasons. Cox-regression analysis with time-dependent variables, propensity score matching and the use of an instrumental variable (facility-level analysis) were used.

Results
After adjustments using three different multivariate models, patients treated with high-flux membranes showed a lower all-cause and cardiovascular mortality risks {hazard ratio (HR) = 0.76 [95% confidence interval (CI) 0.61–0.96] and HR = 0.61 (95% CI 0.42–0.87), respectively}, that remained significant after matching by propensity score for all-cause mortality (HR = 0.69, 95% CI 0.52–0.93). However, a facility-level analysis showed no association between the case-mix-adjusted facility percentage of patients dialysed with high-flux membranes and all-cause and cardiovascular mortality.

Conclusions
High-flux dialysis was associated with a lower relative risk of all-cause and cardiovascular mortality. However, dialysis facilities using these dialysis membranes to a greater extent did not show better survival.
Outcome of atypical haemolytic uraemic syndrome relapse after eculizumab withdrawal
Authors: Duineveld Caroline , Bouwmeester Romy , van der Heijden Joost W , Berger Stefan P , van de Kar Nicole C A J , Wetzels Jack F M ,   the Dutch aHUS Working Group
Published: November 2020

Abstract

Background
The introduction of eculizumab has significantly improved the outcome of patients with atypical haemolytic uraemic syndrome (aHUS). Because of the risk of relapse after discontinuation, eculizumab was proposed as life-long therapy. However, data on the outcome of relapse are limited. In the Netherlands, patients with aHUS are treated with a restrictive eculizumab regime and are included in a national observational study (CUREiHUS, Dutch Trial Register NTR5988/NL5833).

Methods
For this interim safety analysis, we evaluated the outcome of all adult patients with a suspected relapse, defined as the need to intensify eculizumab after tapering or withdrawal of therapy.

Results
We describe 11 patients who received renewed eculizumab therapy because of suspected relapse. In three patients with aHUS in native kidneys, estimated glomerular filtration rate (eGFR) returned to baseline value and remained stable without overt proteinuria after follow-up. Six out of eight transplanted patients responded to eculizumab therapy with improvement in eGFR. After a median follow-up of 24.6 months, a reduction of eGFR ≥25% was observed in three of these transplanted patients, which was attributed to the aHUS relapse in only one patient.

Conclusions
This interim analysis suggests that re-treatment with eculizumab after relapse is safe and feasible. We will continue to use our restrictive treatment strategy.
AHL-priming for enhanced resistance as a tool in sustainable agriculture
Authors: Shrestha Abhishek , Schikora Adam 
Published: November 2020

ABSTRACTBacteria communicate with each other through quorum sensing (QS) molecules. N-acyl homoserine lactones (AHL) are one of the most extensively studied groups of QS molecules. The role of AHL molecules is not limited to interactions between bacteria; they also mediate inter-kingdom interaction with eukaryotes. The perception mechanism of AHL is well-known in bacteria and several proteins have been proposed as putative receptors in mammalian cells. However, not much is known about the perception of AHL in plants. Plants generally respond to short-chained AHL with modification in growth, while long-chained AHL induce AHL-priming for enhanced resistance. Since plants may host several AHL-producing bacteria and encounter multiple AHL at once, a coordinated response is required. The effect of the AHL combination showed relatively low impact on growth but enhanced resistance. Microbial consortium of bacterial strains that produce different AHL could therefore be an interesting approach in sustainable agriculture. Here, we review the molecular and genetical basis required for AHL perception. We highlight recent advances in the field of AHL-priming. We also discuss the recent discoveries on the impact of combination(s) of multiple AHL on crop plants and the possible use of this knowledge in sustainable agriculture.
MiR-142-5p promotes retinoblastoma cell proliferation, migration and invasion by targeting PTEN
Authors: Zhang Yujie , Zheng Ailing 
Published: November 2020

AbstractThe study intends to probe the functions of miR-142-5p in retinoblastoma (RB) and the relationship between miR-142-5p and phosphatase and tensin homolog deleted on chromosome ten (PTEN). In our study, miR-142-5p and PTEN mRNA expression in RB tissue, serum of RB patients and RB cell lines were investigated by quantitative real-time polymerase chain reaction (qRT-PCR). The proliferation, migration, invasion and cell apoptosis were measured using MTT assay, BrdU assay, Transwell experiments and flow cytometry analysis, respectively. Binding sites between miR-142-5p and PTEN were predicted by the TargetScan database and were confirmed via qRT-PCR, western blot and dual-luciferase reporter gene assay. It was demonstrated that miR-142-5p expression was elevated in RB tissue, serum of RB patients and RB cell lines. MiR-142-5p overexpression remarkably promoted the proliferation, migration, invasion and inhibited the apoptosis of WERI-RB-1 cells while miR-142-5p knockdown induced opposite effects in Y79 cells. MiR-142-5p decreased PTEN expression in both mRNA and protein expression levels, and PTEN was identified as a target gene of miR-142-5p. Cotransfection of PTEN overexpression plasmids reversed the influences of miR-142-5p on RB cells. In conclusion, miR-142-5p enhances proliferation, migration and invasion of RB cell by targeting PTEN.
Pathogenic and protective roles of extracellular vesicles in neurodegenerative diseases
Authors: Takeuchi Toshihide 
Published: November 2020

Abstract
Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and polyglutamine diseases are caused by aggregation and abnormal accumulation of the disease-causative proteins in brain and spinal cord. Recent studies have suggested that proteins associated with neurodegenerative diseases are secreted and transmitted intercellularly via extracellular vesicles (EVs), which may be involved in propagation of abnormal protein accumulation and progressive degeneration in patient brains. On the other hand, it has been also reported that EVs have neuroprotective roles in these diseases, which potentially contribute to preventing aggregation formation and aberrant accumulation of the disease-associated proteins. In this review, I summarize the current understanding of the roles of EVs in neurodegenerative diseases, especially focussing on the pathogenic and neuroprotective aspects. Elucidation of these two aspects of EVs would provide insight into not only potential therapeutic targets for treatment of neurodegenerative diseases but also development of EV-based biomarkers for disease diagnostics
Pelvic stress fracture in a Dutch U19 cricketer: a case report
Authors: Grewal S , Dunlop G , Kloen P 
Published: November 2020

Abstract
We report a case of a non-traumatic right-sided os ischium fracture and ramus inferior fracture in an 18-year-old cricket athlete of the national Dutch team. Occasionally, apophyseal avulsion fractures of the pelvis occur; however, non-traumatic isolated fractures of the os ischium are rare. This case highlights the treatment and result of an unusual cricket injury.
Biological Aging Measures Based on Blood DNA Methylation and Risk of Cancer: A Prospective Study
Authors: Dugué Pierre-Antoine , Bassett Julie K , Wong Ee Ming , Joo JiHoon E , Li Shuai , Yu Chenglong , Schmidt Daniel F , Makalic Enes , Doo Nicole Wong , Buchanan Daniel D , Hodge Allison M , English Dallas R , Hopper John L , Giles Graham G , Southey Melissa C , Milne Roger L 
Published: November 2020

AbstractBackgroundWe previously investigated the association between 5 “first-generation” measures of epigenetic aging and cancer risk in the Melbourne Collaborative Cohort Study. This study assessed cancer risk associations for 3 recently developed methylation-based biomarkers of aging: PhenoAge, GrimAge, and predicted telomere length.MethodsWe estimated rate ratios (RRs) for the association between these 3 age-adjusted measures and risk of colorectal (N = 813), gastric (N = 165), kidney (N = 139), lung (N = 327), mature B-cell (N = 423), prostate (N = 846), and urothelial (N = 404) cancer using conditional logistic regression models. We also assessed associations by time since blood draw and by cancer subtype, and we investigated potential nonlinearity.ResultsWe observed relatively strong associations of age-adjusted PhenoAge with risk of colorectal, kidney, lung, mature B-cell, and urothelial cancers (RR per SD was approximately 1.2-1.3). Similar findings were obtained for age-adjusted GrimAge, but the association with lung cancer risk was much larger (RR per SD = 1.82, 95% confidence interval [CI] = 1.44 to 2.30), after adjustment for smoking status, pack-years, starting age, time since quitting, and other cancer risk factors. Most associations appeared linear, larger than for the first-generation measures, and were virtually unchanged after adjustment for a large set of sociodemographic, lifestyle, and anthropometric variables. For cancer overall, the comprehensively adjusted rate ratio per SD was 1.13 (95% CI = 1.07 to 1.19) for PhenoAge and 1.12 (95% CI = 1.05 to 1.20) for GrimAge and appeared larger within 5 years of blood draw (RR = 1.29, 95% CI = 1.15 to 1.44 and 1.19, 95% CI = 1.06 to 1.33, respectively).ConclusionsThe methylation-based measures PhenoAge and GrimAge may provide insights into the relationship between biological aging and cancer and be useful to predict cancer risk, particularly for lung cancer.
The Paternal Transition Entails Neuroanatomic Adaptations that are Associated with the Father’s Brain Response to his Infant Cues
Authors: Paternina-Die María , Martínez-García Magdalena , Pretus Clara , Hoekzema Elseline , Barba-Müller Erika , Martín de Blas Daniel , Pozzobon Cristina , Ballesteros Agustín , Vilarroya Óscar , Desco Manuel , Carmona Susanna 
Published: November 2020

AbstractThe transition into fatherhood is a life-changing event that requires substantial psychological adaptations. In families that include a father figure, sensitive paternal behavior has been shown to positively impact the infant’s development. Yet, studies exploring the neuroanatomic adaptations of men in their transition into fatherhood are scarce. The present study used surface-based methods to reanalyze a previously published prospective magnetic resonance imaging dataset comprised of 20 first-time fathers (preconception-to-postpartum) and 17 childless men. We tested if the transition into fatherhood entailed changes in cortical volume, thickness, and area and whether these changes were related to 2 indicators of paternal experience. Specifically, we tested if such changes were associated with (1) the baby’s age and/or (2) the fathers’ brain activity in response to pictures of their babies compared with an unknown baby. Results indicated that first-time fathers exhibited a significant reduction in cortical volume and thickness of the precuneus. Moreover, higher volume reduction and cortical thinning were associated with stronger brain responses to pictures of their own baby in parental brain regions. This is the first study showing preconception-to-postpartum neuroanatomical adaptations in first-time fathers associated with the father’s brain response to cues of his infant.
Reading the Self: Medical Students’ Experience of Reflecting on Their Writing Over Time
Authors: Cunningham Hetty , Taylor Delphine S. , Desai Urmi A. , Ender Katherine L. , Glickstein Julie , Krishnan Usha S. , Richards Boyd F. , Charon Rita , Balmer Dorene F. 
Published: November 2020

Purpose
To investigate students’ experience (over time) with meta-reflection writing exercises, called Signature Reflections. These exercises were used to strengthen reflective capacity, as part of a 4-year reflective writing portfolio curriculum that builds on a recognized strategy for reflection (narrative medicine) and employs longitudinal faculty–mentors.

Method
In 2018, the authors conducted 5 focus groups with 18 third-year students from the Columbia University Vagelos College of Physicians and Surgeons class of 2019 to examine students’ experience with Signature Reflections. Using an iterative, thematic approach, they developed codes to reflect common patterns in the transcripts, distilled conceptually similar codes, and assembled the code categories into themes.

Results
Three core themes (safe space, narrative experience, mirror of self) and 1 overarching theme (moving through time) were identified. Students frequently experienced relief at having a safe reflective space that promoted grappling with their fears or vulnerabilities and highlighted contextual factors (e.g., trusted faculty–mentors, protected time) that fostered a safe space for reflection and exploration. They often emphasized the value of tangible documentation of their medical school journey (narrative experience) and reported using Signature Reflections to examine their emerging identity (mirror of self). Overlapping with the core themes was a deep appreciation for the temporal perspective facilitated by the Signature Reflections (moving through time).

Conclusions
A longitudinal narrative medicine-based portfolio curriculum with pauses for meta-reflection allowed students, with faculty support, to observe their trajectory through medical school, explore fears and vulnerabilities, and narrate their own growth. Findings suggest that narrative medicine curricula should be required and sufficiently longitudinal to facilitate opportunities to practice the skill of writing for insight, foster relationships with faculty, and strengthen students’ temporal perspectives of their development.
Tolerance for Ambiguity Among Medical Students: Patterns of Change During Medical School and Their Implications for Professional Development
Authors: Geller Gail , Grbic Douglas , Andolsek Kathyrn M. , Caulfield Marie , Roskovensky Lindsay 
Published: November 2020

Purpose
Tolerance for ambiguity (TFA) is important for physicians, with implications for ethical behavior and patient care. This study explores how medical students’ TFA changes from matriculation to graduation and how change in empathy and openness to diversity are associated with this change.

Method
Data for students who took the Matriculating Student Questionnaire (MSQ) in 2013 or 2014 and the Medical School Graduation Questionnaire (GQ) in 2017 or 2018 were drawn from the Association of American Medical Colleges (n = 17,221). Both the MSQ and GQ included a validated TFA scale and a shortened version of the Interpersonal Reactivity Index; the MSQ also included an openness to diversity scale. Tercile groups were used to assess how TFA changed from the MSQ to GQ, and regression analyses were used to assess associations between change in TFA and openness to diversity and between change in TFA and change in empathy.

Results
Mean TFA scores decreased (d = −.67) among students with the highest TFA at matriculation but increased (d = .60) among students with the lowest TFA at matriculation. Regression results showed that change in TFA was significantly and positively associated with change in empathy (beta = .05, P < .001) and that openness to diversity (as reported at matriculation) was significantly and positively associated with TFA at graduation (beta = .05, P < .001).

Conclusions
This is the first nationally representative study to suggest that medical students’ TFA changes over time, but in different directions depending on TFA at matriculation. TFA over time was also associated with change in empathy and openness to diversity. Medical schools should consider strategies to assess TFA in their admissions processes and for cultivating TFA throughout the learning process.