bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 2A Efficacy, Safety, and Tolerability Study of PH80 Nasal Spray for Acute Management of Menopausal Vasomotor Symptoms (Hot Flashes) in Women
Authors: Monti Louis , Baker Ross A , Salmán Ester , Hanover Rita 
Published: January 2025

IntroductionVasomotor symptoms (hot flashes) are the most common symptom of menopause, affecting about 75% of menopausal women and about 40% of perimenopausal women. PH80, an investigational neuroactive nasal spray, is hypothesized to be a potential treatment for moderate to severe hot flashes due to menopause given that it rapidly activates olfactory to limbic-hypothalamic neural circuits that control autonomic activity, including body temperature and sweating. The primary objective of this Phase 2A clinical study was to explore the efficacy, safety, and tolerability of intranasal administration of PH80 for the acute management of hot flashes due to menopause.MethodsThe study was a randomized, double-blind, placebo-controlled, exploratory Phase 2A clinical study. PH80 nasal spray containing epoxyestrenolone 0.8 μg per 50 μL was self-administered intranasally; two sprays in each nostril (total dose = 3.2 μg) up to four times daily as needed for 4 consecutive weeks. One additional dose was allowed at night if subjects were awakened by hot flashes. During the study period, subjects recorded the number and severity of hot flashes, disruption in function, and sweating related to hot flashes. Patient global impression of change (PGI-C) and clinician global impression of severity (CGI-S) were also assessed.ResultsAt baseline, subjects reported a daily mean of 7.7 hot flashes in the PH80 group (n = 18) and 8.0 in the placebo group (n = 18). After 1 week of treatment, the number of hot flashes dropped to 2.8 for PH80 and 6.4 for placebo (P <.001), and after 4 weeks of treatment, the number of hot flashes dropped to 1.5 for PH80 and 5.1 for placebo (P <.001). Treatment with PH80 significantly reduced the severity, disruption in function, and sweating associated with hot flashes during the treatment period as compared with subjects in the placebo group. There was a significant improvement in PGI-C for PH80 vs placebo at endpoint (P = .015) and a strong trend for improvement on CGI-S (P
= .053). PH80 was well-tolerated with no serious adverse events (AEs); the AE profiles of PH80 and placebo were comparable. All 36 subjects completed 4 weeks of treatment and with no study discontinuations due to AEs.ConclusionsThe rapid onset, significant reduction in symptoms, and improved function induced by intranasal PH80 in menopausal women with hot flashes compared with placebo, observed as early as the end of week 1 of treatment, provide a strong signal for continued development of PH80 for the acute treatment of hot flashes due to menopause. The safety data further suggest that, if approved, PH80 will provide a substantial safety benefit over all currently available agents.FundingVistagen Therapeutics, Inc. Editorial assistance was provided by Peloton Advantage, an OPEN Health company, funded by Vistagen Therapeutics, Inc.
S.C.O.P.E. : Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement Platform The Interactive Long-Acting Injectable Antipsychotics Selector
Authors: Correll Christoph U. , Rubio Jose M. , Citrome Leslie , Kane John M. , Mychaskiw Marko A. , Thompson Stephen , Franzenburg Kelli R. , Suett Mark , Kotak Sameer 
Published: January 2025

IntroductionHealthcare professionals (HCPs) face unique challenges when managing patients with schizophrenia. Educational initiatives targeting common clinical dilemmas encountered by clinicians, such as unfamiliarity with prescribing information for long-acting injectable antipsychotics (LAIs), may assist clinicians when treating patients with schizophrenia.MethodsFour experts in schizophrenia management used empirical evidence to identify 11 key clinical dilemmas where LAIs may be useful. These experts then developed a heuristic, educational tool (S.C.O.P.E.™: Schizophrenia Clinical Outcome Scenarios and Patient-Provider Engagement) based on empirical evidence and expert opinion for clinicians to use when encountering similar scenarios to optimize schizophrenia care. S.C.O.P.E.™ also includes supportive elements such as an LAI selector.ResultsS.C.O.P.E.™ is a freely available resource comprising an interactive digital platform providing educational materials for HCPs involved in continued care for patients with schizophrenia. To acquaint HCPs with characteristics of common LAIs used in schizophrenia treatment, S.C.O.P.E.™ offers a selector that filters LAIs by approved indication(s), initiation regimen, reconstitution, dosing strengths and frequency, injection volumes and routes, and supply and storage information based on approved product labels. The LAI selector does not provide LAI safety and efficacy data, so HCPs should visit individual product websites for this information. Therefore, S.C.O.P.E.™ will not replace clinical judgment, guidelines, or continuing medical education, and is not a platform for recording patient-level data, nor intended for payer negotiations or access-related questions by HCPs.ConclusionsS.C.O.P.E.™ is an educational tool for HCPs to use alongside standard psychiatric evaluations to improve understanding of how to manage common clinical dilemmas when treating patients with schizophrenia, the role of LAIs in schizophrenia management, and the product characteristics of available LAIs.FundingTeva Branded Pharmaceutical Products R&D, Inc.
Centanafadine Sustained Release in the Treatment of Adult Attention-Deficit/Hyperactivity Disorder: Secondary Outcomes From a Phase 2a Study
Authors: Zhang Zhen , McDonough Jessica 
Published: January 2025

IntroductionCentanafadine (CTN) is a potential first-in-class norepinephrine/dopamine/serotonin triple reuptake inhibitor (NDSRI) being investigated for the treatment of attention-deficit/hyperactivity disorder (ADHD). In a phase 2a study in adult males with ADHD, CTN sustained release (CTN SR) treatment significantly improved ADHD Rating Scale-IV (ADHD-RS-IV) total and subscale scores and was well tolerated. Additional efficacy outcomes from this study are reported.MethodsThis flexible-dose (CTN SR 200–500 mg/d), single-blind, exploratory study enrolled males aged 18–55 years who met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria for ADHD and had a baseline ADHD-RS-IV total score ≥28 and Clinical Global Impression-Severity score of ≥4. The study had a screening period, a 1-week placebo run-in, and a 4-week CTN SR treatment phase. Previously unreported secondary outcomes of ADHD-RS-IV change from end of the single-blind placebo run-in and ADHD-RS-IV response (≥30% and ≥50% score reductions) at weeks 1, 2, 3 (on-treatment), and 6 (follow-up) are presented. Analyses were based on observed results using descriptive statistics.ResultsOf 45 patients enrolled, 41 received ≥1 dose of study medication and 37 completed the 4-week treatment phase (mean [SD] age, 38.24 [11.88] years; 91.9% White). At baseline, mean (SD) ADHD-RS-IV total, Inattentive subscale, and Hyperactive/Impulsive subscale scores were 38.7 (6.19), 22.81 (2.55), and 15.89 (4.8), respectively. Mean (SD) changes in ADHD-RS-IV total scores were −11.14 (8.64), −16.14 (11.08), and −20.86 (11.11) at weeks 1, 2, and 3, and −11.53 (8.78) at week 6. Correspondingly, mean (SD) changes in Inattentive subscale scores were −6.32 (4.99), −9.76 (6.4), and −12.16 (6.61) at weeks 1, 2, and 3, and −6.36 (5.7) at week 6, and in Hyperactive/Impulsive subscale scores were −4.81 (4.74), −6.38 (5.94), and −8.7 (5.81) at weeks 1, 2, and 3, and −5.17 (4.33) at week 6. ADHD-RS-IV ≥30% response was observed in 13 (35.14%), 23 (62.16%), and 28 (75.68%) patients at weeks 1, 2, and 3, and in 12 (33.33%) patients at week 6. ADHD-RS-IV ≥50% response was observed in 6 (16.22%), 16 (43.24%), and 23 (62.16%) patients at weeks 1, 2, and 3, and in 8 (22.22%) patients at week 6. The pattern of ≥30% and ≥50% response in Inattentive and Hyperactive/Impulsive subscale scores was similar to that observed with ADHD-RS-IV total score response.ConclusionsThese secondary outcomes support published primary results showing that CTN SR improved ADHD-RS-IV total and subscale scores. CTN SR treatment improved total ADHD symptoms within the first 2 weeks and was well tolerated. These findings support the usefulness of CTN SR, a potential first-in-class NDSRI, in providing rapid treatment benefit to adults with ADHD.Study Registration: NCT01939353Previous presentation: ASCP 2023, May 30–June 2, 2023, Miami Beach, FLFundingOtsuka
Cost Efficiency of Esketamine Nasal Spray Versus Quetiapine for Treatment Resistant Depression
Authors: Clemens Kristin , Teeple Amanda , Rive Benoit , Kirson Noam , Desai Urvi , Doran Jason , Eid Dody , Qu Alice , Bowrey Hannah , Joshi Kruti 
Published: January 2025

ObjectiveTo compare the per-patient direct and indirect costs associated with achieving remission with esketamine nasal spray plus oral antidepressants (ESK NS+OAD) versus quetiapine extended release plus oral antidepressants (QTP XR+OAD) among patients with treatment-resistant depression (TRD). This comparison was based on a subanalysis of results from the ESCAPE-TRD Phase 3b trial (ex-US) comparing response and remission rates for ESK NS+OAD vs QTP XR+OAD in TRD patients over 32 weeks.MethodsAn Excel-based model was developed to estimate the cost-per-remitter for ESK NS+OAD and QTP XR+OAD from the perspective of a commercial insurance plan in the US. Remission rates, response rates, and relapse rates (among patients remitting or responding during the first 8 weeks of treatment) were estimated in 4-week intervals over 32 weeks using data from the ESCAPE-TRD Phase 3b clinical trial comparing ESK NS+OAD versus QTP XR+OAD in patients with TRD. Patients not remitting/responding (non-responders) or experiencing a relapse either stayed on current treatment (i.e., ESK NS+OAD or QTP XR+OAD) or discontinued current treatment and initiated either augmented therapy with antipsychotics (APS) or recurring transcranial magnetic stimulation (rTMS). For basecase analysis, equal proportions of non-responders off-treatment initiated rTMS or augmented therapy with APS. In a scenario analysis, all non-responders off-treatment initiated rTMS. Direct costs, including medical and drug costs, were derived from health economic literature and the RED BOOK® drug pricing database. Indirect costs attributed to work productivity loss from presenteeism and absenteeism were derived from a separate analysis of ESCAPE-TRD patients using the Work Productivity and Activity Impairment: Depression (WPAI:D) questionnaire and US Bureau of Labor Statistics survey results.ResultsThe cumulative relapse-free remission rate at 32 weeks was 50% for patients receiving ESK NS+OAD and 33% for patients receiving QTP XR+OAD. In the basecase analysis, the cost-per-remitter (including direct and indirect costs) for ESK NS+OAD was $3,102.17 lower than that of QTP XR+OAD. In the scenario where 100% of non-responders off-treatment were assumed to initiate rTMS, the cost-per-remitter (including direct and indirect costs) for ESK NS+OAD was $15,133.66 lower than that of QTP XR+OAD.ConclusionThese findings suggest that esketamine nasal spray in conjunction with oral antidepressants is a cost-efficient alternative compared with quetiapine extended release for treatment of TRD for commercial insurance plans. The comparative benefits associated with ESK NS+OAD treatment are driven primarily by better short- and long-term efficacy observed in the trial and particularly pronounced when considering the costs associated with lost productivity.FundingJanssen Scientific Affairs, LLC
Money supply and the yield curve
Authors: Xu Libo 
Published: January 2025

Abstract
This paper studies the dynamic interactions between the money supply and the shape of the yield curve in the context of a regime-switching latent factor model. Estimates show that the money supply has important implications for the level, slope, and curvature of the yield curve. Moreover, the Divisia aggregates can provide more information than simple-sum aggregates based on parameter estimates and impulse response functions in understanding the dynamics of the yield curve. The favored broad Divisia aggregate could especially be associated with changes in the yield curve’s level, slope, and curvature over the business cycle. Therefore, this paper highlights the important role of Divisia aggregates in the linkage between financial markets and monetary policy.
Normative Realignment in Domestic Trade Barriers Procedures: Driving Unilateralism in the EU, US, and China
Authors: Chaisse Julien , Su Xueji 
Published: January 2025

Abstract
This article critically examines the evolution and potential of domestic trade barrier procedures in the US, EU, and China. Emblematic of this mechanism is US Section 301. Aimed at facilitating market access, these procedures function as tools of unilateralism and strategic leverage. Employing qualitative and comparative methods, the analysis explores their use in handling private complaints and combating adverse trade practices, highlighting a trend of ‘normative realignment’ in the deployment of these procedures. Once focused on resolving private grievances, such procedures are now increasingly playing a role in securing national interests. This shift marks a departure from traditional international cooperation, reflecting a recalibration of trade policies. Against the backgroup of growing encystment of unilateralism, the article argues that domestic trade barrier procedures could be adapted to address the demands of the current global economic environment. The article posits that, if executed properly, domestic trade barrier procedures may serve as a buffer mechanism vis-a-vis the tectonic shifts in economic order. In doing so, the article envisions a new generation of domestic trade barrier procedural frameworks.
Representations of Metaphysical Temporality in the Libretto of Einojuhani Rautavaara's Vincent with a Corresponding Resemblance to Alban Berg's Wozzeck
Authors: LJUBIBRATIĆ VANJA 
Published: January 2025

Abstract
In his early serialist composition style, Einojuhani Rautavaara expressed indebtedness to the flexible usage of the twelve-tone system that was adapted by Alban Berg. The trace of Berg's influence becomes dramaturgically reminiscent when investigating the philosophical impact that Berg's opera Wozzeck had on Rautavaara's opera Vincent. This study aims to analyse the symbolic content of the Vincent libretto, with a secondary depiction of parallel attributes found in the libretto of Wozzeck. This examination demonstrates how the operas share a philosophical foundation that is based on an expression of metaphysical temporality inherent within the plots of both operas, which juxtapose the duality of the two temporal planes of empirical reality and metaphysical illusion. The outcome of such a comparison illustrates how Rautavaara's opera can be interpreted in a new framework of understanding that is based on the Finnish composer's mirroring of Berg's operatic and dramatic style as seen in Wozzeck.
Geochemistry and Geochronology of A‐Type Intermediate‐Felsic Rocks in NW Himalaya, Pakistan: Implications for Petrogenesis and Tectonic Evolution of Northern Gondwana
Authors: Khan Musa , Li Huan , Algeo Thomas J. , Khan Asad , Förster Michael W. , Ullah Zaheen 
Published: January 2025

AbstractIgneous intrusives in northern Pakistan can provide valuable insights into pre‐Himalayan metaluminous to peraluminous magmatism along the northern boundary of the supercontinent Gondwana and its potential tectonic significance. This study generates new geochronologic, petrographic and geochemical data for intermediate (monzonite, syenite, and foid syenite) and felsic (granite and quartz monzonite) rocks within the NW Himalayan region of Pakistan. Both the intermediate and felsic rocks have values of A/NK > 1.1, implying a metaluminous to peraluminous composition, and are distinguished by high FeOT/(MgO + FeOT) (0.81–1.0), high 10,000 × Ga/Al ratio (2.1–5.1), elevated Nb + Zr + Y + Ce contents (122–1,204 ppm), and negative anomalies of P and Ti, consistent with aluminous A‐type magmatic affinity. These rocks are classified as A1‐type, which is linked to anorogenic intraplate extensional setting. Both rock groups yield high calculated average whole‐rock Zr saturation temperatures (i.e., TZr; 790–823°C), which suggests formation from high‐temperature magmas. Whole‐rock geochemistry, including variable (87Sr/86Sr)i values (0.7034–0.7086), positive εNd(t) (+0.1 to +3.9), high Pb isotopic values (that is, (206Pb/204Pb)i = 18.68 to 19.31, (207Pb/204Pb)i = 15.64 to 15.74, and (208Pb/204Pb)i = 38.93 to 39.78), and variation in zircon εHf(t) values (+0.8 to +7.0), indicates diverse magma sources for the intermediate‐felsic rocks and provide evidence of partial melting of metasomatized lithospheric mantle, producing a primary magma of foid to quartz syenitic composition. Subsequently, this magma was responsible for the partial melting of the overlying juvenile crust, producing granitic, quartz monzonitic and monzonitic magmas. During the magma evolution process of these rocks, this process was primarily determined by partial melting that followed fractionation of K‐feldspar, ilmenite and apatite. TDM2 ages indicate that the parent materials of intermediate‐felsic rocks were generated during the Mesoproterozoic‐Neoproterozoic. LA‐ICP–MS U‐Pb dating of magmatic zircons documents their formation in the Late Paleozoic at ∼278‐268 Ma. The intermediate‐felsic rocks are correlatable with alkaline igneous rocks of the Peshawar Plain, which record the breakup of the supercontinent Gondwana and the subsequent opening of Neo‐Tethys during a Late Paleozoic rifting event. The nepheline syenite records a younger episode during the Cenozoic (37 Ma), corresponding to the collision of the Indian‐Eurasian tectonic plates.
A Study on the Potential Mechanisms Underlying the Seasonal Dependence of 15MLT‐PCA
Authors: Wang Yu , Han De‐Sheng , Feng Hui‐Ting , Xiong Ya‐Ting , Qiu Hui‐Xuan , Zhang Yong‐Liang 
Published: January 2025

AbstractSpecific polar cap auroras, such as 15MLT‐PCA, linked to lobe reconnection due to the influence of the interplanetary magnetic field (IMF) By component, were only observed in the summer. Although the variance in ionospheric conductivity between winter and summer has been proposed as a potential explanation for this seasonal dependency, it has also been argued that the differences in lobe reconnection between the winter and summer hemispheres could be the cause. To address this debate, we examined two data periods with similar IMF conditions when the northern hemisphere was in summer and winter, respectively. Using DMSP/SSUSI and AMPERE observations, we detected clear 15MLT‐PCA and associated field‐aligned currents in the summer, but not in the winter. These observations were compared with global MHD simulations from OpenGGCM. Lobe reconnection signatures were identified for both winter and summer in the simulation results. However, a detailed analysis showed that the pattern of lobe reconnection in the winter hemisphere was different from that in the summer. Based on the combined observation and simulation results, we suggest that particular lobe reconnection in summer is critical for generating 15MLT‐PCA, while the winter's reconnection may lead to transient or small‐scale auroral responses that were not easily identified by DMSP/SSUSI observations as a 15MLT‐PCA event.
Climate Impact of Marine Cloud Brightening Solar Climate Intervention Under a Susceptibility‐Based Strategy Simulated by CESM2
Authors: Chen C.‐C. , Richter J. H. , Lee Walker R. , Tye Mari , MacMartin Douglas G. , Kravitz Ben 
Published: January 2025

AbstractThe efficiency of marine cloud brightening in cooling Earth's surface temperature is investigated using an ensemble of simulations with the Community Earth System Model version 2 (CESM2). We employ a susceptibility‐based cloud seeding strategy, previously developed under the Community Climate System Model version 3 (CCSM3) to counteract the warming of CO2 doubling, in which we target the regions of the ocean most easily brightened, to determine what area extent will be required to induce 1°C cooling under SSP2‐4.5. The results indicate that cloud seeding over 5% of the ocean area is capable of achieving this goal in CESM2. Under this seeding scheme, cloud seeding is mainly deployed over lower latitudes which leads to a La Niña‐like pattern of response which is a major unintended consequence. Potential mechanisms behind such side effects are presented and discussed. The simulations also reveal that the 5% cloud seeding scheme induces an overall reduction in global precipitation, with an increase over land and a decrease over the ocean.
Bias Analysis and Correction of ERA5 Reanalysis in the Context of Tropical Cyclones
Authors: Wei Chunshan , Zhao Xiaofeng , Liu Yudi , Yang Pinglv , Zhou Zeming , Chen Yibin 
Published: January 2025

AbstractA detailed analysis of temperature and relative humidity biases in ERA5 reanalysis under tropical cyclone (TC) conditions is conducted using a composite analysis method based on more than 17,000 dropsonde observations. The statistical results indicate that ERA5 underestimates the warm‐core intensity of TCs. It shows a moist bias at the tropopause and a cold‐moist bias in the boundary layer beyond four times the radius of maximum winds (RMW). In contrast, within 4 RMW, a warm‐dry bias in the boundary layer was observed. The temperature bias is more pronounced at the TC center, and relative humidity exhibits a similar pattern, primarily in the mid and upper troposphere. The bias distribution is asymmetric, most prominent in the right front quadrant of the TC's motion direction. Besides, bias correction is performed using an eXtreme Gradient Boosting (XGBoost) model and the biases can be reduced by approximately 60%. The dependence relationships between relative humidity and the influencing factors are investigated through SHapley Additive exPlanations (SHAP) values. The results indicate that low‐level relative humidity increases and instability intensifies in TCs at night. Additionally, the findings suggest that ERA5 may inadequately capture the diurnal variation of relative humidity in TCs. The SHAP analysis also shows that relative humidity tends to be stronger in TC's motion direction.