bluuebunny/crossref_metadata_2025 huggingface dataset:
SAIGEgds—an efficient statistical tool for large-scale PheWAS with mixed models
Authors: Zheng Xiuwen , Davis J Wade
Published: September 2020

Phenome-wide association studies (PheWASs) are known to be a powerful tool in discovery and replication of genetic association studies. To reduce the computational burden of PheWAS in the large cohorts, such as the UK Biobank, the SAIGE method has been proposed to control for case–control imbalance and sample relatedness in a tractable manner. However, SAIGE is still computationally intensive when deployed in analyzing the associations of thousands of ICD10-coded phenotypes with whole-genome imputed genotype data. Here, we present a new high-performance statistical R package (SAIGEgds) for large-scale PheWAS using generalized linear mixed models. The package implements the SAIGE method in optimized C++ codes, taking advantage of sparse genotype dosages and integrating the efficient genomic data structure file format. Benchmarks using the UK Biobank White British genotype data (N ≈ 430 K) with coronary heart disease and simulated cases show that the implementation in SAIGEgds is 5–6 times faster than the SAIGE R package. When used in conjunction with high-performance computing clusters, SAIGEgds provides an efficient analysis pipeline for biobank-scale PheWAS.

Availability and implementation

https://bioconductor.org/packages/SAIGEgds; vignettes included.

Supplementary information

Supplementary data are available at Bioinformatics online.
HiSCF: leveraging higher-order structures for clustering analysis in biological networks
Authors: Hu Lun , Zhang Jun , Pan Xiangyu , Yan Hong , You Zhu-Hong
Published: September 2020

Motivation

Clustering analysis in a biological network is to group biological entities into functional modules, thus providing valuable insight into the understanding of complex biological systems. Existing clustering techniques make use of lower-order connectivity patterns at the level of individual biological entities and their connections, but few of them can take into account of higher-order connectivity patterns at the level of small network motifs.

Results

Here, we present a novel clustering framework, namely HiSCF, to identify functional modules based on the higher-order structure information available in a biological network. Taking advantage of higher-order Markov stochastic process, HiSCF is able to perform the clustering analysis by exploiting a variety of network motifs. When compared with several state-of-the-art clustering models, HiSCF yields the best performance for two practical clustering applications, i.e. protein complex identification and gene co-expression module detection, in terms of accuracy. The promising performance of HiSCF demonstrates that the consideration of higher-order network motifs gains new insight into the analysis of biological networks, such as the identification of overlapping protein complexes and the inference of new signaling pathways, and also reveals the rich higher-order organizational structures presented in biological networks.

Availability and implementation

HiSCF is available at https://github.com/allenv5/HiSCF.

Supplementary information

Supplementary data are available at Bioinformatics online.
SEEDS: data driven inference of structural model errors and unknown inputs for dynamic systems biology
Authors: Newmiwaka Tobias , Engelhardt Benjamin , Wendland Philipp , Kahl Dominik , Fröhlich Holger , Kschischo Maik
Published: September 2020

Dynamic models formulated as ordinary differential equations can provide information about the mechanistic and causal interactions in biological systems to guide targeted interventions and to design further experiments. Inaccurate knowledge about the structure, functional form and parameters of interactions is a major obstacle to mechanistic modeling. A further challenge is the open nature of biological systems which receive unknown inputs from their environment. The R-package SEEDS implements two recently developed algorithms to infer structural model errors and unknown inputs from output measurements. This information can facilitate efficient model recalibration as well as experimental design in the case of misfits between the initial model and data.

Availability and implementation

For the R-package seeds, see the CRAN server https://cran.r-project.org/package=seeds.
‘She Made You Feel like There’s Hope’: Gaining a Better Understanding of How Children Negotiate Their Relationships with Social Workers from Their Own Accounts
Authors: Gorin Sarah , Baginsky Mary , Moriarty Jo , Manthorpe Jill
Published: September 2020

Recent years have seen a re-emergence of international interest in relationship-based social work. This article uses children’s accounts of their relationships with social workers to build on previous research to promote children’s safety and well-being. Interviews were undertaken with 111 children aged six- to eighteen-years old across ten different local authorities in England, as part of the evaluation of Munro, Turnell and Murphy’s Signs of Safety pilots within the Department for Education’s Children’s Social Care Innovation Programme. The interviews reveal four key findings: that children look for care and reciprocity in their relationships with social workers and this can be achieved through listening and small acts of kindness; that they are adept at recognising aspects of social workers’ verbal and non-verbal communications which indicate to the child whether they are listening and interested in them; that there are times in which children are particularly vulnerable especially if parents are resistant to engagement or children’s trust is broken; and that children actively use their agency to control their communication and engagement. The article concludes by highlighting children’s relational resilience and the importance of ensuring opportunities for children to develop new relationships with social workers when previous relationships have broken down.
O-GlcNAcylation regulates dopamine neuron function, survival and degeneration in Parkinson disease
Authors: Lee Byeong Eun , Kim Hye Yun , Kim Hyun-Jin , Jeong Hyeongsun , Kim Byung-Gyu , Lee Ha-Eun , Lee Jieun , Kim Han Byeol , Lee Seung Eun , Yang Yong Ryoul , Yi Eugene C , Hanover John A , Myung Kyungjae , Suh Pann-Ghill , Kwon Taejoon , Kim Jae-Ick
Published: September 2020

The dopamine system in the midbrain is essential for volitional movement, action selection, and reward-related learning. Despite its versatile roles, it contains only a small set of neurons in the brainstem. These dopamine neurons are especially susceptible to Parkinson’s disease and prematurely degenerate in the course of disease progression, while the discovery of new therapeutic interventions has been disappointingly unsuccessful. Here, we show that O-GlcNAcylation, an essential post-translational modification in various types of cells, is critical for the physiological function and survival of dopamine neurons. Bidirectional modulation of O-GlcNAcylation importantly regulates dopamine neurons at the molecular, synaptic, cellular, and behavioural levels. Remarkably, genetic and pharmacological upregulation of O-GlcNAcylation mitigates neurodegeneration, synaptic impairments, and motor deficits in an animal model of Parkinson’s disease. These findings provide insights into the functional importance of O-GlcNAcylation in the dopamine system, which may be utilized to protect dopamine neurons against Parkinson’s disease pathology.
There’s a time and a place: temporal aspects of place-based stigma
Authors: Butler-Warke Alice
Published: September 2020

This paper provides an overview of current debates and themes in literature relating to place-based stigma, including a reflection on terminology use. Generally, we rely on Loïc Wacquant’s framing of territorial stigma as a feature of advanced marginality. In this paper, drawing on my own research in Toxteth, Liverpool, I offer a critique of the Wacquantian approach, highlighting the limits of the advanced marginality framing of place-based stigma. The paper considers the global reach of placed-based stigma and the temporal aspect of stigma that must be taken into consideration when we consider how stigma is currently applied to communities. A key feature of this paper is the foregrounding of the concepts of ‘core’ and ‘event’ stigma, which have generally been a feature of literature in business and management. I argue that our understanding of how communities become stigmatized can be enhanced by framing place-based stigma in this temporal sense. Understanding how stigma becomes adhered to particular spaces, places and landscapes is necessary if we want to comprehend how this stigma transfers to the communities inhabiting these geographies. This paper suggests that we must look to the past, and to the voices who shape the past, in order to understand the present and to plan for the future.
Mechanism and interpretation of two-for-one response to premature atrial complexes during atrioventricular node re-entry tachycardia
Authors: Gilge Jasen L , Bagga Shiv , Ahmed Asim S , Clark Brad A , Patel Parin J , Prystowsky Eric N , Olson Jeff A , Steinberg Leonard A , Padanilam Benzy J
Published: September 2020

Aims

The response to premature atrial complexes (PACs) during tachycardia has been shown to differentiate atrioventricular nodal re-entrant tachycardia (AVNRT) from focal junctional tachycardia (JT). His refractory PAC (HrPACs) perturbing the next His (resetting with fusion) is diagnostic of AVNRT and such a late PAC fusing with the native beat cannot reset the focal source of JT. Early PAC advancing the immediate His with continuation of tachycardia suggests JT but can also occur in AVNRT due to simultaneous conduction through the AV nodal fast and slow pathways [two-for-one response (TFOR)]. The objective of this study was to evaluate the incidence and mechanism of TFOR after early premature atrial complexes (ePACs) during AVNRT and to differentiate it from the known response to ePACs during JT.

Methods and results

Typical AVNRT cases were diagnosed using standard criteria. We evaluated the responses to scanning PACs delivered during tachycardia in 100 patients undergoing AV node slow pathway modification for AVNRT. The responses to HrPACs and ePACs delivered from coronary sinus os or high right atrium were retrospectively reviewed. In 10 patients, ePACs advanced the immediate His with continuation of tachycardia. In all 10 cases, HrPACs advanced the next His, confirming AVNRT as the mechanism, and indicating a TFOR.

Conclusion

A TFOR can occur in a small number of patients during AVNRT and is therefore not diagnostic of JT. However, HrPACs always perturbed the next His in these cases, confirming the diagnosis of AVNRT and allowing for differentiation from JT.
Comparison of microbial diversity during two different wine fermentation processes
Authors: Böhmer Miroslav , Smoľak Dávid , Ženišová Katarína , Čaplová Zuzana , Pangallo Domenico , Puškárová Andrea , Bučková Mária , Cabicarová Tereza , Budiš Jaroslav , Šoltýs Katarína , Rusňáková Diana , Kuchta Tomáš , Szemes Tomáš
Published: September 2020

Wine production is a complex procedure in which an important role is played by many microorganisms, particularly yeasts and bacteria. In modern wineries, alcoholic fermentation is usually carried out by adding microbial starter cultures of Saccharomyces cerevisiae strains for precisely controlled production. Nowadays, in the Slovak Republic, autochthonous vinification is getting more popular. The present article deals with the comparison of two vinification approaches, namely spontaneous fermentation and fermentation controlled by a standard commercial S. cerevisiae starter, from the point of view of microbiota dynamics and the chemical characteristics of the wines produced. The dynamics of microbial populations were determined during the fermentation process by a 16S and 28S rRNA next-generation sequencing approach. A profile of the volatile compounds during these fermentation processes was identified by solid-phase microextraction (SPME) coupled to gas chromatography-mass spectrometry (GC-MS). In summary, the microbial diversity in the m1 phase (initial must) was higher, despite the presence of the starter culture. In the m3 phase (young wine), the microbiome profiles of both batches were very similar. It seems that the crucial phase in order to study the relationship of the microbiome and the resulting product should be based on the m2 phase (fermented must), where the differences between the autochthonous and inoculated batches were more evident.
Shedding the load: moulting as a cause of variability in whole-body metal concentrations
Authors: O’Callaghan Irene , Sullivan Timothy
Published: September 2020

Moulting is a biological process shared by aquatic macroinvertebrates, but while the exoskeleton is believed to be a major sink of metal pollutants, the contribution of the moulting of the crustacean exoskeleton to total accumulated metal concentrations is insufficiently considered. We present a conceptual, qualitative model that illustrates the impact of moulting on the whole-body burden of an unspecified metal analyte in a hypothetical moulting invertebrate. The model demonstrates that moult stage is a contributor to the whole-body pollutant concentration, and that this introduces a temporal component even in steady-state exposure conditions. The applicability of this model is illustrated by comparison to published results of pre- and post-moult accumulations. A solution for reducing this variability in the measurement of whole-body metal concentrations is presented, and its potential application to both ex-situ and in-situ studies of biomonitor species is discussed.
The Unintended Negative Effect of Positive Complementarity
Authors: Shereshevsky Yahli
Published: September 2020

Ending impunity cannot be achieved by international criminal tribunals alone. Therefore, it is important that states will take a significant part in these efforts. The principle of complementarity is aimed to incentivize states to conduct domestic criminal proceedings against alleged perpetrators of international crimes. This article calls for a broader examination of the way in which the principle of complementarity incentivizes domestic actors. It argues that beyond the potential positive effect of complementarity on domestic criminal law, the shadow of the International Criminal Court creates a negative incentive for domestic courts to intervene in constitutional and administrative cases that examine general conduct of hostilities cases. The paper demonstrates this negative effect by examining a shift in the attitude of the Israeli Supreme Court in conduct of hostilities cases. In addition, the paper discusses the ways in which domestic courts attempt to regain their reputation following their increased deference in conduct of hostilities cases.
Incomplete Political Contracts with Secret Ballots: Reciprocity as a Force to Enforce Sustainable Clientelistic Relationships
Authors: Kamei Kenju
Published: September 2020

Clientelism is frequently observed in our societies. Various mechanisms that help sustain incomplete political contracts (e.g., monitoring and punishment) have been studied in the literature to date. However, do such contracts emerge in elections with secret ballots when the interactions are one-shot? How does repetition affect the evolution of incomplete political contracts? Using an incentivized experiment, this article finds that even during one-shot interactions where monitoring is not possible, candidates form incomplete contracts through vote buying and promise-making. The candidates’ clientelistic behaviors are heterogeneous: some target swing voters, whereas others offer the most to loyal voters, or even opposition voters. These tactics distort voting behaviors as well as election outcomes. Repeated interactions significantly magnify candidates’ offers and deepen clientelistic relationships. These results underscore the possibility that clientelism evolves due to people’s strategic behaviors and interdependent preferences, without relying on alternative mechanisms (JEL C92, D72).
Processing Ambiguous Social Identity: Disclosure of Identity and Phenotypic Prototypicality Affect Processing and Evaluation of Persuasive Messages
Authors: Read Glenna L
Published: September 2020

This study investigates how news stories about models’ social identities, models’ actual social identities, and ease of categorization of models into societally predominant gender and racial categories affect processing and evaluation of persuasive messages. Participants read news stories about fashion companies that used transgender or biracial models in advertising campaigns or control stories and then viewed a series of still images edited to look like advertisements. Physiological responding and self-reported attitudes were recorded. Results indicated more positive evaluation of images preceded by news stories about models’ social identities compared to control stories. With a few exceptions, participants did not differ in their evaluation of images based on actual identity, although actual identity did affect processing. While participants responded positively to images with racially ambiguous models, they did not respond positively to images with androgynous models. Results are discussed in regard to theoretical and practical implications.
Instagram Inspiration: How Upward Comparison on Social Network Sites Can Contribute to Well-Being
Authors: Meier Adrian , Gilbert Alicia , Börner Sophie , Possler Daniel
Published: September 2020

Passive exposure to others’ positive self-presentations on social network sites (SNS) such as Instagram has been repeatedly associated with reduced well-being, particularly by triggering upward social comparison and envy. However, prior research has largely neglected that upward comparisons on SNS may also facilitate positive outcomes, specifically media-induced inspiration, a motivational state highly conducive to well-being. We conducted two experiments that tested whether and how cognitive-affective processing of visual SNS postings results in inspiration. Study 1 (N = 270) provides first evidence that users react to more positive, optimized Instagram nature and travel posts with stronger upward comparison, which facilitates inspiration via an assimilative emotional reaction (benign envy), thus enhancing well-being. The preregistered Study 2 (N = 408) replicates these findings. Overall, results indicate that users can be inspired from comparing upwards on SNS, which may briefly improve their well-being. We discuss boundary conditions and implications for future communication research.
Associations Between Parent–Child Communication and Connectedness, Parent Feeding Behavior, and Child Body Mass in Pre-Adolescent Children
Authors: Lowe Kristina D , Lott Mark A , Jensen Chad D
Published: September 2020

Objective 

This study evaluated associations between parent–child connectedness and communication, parent feeding behaviors (restriction, pressure to eat, and monitoring), and age- and sex-standardized child body mass index (zBMI) in a sample of pre-adolescent children aged 8–12 years.

Methods 

A community sample of three hundred and eight child–parent dyads completed measures of communication and connectedness. Parents completed a feeding behavior measure and children were weighed and their height was measured. We examined whether parental feeding behaviors and parent–child communication and connectedness predicted child zBMI and whether parental feeding behaviors moderated the association between parent–child communication and connectedness and child zBMI.

Results 

Feeding restriction was positively associated with zBMI, while both pressure to eat and food monitoring exhibited negative associations with zBMI. Child-reported communication was inversely associated with zBMI and parental pressure to eat moderated this association such that lower pressure to eat predicted a stronger association between communication and zBMI.

Conclusions 

These findings are consistent with previous research suggesting that parent feeding strategies and parent–child communication are important contributors to child weight status. This study also provides preliminary evidence suggesting that adaptive parent–child communication is associated with lower body mass when parents avoid pressuring their child to eat. Our study provides an important extension of this body of research into middle childhood, a relatively understudied developmental stage.
A hadronic emission model for black hole-disc impacts in the blazar OJ 287
Authors: Rodríguez-Ramírez J C , Kushwaha P , de Gouveia Dal Pino E M , Santos-Lima R
Published: September 2020

A supermassive black hole (SMBH) binary in the core of the blazar OJ 287 has been invoked in previous works to explain its observed optical flare quasi-periodicity. Following this picture, we investigate a hadronic origin for the X-ray and γ-ray counterparts of the November 2015 major optical flare of this source. An impact outflow must result after the lighter SMBH (the secondary) crosses the accretion disc of the heavier one (the primary). We then consider acceleration of cosmic ray (CR) protons in the shock driven by the impact outflow as it expands and collides with the active galactic nucleus (AGN) wind of the primary SMBH. We show that the emission of these CRs can reproduce the X-ray and γ-ray flare data self-consistently with the optical component of the 2015 November major flare. The derived emission models are consistent with a magnetic field B ∼ 5 G in the emission region and a power-law index of q ∼ 2.2 for the energy distribution of the emitting CRs. The mechanical luminosity of the AGN wind represents $\lesssim 50{{\ \rm per\ cent}}$ of the mass accretion power of the primary SMBH in all the derived emission profiles.
Fear conditioning prompts sparser representations of conditioned threat in primary visual cortex
Authors: Yin Siyang , Bo Ke , Liu Yuelu , Thigpen Nina , Keil Andreas , Ding Mingzhou
Published: September 2020

Repeated exposure to threatening stimuli alters sensory responses. We investigated the underlying neural mechanism by re-analyzing previously published simultaneous electroencephalogram-functional magnetic resonance imaging (EEG-fMRI) data from humans viewing oriented gratings during Pavlovian fear conditioning. In acquisition, one grating (CS+) was paired with a noxious noise, the unconditioned stimulus (US). The other grating (CS-) was never paired with the US. In habituation, which preceded acquisition, and in extinction, the same two gratings were presented without US. Using fMRI multivoxel patterns in primary visual cortex during habituation as reference, we found that during acquisition, aversive learning selectively prompted systematic changes in multivoxel patterns evoked by CS+. Specifically, CS+ evoked voxel patterns in V1 became sparser as aversive learning progressed, and the sparsified pattern appeared to be preserved in extinction. Concomitant with the voxel pattern changes, occipital alpha oscillations were increasingly more desynchronized during CS+ (but not CS-) trials. Across acquisition trials, the rate of change in CS+-related alpha desynchronization was correlated with the rate of change in multivoxel pattern representations of CS+. Furthermore, alpha oscillations co-varied with blood-oxygen-level-dependent (BOLD) data in the ventral attention network, but not with BOLD in the amygdala. Thus, fear conditioning prompts persistent sparsification of voxel patterns evoked by threat, likely mediated by attention-related mechanisms
Life Course Events and Migration in the Transition to Adulthood
Authors: Horowitz Jonathan , Entwisle Barbara
Published: September 2020

Do life course events stimulate migration during the transition to adulthood? We identify nine specific life events in the family, education, and employment domains and test whether they lead to migration in the short term, using fixed-effects models that remove the influence of all stable individual-level characteristics and controlling for age. Marital and school completion events have substantively large effects on migration compared with individual work transitions, although there are more of the latter over the young adult years. Furthermore, young adults who are white and from higher class backgrounds are more likely to migrate in response to life events, suggesting that migration may be a mechanism for the reproduction of status attainment. Overall, the results demonstrate a close relationship between life course events and migration and suggest a potential role for migration in explaining the effect of life course events on well-being and behavior.
Characterization of Diaporthe spp. Associated With Spruce Decline on Colorado Blue Spruce in Michigan
Authors: Sakalidis Monique L. , Medina-Mora Carmen M. , Shin Keumchul , Fulbright Dennis W.
Published: September 2020

Since 2006 there has been a decline in Colorado blue spruce (CBS; Picea pungens) planted as landscape trees and for Christmas tree production throughout the Lower Peninsula of Michigan. This decline is characterized by a slow loss of needles in the lower portion of the tree starting at branch tips, followed by entire branch dieback, which progresses upward over several years. This dieback has been linked to shallow branch cankers visible in the phloem when the bark layer is removed. Isolates in the fungal genus Diaporthe have been consistently isolated from lesion margins on symptomatic branches. Before the initial reports of declining CBS in landscape and Christmas trees, Diaporthe was known only as a nursery disease of CBS. To determine the species of Diaporthe linked to the decline of CBS in Michigan, seven gene regions were sequenced from a collection of Diaporthe isolates collected in 2011 through 2018 from CBS and other coniferous hosts. Subsequent phylogenetic analyses indicated that Diaporthe eres and a novel Diaporthe clade were present on symptomatic CBS in Michigan. The new species D. brevicancria nov. is described, and Koch’s postulates were confirmed for D. brevicancria nov. and D. eres. D. brevicancria nov. produced the largest cankers in greenhouse pathogenicity trials, and dual inoculations of D. brevicancria nov. and D. eres produced intermediate cankers.
Agreement of Postoperative Pain Assessment by Parents and Clinicians in Children Undergoing Orthopedic Surgery
Authors: Kang Michael Seungcheol , Park Jinhee , Kim Jinhyun
Published: September 2020

Background:

Postoperative pain assessment in children is crucial for proper nursing care. However, research on the agreement of these assessments with a patient's self-reported pain level is lacking. The aim was to investigate the agreement between patients' subjective postoperative pain and corresponding observers' pain assessments.

Methods:

In children who underwent orthopedic limb surgery, we investigated the agreement between their reported pain levels and observers' pain assessments using the Numeric Pain Rating Scale (NPRS) and the Faces Pain Scale-Revised (FPS-R) on postoperative day 1. The parents (specifically the mother) and clinicians (a doctor and a nurse in the field of pediatric orthopedics) participated as observers. Reliabilities using intraclass correlation coefficients (ICCs) and correlations using Spearman's coefficients (rs) were calculated.

Results:

The patients' pain intensities (2.1± 2.1 [NPRS] and 2.0 ± 1.9 [FPS-R]) were overestimated by parents (2.5 ± 2.0 [NPRS],p= .022), but underestimated by clinicians (1.5 ± 1.2 [NPRS],p< .001, and 1.5 ± 1.2 [FPS-R],p= .006). The overall reliabilities between parents and patients were good (ICCs > 0.75 for both NPRS and FPS-R), and the correlations between them were even strong in some circumstances, such as when the patient was a girl, the diagnostic type was a disease, or the lower extremity was operated (rss > 0.7). However, the agreements between clinicians and patients were only moderate.

Conclusions:

The subjective pediatric postoperative pain intensities had different agreements according to the observers. The parents' assessments should be considered for the accurate assessments, but their tendency to overestimate their children's pain should also be taken into account.
Contrast-enhanced Ultrasound Identifies Patent Feeding Vessels in Transarterial Chemoembolization Patients With Residual Tumor Vascularity
Authors: Wessner Corinne E. , Shaw Colette M. , Stanczak Maria , Forsberg Flemming , Lyshchik Andrej , Tan Allison , Eisenbrey John R.
Published: September 2020

Transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) often requires retreatment and identification of feeding vessels supplying the residual/recurrent tumor is an important step in treatment planning. The objective of this study was to determine if contrast-enhanced ultrasound (CEUS) could correctly identify the vessel supplying the residual tumor. To date, 69 patients have undergone CEUS follow-up of HCC TACE therapy at our institution as part of an ongoing institutional review board approved trial (NCT02764801). The CEUS examinations were performed before HCC TACE as well as 1 to 2 weeks and 1 month after treatment using a Logiq E9 scanner with a C1–6 curved array transducer (GE Healthcare, Waukesha, WI). The CEUS images obtained 2 weeks after initial TACE treatment were reviewed, and any feeding vessels supplying the residual HCC were identified. Digital subtraction angiograms during the retreatment TACE were used as reference standard for feeding vessel identification. Thirteen patients with viable HCC post-TACE were included in this study. In these cases, the sonographer correctly identified 85% (11 of 13) of the feeding vessels later confirmed by angiography. Importantly, one of the false-negative cases involved a segment 8 tumor with parasitic blood supply from the medial left hepatic artery. In this case, CEUS identified a largely treated tumor with some residual internal flow, but was unable to visualize any major hepatic vascularity supplying the tumor. In conclusion, CEUS appears to be a valuable tool for planning retreatment of residual HCC post-TACE.
Contrast -Enhanced Ultrasound
Authors: Barr Richard G. , Wilson Stephanie R. , Lyshchik Andrej , McCarville Beth , Darge Kassa , Grant Edward , Robbin Michelle , Wilmann Juergen Karl , Chong Wui K. , Fleischer Arthur , Paltiel Harriet J.
Published: September 2020

The Society of Radiologists in Ultrasound convened a panel of specialists in contrast-enhanced ultrasound (CEUS) to produce a white paper on noncardiac CEUS in North America. The panel met in Chicago, Illinois, on October 24 and 25, 2017. The recommendations are based on analysis of current literature and common practice strategies and are thought to represent a reasonable approach to introduce the advantages of this safe and noninvasive technique for the benefit of our patients. Characterization of liver nodules, and pediatric vascular and intravesicular applications comprise the approved indications for CEUS in the United States. They, along with the very successful off-label use of CEUS for the kidney, are included in this publication.

Other off-label uses are presented with emphasis on their value and literature support in the online version.
White Matter Hyperintensities Contribute to Language Deficits in Primary Progressive Aphasia
Authors: Meier Erin L. , Breining Bonnie L. , Sheppard Shannon M. , Goldberg Emily B. , Tippett Donna C. , Tsapkini Kyrana , Faria Andreia V. , Hillis Argye E.
Published: September 2020

Objective:

To determine the contribution of white matter hyperintensities (WMH) to language deficits while accounting for cortical atrophy in individuals with primary progressive aphasia (PPA).

Method:

Forty-three individuals with PPA completed neuropsychological assessments of nonverbal semantics, naming, and sentence repetition plus T2-weighted and fluid-attenuated inversion recovery scans. Using three visual scales, we rated WMH and cerebral ventricle size for both scan types. We used Spearman correlations to evaluate associations between the scales and scans. To test whether visual ratings—particularly of WMH—are associated with language, we compared a base model (including gray matter component scores obtained via principal component analysis, age, and days between assessment and MRI as independent variables) with full models (ie, the base model plus visual ratings) for each language variable.

Results:

Visual ratings were significantly associated within and between scans and were significantly correlated with age but not with other vascular risk factors. Only the T2 scan ratings were associated with language abilities. Specifically, controlling for other variables, poorer naming was significantly related to larger ventricles (P= 0.033) and greater global (P= 0.033) and periventricular (P= 0.049) WMH. High global WMH (P= 0.034) were also correlated with worse sentence repetition skills.

Conclusion:

Visual ratings of global brain health were associated with language deficits in PPA independent of cortical atrophy and age. While WMH are not unique to PPA, measuring WMH in conjunction with cortical atrophy may elucidate more accurate brain structure–behavior relationships in PPA than cortical atrophy measures alone.
Telemedicine in Behavioral Neurology–Neuropsychiatry: Opportunities and Challenges Catalyzed by COVID-19
Authors: Perez David L. , Biffi Alessandro , Camprodon Joan A. , Caplan David N. , Chemali Zeina , Kritzer Michael D. , Moo Lauren R. , Newhouse Amy L. , Ramirez-Gomez Liliana , Razafsha Mahdi , Tanev Kaloyan S. , Schmahmann Jeremy D.
Published: September 2020

Coronavirus 2019 (COVID-19) has profoundly impacted the well-being of society and the practice of medicine across health care systems worldwide. As with many other subspecialties, the clinical paradigm in behavioral neurology and neuropsychiatry (BN–NP) was transformed abruptly, transitioning to real-time telemedicine for the assessment and management of the vast majorities of patient populations served by our subspecialty. In this commentary, we outline themes from the BN–NP perspective that reflect the emerging lessons we learned using telemedicine during the COVID-19 pandemic. Positive developments include the ability to extend consultations and management to patients in our high-demand field, maintenance of continuity of care, enhanced ecological validity, greater access to a variety of well-reimbursed telemedicine options (telephone and video) that help bridge the digital divide, and educational and research opportunities. Challenges include the need to adapt the mental state examination to the telemedicine environment, the ability to perform detailed motor neurologic examinations in patients where motor features are important diagnostic considerations, appreciating nonverbal cues, managing acute safety and behavioral concerns in less controlled environments, and navigating intervention-based (neuromodulation) clinics requiring in-person contact. We hope that our reflections help to catalyze discussions that should take place within the Society for Behavioral and Cognitive Neurology, the American Neuropsychiatric Association, and allied organizations regarding how to optimize real-time telemedicine practices for our subspecialty now and into the future.
The Need to Intervene Before Time Point 2: Evidence From Clinical and Animal Data That Status Epilepticus Damages the Brain
Authors: Joshi Suchitra , Goodkin Howard P.
Published: September 2020

Status epilepticus, a condition characterized by abnormally prolonged seizures, has the potential to cause irreversible, structural or functional, injury to the brain. Unfavorable consequences of these seizures include mortality, the risk of developing epilepsy, and cognitive impairment. We highlight key findings of clinical and laboratory studies that have provided insights into aspects of cell death, and anatomical and functional alterations triggered by status epilepticus that support the need to intervene before time point 2, the time after which the risk of these long-term consequences increases.
Impact of Screening and Follow-up Colonoscopy Adenoma Sensitivity on Colorectal Cancer Screening Outcomes in the CRC-AIM Microsimulation Model
Authors: Fisher Deborah A. , Saoud Leila , Lich Kristen Hassmiller , Fendrick A. Mark , Ozbay A. Burak , Borah Bijan J. , Matney Michael , Parton Marcus , Limburg Paul J.
Published: September 2020

Background

Real-world data for patients with positive colorectal cancer (CRC) screening stool-tests demonstrates that adenoma detection rates are lower when endoscopists are blinded to the stool-test results. This suggests adenoma sensitivity may be lower for screening colonoscopy than for follow-up to a known positive stool-based test. Previous CRC microsimulation models assume identical sensitivities between screening and follow-up colonoscopies after positive stool-tests. The Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC-AIM) was used to explore the impact on screening outcomes when assuming different adenoma sensitivity between screening and combined follow-up/surveillance colonoscopies.

Methods

Modeled screening strategies included colonoscopy every 10 years, triennial multitarget stool DNA (mt-sDNA), or annual fecal immunochemical test (FIT) from 50-75 years. Outcomes were reported per 1,000 individuals without diagnosed CRC at age 40. Base-case adenoma sensitivity values were identical for screening and follow-up/surveillance colonoscopies. Ranges of adenoma sensitivity values for colonoscopy performance were developed using different slopes of odds ratio adjustments and were designated as small, medium, or large impact scenarios.

Results

As the differences in adenoma sensitivity for screening versus follow-up/surveillance colonoscopies became greater, life-years gained (LYG) and reductions in CRC-related incidence and mortality versus no screening increased for mt-sDNA and FIT and decreased for screening colonoscopy. The LYG relative to screening colonoscopy reached >90% with FIT in the base-case scenario and with mt-sDNA in a “medium impact” scenario.

Conclusions

Assuming identical adenoma sensitivities for screening and follow-up/surveillance colonoscopies underestimates the potential benefits of stool-based screening strategies.
Impact of Model Order Choice on the Results of Parallel Independent Component Analysis
Authors: Jensen D. M. , Zendehrouh E. , Liu J. , Calhoun V. D. , Turner J. A.
Published: September 2020

Parallel independent component analysis (pICA) is a data-driven method that identifies the maximally independent components of multiple imaging modalities while simultaneously investigating the strength of their correlations. Researchers using pICA are given the option to use the suggested model order calculated by the minimum descriptive length (MDL) algorithm, or they can choose their own model order. To date, there are no suggested guidelines for this choice. To test the sensitivity of pICA to the selection of model order, we applied it to a well-researched brain disorder, schizophrenia, looking at the correlations between patterns of grey matter volume (GM) volume and white matter integrity, measured using fractional anisotropy (FA). We varied model orders from low to high, and tested the sensitivity to disorder effects (cases vs controls), similarity of spatial maps identified across model orders, consolidation or distribution effects related to model order selection, and the performance of the minimum descriptive length (MDL) algorithm. The pICA results (multimodal analysis) were also compared to the ICA (unimodal analysis) for each imaging modality. Across model orders, there was consistent sensitivity to disorder effects, and clustered patterns of spatial maps for both the GM and FA reflecting those differences. The MDL-estimated model order captured the majority, but not all, of the spatial patterns present in the GM and FA. There was not the expected consolidation of spatial maps at lower model orders, nor the distribution of spatial maps at higher model orders. The spatial patterns identified in the ICA closely resemble those found in the pICA, although lacking the benefit of the optimization algorithm, were not as highly correlated. This offers some insight and guidance for researchers interested in using pICA with regard to selecting model order for their particular analysis of multiple imaging modalities.
Fully Automated Detection of Paramagnetic Rims in Multiple Sclerosis Lesions on 3T Susceptibility-Based MR Imaging
Authors: Lou Carolyn , Sati Pascal , Absinta Martina , Clark Kelly , Dworkin Jordan D. , Valcarcel Alessandra M. , Schindler Matthew K. , Reich Daniel S. , Sweeney Elizabeth M. , Shinohara Russell T.
Published: September 2020

Background and Purpose

The presence of a paramagnetic rim around a white matter lesion has recently been shown to be a hallmark of a particular pathological type of multiple sclerosis (MS) lesion. Increased prevalence of these paramagnetic rim lesions (PRLs) is associated with a more severe disease course in MS. The identification of these lesions is time-consuming to perform manually. We present a method to automatically detect PRLs on 3T T2*-phase images.

Methods

T1-weighted, T2-FLAIR, and T2*-phase MRI of the brain were collected at 3T for 19 subjects with MS. The images were then processed with lesion segmentation, lesion center detection, lesion labelling, and lesion-level radiomic feature extraction. A total of 877 lesions were identified, 118 (13%) of which contained a paramagnetic rim. We divided our data into a training set (15 patients, 673 lesions) and a testing set (4 patients, 204 lesions). We fit a random forest classification model on the training set and assessed our ability to classify lesions as PRL on the test set.

Results

The number of PRLs per subject identified via our automated lesion labelling method was highly correlated with the gold standard count of PRLs per subject, r = 0.91 (95% CI [0.79, 0.97]). The classification algorithm using radiomic features can classify a lesion as PRL or not with an area under the curve of 0.80 (95% CI [0.67, 0.86]).

Conclusion

This study develops a fully automated technique for the detection of paramagnetic rim lesions using standard T1 and FLAIR sequences and a T2*phase sequence obtained on 3T MR images.

Highlights

A fully automated method for both the identification and classification of paramagnetic rim lesions is proposed.

Radiomic features in conjunction with machine learning algorithms can accurately classify paramagnetic rim lesions.

Challenges for classification are largely driven by heterogeneity between lesions, including equivocal rim signatures and lesion location.
Defining the role of asymptomatic SARS-CoV-2 transmission – a living systematic review
Authors: Qiu Xueting , Nergiz Ali Ihsan , Maraolo Alberto Enrico , Bogoch Isaac I. , Low Nicola , Cevik Muge
Published: September 2020

Background

Reports suggest that asymptomatic individuals (those with no symptoms at all throughout the infection) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are infectious, but the extent of asymptomatic transmission requires further understanding.

Purpose

This living review aims to critically appraise available data about secondary attack rates from people with asymptomatic and pre-symptomatic SARS-CoV-2 infection.

Data sources

Medline, EMBASE, China Academic Journals full-text database (CNKI), and preprint servers were searched from 30 December 2019 to 3 July 2020 using relevant MESH terms.

Study selection

Studies that report on contact tracing of index cases with asymptomatic or pre-symptomatic SARS-CoV-2 infection, in either English or Chinese were included.

Data extraction

Two authors independently extracted data and assessed study quality and risk of bias. We calculated the secondary attack rate as the number of contacts with SARS-CoV-2, divided by the number of contacts tested.

Data synthesis

Of 928 studies identified, 19 were included. Secondary attack rates from asymptomatic index cases ranged from 0% to 2.8% (9 studies). Pre-symptomatic secondary attack rates ranged from 0.7% to 31.8% (10 studies). The highest secondary attack rates were found in contacts who lived in the same household as the index case. Other activities associated with transmission were group activities such as sharing meals or playing board games with the index case.

Limitations

We excluded some studies because the index case or number of contacts were unclear. Owing to the anticipated heterogeneity, we did not produce a summary estimate of the included studies.

Conclusion

Asymptomatic patients can transmit SARS-CoV-2 to others, but our findings indicate that such individuals are responsible for fewer secondary infections than people with symptoms in the same studies.

Systematic review registration

PROSPERO CRD42020188168

Funding

No funding was received
Point Sensitivity of the Multi-target Stool DNA Test for Colorectal Cancer Screening in Individuals Ages 45-49 Years
Authors: Domanico Michael , Statz Sandra , Weiser Emily , Berger Barry M , Limburg Paul
Published: September 2020

Background

Most colorectal cancer (CRC) screening tests have not been rigorously studied in younger age groups.

Aims

To estimate sensitivity of the multi-target stool DNA (mt-sDNA) test in patients ages 45-49 years.

Methods

We identified archived stool samples (Exact Sciences; Madison, WI) from individuals ages 45-49 years who had completed an index colonoscopy and had confirmed diagnoses of CRC or advanced precancerous lesions (APL; defined as high-grade dysplasia, >25% villous morphology, or ≥1 cm in size [conventional adenoma or serrated lesion]). Data annotation referent to potential CRC risk factors, other than age, was limited. Stool samples were collected at least 7 days after the index colonoscopy, prior to lesion excision or treatment. Stool samples were processed and analyzed per established laboratory protocols for the mt-sDNA assay. Mt-sDNA test sensitivity for CRC, APL, and CRC+APL was estimated from the available sample set. Samples were collected from 2010-2013 (NCT01260168) and 2014-2017 (NCT02503631), with sample testing and analysis in 2019.

Results

Stool samples were analyzed from 19 eligible subjects, 13 with CRC and 6 with APL. Estimated mt-sDNA test sensitivity for CRC, APL, and CRC+APL were 92%, 83%, and 89%, respectively.

Conclusions

In this small pilot study using existing archived stool samples from subjects ages 45-49 years, mt-sDNA test sensitivity was similar to previously reported estimates for individuals ages ≥50 years. These results support the application of mt-sDNA screening to 76 average-risk patients beginning at age 45 years. Larger studies are needed to confirm and extend these findings.