bluuebunny/crossref_metadata_2025_split huggingface dataset:
The current landscape of epilepsy genetics: where are we, and where are we going?
Authors: Ruggiero Sarah M. , Xian Julie , Helbig Ingo 
Published: February 2023

Purpose of review
In this review, we aim to analyse the progress in understanding the genetic basis of the epilepsies, as well as ongoing efforts to define the increasingly diverse and novel presentations, phenotypes and divergences from the expected that have continually characterized the field.

Recent findings
A genetic workup is now considered to be standard of care for individuals with an unexplained epilepsy, due to mounting evidence that genetic diagnoses significantly influence treatment choices, prognostication, community support, and increasingly, access to clinical trials. As more individuals with epilepsy are tested, novel presentations of known epilepsy genes are being discovered, and more individuals with self-limited epilepsy are able to attain genetic diagnoses. In addition, new genes causative of epilepsy are being uncovered through both traditional and novel methods, including large international data-sharing collaborations and massive sequencing efforts as well as computational methods and analyses driven by the Human Phenotype Ontology (HPO).

Summary
New approaches to gene discovery and characterization are advancing rapidly our understanding of the genetic and phenotypic architecture of the epilepsies. This review highlights relevant and groundbreaking studies published recently that have pushed forward the field of epilepsy genetics.
Stroke in the young
Authors: Fraser Stuart , Pabst Lisa , Smith Fiona 
Published: February 2023

Purpose of review
The purpose of this review is to review recent findings regarding stroke epidemiology, etiologies, and treatment in children and young adults.

Recent findings
Incidence in young adults is increasing, and incidence, recurrence, and survival is worse in patients with cryptogenic stroke and in developing countries. Careful consideration of patent foramen ovale closure is now recommended in young adults with cryptogenic stroke. Thrombectomy has recently been extended to carefully selected children with acute ischemic stroke, and two recent publications strongly suggest that it can be beneficial for children. Sickle cell is also an important global contributor to stroke burden, but hydroxyurea can be a cost effective medication for stroke prevention in children. Recent advances in genetic testing and treatments may improve outcomes for patients with monogenic causes of stroke, such as deficiency of adenosine deaminase 2, hemophilia, and Fabry's disease.

Summary
Stroke in children and young adults is a morbid disease responsible for enormous indirect societal costs and a high burden of years with disability per affected patient. Recent advances have improved access to care for children with large vessel occlusion and adults with rare causes of stroke. Future research may bring effective treatments for other monogenic causes of stroke as well as increasing access to hyperacute therapies for young stroke patients.
Critical care EEG monitoring: improving access and unravelling potentially epileptic patterns
Authors: Fong Michael W.K. 
Published: February 2023

Purpose of review
The major advances in critical care EEG have been the development of rapid response EEG, major revision of the American Clinical Neurophysiology Society's (ACNS) standardized critical care EEG terminology, and the commencement of treatment trials on rhythmic and periodic patterns (RPPs) that do not qualify as seizures.

Recent findings
Rapid response EEG (rEEG) has proven an important supplement to full montage continuous EEG monitoring (cEEG). This EEG can be applied in a few minutes and provides excellent ability to exclude seizures, selecting those where conversion to cEEG would have the greatest diagnostic yield. Once cEEG has been commenced, the durations required to adequately exclude seizures have been refined. The ACNS provided major revision and expansion to the standardized critical care EEG terminology, which paved the way for determining with great accuracy the RPPs that are associated with seizures and that are capable of causing neurologic symptoms and/or secondary neuronal injury. The current limitations to multicenter treatment trials of these patterns have been highlighted.

Summary
Novel methods of EEG in critical care have been expanding access to all patients where clinically indicated. Standardized EEG terminology has provided the framework to determine what patterns in which presenting causes warrant treatment vs. those that do not.
Social contagion, violence, and suicide among adolescents
Authors: Martínez Vania , Jiménez-Molina Álvaro , Gerber Mónica M. 
Published: February 2023

Purpose of review
Social Contagion is defined as the spread of behaviors, attitudes, and affect through crowds and other types of social aggregates from one member to another. Adolescents are prone to social contagion because they may be especially susceptible to peer influence and social media.
In this article, we provide a brief review of the most recent findings on social contagion, violence, and suicide among adolescents.

Recent findings
Recent evidence support social contagion in gun violence, bullying, cyberbullying, violent offending, and suicide, but is inconclusive on the role of violent video game exposure on aggressive behavior.

Summary
The mechanisms underlying the contagion effect of violence and suicide are currently unclear. It has been argued that social learning, identification with significant others, and the normalization of specific norms play a role. All these mechanisms require understanding social contagion as a complex interaction between individual, relational and social factors. This is key if the social contagion perspective is to be used not only to investigate negative outcomes, but also as a framework for promoting prosocial attitudes and behaviors. Additionally, more research is needed on psychosocial interventions and public policies to minimize the potential spillover effect of violence and suicide.
Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6
Authors: Taha Taha Y. , Chen Irene P. , Hayashi Jennifer M. , Tabata Takako , Walcott Keith , Kimmerly Gabriella R. , Syed Abdullah M. , Ciling Alison , Suryawanshi Rahul K. , Martin Hannah S. , Bach Bryan H. , Tsou Chia-Lin , Montano Mauricio , Khalid Mir M. , Sreekumar Bharath K. , Kumar G. Renuka , Wyman Stacia , Doudna Jennifer A. , Ott Melanie 
Published: February 2023

ABSTRACTAlthough the SARS-CoV-2 Omicron variant (BA.1) spread rapidly across the world and effectively evaded immune responses, its viral fitness in cell and animal models was reduced. The precise nature of this attenuation remains unknown as generating replication-competent viral genomes is challenging because of the length of the viral genome (30kb). Here, we designed a plasmid-based viral genome assembly and rescuestrategy (pGLUE) that constructs complete infectious viruses or noninfectious subgenomic replicons in a single ligation reaction with >80% efficiency. Fully sequenced replicons and infectious viral stocks can be generated in 1 and 3 weeks, respectively. By testing a series of naturally occurring viruses as well as Delta-Omicron chimeric replicons, we show that Omicron nonstructural protein 6 harbors critical attenuating mutations, which dampen viral RNA replication and reduce lipid droplet consumption. Thus, pGLUE overcomes remaining barriers to broadly study SARS-CoV-2 replication and reveals deficits in nonstructural protein function underlying Omicron attenuation.
Clinical Validation of a Multi-protein, Serum-based Assay for Disease Activity Assessments in Multiple Sclerosis
Authors: Chitnis Tanuja , Foley John , Ionete Carolina , Ayoubi Nabil K. El , Saxena Shrishti , Gaitan-Walsh Patricia , Lokhande Hrishikesh , Paul Anu , Saleh Fermisk , Weiner Howard , Venzie Jennifer L. , Qureshi Ferhan , Becich Michael J. , da Costa Fatima Rubio , Gehman Victor M. , Zhang Fujun , Keshavan Anisha , Jalaleddini Kian , Ghoreyshi Ati , Khoury Samia J. 
Published: February 2023

ABSTRACTBackground and objectivesAn unmet need exists for validated quantitative tools to measure multiple sclerosis (MS) disease activity and progression. We developed a custom immunoassay-based MS disease activity (MSDA) Test incorporating 18 protein concentrations into an algorithm to calculate four Disease Pathway scores (Immunomodulation, Neuroinflammation, Myelin Biology, and Neuroaxonal Integrity) and an overall Disease Activity score. The objective was to clinically validate the MSDA Test based on associations between scores and clinical/radiographic assessments.MethodsSerum samples (N=614) from patients with MS at multiple sites were split into Train (n=426; algorithm development) and Test (n=188; evaluation) subsets. Subsets were stratified by demographics, sample counts per site, and gadolinium-positive (Gd+) lesion counts; age and sex were used to demographically adjust protein concentrations. MSDA Test results were evaluated for potential association with Gd+ lesion presence/absence, new and enlarging (N/E) T2 lesion presence, and active versus stable disease status (composite endpoint combining radiographic and clinical evidence of disease activity).ResultsA multi-protein model was developed (trained and cross-validated) using the Train subset. When applied to the Test subset, the model classified the Gd+ lesion presence/absence, N/E T2 lesion presence, and active versus stable disease status assessments with an area under the receiver operating characteristic (AUROC) of 0.781, 0.750, and 0.768, respectively. In each case, the multi-protein model had significantly (bootstrapped, one-sidedp<0.05) greater AUROC performance when compared with the top-performing, demographically adjusted (by age and sex) single-protein model based on neurofilament light polypeptide chain. Algorithmic score thresholds corresponded to low, moderate, or high levels of disease activity. Based on the Test subset, the diagnostic odds ratios determined that the odds of having ≥1 Gd+ lesions among samples with a moderate/high Disease Activity score were 4.49 times that of a low Disease Activity score. The odds of having ≥2 Gd+ lesions among samples with a high Disease Activity score were 20.99 times that of a low/moderate Disease Activity score.DiscussionThe MSDA Test was clinically validated; the multi-protein model had greater performance compared with the top-performing single-protein model. The MSDA Test may serve as a quantitative and objective tool to enhance care for MS.
Derivation and external validation of a clinical prognostic model identifying children at risk of death following presentation for diarrheal care
Authors: Ahmed Sharia M. , Brintz Ben J. , Talbert Alison , Ngari Moses , Pavlinac Patricia B. , Platts-Mills James A. , Levine Adam C. , Nelson Eric J. , Walson Judd L. , Kotloff Karen L. , Berkley James A. , Leung Daniel T. 
Published: February 2023

ABSTRACTDiarrhea continues to be a leading cause of death for children under-five. Amongst children treated for acute diarrhea, mortality risk remains elevated during and after acute medical management. Identification of those at highest risk would enable better targeting of interventions, but available prognostic tools lack validation. We used clinical and demographic data from the Global Enteric Multicenter Study (GEMS) to build predictive models for death (in-treatment, after discharge, or either) in children aged ≤59 months presenting with moderate-to-severe diarrhea (MSD), in Africa and Asia. We screened variables using random forests, and assessed predictive performance with random forest regression and logistic regression using repeated cross-validation. We used data from the Kilifi Health and Demographic Surveillance System (KHDSS) and Kilifi County Hospital (KCH) in Kenya to externally validate our GEMS-derived clinical prognostic model (CPM). Of 8060 MSD cases, 43 (0.5%) children died in treatment and 122 (1.5% of remaining) died after discharge. MUAC at presentation, respiratory rate, age, temperature, number of days with diarrhea at presentation, number of people living in household, number of children <60 months old living in household, and how much the child had been offered to drink since diarrhea started were predictive of death both in treatment and after discharge. Using a parsimonious 2-variable prediction model, we achieve an AUC=0.84 (95% CI: 0.82, 0.86) in the derivation dataset, and an AUC=0.74 (95% CI 0.71, 0.77) in the external dataset. Our findings suggest it is possible to identify children most likely to die after presenting to care for acute diarrhea. This could represent a novel and cost-effective way to target resources for the prevention of childhood mortality.
Mental health, gender, and care-seeking behavior during the COVID-19 pandemic in Sweden: An exploratory study
Authors: Vincze Katalin , Murphy Gillian , Barker Mary , González-Hijón Juan , Kähler Anna K. , Frans Emma M. , Sullivan Patrick F. , Valdimarsdóttir Unnur A. , Fang Fang , Lovik Anikó 
Published: February 2023

AbstractObjectiveTo explore the prevalence of care-seeking avoidance behavior in relation to gender and to describe the effect of (and potential interaction between) gender and care-seeking on mental health during the COVID-19 pandemic in Sweden.MethodsWe performed a cross-sectional study among 27,562 participants of the Omtanke2020 Study, using data collected at three time points concerning sociodemographic factors, mental health symptoms, and care-seeking behavior. Network analysis and prevalence ratios calculated from modified Poisson regressions were used to explore the relationship between gender, care-seeking behavior, and mental health symptoms (depression, anxiety, and COVID-19-related distress).ResultsIn our study, women reported a higher prevalence of mental health symptoms and avoidance of care-seeking due to COVID-19, compared to men. At baseline and six months thereafter, female gender was positively associated with COVID-19-related distress and previous mental health diagnosis. At 12 months after baseline, female gender was positively associated with anxiety and avoidance of care-seeking for mental health. However, previous mental health diagnosis and care avoidance were more strongly associated with a higher prevalence of mental health symptoms among men, compared to women.ConclusionThis study highlights gender differences in mental health outcomes and care-seeking behavior during the COVID-19 pandemic in Sweden.FundingThis work was supported with grants from Nordforsk (COVIDMENT, 105668 and 138929).
Polysubstance addiction and psychiatric, somatic comorbidities among 7,989 individuals with cocaine use disorder: a latent class analysis
Authors: Stiltner Brendan , Pietrzak Robert H. , Tylee Daniel S. , Nunez Yaira Z. , Adhikari Keyrun , Kranzler Henry R. , Gelernter Joel , Polimanti Renato 
Published: February 2023

ABSTRACTAimsWe performed a latent class analysis (LCA) in a sample ascertained for addiction phenotypes to investigate cocaine use disorder (CoUD) subgroups related to polysubstance addiction (PSA) patterns and characterized their differences with respect to psychiatric and somatic comorbidities.DesignCross-sectional studySettingUnited StatesParticipantsAdult participants aged 18-76, 39% female, 47% African American, 36% European American with a lifetime DSM-5 diagnosis of CoUD (N=7,989) enrolled in the Yale-Penn cohort. The control group included 2,952 Yale-Penn participants who did not meet for alcohol, cannabis, cocaine, opioid, or tobacco use disorders.MeasurementsPsychiatric disorders and related traits were assessed via the Semi-structured Assessment for Drug Dependence and Alcoholism. These features included substance use disorders (SUD), family history of substance use, sociodemographic information, traumatic events, suicidal behaviors, psychopathology, and medical history. LCA was conducted using diagnoses and diagnostic criteria of alcohol, cannabis, opioid, and tobacco use disorders.FindingsOur LCA identified three subgroups of PSA (i.e., low, 17%; intermediate, 38%; high, 45%) among 7,989 CoUD participants. While these subgroups varied by age, sex, and racial-ethnic distribution (p<0.001), there was no difference on education or income (p>0.05). After accounting for sex, age, and race-ethnicity, the CoUD subgroup with high PSA had higher odds of antisocial personality disorder (OR=21.96 vs. 6.39, difference-p=8.08×10−6), agoraphobia (OR=4.58 vs. 2.05, difference-p=7.04×10−4), mixed bipolar episode (OR=10.36 vs. 2.61, difference-p=7.04×10−4), posttraumatic stress disorder (OR=11.54 vs. 5.86, difference-p=2.67×10−4), antidepressant medication use (OR=13.49 vs. 8.02, difference-p=1.42×10−4), and sexually transmitted diseases (OR=5.92 vs. 3.38, difference-p=1.81×10−5) than the low-PSA CoUD subgroup.ConclusionsWe found different patterns of PSA in association with psychiatric and somatic comorbidities among CoUD cases within the Yale-Penn cohort. These findings underscore the importance of modeling PSA severity and comorbidities when examining the clinical, molecular, and neuroimaging correlates of CoUD.
Backward masking reveals coarse-to-fine dynamics in human V1
Authors: Schuurmans Jolien P. , Bennett Matthew A. , Petras Kirsten , Goffaux Valérie 
Published: February 2023

AbstractNatural images exhibit luminance variations aligned across a broad spectrum of spatial frequencies (SFs). It has been proposed that, at early stages of processing, the coarse signals carried by the low SF (LSF) of the visual input are sent rapidly from primary visual cortex (V1) to ventral, dorsal and frontal regions to form a coarse representation of the input, which is later sent back to V1 to guide the processing of fine-grained high SFs (i.e., HSF). We used functional resonance imaging (fMRI) to investigate the role of human V1 in the coarse-to-fine integration of visual input. We disrupted the processing of the coarse and fine content of full-spectrum human face stimuli via backward masking of selective SF ranges (LSFs: <1.75cpd and HSFs: >1.75cpd) at specific times (50, 83, 100 or 150ms). In line with coarse-to-fine proposals, we found that (1) the selective masking of stimulus LSF disrupted V1 activity in the earliest time window, and progressively decreased in influence, while (2) an opposite trend was observed for the masking of a stimulus’ HSF. This pattern of activity was found in V1, as well as in ventral (i.e. the Fusiform Face area, FFA), dorsal and orbitofrontal regions. We additionally presented participants with contrast negated stimuli. While contrast negation significantly reduced response amplitudes in the FFA, as well as coupling between FFA and V1, coarse-to-fine dynamics were not affected by this manipulation. The fact that V1 response dynamics to strictly identical stimulus sets differed depending on the masked scale adds to growing evidence that V1 role goes beyond the early and quasi-passive transmission of visual information to the rest of the brain. It instead indicates that V1 may yield a ‘spatially registered common forum’ or ‘blackboard’ that integrates top-down inferences with incoming visual signals through its recurrent interaction with high-level regions located in the inferotemporal, dorsal and frontal regions.
Transgenerational coexistence history attenuates negative direct interactions and strengthens facilitation
Authors: Schmutz Anja , Schöb Christian 
Published: February 2023

AbstractBackgroundInteractions among species are a fundamental aspect of biodiversity and driving ecosystem functioning and services. Species interactions include direct (pairwise) interactions among two species and indirect interactions that occur when a third species interacts with the two others and changes the direct interactions between the two. In a three-species interaction network, these interactions can be transitive (where one species outperforms all others) or intransitive (where each species outperforms another). How direct and indirect interactions influence ecosystem functions in crop systems, and how diversification and evolutionary adaptation can influence those interactions and therefore ecosystem functions has not been studied.MethodsA common garden experiment was conducted with crop communities in monocultures, 2- and 3-species mixtures that had either a common or no coexistence history (i.e. community adaptation) for three years. Net, direct and indirect interaction intensities were estimated and compared between the diversity levels and coexistence histories. Furthermore, species interaction networks were inspected for transitive/intransitive interactions.ResultsWe found evidence for lower competition in mixtures and for reduced negative direct interaction intensity and enhance facilitative effects upon community adaptation. We could further show that indirect interactions were generally less important for community adaptation than direct interactions. Additionally, we showed that community adaptation has the potential to shift interactions in the species interaction networks from competitive intransitive into pairwise competitive interactions where interactions occurred mainly between two species.SynthesisCo-adapted crop species with reduced negative interactions might have the potential to enhance productivity especially in more diverse cropping systems. This supports the notion that intercropping is a vital part towards a more sustainable agriculture and one with further yield potential when developing cultivars adapted to grow in mixtures.
Mass Mortality of Marine Mammals Associated to Highly Pathogenic Influenza Virus (H5N1) in South America
Authors: Gamarra-Toledo Víctor , Plaza Pablo I. , Gutiérrez Roberto , Inga-Diaz Giancarlo , Saravia-Guevara Patricia , Pereyra-Meza Oliver , Coronado-Flores Elver , Calderón-Cerrón Antonio , Quiroz-Jiménez Gonzalo , Martinez Paola , Huamán-Mendoza Deyvis , Nieto-Navarrete José C. , Ventura Sandra , Lambertucci Sergio A. 
Published: February 2023

ABSTRACTWe report a massive mortality of more than 3,000 sea lions (Otaria flavescens) of Peru associated with a Highly Pathogenic Influenza Virus (H5N1). The transmission pathway of H5N1 may have been through the close contact of sea lions with infected wild birds. We cannot rule out direct transmission among sea lions.