bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrocardiogram Monitoring Practices for Hospitalized Adults Receiving Antipsychotics: A Retrospective Cohort Study
Authors: Sinvani Liron , Afroz-Hossain Anika , Muran Andrew , Strunk Andrew , Williams Myia S. , Qiu Michael , Zeltser Roman , Makaryus Amgad N. , Wolf-Klein Gisele , Pekmezaris Renee 
Published: March 2022

Objective:
Antipsychotics are frequently used for managing both acute and chronic neuropsychiatric disorders. While antipsychotics are known to be associated with increased mortality due to cardiac arrhythmia, there is a lack of consensus on the timing and frequency of electrocardiogram (ECG) monitoring.  The goal of this study was to examine current ECG monitoring practices for adults receiving antipsychotics, specifically during hospital admission.

Methods:
The study involved a multisite retrospective chart review of adults admitted across 8 hospitals between January 2010 and December 2015 who received antipsychotics during hospitalization. The primary outcome was the presence of an ECG after receiving an antipsychotic.

Results:
During the study period, there were 26,353 hospitalizations during which adults received antipsychotic medication; the average age of the patients was 61.4 years, 50.1% were female, and 64.8% were white. The average comorbidity score was 1.4 with a median length of stay of 8.3 days. Of the 26,353 patients who were hospitalized, 60.6% (n=15,977) of patients in the sample had an ECG during their hospitalization, and 41.2% (n=10,865) had the ECG following antipsychotic administration. Patients who received a follow-up ECG had a longer length of stay (median: 11.3 d) compared with those who did not receive a follow-up ECG (median: 7.0 d). Follow-up ECGs were more likely among patients who had a history of heart failure [odds ratio (OR)=1.17, 95% confidence interval (CI): 1.06-1.30, P=0.002], who were receiving multiple antipsychotics (OR=1.3, 95% CI: 1.24-1.36, P<0.001) or other QT-prolonging medications (OR=1.09, 95% CI: 1.07-1.1, P<0.001), who were receiving risperidone (OR=1.12, 95% CI: 1.004-1.25, P=0.04), and who showed an increase in QTc duration (OR per 10 ms increase=1.02, 95% CI: 1.01-1.04, P=0.003). Follow-up ECGs were less likely to be administered to patients who were receiving antipsychotics before admission (OR=0.93, 95% CI: 0.87-0.997, P=0.04).

Conclusions:
This study demonstrated that, in a large health system, ECG monitoring is not routinely practiced for hospitalized patients receiving antipsychotics. Further studies are needed to identify patients who would most benefit from ECG monitoring in the acute care setting.
Video Games as a Complementary Therapy for Schizophrenia: A Systematic Review
Authors: Molina Rosa , Díaz-Oliván Isaac , Girela Braulio , Moreno Manon , Jiménez-Muñoz Laura , Delgado-Gómez David , Peñuelas-Calvo Inmaculada , Baca-García Enrique , Porras-Segovia Alejandro 
Published: March 2022

Background:
Schizophrenia is a prevalent and serious disorder. Video games have shown potential as an aid in health care for people who suffer from schizophrenia. Although video games may contribute benefit in the treatment of schizophrenia, reviews on this topic are scarce. In this article, we systematically review the evidence concerning video game-based therapeutic interventions for people diagnosed with schizophrenia.

Methods:
This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The review protocol was registered in the PROSPERO database. We searched 4 databases—PubMed, Web of Science, EMBASE, and clinicaltrials.gov—to identify original studies exploring video game-based therapeutic interventions for people with schizophrenia.

Results:
After initial screening, full-text review, and study selection, 11 articles were included in the review. Most studies used video consoles as the platform, with a minority using a personal computer. Video game-based therapeutic interventions were well accepted and generally effective in improving cognitive areas.

Conclusions:
Cognitive training could be one of the main mechanisms underlying the usefulness and effectiveness of video game-based therapeutic interventions. Software optimization and greater collaboration between developers and health care professionals are some of the priorities for future research in this area.
Transient Clozapine-induced Myocarditis Without Discontinuation of Medication: A Series of 2 Patients
Authors: Klein Nadav , Barnett Laura , Guirgis Hossam , Stearns Walter H. 
Published: March 2022

Background:
Clozapine, an antipsychotic medication used to treat treatment-refractory schizophrenia, has been associated with various dangerous side effects, including myocarditis. However, there have been few published cases reporting on patients with clozapine-induced myocarditis confirmed by cardiac magnetic resonance imaging or the management, treatment, and follow-up of these patients.

Methods:
This report describes 2 cases of patients with treatment-refractory schizophrenia evidencing transient clozapine-induced myocarditis. Detailed information including laboratory values, imaging results, and clinical notes were gathered.

Findings:
The 2 cases demonstrated differing manifestations of clozapine-induced myocarditis. Both cases showed that such myocarditis can be transient and can be treated clinically with close observation without discontinuation of clozapine.

Implications:
These cases show that clozapine-induced myocarditis is transient at times and can self-resolve without discontinuation of clozapine. These observations may suggest a change in clinical practice so that, with close observation, we can avoid risking psychiatric decompensation in select patients with a history of treatment-resistant schizophrenia.
Anosognosia and Memory Encoding in Huntington Disease
Authors: Considine Ciaran Michael , Hughes Shelby , Sellers Gibson Jessie , Isaacs David , McDonell Katherine , Darby R. Ryan , Claassen Daniel 
Published: March 2022

Background:
Anosognosia can manifest as an unawareness of neurobehavioral symptoms in individuals with Huntington disease (HD). Measurement of anosognosia is challenging, but the Anosognosia Scale (AS) represents a brief option with promising findings in small samples.

Objective:
To replicate application of the AS in a larger HD sample than previous studies in order to assess psychometrics and demographic correlates and to investigate the genetic, motor, and neuropsychological correlates of the AS in individuals with HD.

Method:
We retrospectively reviewed the AS ratings of 74 genetically confirmed Huntington gene carriers, nearly all early motor manifest, who had been referred for clinical neuropsychological assessment. Concurrent clinical neurologic examination and neuropsychometric assessment data were compiled, where available (ns = 35–74). The severity of the anosognosia per AS ratings was characterized for the HD sample.

Results:
The AS ratings did not correlate with demographic variables, genetic markers, or motor dysfunction severity. Correlation analyses revealed that higher AS ratings correlated with worse recognition–discrimination memory performance (r = 0.38, P < 0.05) but not cognitive control on executive functioning performance or on collateral-reported frontal–behavioral symptoms. Higher AS ratings also correlated with fewer patient-reported depressive symptoms (r = –0.38, P < 0.01) and diurnal hypersomnia symptoms (r = –0.44, P < 0.01).

Conclusion:
Anosognosia (per AS) is associated with recognition–discrimination deficits and fewer self-reported neuropsychiatric symptoms in individuals with pre-to-early manifest HD, though not with HD severity per genetic or motor markers, nor to executive dysfunction or collateral-reported frontal–behavioral symptoms.
Developing a Standardized Approach to Grading the Level of Brain Dysfunction on EEG
Authors: Dhakar Monica B. , Sheikh Zubeda B. , Desai Masoom , Desai Raj A. , Sternberg Eliezer J. , Popescu Cristina , Baron-Lee Jacqueline , Rampal Nishi , Hirsch Lawrence J. , Gilmore Emily J. , Maciel Carolina B. 
Published: March 2022

Purpose:
To assess variability in interpretation of electroencephalogram (EEG) background activity and qualitative grading of cerebral dysfunction based on EEG findings, including which EEG features are deemed most important in this determination.

Methods:
A web-based survey (Qualtrics) was disseminated to electroencephalographers practicing in institutions participating in the Critical Care EEG Monitoring Research Consortium between May 2017 and August 2018. Respondents answered 12 questions pertaining to their training and EEG interpretation practices and graded 40 EEG segments (15-second epochs depicting patients' most stimulated state) using a 6-grade scale. Fleiss' Kappa statistic evaluated interrater agreement.

Results:
Of 110 respondents, 78.2% were attending electroencephalographers with a mean of 8.3 years of experience beyond training. Despite 83% supporting the need for a standardized approach to interpreting the degree of dysfunction on EEG, only 13.6% used a previously published or an institutional grading scale. The overall interrater agreement was fair (k = 0.35). Having Critical Care EEG Monitoring Research Consortium nomenclature certification (40.9%) or EEG board certification (70%) did not improve interrater agreement (k = 0.26). Predominant awake frequencies and posterior dominant rhythm were ranked as the most important variables in grading background dysfunction, followed by continuity and reactivity.

Conclusions:
Despite the preference for a standardized grading scale for background EEG interpretation, the lack of interrater agreement on levels of dysfunction even among experienced academic electroencephalographers unveils a barrier to the widespread use of EEG as a clinical and research neuromonitoring tool. There was reasonable agreement on the features that are most important in this determination. A standardized approach to grading cerebral dysfunction, currently used by the authors, and based on this work, is proposed.
Variation in hospital cost trajectories at the end of life by age, multimorbidity and cancer type
Authors: Diernberger Katharina , Luta Xhyljeta , Bowden Joanna , Droney Joanne , Lemmon Elizabeth , Tramonti Giovanni , Shinkins Bethany , Gray Ewan , Marti Joachim , Hall Peter S 
Published: March 2022

AbstractBackgroundApproximately thirty thousand people in Scotland are diagnosed with cancer annually, of whom a third live less than one year. The timing, nature and value of hospital-based healthcare for patients with advanced cancer are not well understood. The aim of this study was to describe patterns of hospital-based healthcare use and associated costs in the last year of life for patients with a cancer diagnosis.MethodsWe undertook a Scottish population-wide administrative data linkage study of hospital-based healthcare use for individuals with a cancer diagnosis aged 60 years and over on their date of death, who died between 2012 and 2017. Hospital admissions, length of stay (LOS), number and nature of outpatient and day case appointments were analysed for all cancer types. Generalised linear models were used to adjust costs for age, gender, socioeconomic deprivation status, rural-urban (RU) status and comorbidity.ResultsThe study included 85,732 decedents with a cancer diagnosis, for whom 64,553 (75.3%) cancer was the primary cause of death. Mean age at death was 80.01 (SD 8.15) years. The mean number of inpatient stays in the last year of life was 5.88 (SD 5.68), with a mean LOS of 7 days. Mean total inpatient, outpatient and daycase costs per patient were £10261, £1275 and £977 respectively. Admission rates rose sharply in the last month of life. One year adjusted and unadjusted costs decreased with increasing age. A higher comorbidity burden was associated with higher costs and major cost differences between cancer types were also observed.ConclusionsPeople in Scotland in their last year of life with cancer are high users of secondary care. Hospitalisation accounts for a high proportion of costs, particularly in the last month of life. Further research is needed to examine triggers for unplanned hospitalisation and to identify modifiable reasons for variation in hospital use among different cancer cohorts.
Using Twitter Data for Cohort Studies of Drug Safety in Pregnancy: A Proof-of-Concept with Beta-Blockers
Authors: Klein Ari Z. , O’Connor Karen , Levine Lisa D. , Gonzalez-Hernandez Graciela 
Published: March 2022

AbstractBackgroundDespite that medication is taken during more than 90% of pregnancies, the fetal risk for most medications is unknown, and the majority of medications have no data regarding safety in pregnancy.ObjectiveUsing beta-blockers as a proof-of-concept, the primary objective of this study was to assess the utility of Twitter data for a cohort study design—in particular, whether we could identify (1) Twitter users who have posted tweets reporting that they took a beta-blocker during pregnancy and (2) their associated pregnancy outcomes.MethodsWe searched for mentions of beta-blockers in 2.75 billion tweets posted by 415,690 users who announced their pregnancy on Twitter. We manually reviewed the matching tweets to first determine if the user actually took the beta-blocker mentioned in the tweet. Then, to help determine if the beta-blocker was taken during pregnancy, we used the timestamp of the tweet reporting intake and drew upon an automated natural language processing (NLP) tool that estimates the date of the user’s prenatal time period. For users who posted tweets indicating that they took or may have taken the beta-blocker during pregnancy, we drew upon additional NLP tools to help identify tweets that report their adverse pregnancy outcomes, including miscarriage, stillbirth, preterm birth, low birth weight, birth defects, and neonatal intensive care unit admission.ResultsWe retrieved 5114 tweets, posted by 2339 users, that mention a beta-blocker, and manually identified 2332 (45.6%) tweets, posted by 1195 (51.1%) of the users, that self-report taking the beta-blocker. We were able to estimate the date of the prenatal time period for 356 pregnancies among 334 (27.9%) of these 1195 users. Among these 356 pregnancies, we identified 257 (72.2%) during which the beta-blocker was or may have been taken. We manually verified an adverse pregnancy outcome—preterm birth, neonatal intensive care unit admission, low birth weight, birth defects, or miscarriage—for 38 (14.8%) of these 257 pregnancies.ConclusionsOur ability to detect pregnancy outcomes for Twitter users who posted tweets reporting that they took or may have taken a beta-blocker during pregnancy suggests that Twitter can be a complementary resource for cohort studies of drug safety in pregnancy.
Multicenter analysis of neutrophil extracellular trap dysregulation in adult and pediatric COVID-19
Authors: Carmona-Rivera Carmelo , Zhang Yu , Dobbs Kerry , Markowitz Tovah E. , Dalgard Clifton L. , Oler Andrew J. , Claybaugh Dillon R. , Draper Deborah , Truong Meng , Delmonte Ottavia M. , Licciardi Francesco , Ramenghi Ugo , Crescenzio Nicoletta , Imberti Luisa , Sottini Alessandra , Quaresima Virginia , Fiorini Chiara , Discepolo Valentina , Vecchio Andrea Lo , Guarino Alfredo , Pierri Luca , Catzola Andrea , Biondi Andrea , Bonfanti Paolo , Harlowe Maria Cecilia Poli , Espinosa Yasmin , Astudillo Camila , Rey-Jurado Emma , Vial Cecilia , de la Cruz Javiera , Gonzalez Ricardo , Pinera Cecilia , Mays Jacqueline W. , Ng Ashley , Platt Andrew ,   NIH COVID Autopsy Consortium,   COVID STORM Clinicians, Drolet Beth , Moon John , Cowen Edward W. , Kenney Heather , Weber Sarah E. , Castagnoli Riccardo , Magliocco Mary , Stack Michael A. , Montealegre Gina , Barron Karyl , Hewitt Stephen M. , Arkin Lisa M. , Chertow Daniel S. , Su Helen C. , Notarangelo Luigi D. , Kaplan Mariana J. 
Published: March 2022

AbstractDysregulation in neutrophil extracellular trap (NET) formation and degradation may play a role in the pathogenesis and severity of COVID-19; however, its role in the pediatric manifestations of this disease including MIS-C and chilblain-like lesions (CLL), otherwise known as “COVID toes”, remains unclear. Studying multinational cohorts, we found that, in CLL, NETs were significantly increased in serum and skin. There was geographic variability in the prevalence of increased NETs in MIS-C, in association with disease severity. MIS-C and CLL serum samples displayed decreased NET degradation ability, in association with C1q and G-actin or anti-NET antibodies, respectively, but not with genetic variants of DNases. In adult COVID-19, persistent elevations in NETs post-disease diagnosis were detected but did not occur in asymptomatic infection. COVID-19-affected adults displayed significant prevalence of impaired NET degradation, in association with anti-DNase1L3, G-actin, and specific disease manifestations, but not with genetic variants of DNases. NETs were detected in many organs of adult patients who died from COVID-19 complications. Infection with the Omicron variant was associated with decreased levels of NETs when compared to other SARS-CoV-2 strains. These data support a role for NETs in the pathogenesis and severity of COVID-19 in pediatric and adult patients.SummaryNET formation and degradation are dysregulated in pediatric and symptomatic adult patients with various complications of COVID-19, in association with disease severity. NET degradation impairments are multifactorial and associated with natural inhibitors of DNase 1, G-actin and anti-DNase1L3 and anti-NET antibodies. Infection with the Omicron variant is associated with decreased levels of NETs when compared to other SARS-CoV-2 strains.
EpiBERTope: a sequence-based pre-trained BERT model improves linear and structural epitope prediction by learning long-distance protein interactions effectively
Authors: Park Minjun , Seo Seung-woo , Park Eunyoung , Kim Jinhan 
Published: March 2022

AbstractMotivationEpitopes are the immunogenic regions of antigen that are recognized by antibodies in a highly specific manner to trigger an immune response. Predicting such regions is extremely difficult yet contains profound implications for complex mechanisms of humoral immunogenicity.ResultsHere, we present a BERT-based epitope prediction model called EpiBERTope, a pre-trained model on the Swiss-Prot protein database, which can predict both linear and structural epitopes using protein sequences only. The model achieves an AUC of 0.922 and 0.667 for linear and structural epitope datasets respectively, outperforming all benchmark classification models including random forest, gradient boosting, naive Bayesian, and support vector machine models. In conclusion, EpiBERTope is a sequence-based model that captures content-based global interactions of antigen sequences, which will be transformative in epitope discovery with high specificity.Contactminjun.park@standigm.com
Dynamic molecular evolution of a supergene with suppressed recombination in white-throated sparrows
Authors: Jeong Hyeonsoo , Baran Nicole M. , Sun Dan , Chatterjee Paramita , Layman Thomas S. , Balakrishnan Christopher N. , Maney Donna L. , Yi Soojin V. 
Published: March 2022

AbstractIn white throated sparrows, two alternative morphs differing in plumage and behavior segregate with a large chromosomal rearrangement. As with sex chromosomes such as the mammalian Y, the rearranged version of chromosome two (ZAL2m) is in a near-constant state of heterozygosity, offering opportunities to investigate both degenerative and selective processes during the early evolutionary stages of ‘supergenes.’ Here, we generated, synthesized, and analyzed extensive genome-scale data to better understand the forces shaping the evolution of the ZAL2m chromosome in this species. We found that features of ZAL2m are consistent with substantially reduced recombination and low levels of degeneration. We also found evidence that selective sweeps took place both on ZAL2m and its standard counterpart, ZAL2, after the rearrangement event. Signatures of positive selection were associated with allelic bias in gene expression, suggesting that antagonistic selection has operated on gene regulation. Finally, we discovered a region exhibiting two long-range haplotypes inside the rearrangement on ZAL2m. These two haplotypes appear to have been maintained by balancing selection, retaining genetic diversity within the supergene. Together, our analyses illuminate mechanisms contributing to the evolution of a young chromosomal polymorphism, revealing complex selective processes acting concurrently with genetic degeneration to drive the evolution of supergenes.
Triple Negative Breast Cancer-derived Small Extracellular Vesicles as Modulator of Biomechanics in target cells
Authors: Senigagliesi Beatrice , Samperi Giuseppe , Cefarin Nicola , Gneo Luciana , Petrosino Sara , Apollonio Mattia , Caponnetto Federica , Sgarra Riccardo , Collavin Licio , Cesselli Daniela , Casalis Loredana , Parisse Pietro 
Published: March 2022

AbstractExtracellular vesicle (EV) mediated communication has recently been proposed as one of the pivotal routes in the development of cancer metastasis. EVs are nano-sized vesicles swapped between cells, carrying a biologically active content that can promote tumor–induced immune suppression, metastasis and angiogenesis. Thus, EVs constitute a potential target in cancer therapy. However, their role in triggering the premetastatic niche and in tumor spreading is still unclear. Here, we focused on the EV ability to modulate the biomechanical properties of target cells, known to play a crucial role in metastatic spreading. To this purpose, we isolated and thoroughly characterized triple-negative breast cancer (TNBC)-derived small EVs. We then evaluated variations in the mechanical properties (cell stiffness, cytoskeleton/nuclear/morphology and Yap activity rearrangements) of non-metastatic breast cancer MCF7 cells upon EV treatment. Our results suggest that TNBC-derived small EVs are able to directly modify MCF7 cells by inducing a decrease in cell stiffness, rearrangements in cytoskeleton, focal adhesions and nuclear/cellular morphology, and an increase in Yap downstream gene expression. Testing the biomechanical response of cells after EV addition might represent a new functional assay in metastatic cancer framework that can be exploited for future application both in diagnosis and in therapy.