bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I/II Study of the WEE1 Inhibitor Adavosertib (AZD1775) in Combination with Carboplatin in Children with Advanced Malignancies: Arm C of the AcSé-ESMART Trial
Authors: Gatz Susanne A. , Harttrampf Anne C. , Brard Caroline , Bautista Francisco , André Nicolas , Abbou Samuel , Rubino Jonathan , Rondof Windy , Deloger Marc , Rübsam Marc , Marshall Lynley V. , Hübschmann Daniel , Nebchi Souad , Aerts Isabelle , Thebaud Estelle , De Carli Emilie , Defachelles Anne Sophie , Paoletti Xavier , Godin Robert , Miah Kowser , Mortimer Peter G.S. , Vassal Gilles , Geoerger Birgit 
Published: December 2023

Abstract

Purpose:
AcSé-ESMART Arm C aimed to define the recommended dose and activity of the WEE1 inhibitor adavosertib in combination with carboplatin in children and young adults with molecularly enriched recurrent/refractory malignancies.

Patients and Methods:
Adavosertib was administered orally, twice every day on Days 1 to 3 and carboplatin intravenously on Day 1 of a 21-day cycle, starting at 100 mg/m2/dose and AUC 5, respectively. Patients were enriched for molecular alterations in cell cycle and/or homologous recombination (HR).

Results:
Twenty patients (median age: 14.0 years; range: 3.4–23.5) were included; 18 received 69 treatment cycles. Dose-limiting toxicities were prolonged grade 4 neutropenia and grade 3/4 thrombocytopenia requiring transfusions, leading to two de-escalations to adavosertib 75 mg/m2/dose and carboplatin AUC 4; no recommended phase II dose was defined. Main treatment-related toxicities were hematologic and gastrointestinal. Adavosertib exposure in children was equivalent to that in adults; both doses achieved the cell kill target. Overall response rate was 11% (95% confidence interval, 0.0–25.6) with partial responses in 2 patients with neuroblastoma. One patient with medulloblastoma experienced unconfirmed partial response and 5 patients had stable disease beyond four cycles. Seven of these eight patients with clinical benefit had alterations in HR, replication stress, and/or RAS pathway genes with or without TP53 alterations, whereas TP53 pathway alterations alone (8/10) or no relevant alterations (2/10) were present in the 10 patients without benefit.

Conclusions:
Adavosertib–carboplatin combination exhibited significant hematologic toxicity. Activity signals and identified potential biomarkers suggest further studies with less hematotoxic DNA-damaging therapy in molecularly enriched pediatric cancers.
Roles of cGAS-STING Pathway in Radiotherapy Combined with Immunotherapy for Hepatocellular Carcinoma
Authors: Ma Jianing , Xin Yuning , Wang Qiang , Ding Lijuan 
Published: December 2023

Abstract
Although great strides have been made in the management and treatment of hepatocellular carcinoma (HCC), its prognosis is still poor yielding a high mortality. Immunotherapy is recommended for treating advanced HCC, but its efficiency is hampered because of hepatic immunosuppression. Stimulator of interferon genes (STING) pathway, serving as a critical cytoplasmic DNA-sensing process, is reported to initiate the antitumor immune response, and link the innate immunity to the adaptive immune system. Radiotherapy has been well acknowledged to induce destruction and release of tumor-derived DNA into the cytoplasm, which then activates the cGAS-STING pathway. On this basis, radiotherapy can be used as a sensitizer for immunotherapy, and its combination with immunotherapy may bring in changes to the suboptimal efficacy of immune checkpoint inhibitor monotherapy. In this review, we summarized the roles of cGAS-STING pathway in regulation of radiotherapy combined with immunotherapy for treating HCC.
Cocaine Use Prediction With Tensor-Based Machine Learning on Multimodal MRI Connectome Data
Authors: Zhang Anru R. , Bell Ryan P. , An Chen , Tang Runshi , Hall Shana A. , Chan Cliburn , Al-Khalil Kareem , Meade Christina S. 
Published: December 2023

Abstract
This letter considers the use of machine learning algorithms for predicting cocaine use based on magnetic resonance imaging (MRI) connectomic data. The study used functional MRI (fMRI) and diffusion MRI (dMRI) data collected from 275 individuals, which was then parcellated into 246 regions of interest (ROIs) using the Brainnetome atlas. After data preprocessing, the data sets were transformed into tensor form. We developed a tensor-based unsupervised machine learning algorithm to reduce the size of the data tensor from 275 (individuals) × 2 (fMRI and dMRI) × 246 (ROIs) × 246 (ROIs) to 275 (individuals) × 2 (fMRI and dMRI) × 6 (clusters) × 6 (clusters). This was achieved by applying the high-order Lloyd algorithm to group the ROI data into six clusters. Features were extracted from the reduced tensor and combined with demographic features (age, gender, race, and HIV status). The resulting data set was used to train a Catboost model using subsampling and nested cross-validation techniques, which achieved a prediction accuracy of 0.857 for identifying cocaine users. The model was also compared with other models, and the feature importance of the model was presented.
Overall, this study highlights the potential for using tensor-based machine learning algorithms to predict cocaine use based on MRI connectomic data and presents a promising approach for identifying individuals at risk of substance abuse.
Performance Evaluation of Matrix Factorization for fMRI Data
Authors: Endo Yusuke , Takeda Koujin 
Published: December 2023

AbstractA hypothesis in the study of the brain is that sparse coding is realized in information representation of external stimuli, which has been experimentally confirmed for visual stimulus recently. However, unlike the specific functional region in the brain, sparse coding in information processing in the whole brain has not been clarified sufficiently. In this study, we investigate the validity of sparse coding in the whole human brain by applying various matrix factorization methods to functional magnetic resonance imaging data of neural activities in the brain. The result suggests the sparse coding hypothesis in information representation in the whole human brain, because extracted features from the sparse matrix factorization (MF) method, sparse principal component analysis (SparsePCA), or method of optimal directions (MOD) under a high sparsity setting or an approximate sparse MF method, fast independent component analysis (FastICA), can classify external visual stimuli more accurately than the nonsparse MF method or sparse MF method under a low sparsity setting.
A Relative Sea Surface Temperature Index for Classifying ENSO Events in a Changing Climate
Authors: L’Heureux Michelle L. , Tippett Michael K. , Wheeler Matthew C. , Nguyen Hanh , Narsey Sugata , Johnson Nathaniel , Hu Zeng-Zhen , Watkins Andrew B. , Lucas Chris , Ganter Catherine , Becker Emily , Wang Wanqiu , Di Liberto Tom 
Published: December 2023

Abstract
El Niño–Southern Oscillation (ENSO) is often characterized through the use of sea surface temperature (SST) departures from their climatological values, as in the Niño-3.4 index. However, this approach is problematic in a changing climate when the climatology itself is varying. To address this issue, van Oldenborgh et al. proposed a relative Niño-3.4 SST index, which subtracts the tropical mean SST anomaly from the Niño-3.4 index and multiplies by a scaling factor. We extend their work by providing a simplified calculation procedure for the scaling factor, and confirm that the relative index demonstrates reduced sensitivity to climate change and multidecadal variability. In particular, we show in three observational SST datasets that the relative index provides a more consistent classification of historical El Niño and La Niña oceanic conditions that is more robust across climatological periods compared to the nonrelative index. Forecast skill of the relative Niño-3.4 index in the North American Multimodel Ensemble (NMME) and ACCESS-S2 is slightly reduced for targets during the first half of the year because subtracting the tropical mean removes a source of additional skill. For targets in the second half of the year, the relative and nonrelative indices are equally skillful. Observed ENSO teleconnections in 200-hPa geopotential height and precipitation during key seasons are sharper and explain more variability over Australia and the contiguous United States when computed with the relative index. Overall, the relative Niño-3.4 index provides a more robust option for real-time monitoring and forecasting ENSO in a changing climate.

Significance Statement
The goal of this study is to further explore a relative sea surface temperature index for monitoring and prediction of El Niño–Southern Oscillation. Sea surface temperature indices are typically computed as a difference from a 30-yr climatological average, and El Niño and La Niña events occur when values exceed a certain threshold. This method is suitable when the climate is stationary. However, because of climate change and other lower-frequency variations, historical El Niño and La Niña events are reclassified depending on which climatological period is selected. A relative index is investigated to ameliorate this problem.
Energetic Stratified Turbulence Generated by Kuroshio–Seamount Interactions in Tokara Strait
Authors: Takahashi Anne , Lien Ren-Chieh , Kunze Eric , Ma Barry , Nakamura Hirohiko , Nishina Ayako , Tsutsumi Eisuke , Inoue Ryuichiro , Nagai Takeyoshi , Endoh Takahiro 
Published: December 2023

Abstract
Generating mechanisms and parameterizations for enhanced turbulence in the wake of a seamount in the path of the Kuroshio are investigated. Full-depth profiles of finescale temperature, salinity, horizontal velocity, and microscale thermal-variance dissipation rate up- and downstream of the ∼10-km-wide seamount were measured with EM-APEX profiling floats and ADCP moorings. Energetic turbulent kinetic energy dissipation rates and diapycnal diffusivities above the seamount flanks extend at least 20 km downstream. This extended turbulent wake length is inconsistent with isotropic turbulence, which is expected to decay in less than 100 m based on turbulence decay time of N−1 ∼ 100 s and the 0.5 m s−1 Kuroshio flow speed. Thus, the turbulent wake must be maintained by continuous replenishment which might arise from (i) nonlinear instability of a marginally unstable vortex wake, (ii) anisotropic stratified turbulence with expected downstream decay scales of 10–100 km, and/or (iii) lee-wave critical-layer trapping at the base of the Kuroshio. Three turbulence parameterizations operating on different scales, (i) finescale, (ii) large-eddy, and (iii) reduced-shear, are tested. Average ε vertical profiles are well reproduced by all three parameterizations. Vertical wavenumber spectra for shear and strain are saturated over 10–100 m vertical wavelengths comparable to water depth with spectral levels independent of ε and spectral slopes of −1, indicating that the wake flows are strongly nonlinear. In contrast, vertical divergence spectral levels increase with ε.
Dynamics of the Agulhas Current Influenced by the North–South Shift of Subtropical Front
Authors: Mei Huan , Dong Jianxin , Wu Xiangbai 
Published: December 2023

Abstract
The influence of meridional shift of the oceanic subtropical front (STF) on the Agulhas Current (AC) regime shifts is studied using satellite altimeter data and a 1.5-layer ocean model. The satellite observations suggest the northward shift of the STF leads to the AC leaping across the gap with little Agulhas leakage, and the southward shift of the STF mainly results in the AC intruding into the Atlantic Ocean in the forms of a loop current and an eddy-shedding path, while there are three flow patterns of AC for moderate latitude of the STF. The ocean model results suggest no hysteresis (associated with multiple equilibrium states) exists in the AC system. The model reproduces similar AC regimes depending on different gap widths as in the observations, and model results can be used to explain the observed Agulhas leakage well. We also present the parameter space of the critical AC strength that results in different AC flow patterns as a function of the gap width. The vorticity dynamics of the AC regime shift suggests that the β term is mainly balanced by the viscosity term for the AC in the leaping and loop current paths, while the β and instantaneous vorticity terms are mainly balanced by the advection and viscosity terms for the AC in the eddy-shedding path. These findings help explain the dynamics of the AC flowing across the gateway beyond the tip of Africa affected by the north–south shift of the STF in the leaping regime or penetrating regime.
Development of the Protective Strategies for Psychedelics Scale: A novel inventory to assess safety strategies in the context of psychedelics
Authors: Mian Maha N , Altman Brianna R , Low Fiona , Earleywine Mitch 
Published: December 2023

Background: Individuals who use psychedelics take efforts to mitigate unintended consequences. Despite the demonstrated utility of analogous protective behavioral strategies (PBS) assessments for other substances, no standardized scale exists to capture these protective strategies for psychedelic use. Objective: The present study addresses a notable gap concerning the assessment of psychedelic use, specifically by developing a scale measuring the protective strategies employed around use, called the Protective Strategies for Psychedelics Scale (PSPS). Methods: A sample ( Mage = 36.85 years old, standard deviation = 10.3; male = 61.9%; White = 85.2%) of 434 adults with lifetime use of psychedelics reported on initial qualitatively developed items for the PSPS, PBS scales for cannabis and alcohol, and use of alcohol, cannabis, and psychedelics. Results: Iterative principal components analyses began with 37 items and yielded a 32-item two-factor solution demonstrating excellent internal reliability (Cronbach’s α = .95) and accounted for 51.3% of the variance. Nineteen items loaded on PSPS factor 1, which focused on long-term preparation, emphasizing strategies focused on mood/intentions, preparing the substance, environment, and scheduling episode of use; 13 items loaded on factor 2, which focused on short-term preparation, highlighting strategies surrounding social context, health, and other substances. The PSPS demonstrated convergent validity with validated PBS scales for cannabis and alcohol ( r = 0.71–0.79, p < 0.001), and was moderately associated with lifetime psychedelic use ( r = 0.28, p < 0.001). Conclusion: The PSPS demonstrates promising psychometric properties, and future work validating the scale for diverse samples across research and clinical settings is warranted.
How do Public-Private Partnerships Affect Public Service Principles? A Case of City Hospitals in Türkiye
Authors: Aydin Yunus Emre , Altindag Halil 
Published: December 2023

Public-private partnership (PPP) policies have been on the Turkish Government’s healthcare agenda for a long time. Türkiye has implemented a series of policies with various elements of neoliberal reforms over the last 20 years and the Turkish Government initiated the PPP policy in 2013 as the final step of the Health Transformation Program. This article reviews the policy process that led to extensive collaboration with the private sector in public health and also examines the effect of the policy on the principles of public service. Türkiye’s policy experience has elements that reinforce the principles of continuity, variability, and equality in many ways. However, this policy was found to have weakened the long-term financial viability of healthcare and led to its fragmentation and the government eventually abandoned this policy in the construction of new hospitals. Türkiye’s experience demonstrates that governments seeking to establish sustainable PPP policies for healthcare must consider the unique dynamics inherent to public service.
The Efficacy of Second-Stage Endovascular Repair Strategy for Acute Type A Aortic Dissection
Authors: Yamana Fumio , Kuratani Toru , Domae Keitaro , Sakamoto Tomohiko , Hata Masatoshi , Shirakawa Yukitoshi , Masai Takafumi , Sawa Yoshiki 
Published: December 2023

Purpose: To evaluate the usefulness of a hybrid treatment strategy for acute type A aortic dissection (AAAD). Methods: We retrospectively evaluated the outcomes of 39 partial arch replacements (PAR; 26 male/13 female, mean age=67.9 years) in 62 patients with AAAD operated at our hospital from January 2019 to January 2023. The technique included PAR with graft-designed landing length and translocated the brachiocephalic artery inflow site during the initial surgery to minimize the invasiveness of the surgery. Thereafter, second-stage thoracic endovascular aortic repair (second TEVAR) for distal aortic events in the chronic phase was performed. Results: There was 1 case of 30-day mortality (2.6%) and 2 cases of postprocedural cerebral infarction (5.1%). The cumulative survival rates were 97.4%/1 year and 97.4%/3 years. The cumulative freedom from aorta-related second-stage procedure for the distal aortic event after initial PAR, which was performed in 13 patients (33.3%), was 63.9%/1 year and 59.7%/3 years. All patients requiring re-intervention after initial PAR underwent a second TEVAR with a 100% success rate and no postoperative complications. Conclusion: Initial PAR for AAAD in anticipation of the second TEVAR is a valuable strategy for enabling minimally invasive additional treatment of aorta-related re-intervention for distal aortic events in the chronic phase. Clinical Impact This study provides detailed information on the hybrid aortic repair strategy of the initial open partial arch repair and second staged endovascular repair for the acute type A aortic dissection. Based on this study, distal aortic re-intervention after initial open partial arch repair was necessary only in about 30% of cases, and no cases of SCI were observed in the initial treatment or in the second-stage endovascular repair and no cases of distal SINE were observed after the second staged endovascular repair. Overall, the results suggest that limiting the initial open partial arch repair can achieve good perioperative and early outcomes of initial surgery, and that second staged endovascular re-intervention for distal aortic events can be performed reliably, safely, and with minimal invasiveness.
Prevalence and risk factors for early medical and surgical complications following an admission for acute severe ulcerative colitis
Authors: Li Angel , Coote Matthew , Thin Lena 
Published: December 2023

Background: Risk factors for colectomy following an episode of acute severe ulcerative colitis (ASUC) have been well studied, but data examining the early complications following an episode is limited. Objectives: We aimed to evaluate the prevalence and risk factors for medical and surgical complications within 90 days of an ASUC admission and determine if a high-intensity induction infliximab dose is associated with these complications. Design: Retrospective analysis. Methods: We conducted a retrospective study of ASUC admissions between January 2015 and July 2021 at a tertiary hospital. The primary outcome was the prevalence of total, medical and surgical complications within 90 days following an ASUC admission. Multivariate linear regression analysis assessed for factors associated with the prevalence of complications. Results: A total of 150 patients had 186 hospital admissions for ASUC. In total, 101/186 (54.3%) admissions required rescue medical therapy. Standard infliximab induction occurred in 65/100 admissions, accelerated infliximab induction in 35/100 and cyclosporine in 1/100 of admissions. In total, 117 complications, including 74/117 (63.2%) medical and 43/117 (36.8%) surgical complications, arose. Low serum albumin was independently associated with a higher incidence of total [β = −0.08 (95% confidence interval (CI): −0.15, −0.01), p = 0.03] and surgical complications [β = −0.1 (95% CI: −0.18, −0.001), p = 0.047], while an increased age was associated with increased incidence of surgical complications [β = 0.06 (95% CI: 0.01, 0.12), p = 0.02]. A higher Charlson score was associated with increased medical complications [β = 0.12 (95% CI: 0.01, 0.24), p = 0.03]. Infliximab induction dose intensity was not associated with an increased incidence of any complications. Conclusion: Early complications following an ASUC admission is prevalent although the majority are not serious. Risk factors associated with complications include low serum albumin, older age and a higher comorbidity score. Induction infliximab dose intensity, however, is not a risk factor.
Out-of-pocket expenditures and catastrophic expenditures on inpatient care among households of an urban village in Delhi
Authors: Prakash Singh Suraj , Khokhar Anita 
Published: December 2023

Background: Out-of-pocket expenditure (OOPE) for inpatient care has been known to cause maximum impoverishment. It can have debilitating consequences for urban poor households. It is necessary to study inpatient care costs and the related factors among the households of an urban village to determine their vulnerability to catastrophic expenditure and to protect them from it. Objective: The study aimed to calculate the mean OOPE on inpatient care, and catastrophic health expenditure among households of an urban village in Delhi. Design: This was a cross-sectional study conducted over 18 months among urban village households of Delhi who have been residing for the last 1 year. Methods: A sample size of 188 was calculated based on another study, and households were selected using systematic random sampling. A pre-designed, pre-tested, semi-structured, and interviewer-administered questionnaire in Hindi was used to elicit and record relevant information. Data were recorded and coded, and analysis was done using licensed SPSS v.26 software. Tables were generated for relevant data, and cross-tables were used to assess statistical association with chi-square or Fisher exact tests, as required. A p-value of 0.05 was considered statistically significant. Results: The mean annual OOPE borne by a household on inpatient care was INR 6870.3 (SD ± 30,580.6), where 93.3% of OOPE was incurred while seeking treatment from public facilities. The OOPE on inpatient care had a statistically significant association with households having joint family, members from vulnerable population, and belonging to Delhi. Conclusion: The households of an urban village of Aliganj, Delhi, have high OOPE on inpatient care (60.6%) and catastrophic health expenditure (75.6%).