bluuebunny/crossref_metadata_2025 huggingface dataset:
138 We Tried This At Home – Safety Analysis and Outcome of Community Resource Services
Authors: Norris S , Kumar A , Carney K , Jones A , Sweeting O , Kitson J
Published: March 2021

Introduction

There are several data sets published for acute frailty services in hospital but there is a lack of supporting data in the emerging field of Intermediate Care. Gwent has well-established Community Resource Teams (CRT) that were set up as “Hospital at Home” services. The objective being to treat frail, acute or sub-acute medically ill patients in their own environment by a consultant-led hospital-like team using a Comprehensive Geriatric Assessment. Although “Hospital at Home” services are often preferred by the patient and are in-line with Health board strategies “Care Closer to home” and “Clinical Futures”; it is important to ask ourselves whether we are able to deliver clinical care in the community safely?

Method

One year of data from 2018 was extracted from the CRT Portal, analysed and then validated by the health board’s performance teams. From the established data set, origin of referrals and discharge outcomes were identified. Finally, at 28 days of discharge from Gwent CRTs mortality and hospital admission rates were examined.

Results

4,308 out of 5,395 referrals (85%) were accepted to Gwent CRTs of which 59.60% (2,863) referrals were from primary care and 33.54% (1,445) were from secondary care. Our admission rates to secondary care services were 15.27% (658) whilst mortality rate was 3.92% (169). After successful medical management from Gwent CRTs of 3,481 patients in their own place of residence, 28 day hospital admission rate was 13.84% (482) whilst 28 day mortality rate (expected and unexpected) was 6.89% (240).

Conclusion

Although no equivalent data is currently available for comparison, a significant number of patients can be medically managed in their own place of residence. More than 80% of patients did not require hospital admission whilst mortality rates were encouraging. Further future re-evaluation of our service performance and its value is required.
Are Recent Cohorts Getting Worse? Trends in US Adult Physiological Status, Mental Health, and Health Behaviors Across a Century of Birth Cohorts
Authors: Zheng Hui , Echave Paola
Published: March 2021

Morbidity and mortality have been increasing among middle-aged and young-old Americans since the turn of the century. We investigated whether these unfavorable trends extend to younger cohorts and their underlying physiological, psychological, and behavioral mechanisms. Applying generalized linear mixed-effects models to data from 62,833 adults from the National Health and Nutrition Examination Surveys (1988–2016) and 625,221 adults from the National Health Interview Surveys (1997–2018), we found that for all sex and racial groups, physiological dysregulation has increased continuously from Baby Boomers through late-Generation X and Generation Y. The magnitude of the increase was higher for White men than for other groups, while Black men had a steepest increase in low urinary albumin (a marker of chronic inflammation). In addition, Whites underwent distinctive increases in anxiety, depression, and heavy drinking, and they had a higher level than Blacks and Hispanics of smoking and drug use in recent cohorts. Smoking is not responsible for the increasing physiological dysregulation across cohorts. The obesity epidemic contributes to the increase in metabolic syndrome but not in low urinary albumin. The worsening physiological and mental health profiles among younger generations imply a challenging morbidity and mortality prospect for the United States, one that might be particularly inauspicious for Whites.
Severe Maternal Morbidity: A Comparison of Definitions and Data Sources
Authors: Snowden Jonathan M , Lyndon Audrey , Kan Peiyi , El Ayadi Alison , Main Elliott , Carmichael Suzan L
Published: March 2021

Severe maternal morbidity (SMM) is a composite outcome measure that indicates serious, potentially life-threatening maternal health problems. There is great interest in defining SMM using administrative data for surveillance and research. In the United States, one common way of defining SMM at the population level is an index developed by the Centers for Disease Control and Prevention. Modifications to this index (e.g., exclusion of maternal blood transfusion) have been proposed; some research defines SMM using an index introduced by Bateman et al. (Obstet Gynecol. 2013;122(5):957–965). Birth certificate data are also increasingly being used to define SMM. We compared commonly used US definitions of SMM among all California births (2007–2012) using the kappa (κ) statistic and other measures. We also evaluated agreement between maternal morbidity fields on the birth certificate as compared with health insurance claims data. Concordance between the 7 definitions of SMM analyzed was generally low (i.e., κ < 0.41 for 13 of 21 two-way comparisons). Low concordance was particularly driven by the presence/absence of transfusion and claims data versus birth certificate definitions. Low agreement between administrative data–based definitions of SMM highlights that results can be expected to differ between them. Further research on validity of SMM definitions, using more fine-grained data sources, is needed.
Drug purchase price volatility in an academic medical center
Authors: Cortes Armando , Park Megan , McCarthy Bryan C
Published: March 2021

Purpose

Inpatient drug purchase price trends at an 811-bed academic medical center are described.

Recent highly publicized drug price increases by pharmaceutical manufacturers have generated public interest in regulatory solutions to reduce drug costs. Monitoring drug price changes through internal dashboards has been demonstrated to aid in purchasing decisions to reduce the impact of drug price changes on inpatient pharmacy drug budgets. In this research, University of Chicago Medicine created an internal dashboard to detail specific inpatient drug purchase price trends. Dashboard data input included all medications purchased through the organization’s group purchasing organization over a 25-month time frame. A total of 69,245 drug purchases of 2,432 unique medications and/or dosage strengths were analyzed in the study. Within the 25-month time period, 706 medications (29%) had a net drug purchase price increase, while 898 (37%) had a net drug purchase price decrease. The range of net price percentage changes for medications with price increases was 0.01% to 733.6%; the range for medications with price decreases was 0.01% to 97.5%.

Conclusion

Relative to previous purchase prices, drug purchase prices decreased or remained the same more often than they increased over a 25-month time frame. However, drug purchase price percentage changes were far greater for medications whose prices increased rather than decreased.
SGANRDA: semi-supervised generative adversarial networks for predicting circRNA–disease associations
Authors: Wang Lei , Yan Xin , You Zhu-Hong , Zhou Xi , Li Hao-Yuan , Huang Yu-An
Published: March 2021

Emerging research shows that circular RNA (circRNA) plays a crucial role in the diagnosis, occurrence and prognosis of complex human diseases. Compared with traditional biological experiments, the computational method of fusing multi-source biological data to identify the association between circRNA and disease can effectively reduce cost and save time. Considering the limitations of existing computational models, we propose a semi-supervised generative adversarial network (GAN) model SGANRDA for predicting circRNA–disease association. This model first fused the natural language features of the circRNA sequence and the features of disease semantics, circRNA and disease Gaussian interaction profile kernel, and then used all circRNA–disease pairs to pre-train the GAN network, and fine-tune the network parameters through labeled samples. Finally, the extreme learning machine classifier is employed to obtain the prediction result. Compared with the previous supervision model, SGANRDA innovatively introduced circRNA sequences and utilized all the information of circRNA–disease pairs during the pre-training process. This step can increase the information content of the feature to some extent and reduce the impact of too few known associations on the model performance. SGANRDA obtained AUC scores of 0.9411 and 0.9223 in leave-one-out cross-validation and 5-fold cross-validation, respectively. Prediction results on the benchmark dataset show that SGANRDA outperforms other existing models. In addition, 25 of the top 30 circRNA–disease pairs with the highest scores of SGANRDA in case studies were verified by recent literature. These experimental results demonstrate that SGANRDA is a useful model to predict the circRNA–disease association and can provide reliable candidates for biological experiments.
usDSM: a novel method for deleterious synonymous mutation prediction using undersampling scheme
Authors: Tang Xi , Zhang Tao , Cheng Na , Wang Huadong , Zheng Chun-Hou , Xia Junfeng , Zhang Tiejun
Published: March 2021

Although synonymous mutations do not alter the encoded amino acids, they may impact protein function by interfering with the regulation of RNA splicing or altering transcript splicing. New progress on next-generation sequencing technologies has put the exploration of synonymous mutations at the forefront of precision medicine. Several approaches have been proposed for predicting the deleterious synonymous mutations specifically, but their performance is limited by imbalance of the positive and negative samples. In this study, we firstly expanded the number of samples greatly from various data sources and compared six undersampling strategies to solve the problem of the imbalanced datasets. The results suggested that cluster centroid is the most effective scheme. Secondly, we presented a computational model, undersampling scheme based method for deleterious synonymous mutation (usDSM) prediction, using 14-dimensional biology features and random forest classifier to detect the deleterious synonymous mutation. The results on the test datasets indicated that the proposed usDSM model can attain superior performance in comparison with other state-of-the-art machine learning methods. Lastly, we found that the deep learning model did not play a substantial role in deleterious synonymous mutation prediction through a lot of experiments, although it achieves superior results in other fields. In conclusion, we hope our work will contribute to the future development of computational methods for a more accurate prediction of the deleterious effect of human synonymous mutation. The web server of usDSM is freely accessible at http://usdsm.xialab.info/.
LocusZoom.js: interactive and embeddable visualization of genetic association study results
Authors: Boughton Andrew P , Welch Ryan P , Flickinger Matthew , VandeHaar Peter , Taliun Daniel , Abecasis Gonçalo R , Boehnke Michael
Published: March 2021

LocusZoom.js is a JavaScript library for creating interactive web-based visualizations of genetic association study results. It can display one or more traits in the context of relevant biological data (such as gene models and other genomic annotation), and allows interactive refinement of analysis models (by selecting linkage disequilibrium reference panels, identifying sets of likely causal variants, or comparisons to the GWAS catalog). It can be embedded in web pages to enable data sharing and exploration. Views can be customized and extended to display other data types such as phenome-wide association study (PheWAS) results, chromatin co-accessibility, or eQTL measurements. A new web upload service harmonizes datasets, adds annotations, and makes it easy to explore user-provided result sets.

Availability and implementation

LocusZoom.js is open-source software under a permissive MIT license. Code and documentation are available at: https://github.com/statgen/locuszoom/. Installable packages for all versions are also distributed via NPM. Additional features are provided as standalone libraries to promote reuse. Use with your own GWAS results at https://my.locuszoom.org/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Differences in the proteome of stallion spermatozoa explain stallion-to-stallion variability in sperm quality post-thaw†
Authors: Gaitskell-Phillips Gemma , Martín-Cano Francisco E , Ortiz-Rodríguez José M , Silva-Rodríguez Antonio , Gil Maria C , Ortega-Ferrusola Cristina , Peña Fernando J
Published: March 2021

The identification of stallions and or ejaculates that will provide commercially acceptable quality post-thaw before cryopreservation is of great interest, avoiding wasting time and resources freezing ejaculates that will not achieve sufficient quality to be marketed. Our hypothesis was that after bioinformatic analysis, the study of the stallion sperm proteome can provide discriminant variables able to predict the post-thaw quality of the ejaculate. At least three ejaculates from 10 different stallions were frozen following a split sample design. Half of the ejaculate was analyzed as a fresh aliquot and the other half was frozen and then analyzed as a frozen-thawed aliquot. Computer-assisted sperm analysis and flow cytometry were used to analyze sperm quality. Detailed proteomic analysis was performed on fresh and frozen and thawed aliquots, and bioinformatic analysis was used to identify discriminant variables in fresh samples able to predict the outcome of cryopreservation. Those with a fold change > 3, a P = 8.2e-04, and a q = 0.074 (equivalent to False discovery rate (FDR)) were selected, and the following proteins were identified in fresh samples as discriminant variables of good motility post-thaw: F6YTG8, K9K273, A0A3Q2I7V9, F7CE45, F6YU15, and F6SKR3. Other discriminant variables were also identified as predictors of good mitochondrial membrane potential and viability post-thaw. We concluded that proteomic approaches are a powerful tool to improve current sperm biotechnologies.
Sperm–oocyte signaling: the role of IZUMO1R and CD9 in PTK2B activation and actin remodeling at the sperm binding site
Authors: Wang Huizhen , Hong Xiaoman , Kinsey William H
Published: March 2021

Sperm–oocyte binding initiates an outside-in signaling event in the mouse oocyte that triggers recruitment and activation of the cytosolic protein kinase PTK2B in the cortex underlying the bound sperm. While not involved in gamete fusion, PTK2B activity promotes actin remodeling events important during sperm incorporation. However, the mechanism by which sperm–oocyte binding activates PTK2B is unknown, and the present study examined the possibility that sperm interaction with specific oocyte surface proteins plays an important role in PTK2B activation. Imaging studies revealed that as IZUMO1R and CD9 became concentrated at the sperm binding site, activated (phosphorylated) PTK2B accumulated in the cortex underlying the sperm head and in microvilli partially encircling the sperm head. In order to determine whether IZUMO1R and/or CD9 played a significant role in PTK2B recruitment and activation at the sperm binding site, the ability of oocytes null for Izumo1r or Cd9, to initiate an increase in PTK2B content and activation was tested. The results revealed that IZUMO1R played a minor role in PTK2B activation and had no effect on actin remodeling; however, CD9 played a very significant role in PTK2B activation and subsequent actin remodeling at the sperm binding site. These findings suggest the possibility that interaction of sperm surface proteins with CD9 or CD9-associated oocyte proteins triggers PTK2B activation at the sperm binding site.
Segregation Seekers: an Alternative Perspective on the Solitary Confinement Debate
Authors: Laws Ben
Published: March 2021

Recent calls from senior managers, human rights groups and academics continue to scrutinize the impact of solitary confinement. But much less attention has been paid to prisoners’ own motivations for segregation. By analysing interviews with 16 segregated men in a high-security prison (Category-A) in England, this article foregrounds motivation. The argument involves a detailed description of the complex, and sometimes contradictory, motives that may lead prisoners into seeking isolation. It further attempts to explore the relationship between segregation and the wider prison environment. For many prisoners, segregation has a ‘negative benefit’ or amounts to a form of ‘lesser evil’. Such phrasing hints at the difficult decisions that prisoners navigate and offers an alternative perspective on solitary confinement.
Variable impact of COVID-19 on urgent intervention in Ontario
Authors: de Mestral C , Gomez D , Sue-Chue-Lam C , Dossa F , Nantais J , Simpson A N , Urbach D , Austin P C , Wilton A S , Baxter N N
Published: March 2021

COVID-19 had a variable impact on urgent interventions among hospitalized patients in Ontario Canada.
BMP receptor blockade overcomes extrinsic inhibition of remyelination and restores neurovascular homeostasis
Authors: Petersen Mark A , Tognatta Reshmi , Meyer-Franke Anke , Bushong Eric A , Mendiola Andrew S , Yan Zhaoqi , Muthusamy Abinaya , Merlini Mario , Meza-Acevedo Rosa , Cabriga Belinda , Zhou Yungui , Thomas Reuben , Ryu Jae Kyu , Lassmann Hans , Ellisman Mark H , Akassoglou Katerina
Published: March 2021

Extrinsic inhibitors at sites of blood–brain barrier disruption and neurovascular damage contribute to remyelination failure in neurological diseases. However, therapies to overcome the extrinsic inhibition of remyelination are not widely available and the dynamics of glial progenitor niche remodelling at sites of neurovascular dysfunction are largely unknown. By integrating in vivo two-photon imaging co-registered with electron microscopy and transcriptomics in chronic neuroinflammatory lesions, we found that oligodendrocyte precursor cells clustered perivascularly at sites of limited remyelination with deposition of fibrinogen, a blood coagulation factor abundantly deposited in multiple sclerosis lesions. By developing a screen (OPC-X-screen) to identify compounds that promote remyelination in the presence of extrinsic inhibitors, we showed that known promyelinating drugs did not rescue the extrinsic inhibition of remyelination by fibrinogen. In contrast, bone morphogenetic protein type I receptor blockade rescued the inhibitory fibrinogen effects and restored a promyelinating progenitor niche by promoting myelinating oligodendrocytes, while suppressing astrocyte cell fate, with potent therapeutic effects in chronic models of multiple sclerosis. Thus, abortive oligodendrocyte precursor cell differentiation by fibrinogen is refractory to known promyelinating compounds, suggesting that blockade of the bone morphogenetic protein signalling pathway may enhance remyelinating efficacy by overcoming extrinsic inhibition in neuroinflammatory lesions with vascular damage.
Towards realizing the vision of precision medicine: AI based prediction of clinical drug response
Authors: de Jong Johann , Cutcutache Ioana , Page Matthew , Elmoufti Sami , Dilley Cynthia , Fröhlich Holger , Armstrong Martin
Published: March 2021

Accurate and individualized prediction of response to therapies is central to precision medicine. However, because of the generally complex and multifaceted nature of clinical drug response, realizing this vision is highly challenging, requiring integrating different data types from the same individual into one prediction model. We used the anti-epileptic drug brivaracetam as a case study and combine a hybrid data/knowledge-driven feature extraction with machine learning to systematically integrate clinical and genetic data from a clinical discovery dataset (n = 235 patients). We constructed a model that successfully predicts clinical drug response [area under the curve (AUC) = 0.76] and show that even with limited sample size, integrating high-dimensional genetics data with clinical data can inform drug response prediction. After further validation on data collected from an independently conducted clinical study (AUC = 0.75), we extensively explore our model to gain insights into the determinants of drug response, and identify various clinical and genetic characteristics predisposing to poor response. Finally, we assess the potential impact of our model on clinical trial design and demonstrate that, by enriching for probable responders, significant reductions in clinical study sizes may be achieved. To our knowledge, our model represents the first retrospectively validated machine learning model linking drug mechanism of action and the genetic, clinical and demographic background in epilepsy patients to clinical drug response. Hence, it provides a blueprint for how machine learning-based multimodal data integration can act as a driver in achieving the goals of precision medicine in fields such as neurology.
The Developing Human Connectome Project: typical and disrupted perinatal functional connectivity
Authors: Eyre Michael , Fitzgibbon Sean P , Ciarrusta Judit , Cordero-Grande Lucilio , Price Anthony N , Poppe Tanya , Schuh Andreas , Hughes Emer , O’Keeffe Camilla , Brandon Jakki , Cromb Daniel , Vecchiato Katy , Andersson Jesper , Duff Eugene P , Counsell Serena J , Smith Stephen M , Rueckert Daniel , Hajnal Joseph V , Arichi Tomoki , O’Muircheartaigh Jonathan , Batalle Dafnis , Edwards A David
Published: March 2021

The Developing Human Connectome Project is an Open Science project that provides the first large sample of neonatal functional MRI data with high temporal and spatial resolution. These data enable mapping of intrinsic functional connectivity between spatially distributed brain regions under normal and adverse perinatal circumstances, offering a framework to study the ontogeny of large-scale brain organization in humans. Here, we characterize in unprecedented detail the maturation and integrity of resting state networks (RSNs) at term-equivalent age in 337 infants (including 65 born preterm). First, we applied group independent component analysis to define 11 RSNs in term-born infants scanned at 43.5–44.5 weeks postmenstrual age (PMA). Adult-like topography was observed in RSNs encompassing primary sensorimotor, visual and auditory cortices. Among six higher-order, association RSNs, analogues of the adult networks for language and ocular control were identified, but a complete default mode network precursor was not. Next, we regressed the subject-level datasets from an independent cohort of infants scanned at 37–43.5 weeks PMA against the group-level RSNs to test for the effects of age, sex and preterm birth. Brain mapping in term-born infants revealed areas of positive association with age across four of six association RSNs, indicating active maturation in functional connectivity from 37 to 43.5 weeks PMA. Female infants showed increased connectivity in inferotemporal regions of the visual association network. Preterm birth was associated with striking impairments of functional connectivity across all RSNs in a dose-dependent manner; conversely, connectivity of the superior parietal lobules within the lateral motor network was abnormally increased in preterm infants, suggesting a possible mechanism for specific difficulties such as developmental coordination disorder, which occur frequently in preterm children. Overall, we found a robust, modular, symmetrical functional brain organization at normal term age. A complete set of adult-equivalent primary RSNs is already instated, alongside emerging connectivity in immature association RSNs, consistent with a primary-to-higher order ontogenetic sequence of brain development. The early developmental disruption imposed by preterm birth is associated with extensive alterations in functional connectivity.
BiallelicPI4KAvariants cause a novel neurodevelopmental syndrome with hypomyelinating leukodystrophy
Authors: Verdura Edgard , Rodríguez-Palmero Agustí , Vélez-Santamaria Valentina , Planas-Serra Laura , de la Calle Irene , Raspall-Chaure Miquel , Roubertie Agathe , Benkirane Mehdi , Saettini Francesco , Pavinato Lisa , Mandrile Giorgia , O’Leary Melanie , O’Heir Emily , Barredo Estibaliz , Chacón Almudena , Michaud Vincent , Goizet Cyril , Ruiz Montserrat , Schlüter Agatha , Rouvet Isabelle , Sala-Coromina Julia , Fossati Chiara , Iascone Maria , Canonico Francesco , Marcé-Grau Anna , de Souza Precilla , Adams David R , Casasnovas Carlos , Rehm Heidi L , Mefford Heather C , González Gutierrez-Solana Luis , Brusco Alfredo , Koenig Michel , Macaya Alfons , Pujol Aurora
Published: March 2021

Phosphoinositides are lipids that play a critical role in processes such as cellular signalling, ion channel activity and membrane trafficking. When mutated, several genes that encode proteins that participate in the metabolism of these lipids give rise to neurological or developmental phenotypes. PI4KA is a phosphoinositide kinase that is highly expressed in the brain and is essential for life. Here we used whole exome or genome sequencing to identify 10 unrelated patients harbouring biallelic variants in PI4KA that caused a spectrum of conditions ranging from severe global neurodevelopmental delay with hypomyelination and developmental brain abnormalities to pure spastic paraplegia. Some patients presented immunological deficits or genito-urinary abnormalities. Functional analyses by western blotting and immunofluorescence showed decreased PI4KA levels in the patients’ fibroblasts. Immunofluorescence and targeted lipidomics indicated that PI4KA activity was diminished in fibroblasts and peripheral blood mononuclear cells. In conclusion, we report a novel severe metabolic disorder caused by PI4KA malfunction, highlighting the importance of phosphoinositide signalling in human brain development and the myelin sheath.
Resting-State Functional Connectivity and Psychopathology in Klinefelter Syndrome (47, XXY)
Authors: Whitman Ethan T , Liu Siyuan , Torres Erin , Warling Allysa , Wilson Kathleen , Nadig Ajay , McDermott Cassidy , Clasen Liv S , Blumenthal Jonathan D , Lalonde François M , Gotts Stephen J , Martin Alex , Raznahan Armin
Published: March 2021

Klinefelter syndrome (47, XXY; henceforth: XXY syndrome) is a high-impact but poorly understood genetic risk factor for neuropsychiatric impairment. Here, we provide the first study to map alterations of functional brain connectivity in XXY syndrome and relate these changes to brain anatomy and psychopathology. We used resting-state functional magnetic resonance imaging data from 75 individuals with XXY and 84 healthy XY males to 1) implement a brain-wide screen for altered global resting-state functional connectivity (rsFC) in XXY versus XY males and 2) decompose these alterations through seed-based analysis. We then compared these rsFC findings with measures of regional brain anatomy, psychopathology, and cognition. XXY syndrome was characterized by increased global rsFC in the left dorsolateral prefrontal cortex (DLPFC)—reflecting DLPFC overconnectivity with diverse rsFC networks. Functional overconnectivity was partly coupled to co-occurring regional volumetric changes in XXY syndrome, and variation in DLPFC–precuneus rsFC was correlated with the severity of psychopathology. By providing the first view of altered rsFC in XXY syndrome and contextualizing observed changes relative to neuroanatomy and behavior, our study helps to advance biological understanding of XXY syndrome—both as a disorder in its own right and more broadly as a model of genetic risk for psychopathology.
Representational Pattern Similarity of Electrical Brain Activity Reveals Rapid and Specific Prediction during Language Comprehension
Authors: Hubbard Ryan J , Federmeier Kara D
Published: March 2021

Predicting upcoming events is a critical function of the brain, and language provides a fertile testing ground for studying prediction, as comprehenders use context to predict features of upcoming words. Many aspects of the mechanisms of prediction remain elusive, partly due to a lack of methodological tools to probe prediction formation in the moment. To elucidate what features are neurally preactivated and when, we used representational similarity analysis on previously collected sentence reading data. We compared EEG activity patterns elicited by expected and unexpected sentence final words to patterns from the preceding words of the sentence, in both strongly and weakly constraining sentences. Pattern similarity with the final word was increased in an early time window following the presentation of the pre-final word, and this increase was modulated by both expectancy and constraint. This was not seen at earlier words, suggesting that predictions were precisely timed. Additionally, pre-final word activity—the predicted representation—had negative similarity with later final word activity, but only for strongly expected words. These findings shed light on the mechanisms of prediction in the brain: rapid preactivation occurs following certain cues, but the predicted features may receive reduced processing upon confirmation.
Investing in the Future: A Role for Professional Societies to Prepare the Next Generation of Healthcare Leaders Through Curriculum Development and Dissemination
Authors: Luther Vera P , Shnekendorf Rachel , Logan Ashleigh , Advani Sonali D , Barsoumian Alice E , Beeler Cole , Bennani Kenza , Cherabuddi Kartikeya , Holubar Marisa , Huang Misha , Ince Dilek , Justo Julie Ann , Lee Matthew S L , MacDougall Conan , Nori Priya , Ohl Christopher A , Patel Payal K , Pottinger Paul S , Spicer Jennifer O , Stack Conor , Van Schooneveld Trevor C , Willis Zachary I
Published: March 2021

Professional societies serve many functions that benefit constituents; however, few professional societies have undertaken the development and dissemination of formal, national curricula to train the future workforce while simultaneously addressing significant healthcare needs. The Infectious Diseases Society of America (IDSA) has developed 2 curricula for the specific purpose of training the next generation of clinicians to ensure the future infectious diseases (ID) workforce is optimally trained to lead antimicrobial stewardship programs and equipped to meet the challenges of multidrug resistance, patient safety, and healthcare quality improvement. A core curriculum was developed to provide a foundation in antimicrobial stewardship for all ID fellows, regardless of career path. An advanced curriculum was developed for ID fellows specifically pursuing a career in antimicrobial stewardship. Both curricula will be broadly available in the summer of 2021 through the IDSA website.
AACC Practical Recommendations for Implementing and Interpreting SARS-CoV-2 Emergency Use Authorization and Laboratory-Developed Test Serologic Testing in Clinical Laboratories
Authors: Zhang Y Victoria , Wiencek Joesph , Meng Qing H , Theel Elitza S , Babic Nikolina , Sepiashvili Lusia , Pecora Nicole D , Slev Patricia , Cameron Andrew , Konforte Danijela
Published: March 2021

Background

The clinical laboratory continues to play a critical role in managing the coronavirus pandemic. Numerous US Food and Drug Administration emergency use authorization (EUA) and laboratory-developed test (LDT) serologic assays have become available. The performance characteristics of these assays and their clinical utility continue to be defined in real time during this pandemic. The AACC convened a panel of experts from clinical chemistry, microbiology, and immunology laboratories; the in vitro diagnostics industry; and regulatory agencies to provide practical recommendations for implementation and interpretation of these serologic tests in clinical laboratories.

Content

The currently available EUA serologic tests and platforms, information on assay design, antibody classes including neutralizing antibodies, and the humoral immune responses to SARS-CoV-2 are discussed. Verification and validation of EUA and LDT assays are described, along with a quality management approach. Four indications for serologic testing are outlined. Recommendations for result interpretation, reporting comments, and the role of orthogonal testing are also presented.

This document aims to provide a comprehensive reference for laboratory professionals and healthcare workers to appropriately implement SARS-CoV-2 serologic assays in the clinical laboratory and to interpret test results during this pandemic. Given the more frequent occurrence of outbreaks associated with either vector-borne or respiratory pathogens, this document will be a useful resource in planning for similar scenarios in the future.
Consolidating identities in anonymous ego-centred collaboration networks
Authors: Gomide Janaina , Kling Hugo , Figueiredo Daniel
Published: March 2021

Individuals often appear with multiple names when considering large datasets collected from different sources, giving rise to the name ambiguities. Classical techniques that tackle this problem leverage personal information such as names and institutions. However, as privacy concerns continues to rise, Personally Identifiable Information (PII) may not be available in publicly released data. This work considers the synonym name ambiguity problem in anonymous ego-centred collaboration networks. The ego-centred collaboration network is generated from the individual’s profile and stripped of all PII. Using just the anonymous network, and no other side information, we propose an algorithm based on dominating sets to identify the different nodes that corresponds to the profile owner (synonyms). The proposed approach is applied to different datasets originating from profiles in DBLP and Google Scholar, showing an a relative high precision (e.g. 75% of profiles were perfectly mapped). This methodology indicates that ambiguous ego-centred networks have enough structural information to correctly identify synonyms of the individual.
“Only a Bird in a Gilded Cage”: Avianthropes and the Embodiment of the Canorographic Voice in Angela Carter’s “The Erl-King” andNights at the Circus
Authors: Paulusma Polly
Published: March 2021

Renowned for her fiction, Angela Carter was also a folk singer in the 1960s, played English concertina, and cofounded a folk club. A newly unearthed archive of her notes, musical notations, and recordings provides a window into her folk song praxis. When juxtaposed with her diaries, album sleeve notes, and unpublished papers, a new understanding of Carter’s writing processes emerges. This essay explores her “canorographic” writing or “songful” writing, embodied in avianthropes: the bird-girls in “The Erl-King” and Fevvers in Nights at the Circus. I compare Child Ballad “Lady Isabel and the Elf-Knight,” Ovid’s Philomel, and Petrarch’s nightingale with Carter’s bird-women to show how her tropes transcode the singing voice into prose, disclosing the porous boundaries between literature and song and reimagining prose as performance.
Disturbance cue communication is shaped by emitter diet and receiver background risk in Trinidadian guppies
Authors: Goldman Jack A , Crane Adam L , Feyten Laurence E A , Collins Emily , Brown Grant E
Published: March 2021

In animal communication systems, individuals that detect a cue (i.e., “receivers”) are often influenced by characteristics of the cue emitter. For instance, in many species, receivers avoid chemical cues that are released by emitters experiencing disturbance. These chemical “disturbance cues” appear to benefit receivers by warning them about nearby danger, such as a predator’s approach. While the active ingredients in disturbance cues have been largely unexplored, by-products of metabolized protein are thought to play a role for some species. If so, the content (quality) and volume (quantity) of the emitter’s diet should affect their disturbance cues, thus altering how receivers perceive the cues and respond. Guppies Poecilia reticulata are a species known to discriminate among disturbance cues from different types of donors, but dietary variation has yet to be explored. In this study, we found evidence that diet quality and quantity can affect disturbance cues released by guppy emitters (i.e., experimental “donors”). Receivers discriminated between donor cue treatments, responding more strongly to cues from donors fed a protein-rich bloodworm diet (Experiment 1), as well as an overall larger diet (Experiment 2). We also found that receivers exposed to higher background risk were more sensitive to disturbance cue variation, with the strongest avoidance responses displayed by high-risk receivers toward disturbance cues from donors fed the high-quality diet. Therefore, diet, and perhaps protein specifically, affects either the concentration or composition of disturbance cues released by guppies. Such variation may be important in information signaling in social species like the guppy.
Management of chyle leaks following esophageal resection: a systematic review
Authors: Power Robert , Smyth Philip , Donlon Noel E , Nugent Timothy , Donohoe Claire L , Reynolds John V
Published: March 2021

Background

Chyle leakage is an uncommon but potentially life-threatening complication following esophageal resections. The optimal management strategy is not clear, with a limited evidence base.

Methods

Searches were conducted up to 31 December 2020 on MEDLINE, Embase, and Web of Science for randomized trials or retrospective studies that evaluated the management of chyle leakage following esophageal resection. Two authors independently screened studies, extracted data, and assessed for bias. The protocol was prospectively registered on PROSPERO (CRD: 42021224895) and reported in accordance with preferred reporting items for systematic reviews and meta-analyses guidelines.

Results

A total of 530 citations were reviewed. Twenty-five studies, totaling 1016 patients met the inclusion criteria, including two low-quality clinical trials and 23 retrospective case series. Heterogeneity of study design and outcomes prevented meta-analysis. The overall incidence of chyle leak/fistula was 3.2%. Eighteen studies describe management of chyle leaks conservatively, 17 by surgical ligation of the thoracic duct, 5 by pleurodesis, and 6 described percutaneous lymphangiography with thoracic duct embolization or disruption.

Conclusions

The evidence base for optimal management of chyle leakage postesophagectomy is lacking, which may be related to its low incidence. There is a paucity of high-quality prospective studies directly comparing treatment modalities, but there is some low-certainty evidence that percutaneous approaches have reduced morbidity but lower efficacy compared with surgery. Further high-quality, prospective studies that compare interventions at different levels of severity are needed to determine the optimal approach to treatment.
Results of endovascular aortic arch repair using the Relay Branch system
Authors: Czerny Martin , Berger Tim , Kondov Stoyan , Siepe Matthias , Saint Lebes Bertrand , Mokrane Fatima , Rousseau Herve , Lescan Mario , Schlensak Christian , Andic Mateja , Hazenberg Constatijn , Bloemert-Tuin Trijntje , Braithwaite Sue , van Herwaarden Joost , Hyhlik-Dürr Alexander , Gosslau Yvonne , Pedro Luís Mendes , Amorim Pedro , Kuratani Toru , Cheng Stephen , Heijmen Robin , van der Weijde Emma , Pleban Eliza , Szopiński Piotr , Rylski Bartosz
Published: March 2021

OBJECTIVES

Our goal was to evaluate results of endovascular aortic arch repair using the Relay Branch system.

METHODS

Forty-three patients with thoracic aortic pathology involving the aortic arch have been treated with the Relay Branch system (Terumo Aortic, Sunrise, FL, USA) in 10 centres. We assessed in-hospital mortality, neurological injury, treatment success according to current reporting standards and the need for secondary interventions. In addition, outcome was analysed according to the underlying pathology: non-dissective disease versus residual aortic dissection (RAD) (defined as remaining dissection after previous type A repair, chronic type B aortic dissections).

RESULTS

In-hospital mortality was 9% (0% in patients with RAD). Disabling stroke occurred in 7% (0% in patients with RAD); non-disabling stroke occurred in 19% (7% in patients with RAD). Early type IA and B endoleak formation occurred in 4%. Median follow-up was 16 ± 18 months. During the follow-up period, 23% of the patients died. Aortic-related deaths were low (3% in patients with RAD).

CONCLUSIONS

The results of endovascular aortic arch repair using the Relay Branch system in a selected patient population with regard to technical success are good. In-hospital mortality is acceptable, the number of disabling strokes is low and technical success is high. Non-disabling stroke is a major concern, and every effort has to be taken to reduce this to a minimum. The best outcome is seen in patients with underlying RAD. Finally, more data are needed.
Leveraging clinical epigenetics in heart failure with preserved ejection fraction: a call for individualized therapies
Authors: Hamdani Nazha , Costantino Sarah , Mügge Andreas , Lebeche Djamel , Tschöpe Carsten , Thum Thomas , Paneni Francesco
Published: March 2021

Described as the ‘single largest unmet need in cardiovascular medicine’, heart failure with preserved ejection fraction (HFpEF) remains an untreatable disease currently representing 65% of new heart failure diagnoses. HFpEF is more frequent among women and associates with a poor prognosis and unsustainable healthcare costs. Moreover, the variability in HFpEF phenotypes amplifies complexity and difficulties in the approach. In this perspective, unveiling novel molecular targets is imperative. Epigenetic modifications—defined as changes of DNA, histones, and non-coding RNAs (ncRNAs)—represent a molecular framework through which the environment modulates gene expression. Epigenetic signals acquired over the lifetime lead to chromatin remodelling and affect transcriptional programmes underlying oxidative stress, inflammation, dysmetabolism, and maladaptive left ventricular remodelling, all conditions predisposing to HFpEF. The strong involvement of epigenetic signalling in this setting makes the epigenetic information relevant for diagnostic and therapeutic purposes in patients with HFpEF. The recent advances in high-throughput sequencing, computational epigenetics, and machine learning have enabled the identification of reliable epigenetic biomarkers in cardiovascular patients. Contrary to genetic tools, epigenetic biomarkers mirror the contribution of environmental cues and lifestyle changes and their reversible nature offers a promising opportunity to monitor disease states. The growing understanding of chromatin and ncRNAs biology has led to the development of several Food and Drug Administration approved ‘epidrugs’ (chromatin modifiers, mimics, anti-miRs) able to prevent transcriptional alterations underpinning left ventricular remodelling and HFpEF. In the present review, we discuss the importance of clinical epigenetics as a new tool to be employed for a personalized management of HFpEF.
Effectiveness of tailored intervention with a salutogenic approach to improve adherence in adults with hypertension: a non-randomized trial
Authors: Esquivel Garzón Natalia , Díaz Heredia Luz Patricia , Grisales Romero Hugo , Cañon-Montañez Wilson
Published: March 2021

Aims

Hypertension (HTN) is a chronic long-term, slowly progressing disease. For HTN control, management, and prevention of associated complications, adequate adherence to treatment is required. It has been proposed that tailored interventions to individual needs are required to address the phenomenon of adherence to treatment. However, studies evaluating the effects of tailored interventions to improve adherence are still scarce. The aim of this study is to evaluate the effectiveness of a tailored intervention using a salutogenic approach, to improve adherence in patients with HTN.

Methods and results

A non-randomized trial design was used in this study. Adult patients with HTN were allocated in two groups: tailored intervention (n = 75) and standard care (n = 78). The content of the tailored intervention was based on personal resources and elaboration of an action plan with objectives in agreement with the patients. Patient outcomes (treatment adherence, blood pressure) were assessed both at the beginning of the study and at the 4-week follow-up for the intervention group and the standard care group. The Treatment Adherence Questionnaire for Patients with Hypertension was used to measure adherence. The results of this study showed that the total score and each dimension of the adherence questionnaire (medications, diet, physical activity, weight control, stimulation, and stress relief) increased significantly in the experimental group compared with the control group (P < 0.05). For the group assigned to tailored intervention, the delta score of the total adherence score increased in the final evaluation to 9.4 (95% CI = 8.60–10.28).

Conclusion

A tailored intervention with a salutogenic approach appears to be effective for improving adherence in patients with HTN. Randomized controlled trials are required to confirm the effect of tailored interventions in this type of population.
Lipoprotein (a) as a treatment target for cardiovascular disease prevention and related therapeutic strategies: a critical overview
Authors: Parthymos Ioannis , Kostapanos Michael S , Mikhailidis Dimitri P , Florentin Matilda
Published: March 2021

Advances in several fields of cardiovascular (CV) medicine have produced new treatments (e.g. to treat dyslipidaemia) that have proven efficacy in terms of reducing deaths and providing a better quality of life. However, the burden of CV disease (CVD) remains high. Thus, there is a need to search for new treatment targets. Lipoprotein (a) [Lp(a)] has emerged as a potential novel target since there is evidence that it contributes to CVD events. In this narrative review, we present the current evidence of the potential causal relationship between Lp(a) and CVD and discuss the likely magnitude of Lp(a) lowering required to produce a clinical benefit. We also consider current and investigational treatments targeting Lp(a), along with the potential cost of these interventions.
Highly effective proximate labeling in Drosophila
Authors: Zhang Bo , Zhang Yuanbing , Liu Ji-Long
Published: March 2021

The protein–protein interaction (PPI) is a basic strategy for life to operate. The analysis of PPIs in multicellular organisms is very important but extremely challenging because PPIs are particularly dynamic and variable among different development stages, tissues, cells, and even organelles. Therefore, understanding PPI needs a good resolution of time and space. More importantly, understanding in vivo PPI needs to be realized in situ. Proximity-based biotinylation combined with mass spectrometry (MS) has emerged as a powerful approach to study PPI networks and protein subcellular compartmentation. TurboID, the newly engineered promiscuous ligase, has been reported to label proximate proteins effectively in various species. In Drosophila, we systematically apply TurboID-mediated biotinylation in a wide range of developmental stages and tissues, and demonstrate the feasibility of TurboID-mediated labeling system in desired cell types. For a proof-of-principle, we use the TurboID-mediated biotinylation coupled with MS to distinguish CTP synthase with or without the ability to form filamentous cytoophidia, retrieving two distinct sets of proximate proteomes. Therefore, this makes it possible to map PPIs in vivo and in situ at a defined spatiotemporal resolution, and demonstrates a referable resource for cytoophidium proteome in Drosophila.