bluuebunny/crossref_metadata_2025_split huggingface dataset:
China’s and Japan’s winding path to the Refugee Convention: State identity transformations and the evolving international refugee regime
Authors: Chiavacci David , Soboleva Elena 
Published: April 2023

AbstractIn the early 1980s, the People’s Republic of China (PRC) and Japan joined the international refugee regime. This timing similarity is puzzling due to the stark differences between the PRC as a communist and authoritarian state versus Japan as a prime example of capitalist development and democratization. Moreover, although both signed the 1951 Refugee Convention and the 1967 Refugee Protocol without major reservations, neither of them has fully implemented these treaties. Discussions regarding the PRC’s and Japan’s engagement with the international refugee regime tend to start with the beginning of the Indochina refugee crisis in 1975. However, this article shows that the early decades of their interaction with the international refugee regime are of crucial importance for a full understanding of the timing and form of accession to the international refugee regime. Although the Southeast Asian refugee crisis played an important role as a trigger, it was the changing character of the international refugee regime and the transformations of state identity in both countries that set the ground for the signing of the refugee-related conventions.
Context and domain matter: the error-related negativity in peer presence predicts fear of negative evaluation, not global social anxiety, in adolescents
Authors: Niu Yanbin , Li Zixuan , Pettit Jeremy W. , Buzzell George A. , Zhao Jingjing 
Published: April 2023

AbstractBackgroundSocial anxiety symptoms are most likely to emerge during adolescence, a developmental window marked by heightened concern over peer evaluation. However, the neurocognitive mechanism(s) underlying adolescent social anxiety remain unclear. Emerging work points to the error-related negativity (ERN) as a potential neural marker of exaggerated self/error-monitoring in social anxiety, particularly for errors committed in front of peers. However, social anxiety symptoms are marked by heterogeneity and it remains unclear exactly what domain(s) of social anxiety symptoms are associated with ERN variation in peer presence, particularly within the adolescent period.MethodsTo advance and deepen the mechanistic understanding of the ERN's putative role as a neural marker for social anxiety in adolescence, we leveraged a social manipulation procedure and assessed a developmentally salient domain of social anxiety during adolescence – fear of negative evaluation (FNE). Adolescents residing in Hanzhong, a small city in the southwestern region of mainland China, had EEG recorded while performing a flanker task, twice (peer presence/absence); FNE, as well as global social anxiety symptoms, was assessed.ResultsOverall ERN increases in peer presence. FNE specifically, but not global levels of social anxiety symptoms, predicted ERN in peer presence.ConclusionsThese data are the first demonstration that the ERN relates to a specific domain of social anxiety in adolescents, as well as the first evidence of such relations within a non-WEIRD (Western, Educated, Industrialized, Rich and Democratic) sample. Results have important implications for theory and research into adolescent social anxiety.
Game of Scipios: Habsburg Interpretations, Adaptations, and Uses of Scipio Africanus in Early Modern Europe
Authors: Grudnicka Anastazja Maria 
Published: April 2023

AbstractAt the turn of the sixteenth century, the Habsburgs formulated a distinct dynastic identity that centered around their claims of ancient ancestry. They promoted this identity through an elaborate symbolic apparatus that extensively evoked historical and mythological figures from antiquity. This article identifies one such strand in the Habsburgs’ symbolic repertoires that centered upon their identification with Scipio Africanus (236/235–183 BC), the famous Roman general celebrated for his campaigns against Carthage. By tracing the Habsburgs’ uses of Scipio, this article offers a reassessment of the dynasty's relationship with these images. Traditionally, the Habsburgs’ shared symbolic repertoires have been understood to be a source of strength, providing a degree of unity and uniformity to the dynasty scattered across early modern Europe. This article argues that this dynastic uniformity ought not to be taken for granted. While the Habsburgs shared an attachment to Scipio, their interpretations of this Roman hero differed from each other in ways that were revealing of their individual needs, ambitions, and struggles as well as rivalries and animosities within the dynasty. The Habsburgs’ different—ultimately competing—uses of Scipio demonstrate that while their reliance on shared symbolic repertoires presented a significant advantage, it also rendered them uniquely vulnerable.
Dynamic eye-tracking evaluation of responding joint attention abilities and face scanning patterns in children with attention deficit hyperactivity disorder
Authors: Temeltürk Rahime Duygu , Aydın Özgür , Üstün Güllü Belgin , Kılıç Birim Günay 
Published: April 2023

AbstractThere has been growing evidence that autistic traits are more represented in children with attention-deficit hyperactivity disorder (ADHD). The purpose of this study was to investigate autistic traits associated with responding joint attention (RJA) abilities and face scanning patterns using eye-tracking in children with ADHD, and to compare with typically developing peers (TDs). All child participants viewed a series of videos related to male and female children under congruent and incongruent conditions during eye-tracking evaluation. The object and face regions of the models within the videos were determined as areas of interest (AOIs). Children with ADHD had significantly elevated ratings of autistic traits than TDs. Time course analysis of the proportion of fixations (PoF) on object region determined that children with ADHD tended to show more interest in the objects and had higher PoF on face interest area, including eyes and mouth compared to TD children in the videos when the male/female model shifts his/her gaze to the corner. Higher SRS scores were associated with higher PoF on the Face AOI in both groups. Given these findings, social skill interventions directly targeting the core deficits of RJA and problems in facial scanning appears to be beneficial in children with ADHD.
STARS Adjunct Trial: Evidence for the Effectiveness of a Digital Therapeutic as Adjunct to Treatment With Medication in Pediatric ADHD
Authors: Maple Amanda , Palko Lisa , Cañadas Elena , Jina Anil 
Published: April 2023

AbstractBackgroundTreatment of attention deficit hyperactivity disorder (ADHD) includes pharmacological and non-pharmacological interventions, both of which have demonstrated short-term efficacy. While efficacious, there are limitations to both modalities of treatment. Due partly to these limitations, there has been considerable interest in additional approaches to augmenting ADHD management. Digital therapeutics may offer improved access, minimal side effects, and low potential for abuse, while providing targeted treatment options for improving cognitive functions such as attention. AKL-T01 (EndeavorRx®) is the first and only FDA-cleared nonpharmacological prescription digital therapeutic delivered through a video game interface for the treatment of ADHD.ObjectiveThe objective is to summarize the data from a clinical trial in support of FDA clearance using AKL-T01 adjunctively in children currently taking stimulant medication for ADHD.MethodsThe STARS-Adjunct Trial was a multicenter, 12-week, open-label study of AKL-T01 in 206 children aged 8 to 14 years with a confirmed diagnosis of primarily inattentive or combined-type ADHD. The study included two cohorts: (1) subjects currently treated with ADHD medication (n=130) and (2) subjects not on any ADHD medication (n=76). Subjects had an ADHD Impairment Rating Scale (IRS) score ≥3 at baseline, and both cohorts used AKL-T01 for approximately 25 minutes per day, 5 days per week, over two 4-week treatment periods separated by a 4-week treatment pause.ResultsAKL-T01 significantly improved (lowered) ADHD-related impairment as measured with the IRS (clinician rated) after the first 4-week treatment in both cohorts (P< 0.001). Results show that effects persist during a 4-week treatment pause and further improve with a second 4-week treatment period. A majority of parents and children indicated a perceived improvement in ability to pay attention after the trial. Most common device-related adverse events were decreased frustration tolerance, headache, and irritability which ranged from mild to moderate. No serious adverse events were reported.ConclusionsThis study adds to and extends the clinical evidence base for AKL-T01, a video game-based treatment for improving attentional functioning in 8–12-year-old children with ADHD. Continued evaluation of the effects of AKL-T01 on other important aspects of functioning, like academic and social functioning, health utilization, and health outcomes, would continue to add to the evidence base that the effects observed in this and previous studies have substantial clinical and functional impact.FundingAkili Interactive
Preclinical Pharmacology of Solriamfetol: Potential Mechanisms for Wake Promotion
Authors: Gursahani Hema , Jolas Thierry , Martin Maryse , Cotier Sandrine , Hughes Sandrine , Macfadden Wayne , Parks Gregory , Chepke Craig 
Published: April 2023

AbstractIntroductionSolriamfetol is a wake-promoting agent (WPA) approved for the treatment of excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea. The wake-promoting mechanism of solriamfetol may result from dopamine and norepinephrine reuptake inhibition. Preclinical pharmacology studies were conducted to further elucidate the molecular targets activated by solriamfetol and compare them to that of known WPAs and traditional stimulants.MethodsIn vitro binding and functional studies were conducted in a panel of cell lines or membrane preparations expressing transmembrane receptors and monoamine transporters to measure the activity of solriamfetol, comparator WPAs, and traditional stimulants. Electrophysiology studies were conducted in slice preparations from mouse ventral tegmental area (VTA). Studies to measure locomotor activity and wake-promoting effects were conducted in mice.ResultsIn vitro functional studies showed agonist activity of solriamfetol at human, mouse, and rat TAAR1 receptors. hTAAR1 EC50 values (10–16 μM) were within the clinically observed therapeutic solriamfetol plasma concentration range and overlapped with the observed DAT/NET inhibitory potencies of solriamfetol in vitro. TAAR1 agonist activity was unique to solriamfetol; neither the WPA modafinil nor the DAT/NET inhibitor bupropion had TAAR1 agonist activity. Solriamfetol (1–10 μM) dose-dependently inhibited the firing frequency of dopaminergic VTA neurons in mouse brain slices, similar to known TAAR1 agonists; however, these effects were inhibited by a D2 antagonist, suggesting a DAT-mediated effect. Unlike traditional stimulants, solriamfetol did not increase locomotor activity in naive mice, but inhibited the increase in locomotor activity in DAT knockout mice.ConclusionsPreclinical studies have identified agonist activity at the TAAR1 receptor and, possibly, lower potency agonist activity at 5-HT1A receptors as potential pharmacological targets for solriamfetol, in addition to its activity as a DAT/NET inhibitor. Given the current understanding of TAAR1 agonists as modulators of monoamine transmission with potential wake-promoting effects in multiple preclinical species, agonist activity at the hTAAR1 receptor may represent an additional pharmacological target underlying the wake-promoting effects for solriamfetol, in addition to its DNRI activity.FundingAxsome Therapeutics, Jazz Pharmaceuticals
Digital CBT-I Treatment Improves Sleep and Reduces Anxiety and Depression Symptoms in Adults With Chronic Insomnia: Interim Analysis of DREAM Study
Authors: Morin Charles , Thorndike Frances P , Ojile Joseph M. , Gerwien Robert , Wendorf Angela , Maricich Yuri A 
Published: April 2023

AbstractIntroductionChronic insomnia (CI) often co-occurs with depression and anxiety, and treatment may positively impact mood. This ongoing study collected real-world data on changes in insomnia, depression, and anxiety symptoms among adults with CI treated with a prescription digital therapeutic (PDT) delivering cognitive-behavioral therapy for insomnia (CBT-I; Somryst®, previously SHUTi).MethodsThis prospective, single-arm, pragmatic clinical study enrolled adults (≥18 years) in the US with CI and mobile device access. The PDT consists of six core modules completed over 6–9 weeks. In this interim analysis, participants completed the Insomnia Severity Index (ISI), 8-item Patient Health Questionnaire (PHQ-8), and Generalized Anxiety Disorder-7 scale (GAD-7) and other self-reported outcomes—at screening (baseline/prior to Core 1), end of treatment (Day 63), and 6-month follow-up (Day 243).ResultsMean ISI scores decreased (p<0.0001) from baseline (n=991) to post-treatment (n=777;18.8 vs 11.3) and to Day 243 (n=193; 18.8 vs 12.1). Mean GAD-7 scores improved from baseline to Day 63 (n=744; p<0.0001, Cohen’s d = 0.48) and to Day 243 (n=186; p<0.0001, d = 0.45). Similarly, PHQ-8 scores improved from baseline to Day 63 (n=747; p<0.001, d = 0.76) and to Day 243 (n=186; p<0.0001, d = 0.60). These patterns persisted across baseline anxiety and depressive severity levels among people with any baseline depressive or anxiety symptoms (all p<0.05 for depression, all p<0.0001 for anxiety), with large effect sizes observed for severe anxiety (d=1.43 Day 63, d=1.55 Day 243) and for moderate to severe depression (d range = 0.96-1.51).ConclusionIn this study, treatment with digital CBT-I was associated with significant reductions in ISI, anxiety, and depression at posttreatment and at 6 months. The largest observed decreases in GAD-7 and PHQ-8 scores were among people with more severe baseline mood symptoms.FundingPear Therapeutics (US), Inc.
Reduced Healthcare Resource Utilization in Patients With Chronic Insomnia 24 Months After Treatment With Digital CBT-I: A Matched-Control Study
Authors: Forma Felicia , Knight Tyler , Baik Rebecca , Wallace Matthew , Malone Dan , Xiong Xiaorui , Velez Fulton , Thorndike Frances , Maricich Yuri 
Published: April 2023

AbstractIntroductionThis analysis examined the impact of a digital therapeutic for treating chronic insomnia (currently marketed as Somryst®, at the time called Sleep Healthy Using The internet [SHUTi]) on healthcare resource use (HCRU) by comparing patients treated with the digital cognitive behavioral therapy for insomnia (dCBTi) to patients not treated with dCBTi, but with insomnia medications.MethodsA retrospective observational study using health claims data was conducted in two cohorts across the United States: patients who registered for dCBTi (cases) between June 1, 2016 and October 31, 2018 (index date) vs. patients who did not register for dCBTi but initiated a second prescription for an insomnia medication in the same time period (controls). Observation period was 16–24 months. No other inclusion/exclusion criteria were used. Control patients were matched using a nearest neighbor within-caliper matching without replacement approach. Incidence rates for HCRU encounter type were calculated using a negative binomial model for both cohorts. Costs were estimated by multiplying HCRU by published average costs for each medical resource.ResultsEvaluated were 248 cases (median age 56.5 years, 57.3% female, 52.4% treated with sleep-related medications) and 248 matched controls (median age 55.0 years, 56.0% female, 100.0% treated with sleep-related medications). Over the course of 24 months post-initiation, cases had significantly lower incidences of inpatient stays (55% lower, IRR: 0.45; 95% CI: 0.28–0.73; P=0.001), significantly fewer emergency department (ED) visits without inpatient admission (59% lower; IRR: 0.41; 95% CI: 0.27–0.63; P<0.001), and significantly fewer hospital outpatient visits (36% lower; IRR: 0.64; 95% CI: 0.49–0.82; P<0.001). There was also a trend for fewer ambulatory surgical center visits (23% lower; IRR: 0.77; 95% CI: 0.52–1.14; P=0.197) and fewer office visits (7% lower; IRR: 0.93; 95% CI: 0.81–1.07; P=0.302) with the use of SHUTi. Use of sleep medications was more than four times greater in controls vs. cases, with 9.6 (95% CI: 7.88–11.76) and 2.4 (95% CI: 1.91–2.95) prescriptions/patient, respectively (P<0.001). All-cause per-patient HCRU costs were $8,202 lower over 24 months for cases vs. controls, driven primarily by a lower incidence of hospitalizations (-$4,996 per patient) and hospital outpatient visits (-$2,003 per patient).ConclusionsPatients with chronic insomnia who used a digital CBTi treatment had significant and durable real-world reductions in hospital inpatient stays, ED visits, hospital outpatient visits, and office visits compared to matched controls treated with medications.FundingPear Therapeutics (US), Inc.
Sustained Treatment Response With Long-Term Valbenazine in Patients With Tardive Dyskinesia
Authors: Correll Christoph U. , Lindenmayer Jean-Pierre , Farahmand Khody , Jen Eric , Siegert Scott , Dunayevich Eduardo 
Published: April 2023

AbstractBackgroundValbenazine is a once-daily VMAT2 inhibitor approved for the treatment of tardive dyskinesia (TD), a persistent and potentially disabling movement disorder associated with prolonged exposure to antipsychotics, antiemetics, and other dopamine receptor blocking agents. The efficacy, safety, and tolerability of valbenazine has been established in several phase 3 trials, including a long-term study (KINECT 4 [NCT02405091]) in which participants received open-label valbenazine (40 or 80 mg) for 48 weeks. Post hoc analyses of KINECT 4 data were conducted to assess patterns of treatment response.MethodsData from KINECT 4 treatment completers (participants who reached the Week 48 visit and had the longest duration of treatment) were analyzed post hoc. TD was assessed using the Abnormal Involuntary Movement Scale (AIMS) total score (sum of items 1–7, as rated by the study investigator), the Clinical Global Impression of Change-Tardive Dyskinesia (CGI-TD), and the Patient Global Impression of Change (PGIC). Analyses were conducted at Week 8 (first study visit after the valbenazine dose-optimization period) and Week 48 using the following definitions of response: ≥50% and ≥70% improvement from baseline in AIMS total score; rating of “much improved” or “very much improved” (score ≤2) on the CGI-TD and PGIC.ResultsOf the 167 participants who entered KINECT 4, 103 (62%) were treatment completers and included for analysis. Of these 103 participants, 39% and 86% met the ≥50% AIMS response threshold at Weeks 8 and 48, respectively. The percentages of participants who met the highly rigorous AIMS ≥70% response threshold at Weeks 8 and 48 were 17% and 52%, respectively. Of the 40 participants with AIMS ≥50% total score improvement at Week 8, 95% also met this threshold at Week 48 (“sustained response”). Of the 63 participants with <50% AIMS improvement at Week 8, 81% achieved the ≥50% response threshold by end of treatment at Week 48. The proportion of participants meeting the threshold for CGI-TD response also increased over time, from 50% at Week 8 to 92% at Week 48. PGIC results were similar, with response rates of 53% and 88% at Weeks 8 and 48, respectively.ConclusionsPost hoc analyses of data from a 48-week, open-label study of once-daily valbenazine showed that the proportion of participants meeting rigorous treatment response thresholds increased over time. By the end of treatment at Week 48, >80% of participants demonstrated robust improvements in TD, as assessed using the AIMS (≥50% improvement), CGI-TD (score ≤2), and PGIC (score ≤2).FundingNeurocrine Biosciences, Inc.
Unique Considerations in the Treatment of Psychosis in DiGeorge Syndrome: A Case Report
Authors: Williams Laura , Jadapalle Sree , Lamm Kevin 
Published: April 2023

AbstractIntroductionDiGeorge Syndrome is a microdeletion of chromosome 22q11.2 and is most commonly de novo. Manifestations of DiGeorge are wide-spread including cardiac malformations, palatal abnormalities, intellectual disability, hypocalcemia, dysmorphic facial features, and psychiatric disorders (psychotic disorders, Autism, ADHD, etc). This case report highlights difficulties with diagnosis and treatment of psychosis in DiGeorge. This 29 yo male with history of DiGeorge and associated cardiac anomalies presented to the outpatient clinic with prior diagnoses of schizoaffective disorder, bipolar disorder, DMDD, autism, and ADHD. Patient denied all symptoms, though mother noted hallucinations for 5–6 years. He was previously on aripiprazole and divalproex and developed a resting tremor. With family history of Parkinson’s disease (PD), increased risk of PD in DiGeorge, and no improvement in tremor with dose reduction of aripiprazole or discontinuation of divalproex, neurology diagnosed PD, which was later negated when tremor resolved with complete discontinuation of aripiprazole. In our clinic we slowly increased divalproex and olanzapine, though parent concern of sedation limited higher doses. Patient had moderate improvement in symptoms per parents, but after several months on moderate-dose olanzapine, he developed a tremor. Sensitivity to extrapyramidal symptoms limits medication selection. Furthermore, QT prolongation in a population with cardiac abnormalities poses a unique risk. Given complexity and poor response, we researched pathogenesis and treatment of psychosis in DiGeorge.MethodsWe reviewed literature on PubMed with keywords including “DiGeorge,” “treatment,” “psychosis.” Specifically, we looked at articles addressing treatment response, efficacy, side effects, novel treatments, and the pathogenesis as it relates to treatment.ResultsLiterature indicates that psychotic symptoms are more treatment resistant compared to psychotic disorders not associated with DiGeorge and there is little consensus on which antipsychotics are more effective. The 22q11.2 deletion contains the gene segment for catechol-O-methyltransferase (COMT) and the resulting COMT deficiency leads to excess catecholamines. The presence of the low activity COMT variant on the remaining allele is associated with possibly more severe psychiatric symptoms. Metyrosine may be a potential medication in the treatment of psychosis in DiGeorge by interfering with dopamine synthesis. Overall there is sparse research on treatment of psychosis in DiGeorge and a lack of firm recommendations.ConclusionThis case study exemplifies the need for further research on DiGeorge Syndrome and treatment of psychosis. Treatment is complicated by cardiac abnormalities, comorbid neuropsychiatric conditions confounding diagnosis, and little research on treatments that target the unique pathogenesis. Research is inconsistent concerning recommendations and novel treatments are primarily anecdotal.FundingNo Funding