bluuebunny/crossref_metadata_2025_split huggingface dataset:
AXS-05 (DEXTROMETHORPHAN-BUPROPION) Improves Depressive Symptoms and Functioning in Patients With One Prior Treatment Failure: Results From the Evolve Long-Term, Open Label Study
Authors: Jones Amanda , Streicher Caroline , Alter Shawn , Thomas Zachariah , Tabuteau Herriot 
Published: April 2023

AbstractBackgroundIn STAR*D, following non-remission with an SSRI, remission rates for second-line treatments were ~ 25%, regardless of the switch strategy employed. Antidepressants with novel mechanisms may improve outcomes in MDD. AXS-05 (dextromethorphan HBr 45 mg- bupropion HCl 105 mg) is a novel, oral, investigational, NMDA receptor antagonist with multimodal activity. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan.MethodsEVOLVE was an open-label study, in which patients were treated with AXS-05 twice daily for up to 15 months. Subjects had either rolled in after a prior AXS-05 study or were directly enrolled and had a DSM-5 diagnosis of MDD, a MADRS score of ≥25, and had been treated with ≥1 antidepressant in the current major depressive episode (MDE). A total of 186 patients were enrolled. Here we present the results for the directly enrolled patients (n =146).ResultsMean change in MADRS total score from a baseline of 32.2 were -9.1±7.64, -13.3±8.58, and -20.4±7.79 points at Weeks 1, 2, and 6, respectively (p< 0.001 for all). Remission (MADRS ≤10) was achieved by 5.7%, 16.2%, and 46.0% of patients at Weeks 1, 2, and 6, respectively. Improvement in functioning, measured by the SDS, was seen starting at Week 1 (p < 0.001). Improvements in MADRS and SDS were sustained at Month 12.Long-term treatment with AXS-05 was generally well tolerated. The most commonly reported adverse events were COVID-19 infection (8.9%), nausea (8.9%), headache (7.5%), dry mouth (6.2%), insomnia (5.5%), and dizziness (5.5%).ConclusionsAXS-05 improved depression and functioning in patients who failed one prior antidepressant in the current MDE.FundingAxsome Therapeutics
Efficacy and Safety of Lurasidone in a Younger Population With Bipolar Depression: Pooled Post-hoc Analysis of Two Placebo-controlled Studies
Authors: Davey Chris , Ratheesh Aswin , Tocco Michael , Mao Yongcai , George; David , Pikalov Andrei , Singh Manpreet K 
Published: April 2023

AbstractIntroductionEarly onset of bipolar disorder is associated with high rates of psychiatric comorbidity (e.g., anxiety disorders, ADHD, PTSD), high rates of recurrence, and marked impairment in functioning and quality of life. The aim of this analysis was to evaluate the efficacy and safety of lurasidone in bipolar depression in youth and young adult patients (10–30 years old).MethodsData from two 6-week, double-blind, placebo-controlled studies of lurasidone monotherapy for bipolar I depression were pooled for this analysis. In the 1st study, patients 10–17 years old were evaluated using the Children’s Depression Rating Scale–Revised (CDRS-R) and the Clinical Global Impression-Bipolar Severity (CGI-BP-S) depression scale; in the 2nd study, a subgroup of adult patients (18–30 years old) were evaluated by CGI-BP-A, and the MADRS, with the latter being converted to a CDRS-R scores using a validated conversion algorithm.ResultsThe safety population consisted of 465 patients (mean age, 17.1 years; mean age of onset, 14.1; mean CDRS-R total score, 60.8). 400 patients (85.7%) completed the study. For lurasidone vs. placebo, LS mean Week 6 change was -21.4 vs. -15.3 for the CDRS-R total score (P<0.0001; ES, 0.46); and -1.6 vs. -1.1 for the CGI-BP-S score (P<0.0001; ES, 0.50). Adverse events (≥5%) on lurasidone vs. placebo were nausea (15.9% vs. 5.2%), headache (15.1% vs. 13.1%), somnolence (7.9% vs. 3.8%), vomiting (5.2% vs. 3.3%), and weight increase (5.2% vs. 2.3%). No clinically meaningful changes were observed in weight, metabolic parameters, or prolactin.ConclusionsIn this post-hoc analysis of two placebo-controlled trials, lurasidone demonstrated clinically meaningful improvement of depressive symptoms in youth and young adults with bipolar depression. Lurasidone was generally safe, well-tolerated, and associated with minimal effects on weight, metabolic parameters, and prolactin.FundingServier Laboratories (Aust.) Pty. Ltd., and Sunovion Pharmaceuticals Inc.
Prevention in Practice: Improving Communication on the Benefits of Treatments for Schizophrenia
Authors: Such Pedro , Madera-McDonough Jessica , Yildirim Murat 
Published: April 2023

AbstractIntroductionAntipsychotic treatment can help improve outcomes in schizophrenia by reducing the risk of relapse and psychiatric hospitalization, and increasing rates of remission and recovery, particularly when used early in the disease course. However, adherence to oral antipsychotics is often poor. Long-acting injectable (LAI) antipsychotic formulations are associated with significant improvements in treatment adherence compared with oral medications, but LAIs are not widely used in early-phase schizophrenia.MethodsAn educational training program, called “Prevention in Practice,” was developed to offer clinicians a range of innovative, web-based, patient-centered resources, including virtual role-play and educational films, that aim to improve communication between clinicians and patients and help progress care for patients with early-phase schizophrenia. The program was based on findings from the PRELAPSE study, in which clinicians received training to improve communication with patients. The PRELAPSE trial was a cluster randomized study conducted in 39 mental health centers across 19 US states. Sites were randomized to encourage treatment with the LAI aripiprazole once-monthly 400 mg (AOM 400) or to provide treatment as usual. Eligible patients had a diagnosis of schizophrenia, <5 years of lifetime antipsychotic use, and were aged 18–35 years. The objective was to evaluate whether use of the LAI delayed time to first hospitalization in early-phase schizophrenia, compared with usual care. Clinicians received training on the rationale for LAI use in early psychosis, transitioning to LAIs, and discussing LAIs with patients and families. Communication training included the principles of shared decision-making, suggested responses to frequently asked questions, and role-playing.ResultsIn PRELAPSE, the sites randomized to encourage LAI treatment enrolled 234 patients and the sites randomized to usual care enrolled 255 patients. Training clinicians to improve their communication with patients made a difference—91% of patients with early-phase schizophrenia were willing to use LAI treatment at least once in the first 3 months of the study. Furthermore, the results showed that AOM 400 significantly prolonged time to first psychiatric hospitalization compared with usual care (hazard ratio: 0.56 [95% confidence interval: 0.34, 0.92]; p=0.02).ConclusionsOffering clinicians training to improve their communication with patients, through techniques such as shared decision-making and motivational interviewing, may increase LAI use in early-phase schizophrenia. ”Prevention in Practice” is now available in in different countries and languages.FundingOtsuka Pharmaceutical Development & Commercialization, Inc. (Princeton, NJ, USA) and H. Lundbeck A/S (Valby, Denmark).
Rapid Antidepressant Effects and MADRS Item Improvements With AXS-05 (DEXTROMETHORPHAN-BUPROPION), an Oral NMDA Receptor Antagonist in Major Depressive Disorder: Results From Two Randomized Double-Blind, Controlled Trials
Authors: Jones Amanda , Streicher Caroline , Alter Shawn , Thomas Zachariah , Tabuteau Herriot 
Published: April 2023

AbstractBackgroundAXS-05 (dextromethorphan-bupropion) is a novel, oral, investigational, NMDA receptor antagonist with multimodal activity being developed for MDD. The dextromethorphan component of AXS-05 is an NMDA receptor antagonist and a sigma-1 receptor agonist. The bupropion component of AXS-05 serves primarily to increase the bioavailability of dextromethorphan.MethodsAXS-05 was evaluated in two double-blind, randomized, controlled, 6-week trials. The GEMINI trial (N=327) was placebo-controlled and the ASCEND trial (N=80) used bupropion as the control. Here we focus on efficacy in the first 2 weeks of treatment and present a pooled analysis of the individual items of the MADRS for AXS-05 as compared to control.ResultsIn GEMINI, starting at Week 1, AXS 05 was superior (p < 0.05) to placebo on: mean MADRS improvement (7.3 vs. 4.9), MADRS response (15% vs. 7%), CGI-I (22% vs. 13%), CGI-S (0.7 vs. 0.4) and Q-LES-Q-SF (9.0% vs. 5.8%). At Week 2, AXS-05 was also statistically superior to placebo on MADRS remission (17% vs.8%) and on the SDS (6.8 vs. 4.5).In ASCEND, from Week 2, AXS-05 was superior (p< 0.05) to bupropion on: mean MADRS improvement (12.5vs. 7.8), MADRS remission (26% vs. 3%), and CGI-S (1.41 vs. 0.9).At Week 1, treatment with AXS-05 resulted in greater improvements (p< 0.05) in reported sadness, inner tension, inability to feel, pessimistic thoughts, and suicidal thoughts, as compared to control. At Week 6, AXS-05 demonstrated significant improvements over control on seven of the ten MADRS items.In the GEMINI trial, the most commonly reported adverse events were dizziness, nausea, headache, diarrhea, somnolence, and dry mouth.ConclusionsTreatment with AXS-05 resulted in rapid and broad antidepressant efficacy.FundingAxsome Therapeutics
Targeting lncRNA NEAT1 Impedes Alzheimer’s Disease Progression via MicroRNA-193a Mediated CREB/BDNF and NRF2/NQO1 Pathways
Authors: Li Yuanlong 
Published: April 2023

AbstractBackgroundLong noncoding RNA nuclear-enriched abundant transcript 1 (lnc-NEAT1) is closely implicated in neurological or degenerative diseases, while its implication in AD is rarely reported. This study aimed to investigate the effect of lnc-NEAT1 knockdown on neuron injury, inflammation, and oxidative stress in AD, as well as its interaction with downstream targets and pathways.MethodsAPPswe/PS1dE9 transgenic mice were injected with negative control or lnc-NEAT1 interference lentivirus. Besides, AD cellular model was constructed by amyloid β treatment in mice primary neuron cells; then, knockdown of lnc-NEAT1 and microRNA-193a (miR-193a) was performed alone or in combination.ResultsIn vivo experiments revealed that Lnc-NEAT1 knockdown improved cognition in AD mice reflected by Morrison water maze and Y-maze assays. Besides, lnc-NEAT1 knockdown reduced injury and apoptosis, decreased TNF-α and IL-1β levels (indicating lower inflammation level), repressed ROS, MDA but promoted ATP and SOD levels (suggesting lower oxidative stress level), and activated CREB/BDNF and NRF2/NQO1 pathways in hippocampi of AD mice. Notably, lnc-NEAT1 down-regulated miR-193a both in vitro and in vivo; also, it acted as a decoy of miR-193a. In vitro experiments showed that lnc-NEAT1 knockdown decreased apoptosis and oxidative stress, improved cell viability, and also activated CREB/BDNF and NRF2/NQO1 pathways in AD cellular model. Meanwhile, miR-193a knockdown showed the opposite effects, which also attenuated lnc-NEAT1 knockdown-mediated reduction in injury, oxidative stress, and activation of CREB/BDNF and NRF2/NQO1 pathways of AD cellular model.ConclusionLnc-NEAT1 knockdown reduces neuron injury, inflammation, and oxidative stress through activating miR-193a mediated CREB/BDNF and NRF2/NQO1 pathways in AD.FundingNo Funding
It’s complicated: Executive functioning moderates impacts of daily busyness on everyday functioning in community-dwelling older adults
Authors: Suchy Yana , Gereau Mora Michelle , DesRuisseaux Libby A. , Brothers Stacey L. 
Published: April 2023

AbstractObjective:Research shows that cognitively healthy older adults with mild executive function (EF) weaknesses are vulnerable to the negative impacts of life complexity (or daily busyness) when performing instrumental activities of daily living (IADLs). However, past research assessed life complexity only at one timepoint, not capturing daily fluctuations. Importantly, fluctuations in busyness can themselves have deleterious impacts on functioning. This study extended past research by examining whether (1) variability in daily busyness would be more detrimental than level of busyness to performance of IADLs, and (2) EF assessed at home would moderate deleterious impact of busyness on IADLs.Method:Fifty-two community-dwelling older adults aged 60 to 95 completed daily IADL tasks and daily measures of EF and busyness via ecological momentary assessment, independently at home for 18 days.Results:(1) In a subset of participants with mild EF weaknesses, high variability in busyness across days was associated with fewer tasks completed correctly; and (2) across all participants (regardless of EF), high levels of daily busyness were associated with fewer tasks completed on time.Conclusions:Findings indicate that high variability in daily busyness, potentially reflecting a lack of daily routine, was associated with IADL errors among cognitively healthy older adults with mild EF weaknesses. Additionally, consistently high levels of busyness were associated with failures to complete tasks, or failures to complete them on time, regardless of EF. These results further support the Contextually Valid Executive Assessment (ConVExA) model, which posits that EF and contextual factors interact to predict functional outcomes.
A ConvLSTM‐Based Prediction Model of Aurora Evolution During the Substorm Expansion Phase
Authors: Jiang Jianan , Zou Ziming , Lu Yang 
Published: April 2023

AbstractAurora is an important manifestation of solar‐terrestrial physical processes. The aurora activities have rapid changes in spatial and intensity distribution during a substorm, especially the expansion phase. In this paper, a newly developed aurora evolution model is built based on the Convolutional Long Short‐Term Memory network, using the aurora images captured by the ultraviolet imager on the Polar satellite during the substorm expansion phases. Given the images after the onset, the model can predict the evolution of aurora with reasonable accuracy. The structure similarity, Peak Signal‐to‐Noise Ratio (Peak Signal to Noise Ratio), and Root Mean Square Error are used to evaluate the similarity between the predicted and observed images. The results demonstrate that the model performs well at different scales of evolution. Additionally, the model can estimate the evolution of both the aurora intensities and the movement of the poleward boundary. Furthermore, three cases are displayed to illustrate the behavior of the model and its limitation.
Discovery of a New Inter‐Basin Climate Pattern: Australia Boundary Current Dipole
Authors: Han Jie‐Hong , Li Jianping 
Published: April 2023

AbstractA new inter‐basin teleconnection analysis method is proposed to comprehensively investigate the connection among global oceans. The strong negative correlation (−0.59) between sea surface temperature (SST) along Leeuwin Current (LC) and East Australia Current (EAC) is discovered and named as Australia Boundary Current Dipole (ABCD). This new inter‐basin air‐sea coupled mode exhibits remarkable interannual variability, with a peak phase in austral summer. The related SST anomalies are mainly generated by anomalous Australia High induced opposite alongshore surface winds to enhance/suppress the heat transport of the two warm currents, in turn, reinforce the wind anomalies by heating/cooling the overlying atmosphere and changing regional pressure anomalies. The meridional ocean advections control the anomalous SST, indicating the essential role of coastal Bjerknes feedback. The kinetic energy analysis further demonstrates that ABCD represents the reverse variation pattern of LC and EAC.
Induced Earthquake Source Parameters, Attenuation, and Site Effects From Waveform Envelopes in the Fennoscandian Shield
Authors: Eulenfeld Tom , Hillers Gregor , Vuorinen Tommi A. T. , Wegler Ulrich 
Published: April 2023

AbstractWe analyze envelopes of 233 and 22 ML0.0 to ML1.8 earthquakes induced by two geothermal stimulations in the Helsinki, Finland, metropolitan area. We separate source spectra and site terms and determine intrinsic attenuation and the scattering strength of shear waves in the 3–200 Hz frequency range using radiative transfer based synthetic envelopes. Displacement spectra yield scaling relations with a general deviation from self‐similarity, with a stronger albeit more controversial signal from the weaker 2020 stimulation. The 2020 earthquakes also tend to have a smaller local magnitude compared to 2018 earthquakes with the same moment magnitude. We discuss these connections in the context of fluid effects on rupture speed or medium properties. Site terms demonstrate that the spectral amplification relative to two reference borehole sites is not neutral at the other sensors; largest variations are observed at surface stations at frequencies larger than 30 Hz. Intrinsic attenuation is exceptionally low with values down to 2.4 × 10−5 at 20 Hz, which allows the observation of a diffuse reflection at the ∼50 km deep Moho. Scattering strength is in the range of globally observed data with between 10−3 and 10−4. The application of the employed Qopen analysis program to the 2020 data in a retrospective monitoring mode demonstrates its versatility as a seismicity processing tool. The diverse results have implications for scaling relations, hazard assessment and ground motion modeling, and imaging and monitoring using ballistic and scattered wavefields in the crystalline Fennoscandian Shield environment.
Semicentennial Response of a Bifurcation Region in an Engineered River to Peak Flows and Human Interventions
Authors: Chowdhury M. Kifayath , Blom Astrid , Ylla Arbós Clàudia , Verbeek Merel C. , Schropp Max H. I. , Schielen Ralph M. J. 
Published: April 2023

AbstractA bifurcation in an engineered river system (i.e., fixed planform and width) has fewer degrees of freedom in its response to interventions and natural changes than a natural bifurcation system. Our objective is to provide insight into how a bifurcation in an engineered river responds to peak flows and human interventions. To this end, we analyze the change in hydraulics, bed level, and bed surface grain size in the region of two bifurcations in the upper Rhine delta in the Netherlands over the last century. We show that, over the last two decades, the water discharge in one bifurcate (the Waal branch) has steadily increased at the expense of the other. This gradual increase in the water discharge of the first branch is associated with its erosion rate being larger than the other branch. The quick succession of two or three peak flow events (1993, 1995, and 1998) caused rapid sediment deposition over the upstream part of the bifurcate that has gradually lost discharge, which seems to have triggered the slow change in flow partitioning.
Hydroclimate Drives Seasonal Riverine Export Across a Gradient of Glacierized High‐Latitude Coastal Catchments
Authors: Jenckes J. , Munk L. A. , Ibarra D. E. , Boutt D. F. , Fellman J. , Hood E. 
Published: April 2023

AbstractGlacierized coastal catchments of the Gulf of Alaska (GoA) are undergoing rapid hydrologic fluctuations in response to climate change. These catchments deliver dissolved and suspended inorganic and organic matter to nearshore marine environments, however, these glacierized coastal catchments are relatively understudied and little is known about total solute and particulate fluxes to the ocean. We present hydrologic, physical, and geochemical data collected during April–October 2019–2021 from 10 streams along gradients of glacial fed to non‐glacial (i.e., precipitation) fed, in one Southcentral and one Southeast Alaska region. Hydrologic data reveal that glaciers drive the seasonal runoff patterns. The ẟ18O signature and specific conductance show distinctive seasonal variations in stream water sources between the study regions apparently due to the large amounts of rain in Southeast Alaska. Total dissolved solids concentrations and yields were elevated in the Southcentral region, due to lithologic influence on dissolved loads, however, the hydroclimate is the primary driver of the timing of dissolved and suspended yields. We show the yields of dissolved organic carbon is higher and that the δ13CPOC is enriched in the Southeast streams illustrating contrasts in organic carbon export across the GoA. Finally, we illustrate how future yields of solutes and sediments to the GoA may change as watersheds evolve from glacial influenced to precipitation dominated. This integrated analysis provides insights into how watershed characteristics beyond glacier coverage control properties of freshwater inputs to the GoA and the importance of expanding study regions to multiple hydroclimate regimes.
The prevalence and profile of spinal cord injury in public healthcare rehabilitation units in Gauteng, South Africa
Authors: Alves Michael Alexandre , Pilusa Sonti , Mashola Mokgadi Kholofelo 
Published: April 2023

Abstract
Study design
Retrospective medical record review.

Objective
To determine the prevalence and describe the profile of person with SCI (PWSCI) admitted in the public healthcare sector in Gauteng, South Africa.

Setting
Specialized public healthcare rehabilitation units in Gauteng, South Africa.

Methods
Medical records of PWSCI admitted to public healthcare rehabilitation units between 01 January 2018 and 31 December 2019 were perused. Data were collected anonymously and then summarised using descriptive and inferential statistics. Significance was set at p < 0.05.

Results
386 of 998 participants (38.7%) were admitted following SCI and the mean age was 36.9 years. Most participants were male (69.9%), with females significantly more likely to sustain a NTSCI (p < 0.001), which was the least common cause of SCI (34.9%). Those sustaining a TSCI were found to be significantly younger than their NTSCI counterparts (p < 0.001). Assault was the leading cause of injury (35.2%), and a positive HIV status with the presence of comorbidities were found to be significant risk factors for developing a NTSCI (p < 0.001). Most injuries were between T7-T12 (39.9%) and were complete (56.9%). The rehabilitation length of stay 85.6 days, with a mortality rate of 6.48%.

Conclusions
Gauteng has among the highest global proportion of TSCI due to assault. Of interest, more females sustained a NTSCI than their male counterparts. There is a need to strengthen SCI prevention strategies, particularly targeting assault in young males and infectious causes in females and older populations. Further epidemiological and outcomes-based research is required for PWSCI.