bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital pitting scars are associated with a severe disease course and death in systemic sclerosis: a study from the EUSTAR cohort
Authors: Hughes Michael , Heal Calvin , Henes Jörg , Balbir-Gurman Alexandra , Distler Jörg H W , Airò Paolo , Müller-Ladner Ulf , Hunzelmann Nicolas , Kerzberg Eduardo , Rudnicka Lidia , Truchetet Marie-Elise , Stebbings Simon , Tanaka Yoshiya , Hoffman-Vold Anna Maria , Gabrielli Armando , Distler Oliver , Matucci-Cerinic Marco ,   the EUSTAR Collaborators, Ananieva Lidia P , de Vries-Bouwstra Jeska , Bruni Cosimo , Cantatore Francesco Paolo , Castellví Ivan , Cutolo Maurizio , Damjanov Nemanja , Farge-Bancel Dominique , Gheorghiu Ana Maria , Hachulla Eric , Hsu Vivien M , Iannone Florenzo , Ingegnoli Francesca , Ionescu Ruxandra , de la Peña Lefebvre Paloma García , Li Mengtao , Mohamed Walid Ahmed Abdel Atty , Montecucco Carlomaurizio , Mouthon Luc , Pellerito Raffaele , Randone Silvia Bellando , Riccieri Valeria , Riemekasten Gabriela , Siegert Elise , Spertini François , Smith Vanessa , Stamenkovic Bojana , Tikly Mohammed , Ullman Susanne , Vanthuyne Marie , Walker Ulrich 
Published: June 2021

Abstract

Objective
Digital pitting scars (DPS) are frequent, but little studied in SSc to date.

Methods
An analysis of SSc patients enrolled in the EUSTAR database. Primary objectives were to (i) examine DPS prevalence; (ii) examine whether DPS are associated with digital ulcers (DUs) and active digital ischaemia (DUs or gangrene); and (iii) describe other associations with DPS including internal organ complications. Secondary objectives were whether DPS are associated with (i) functional impairment; (ii) structural microvascular disease; and (iii) mortality. Descriptive statistics and parametric/non-parametric tests were used. Binary logistic regression was used to examine the association between DPS and DUs, active digital ischaemia and mortality.

Results
A total of 9671 patients were included with reported DPS at any time point (n = 4924) or ‘never’ DPS (n = 4747). The majority (86.9%) were female and mean age was 55.7 years. DPS were associated with longer disease and Raynaud’s duration (both P ≤ 0.001). DPS were associated with interstitial lung disease, pulmonary hypertension, conduction blocks, telangiectases, calcinosis (all P ≤ 0.001) and joint synovitis (P = 0.021). Patients were more likely to have more severe capillaroscopic abnormality and greater hand functional impairment. Multivariable logistic regression analyses showed that DPS were associated (odds ratio) with DUs: 22.03 (19.51–24.87), active digital ischaemia: 6.30 (5.34–7.42) and death: 1.86 (1.48–2.36).

Conclusion
DPS are associated with a severe disease course including death. The impact of DPS on hand function and ischaemia is significant. The presence of DPS should alert the clinician to a poor prognosis and need to optimize the therapeutic strategy.
Point-of-Care Ultrasound for the Evaluation of Neck Masses in the Pediatric Emergency Department
Authors: Stem Christopher T. , Marin Jennifer R. , Perera AG Nuwan D. , Azhdam Devora B. 
Published: June 2021

Abstract
Point-of-care ultrasound can be an effective tool for pediatric emergency medicine providers in the evaluation of soft tissue lesions. We present a series of 4 pediatric patients with neck lesions in whom point-of-care ultrasound identified the type of lesion, guided decision-making on the need for computed tomography imaging, and led to definitive management.
The Risk of Postkidney Transplant Outcomes by Induction Choice Differs by Recipient Age
Authors: Ahn JiYoon B. , Bae Sunjae , Chu Nadia M. , Wang Lingyu , Kim Jongyeon , Schnitzler Mark , Hess Gregory P. , Lentine Krista L. , Segev Dorry L. , McAdams-DeMarco Mara A. 
Published: June 2021

Background.
Among adult kidney transplant (KT) recipients, the risk of post-KT adverse outcomes differs by type of induction immunosuppression. Immune response to induction differs as recipients age; yet, choice of induction is barely tailored by age likely due to a lack of evidence of the risks and benefits.

Methods.
Using Scientific Registry of Transplant Recipients data, we identified 39336 first-time KT recipients (2010–2016). We estimated the length of stay (LOS), acute rejection (AR), graft failure, and death by induction type using logistic and Cox regression weighted by propensity score to adjust for confounders. We tested whether these estimates differed by age (65+ versus 18–64 y) using a Wald test.

Results.
Overall, rabbit antithymocyte globulin (rATG) was associated with a decreased risk of AR (odds ratio = 0.79, 95% confidence interval [CI], 0.72-0.85) compared with basiliximab. The effect of induction on LOS and death (interaction P = 0.03 and 0.003) differed by recipient age. Discharge was on average 11% shorter in rATG among younger recipients (relative time = 0.89; 95% confidence interval [CI], 0.81-0.99) but not among older recipients (relative time = 1.01; 95% CI, 0.95-1.08). rATG was not associated with mortality among older (hazard ratio = 1.05; 95% CI, 0.96-1.15), but among younger recipients (hazard ratio = 0.87; 95% CI, 0.80-0.95), it was associated with reduced mortality risk.

Conclusions.
rATG should be considered to prevent AR, especially among recipients with high-immunologic risk regardless of age; however, choice of induction should be tailored to reduce LOS and risk of mortality, particularly among younger recipients.
Nurse-facilitated reflective exercise post patient death in the ICU: a best practice implementation project
Authors: VanHorn Erica K. , Worobel-Luk Pamela , Tanner Ben , Jang Hannah 
Published: June 2021

ABSTRACT

Introduction:
ICUs are stressful environments where patient care is complex and demanding; death is not an unusual outcome. Nurses can become emotionally distressed from experiencing multiple, unexpected, or traumatic patient deaths. Performing a reflective exercise immediately post death is one coping strategy which encourages healthcare staff and family to debrief their feelings in a timelier manner.

Objectives:
The aim of this project was to educate the nurses in the ICU with emotional coping skills pertaining to the effects of patient deaths. The objective was to implement a nurse-guided reflective exercise following each patient death in three adult ICUs in a quaternary academic medical center.

Methods:
The current change project used the Joanna Briggs Institute's Getting Research into Practice and Practical Application of Clinical Evidence Systems for auditing and strategy development. After standardizing the reflective exercise procedure, teaching methods were employed to support implementation. One follow-up audit measured compliance with completing a reflective exercise for all deaths occurring in the three ICUs. Contextual data were collected for completed exercises including type of death and words to describe nurses’ emotions.

Results:
The reflective exercise script was revised and the standard procedure posted to the intranet for easy access. All ICU nurses received education on the use of this reflective exercise. For each of the two ICUs where this practice was new, compliance with nurses initiating and completing a reflective exercise was at a rate of 17 and 2%, respectively. For the ICU where reflective exercise was reintroduced, compliance was 30%. All deaths included in this study were anticipated (e.g., patient on comfort care) and calm, with the exception of one post cardiac arrest death.

Conclusion:
Despite multipronged teaching for why, when, and how to use reflective exercise, there was minimal success in completing reflective exercises in the two units where the practice was new. This outcome was most likely due to higher than anticipated levels of needed support or the unpredictability of frequency of deaths on each unit. However, the main achievement was having the Minute of Silence procedure with a standardized script readily available at all times for nursing staff. Reimplementation success in the other ICU was attributed to more recently established reflective practices. Further exploration of barriers, such as type of death, and re-education are essential strategies to bolster and sustain practice and to provide support for our nursing staff to prevent emotional distress.
The Clinical Utility of Serial Procalcitonin and Procalcitonin Clearance in Predicting the Outcome of COVID-19 Patients
Authors: Taha Sara I. , Shata Aalaa K. , Baioumy Shereen A. , Fouad Shaimaa H. , Moussa Aya H. , Youssef Mariam K. 
Published: June 2021

ABSTRACTBackgroundThe pandemic of coronavirus disease 2019 (COVID-19) represents a significant threat to global health. Sensitive tests that effectively predict the disease outcome are essentially required to guide proper intervention.ObjectivesTo evaluate the predictive ability of serial procalcitonin (PCT) measurement to predict the outcome of COVID-19 patients, using PCT clearance (PCT-c) as a tool to reflect its dynamic changes.MethodsA prospective observational study of inpatients diagnosed with COVID-19 at the Quarantine Hospitals of Ain-Shams University, Cairo, Egypt. During the first five days of hospitalization, serial PCT and PCT-c values were obtained and compared between survivors and non-survivors. Patients were followed up to hospital discharge or in-hospital mortality.ResultsCompared to survivors, serial PCT levels of non-survivors were significantly higher (p ≤ 0.001) and progressively increased during follow-up. In contrast, PCT-c values were significantly lower (p < 0.01) and progressively decreased. Receiver operating characteristic (ROC) curve analysis showed that using the initial PCT value alone, at a cut-off value of 0.80 ng/ml, the area under the curve for predicting in-hospital mortality was 0.81 with 61.1% sensitivity and 87.3% accuracy. Serial measurements showed better predictive performance, and the combined prediction value was better than the single prediction by the initial PCT alone.ConclusionsSerial PCT measurement could be a helpful laboratory tool to predict the prognosis and outcome of COVID-19 patients. Moreover, PCT-c could be a reliable tool to assess PCT progressive kinetics.
A Unified Model for Entrainment by Circadian Clocks: Dynamic Circadian Integrated Response Characteristic (dCiRC)
Authors: An Zheming , Piccoli Benedetto , Merrow Martha , Lee Kwangwon 
Published: June 2021

AbstractCircadian rhythm is a ubiquitous phenomenon, and it is observed in all biological kingdoms. In nature, their primary characteristic or phenotype is the phase of entrainment. There are two main hypotheses related to how circadian clocks entrain, parametric and non-parametric models. The parametric model focuses on the gradual changes of the clock parameters in response to the changing ambient condition, whereas the non-parametric model focuses on the instantaneous change of the phase of the clock in response to the zeitgeber. There are ample empirical data supporting both models. However, only recently has a unifying model been proposed, the circadian integrated response characteristic (CiRC). In the current study, we developed a system of ordinary differential equations, dynamic CiRC (dCiRC), that describes parameters of circadian rhythms and predicts the phase of entrainment in zeitgeber cycles. dCiRC mathematically extracts the underlying information of velocity changes of the internal clock that reflects the parametric model and the phase shift trajectory that reflects the non-parametric model from phase data under entraining conditions. As a proof of concept, we measured clock parameters of 26 Neurospora crassa ecotypes in both cycling and constant conditions using dCiRC. Our data showed that the morning light shortens the period of the clock while the afternoon light lengthens it. We also found that individual ecotypes have different strategies of integrating light effects to accomplish the optimal phase of entrainment, a model feature that is consistent with our knowledge of how circadian clocks are organized and encoded. The unified model dCiRC will provide new insights into how circadian clocks function under different zeitgeber conditions. We suggest that this type of model may be useful in the advent of chronotherapies.
Analysis of conditional colocalization relationships and hierarchies in three-color microscopy images
Authors: Vega-Lugo Jesus , da Rocha-Azevedo Bruno , Dasgupta Aparajita , Touret Nicolas , Jaqaman Khuloud 
Published: June 2021

AbstractColocalization analysis of multicolor microscopy images is a cornerstone approach in cell biology. It provides information on the localization of molecules within various subcellular compartments and allows the interrogation of molecular interactions in their cellular context. However, almost all colocalization analyses are designed for two-color images. This limits their applicability and the type of information that they reveal, leading to underutilization of multicolor microscopy images. Here we describe an approach, termed “conditional colocalization analysis,” for analyzing the colocalization relationships between three molecular entities in three-color microscopy images. Going beyond the question of whether colocalization is present or not, it addresses the question of whether the colocalization between two entities is influenced, positively or negatively, by their colocalization with a third entity. We showcase two applications of conditional colocalization analysis, one addressing the question of compartmentalization of molecular interactions, and one investigating the hierarchy of molecular interactions in a multimolecular complex. The software for conditional colocalization analysis is available at https://github.com/kjaqaman/conditionalColoc.
Emergent Statistical Laws in Single-Cell Transcriptomic Data
Authors: Lazzardi Silvia , Valle Filippo , Mazzolini Andrea , Scialdone Antonio , Caselle Michele , Osella Matteo 
Published: June 2021

AbstractLarge scale data on single-cell gene expression have the potential to unravel the specific transcriptional programs of different cell types. The structure of these expression datasets suggests a similarity with several other complex systems that can be analogously described through the statistics of their basic building blocks. Transcriptomes of single cells are collections of messenger RNA abundances transcribed from a common set of genes just as books are different collections of words from a shared vocabulary, genomes of different species are specific compositions of genes belonging to evolutionary families, and ecological niches can be described by their species abundances. Following this analogy, we identify several emergent statistical laws in single-cell transcriptomic data closely similar to regularities found in linguistics, ecology or genomics. A simple mathematical framework can be used to analyze the relations between different laws and the possible mechanisms behind their ubiquity. Importantly, treatable statistical models can be useful tools in transcriptomics to disentangle the actual biological variability from general statistical effects present in most component systems and from the consequences of the sampling process inherent to the experimental technique.Author summaryGene expression profiles represent how different cells use their genetic information. Similarly, books are specific collections of words chosen from a shared vocabulary, and many complex systems can be ultimately described by the statistics of their basic components. Leveraging on this analogy, we identified several emergent statistical laws in single-cell transcriptomic data that are universally found in complex component systems. A simple mathematical description sets these laws in a treatable quantitative framework and represents a useful tool for dissecting the different sources of gene expression variability.
Evolution of Drosophila buzzatii wings: Modular genetic organization, sex-biased integrative selection and intralocus sexual conflict
Authors: Iglesias PP , Machado FA , Llanes S , Hasson E , Soto EM 
Published: June 2021

AbstractThe Drosophila wing is a structure shared by males and females with the main function of flight. However, in males, wings are also used to produce songs, or visual displays during courtship. Thus, observed changes in wing phenotype depend on the interaction between sex-specific selective pressures and the genetic and ontogenetic restrictions imposed by a common genetic architecture. Here, we investigate these issues by studying how the wing has evolved in twelve populations of Drosophila buzzatii raised in common-garden conditions and using an isofemale line design. The between-population divergence shows that sexual dimorphism is greater when sex evolves in different directions. Multivariate Qst-Fst analyses confirm that male wing shape is the target for multiple selective pressures, leading males’ wings to diverge more than females’ wings. While the wing blade and the wing base appear to be valid modules at the genetic (G matrix) and among-population (D matrix) levels, the reconstruction of between-population adaptive landscapes (Ω matrix) shows selection as an integrative force. Also, cross-sex covariances reduced the predicted response to selection in the direction of the extant sexual dimorphism, suggesting that selection had to be intensified in order to circumvent the limitations imposed by G. However, such intensity of selection was not able to break the modularity pattern of the wing. The results obtained here show that the evolution of D. buzzatii wing shape is the product of a complex interplay between ontogenetic constraints and conflicting sexual and natural selections.
Parallel shifts of visual sensitivity and body colouration in replicate populations of extremophile fish
Authors: Owens Gregory L. , Veen Thor , Moxley Dylan R. , Arias-Rodriguez Lenin , Tobler Michael , Rennison Diana J. 
Published: June 2021

AbstractVisual sensitivity and body pigmentation are often shaped by both natural selection from the environment and sexual selection from mate choice. One way of quantifying the impact of the environment is by measuring how traits have changed after colonization of a novel habitat. To do this, we studiedPoecilia mexicanapopulations that have repeatedly adapted to extreme sulphidic (H2S containing) environments. We measured visual sensitivity using opsin gene expression, as well as body pigmentation and water transmission for populations in four independent drainages. Both visual sensitivity and body pigmentation showed significant parallel shifts towards greater medium wavelength sensitivity and reflectance in sulphidic populations. The light spectrum was only subtly different between environments and overall, we found no significant correlations between the light environment and visual sensitivity or body pigmentation. Altogether we found that sulphidic habitats select for differences in visual sensitivity and pigmentation; our data suggest that this effect is unlikely to be driven purely by the water’s spectral properties and may instead be from other correlated ecological changes.
Satelight: Self-Attention-Based Model for Epileptic Spike Detection from Multi-Electrode EEG
Authors: Fukumori Kosuke , Yoshida Noboru , Sugano Hidenori , Nakajima Madoka , Tanaka Toshihisa 
Published: June 2021

AbstractObjectiveBecause of the lack of highly skilled experts, automated technologies that support electroencephalogram (EEG)-based in epilepsy diagnosis are advancing. Deep convolutional neural network-based models have been used successfully for detecting epileptic spikes, one of the biomarkers, from EEG. However, a sizeable number of supervised EEG records are required for training.ApproachThis study introduces the Satelight model, which uses the self-attention (SA) mechanism. The model was trained using a clinical EEG dataset labeled by five specialists, including 16,008 epileptic spikes and 15,478 artifacts from 50 children. The SA mechanism is expected to reduce the number of parameters and efficiently extract features from a small amount of EEG data. To validate the effectiveness, we compared various spike detection approaches with the clinical EEG data.Main resultsThe experimental results showed that the proposed method detected epileptic spikes more effectively than other models (accuracy = 0.876 and false positive rate = 0.133).SignificanceThe proposed model had only one-tenth the number of parameters as the other effective model, despite having such a high detection performance. Further exploration of the hidden parameters revealed that the model automatically attended to the EEG’s characteristic waveform locations of interest.
Automated compound testing in zebrafish xenografts identifies combined MCL-1 and BCL-XL inhibition to be effective against Ewing sarcoma
Authors: Grissenberger Sarah , Sturtzel Caterina , Wenninger-Weinzierl Andrea , Scheuringer Eva , Bierbaumer Lisa , Pascoal Susana , Tötzl Marcus , Tomazou Eleni , Delattre Olivier , Surdez Didier , Kovar Heinrich , Halbritter Florian , Distel Martin 
Published: June 2021

AbstractEwing sarcoma is a pediatric bone and soft tissue cancer for which new therapies to improve disease outcome and to reduce adverse effects of current standard treatments are urgently needed. To identify new and effective drugs, phenotypic drug screening has proven to be a powerful method and a cancer model ideally suited for this approach is the larval zebrafish xenograft system. Complementing mouse xenografts, zebrafish offer high-througput screening possibilities in an intact complex vertebrate organism. Here, we generated Ewing sarcoma xenografts in zebrafish larvae and established a workflow for automated imaging of xenografts, tumor cell recognition within transplanted zebrafish and quantitative tumor size analysis over consecutive days by high-content imaging. The increased throughput of our in vivo screening setup allowed us to identify combination therapies effective against Ewing sarcoma cells. Especially, combined inhibition of MCL-1 and BCL-XL, two anti-apoptotic proteins, was highly efficient at eradicating tumor cells in our zebrafish xenograft assays with two Ewing sarcoma cell lines and with patient-derived cells. Transcriptional analysis across Ewing sarcoma cell lines and tumors revealed that MCL-1 and BCL2L1, coding for BCL-XL, are the most abundantly expressed anti-apoptotic genes, suggesting that combined MCL-1/BCL-XL inhibition might be a broadly applicable strategy for Ewing sarcoma treatment.