bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute Promyelocytic Leukemia Asian Consortium study of arsenic trioxide in newly diagnosed patients: impact and outcome
Authors: Gill Harinder , Raghupathy Radha , Hou Hsin-An , Cheng-Hong Tsai Xavier , Tantiworawit Adisak , Ooi Melissa G. , Gan Gin-Gin , Wong Chieh-Lee , Yim Rita , Chin Lynn , Lee Paul , Li Vivian W.K. , Au Lester , Zhang Qi , Leung Garret M.K. , Wu Tony K.Y. , Lee Carmen Y.Y. , Chng Wee-Joo , Tien Hwei-Fang , Kumana Cyrus R. , Kwong Yok-Lam
Published: December 2024

The Acute Promyelocytic Leukemia (APL) Asian Consortium analyzed a contemporaneous cohort of newly diagnosed patients with APL treated with and without frontline arsenic trioxide (ATO) in 6 centers. The objectives were to define the impact of ATO on early deaths and relapses and its optimal positioning in the overall treatment strategy. In a 21.5-year period, 324 males and 323 females at a median age of 45.5 years (range, 18.1-91.8; low/intermediate risk, n = 448; high risk, n = 199) were treated. Regimens included frontline all-trans retinoic acid (ATRA)/chemotherapy and maintenance with/without ATO (n = 436), ATRA/IV-ATO/chemotherapy (ATRA/IV-ATO; n = 61), and ATRA/oral-ATO/ascorbic acid with ATO maintenance (oral-AAA; n = 150). The ATRA/chemotherapy group had significantly more frequent early deaths within 60 days (8.3% vs 3.3%; P = .05), inferior 60-day survival (91.7% vs 98.4%/96%; P < .001), inferior 5-year relapse-free survival (RFS; 76.9% vs 92.8%/97.8%; P < .001), and inferior 5-year overall survival (OS; 84.6% vs 91.4%/92.3%; P = .03) than ATO-containing groups (ATRA/IV-ATO and oral-AAA). The addition of oral-ATO maintenance partly mitigated the inferior 5-year RFS resulting from the omission of ATO during induction (ATRA/chemotherapy/non-ATO maintenance vs ATRA/chemotherapy/ATO maintenance vs ATRA/IV-ATO vs oral-AAA, 71.1% vs 87.9% vs 92.8% vs 97.8%; P < .001). The favorable survival impacts of ATO were observed in all risk groups. In conclusion, ATO decreased early deaths, improved 60-day survival, and resulted in significantly superior RFS and OS. This trial was registered at www.clinicaltrials.gov as #NCT04251754.
Exploring barriers and enablers of last-mile crowdshipping: understanding the motivation of potential groups of crowdshippers in the slovenian context
Authors: Bajec Patricija , Tuljak-Suban Danijela
Published: December 2024

The impact of motivational and demotivational factors on the willingness to work (WTW) as crowdshippers, specifically focusing on different groups of crowdshippers, has been largely neglected or overlooked in the literature. This study therefore aims to address this gap by determining and examining a comprehensive set of potential factors that either hinder or encourage the WTW of crowdshippers and tests their impact on four key groups of potential crowdshippers in Slovenia: employed individuals, retirees, students, and unemployed. Significant interactions between the groups and statistical differences between them were detected using the significance level and correlation approaches. The findings of this study confirm that not only are potential crowdshipper groups heterogeneous, but there is also heterogeneity within crowdshipper groups such as retirees and students. Furthermore, the study highlights that the influence of these factors slightly varies depending on the specific business models (business to customer and business to business).
Fungal infection-related conditions and outcomes in severe COVID-19: a nationwide case-control study
Authors: Maeshima Katsuya , Yamamoto Ryo , Matsumura Kazuki , Kaito Daiki , Homma Koichiro , Yamakawa Kazuma , Tagami Takashi , Hayakawa Mineji , Ogura Takayuki , Hirayama Atsushi , Yasunaga Hideo , Sasaki Junichi ,   the J-RECOVER study group
Published: December 2024

Background

Fungal infections are significant complications of severe coronavirus disease 2019 (COVID-19). Although various risk factors for poor outcomes in patients with COVID-19 have been identified, clinical and treatment factors associated with fungal infections in patients with severe COVID-19 remain unclear. This study aimed to elucidate clinical factors associated with fungal infections during severe COVID-19 treatment.

Methods

This was a post hoc analysis of the J-RECOVER study, a multicenter retrospective observational study involving patients with COVID-19 who required admission at 66 hospitals between January and September 2020. Inclusion criteria were ages ≥ 18 years, COVID-19 diagnosis with reverse-transcription polymerase chain reaction, and treatment with mechanical ventilation (MV). Patients who received antifungal drugs before MV were excluded. Potential predictors were identified through univariate analysis of patient and treatment characteristics between patients with- and those without fungal infection, which was defined as antifungal agent use for ≥ 5 days. To account for facility-specific data clustering, generalized estimating equations (GEE) were employed as adjusted analyses to calculate the relative risks of potentially associated factors. Two sensitivity analyses were performed with modified definitions for the two groups: patients who received antifungal drugs for ≤ 4 days were excluded, and fungal infection was re-defined as antifungal drug use for ≥ 14 days.

Results

Among 4,915 patients in the J-RECOVER study, 559 adults with COVID-19 who required MV were included. Fungal infections occurred in 57 (10.2%) patients. Univariate analyses identified age, age ≥ 65 years, D-dimer level, remdesivir use, steroid use, and duration of steroid therapy as potential predictors of fungal infections. Multivariate analysis using GEE on these six factors revealed that only the duration of steroid use was significantly associated with an increased risk of fungal infection (odds ratio [OR] for a day increase: 1.01; 95% confidence interval [CI]: 1.00–1.01; p < 0.001). The two sensitivity analyses similarly showed that the duration of steroid use was associated with fungal infection (odds ratio for a day increase: 1.01; 95% CI: 1.00–1.01; p < 0.001 for both).

Conclusions

In patients with severe COVID-19 requiring MV, each additional day of steroid use was associated with prolonged use of antifungal medications for ≥ 5 days.
Exploring the relaxation effects of Coptis chinensis and berberine on the lower esophageal sphincter: potential strategies for LES motility disorders
Authors: Koh Wen-Harn , Lin Li-Wei , Lin Ting-I , Liu Ching-Wen , Chang Li-Ching , Lin I-Chun , Wu Ming-Shiang , Tsai Ching-Chung
Published: December 2024

Background

Esophageal achalasia, a primary disorder impacting the lower esophageal sphincter (LES), presents symptoms such as dysphagia, regurgitation, chest pain, and weight loss. Traditional treatments, including calcium channel blockers and nitrates, offer limited relief, prompting exploration into alternative therapies. This study examines the efficacy of Traditional Chinese Medicine (TCM), focusing on Coptis chinensis (C. chinensis) and its principal component, berberine, for modulating LES relaxation, offering a new perspective on treatment possibilities.

Methods

This research evaluated the impact of C. chinensis extract and berberine on the relaxation of LES contraction pre-induced by carbachol, observing the effects across different concentrations. We employed a series of inhibitors, including tetrodotoxin, ω-conotoxin GVIA, rolipram, vardenafil, KT5823, KT5720, NG-nitro-L-arginine, tetraethylammonium (TEA), apamine, iberiotoxin, and glibenclamide, to investigate the underlying mechanisms of berberine-induced LES relaxation.

Results

Both C. chinensis extract and berberine induced significant, concentration-dependent relaxation of the LES. The relaxation effect of berberine was significantly reduced by TEA, indicating the involvement of potassium channels in this process.

Conclusions

This study demonstrates that C. chinensis and berberine significantly promote LES relaxation, primarily through potassium channel activation. These findings provide a foundation for further investigation of these compounds’ potential therapeutic applications in esophageal motility disorders, such as achalasia.

Graphical Abstract
Assessing the need for a doctor of philosophy (Ph.D.) degree in Endodontics: perspective and implication for advancing dental education and research in Saudi Arabia
Authors: Alsofi Loai
Published: December 2024

Aim

This study aims to evaluate the necessity and feasibility of integrating a Doctor of Philosophy (Ph.D.) degree into Endodontic programs at the Faculty of Dentistry King Abdulaziz University, (KAUFD), Jeddah, Saudi Arabia, and to gather insights from key stakeholders regarding the value and necessity of a Ph.D. in enhancing the field of Endodontics.

Materials and Methods

An online questionnaire link was distributed among potential Ph.D. candidates and key decision-makers in Endodontics in Saudi Arabia through social media and emails to members of the Saudi Endodontic Society and the Saudi Endodontic Journal. The questionnaire assessed demographics, professional background, interest in Ph.D. programs, program preferences, perceived need for Ph.D. programs in various sectors, and university selection criteria. Data were analyzed using IBM SPSS Statistics (Version 23).

Results

141 responses were received. Most respondents were aged 31–40, with an almost equal gender distribution. In terms of current position, a significant number were Endodontic consultants (35.7%) and Endodontic residents/Master students (28.6%) (P = 0.006). Additionally, a considerable proportion of probable prospective students had less than 5 years of expertise (45.7%) (p = 0.013), and the highest degree held by many was a bachelor’s degree (35.7%) (P = 0.007). Key considerations for prospective students were program duration, Saudi Commission for Health Specialists (SCFHS) recognition, part-time options, and cost. The importance of acquiring research skills, such as learning new research technologies and gaining publication experience, was also highlighted.

Conclusion

The findings strongly suggest a need for a Ph.D. program in Endodontics in Saudi Arabia. The results provide valuable insights for developing a program that aligns with potential candidates’ and key stakeholders’ needs and preferences, thereby advancing Endodontic research and education within the country.
The perception of facilitators and barriers to the use of e-health solutions in Poland: a qualitative study
Authors: Smoła Paulina , Młoźniak Iwona , Wojcieszko Monika , Zwierczyk Urszula , Kobryn Mateusz , Rzepecka Elżbieta , Duplaga Mariusz
Published: December 2024

Background

E-health entails the use of information and communication technologies in support of health and health-related activities. E-health increased significantly during the COVID-19 pandemic in Poland. The pandemic showed that the e-health environment may be an important element of the response to epidemiological challenges. Polish citizens were provided with an array of e-health tools supporting the provision of health services.

Methods

The main aim of the study was to assess the knowledge, use, and opinions about e-health solutions in Polish society. Fifty participants representing the general population took part in in-depth interviews. The interviews were conducted face-to-face with participants in their homes or via a teleconferencing platform from November 2023 to January 2024. At first, the interviewees were recruited by convenience, and at a later stage, a snowballing approach was applied. A semi-structured guide covered the knowledge about and use of e-health solutions, attitudes toward new technologies, and opinions about artificial intelligence and robots in healthcare. The interviewers interviewed 50 participants, of whom 26 were females. The interview transcriptions were analyzed with MAXQDA Analytics Pro 2022 (Release 22.7.0). An approach based on thematic analysis was employed to evaluate the interviews’ content.

Results

Thematic analysis of the interviews resulted in the identification of three main themes: (1) knowledge about e-health, (2) barriers, and (3) facilitators of e-health use. Recognition of the term ‘e-health’ was limited among study participants, although they used e-health solutions frequently. The main barriers included limited digital skills and unfavorable attitudes to new technologies. Some of the participants complained about technical difficulties, e.g., poor Internet access. The main facilitators identified based on the interviews include saving time and reducing costs, as well as the ability to access medical records in one repository, as in the case of the Internet Patient Account. Some people believed e-health to be an element of progress. Overall, the study participants supported sharing their medical data for research.

Conclusions

Implementing e-health solutions seems to be perceived as an inevitable consequence of technological progress. However, a lack of adequate technical skills remains one of the major obstacles to efficiently utilizing e-health’s potential.
Norwegian adaptation of the Quality in Psychiatric Care – In-Patient instrument: psychometric properties and factor structure
Authors: Fossum Siri Ødegaard , Gonzalez Marianne Thorsen , Lundqvist Lars-Olov , Moen Øyfrid Larsen , Schröder Agneta , Skundberg-Kletthagen Hege
Published: December 2024

Background

Validated instruments measuring the quality of mental healthcare from patients’ perspectives are scarce, and available instruments have been requested. One of the few instruments measuring the quality of care from a patient’s perspective is the Swedish Quality in Psychiatric Care–In–Patient (QPC-IP). This cross-sectional study aimed to translate and adapt the QPC-IP instrument for a Norwegian context and assess its psychometric properties.

Methods

The QPC-IP was translated and adapted to a Norwegian context using a translation back-translation process model. A total of 169 inpatients from specialised mental health services responded to the questionnaire. The QPC-IP comprises six dimensions: Encounter (eight items), Participation (eight items), Discharge (four items), Support (four items), Secluded Environment (three items), and Secure Environment (three items), totalling 30 items. Confirmatory factor analysis was conducted to assess the instrument’s factor structure. Additionally, Cronbach’s alpha was used to establish the instrument's internal consistency.

Results

The results indicated that the Norwegian adaptation of the QPC-IP possesses good psychometric properties, including internal consistency, content, and construct validity, as confirmed by the confirmatory factor analysis results. The confirmatory factor analysis demonstrated an adequate fit for the six-factor structure, consistent with the original Swedish instrument.

Conclusions

The QPC-IP is a user-friendly and easily implementable tool that assesses various dimensions of the quality of inpatient mental healthcare from a patient’s perspective. Moreover, the Norwegian QPC-IP holds potential for use in comparative, cross-cultural studies within mental healthcare services to monitor the quality of the provided services.
Psychogenic fever and neurodevelopmental disorders among Japanese children
Authors: Okada Ayumi , Shigeyasu Yoshie , Fujii Chikako , Tanaka Chie , Hanzawa Mana , Sugihara Akiko , Horiuchi Makiko , Tsukahara Hirokazu
Published: December 2024

Background

Psychosocial stress can induce various physical symptoms, including fever, which is a commonly seen symptom in pediatric practice. In cases of unexplained fever, psychogenic fever should be considered as a potential cause. Children with neurodevelopmental disorders may be more vulnerable to stress and therefore more prone to developing somatic symptoms than their peers. This study aimed to elucidate the characteristics of children with psychogenic fever and comorbidity.

Methods

This study included 21 patients with psychogenic fever who visited the Department of Pediatric Psychosomatic Medicine, Okayama University Hospital. Information on age, sex, disease onset, final estimated diagnosis, comorbidities, treatment course, and outcome was obtained from the patients’ medical records.

Results

Of the 21 patients included, 7 were boys and 14 were girls, and their median age was 13.0 (range: 8.6–14.6) years. A total of 19 patients had no attendance at school, and all patients showed signs of maladjustment in school. The comorbidities included orthostatic dysregulation (n = 4) and migraine (n = 3). Neurodevelopmental disorders were observed in nine patients, eight of whom were diagnosed after the initial visit. The mean treatment duration was 37.2 months. The outcomes were complete remission (n = 9), improvement (n = 4), discontinuation (n = 1), and referral to another physician (n = 7).

Conclusion

Various comorbidities were observed in the patients of this study with psychogenic fever, including the coexistence of neurodevelopmental disorders, such as autistic spectrum disorder. Children with neurodevelopmental disorders are prone to psychological stress resulting from difficulties in social adjustment. It is crucial to understand the developmental characteristics and environmental adaptation of patients to facilitate accurate diagnosis and treatment.
Novelty triggers time-dependent theta oscillatory dynamics in cortical-hippocampal-midbrain circuitry
Authors: Park Alan Jung
Published: December 2024

Rapid adaptation to novel environments is crucial for survival, and this ability is impaired in many neuropsychiatric disorders. Understanding neural adaptation to novelty exposure therefore has therapeutic implications. Here, I found that novelty induces time-dependent theta (4-12Hz) oscillatory dynamics in brain circuits including the medial prefrontal cortex (mPFC), ventral hippocampus (vHPC), and ventral tegmental area (VTA), but not dorsal hippocampus (dHPC), as mice adapt to a novel environment. Local field potential (LFP) recordings were performed while mice were freely behaving in a novel or a familiar arena for 10 min. Initially, mice exhibited increased exploratory behavior upon exposure to novelty, which gradually decreased to levels observed in mice exposed to the familiar arena. Over the same time course, the mPFC, vHPC, and VTA displayed progressively increasing theta power through novelty exposure. Additionally, theta coherence and theta phase synchrony measures demonstrated that novelty weakened the connectivity between these areas, which then gradually strengthened to the level observed in the familiar group. Conversely, mice exposed to the familiar arena showed steady and consistent behavior as well as theta dynamics in all areas. Treatment with a dopamine D1-receptor (D1R) antagonist in the vHPC disrupted neurophysiological adaptation to novelty specifically in the vHPC-mPFC and vHPC-VTA circuits, without affecting behavior. Thus, novelty induces distinct theta dynamics that are not readily dictated by behavior in the mPFC, vHPC, and VTA circuits, a process mediated by D1Rs in the vHPC. The observed time-dependent circuit dynamics in the key learning and memory circuit would provide new insights for treating neuropsychiatric disorders that often show impaired novelty processing.
Biofilm application for anaerobic digestion: a systematic review and an industrial scale case
Authors: Abera Getachew Birhanu , Trømborg Erik , Solli Linn , Walter Juline M. , Wahid Radziah , Govasmark Espen , Horn Svein Jarle , Aryal Nabin , Feng Lu
Published: December 2024

Biofilm is a syntrophic community of microorganisms enveloped by extracellular polymeric substances and displays remarkable adaptability to dynamic environments. Implementing biofilm in anaerobic digestion has been widely investigated and applied as it promotes microbial retention time and enhances the efficiency. Previous studies on anaerobic biofilm primarily focused on application in wastewater treatment, while its role has been significantly extended to accelerate the degradation of lignocellulosic biomass, improve gas–liquid mass transfer for biogas upgrading, or enhance resistance to inhibitors or toxic pollutants. This work comprehensively reviewed the current applications of biofilm in anaerobic digestion and focused on impacting factors, optimization strategies, reactor set-up, and microbial communities. Moreover, a full-scale biofilm reactor case from Norway is also reported. This review provides a state of-the- art insight on the role of biofilm in anaerobic digestion.

Graphical Abstract
Epigenome-wide mediation analysis of the relationship between psychosocial stress and cardiometabolic risk factors in the Health and Retirement Study (HRS)
Authors: Opsasnick Lauren A. , Zhao Wei , Ratliff Scott M. , Du Jiacong , Faul Jessica D. , Schmitz Lauren L. , Zhou Xiang , Needham Belinda L. , Smith Jennifer A.
Published: December 2024

Background

Exposure to psychosocial stress is linked to a variety of negative health outcomes, including cardiovascular disease and its cardiometabolic risk factors. DNA methylation has been associated with both psychosocial stress and cardiometabolic disease; however, little is known about the mediating role of DNA methylation on the association between stress and cardiometabolic risk. Thus, using the high-dimensional mediation testing method, we conducted an epigenome-wide mediation analysis of the relationship between psychosocial stress and ten cardiometabolic risk factors in a multi-racial/ethnic population of older adults (n = 2668) from the Health and Retirement Study (mean age = 70.4 years).

Results

A total of 50, 46, 7, and 12 CpG sites across the epigenome mediated the total effects of stress on body mass index, waist circumference, high-density lipoprotein cholesterol, and C-reactive protein, respectively. When reducing the dimensionality of the CpG mediators to their top 10 uncorrelated principal components (PC), the cumulative effect of the PCs explained between 35.8 and 46.3% of these associations.

Conclusions

A subset of the mediating CpG sites were associated with the expression of genes enriched in pathways related to cytokine binding and receptor activity, as well as neuron development. Findings from this study help to elucidate the underlying mechanisms through which DNA methylation partially mediates the relationship between psychosocial stress and cardiometabolic risk factors.
Sex differences in mitochondrial gene expression during viral myocarditis
Authors: Di Florio Damian N. , Weigel Gabriel J. , Gorelov David J. , McCabe Elizabeth J. , Beetler Danielle J. , Shapiro Katie A. , Bruno Katelyn A. , Chekuri Isha , Jain Angita , Whelan Emily R. , Salomon Gary R. , Khatib Sami , Bonvie-Hill Natalie E. , Fliess Jessica J. , Giresi Presley G. , Hamilton Charwan , Hartmoyer Cameron J. , Balamurugan Varsini , Darakjian Ashley A. , Edenfield Brandy H. , Kocsis S. Christian , McLeod Christopher J. , Cooper Leslie T. , Audet-Walsh Étienne , Coronado Michael J. , Sin Jon , Fairweather DeLisa
Published: December 2024

Background

Myocarditis is an inflammation of the heart muscle most often caused by viral infections. Sex differences in the immune response during myocarditis have been well described but upstream mechanisms in the heart that might influence sex differences in disease are not completely understood.

Methods

Male and female BALB/c wild type mice received an intraperitoneal injection of heart-passaged coxsackievirus B3 (CVB3) or vehicle control. Bulk-tissue RNA-sequencing was conducted to better understand sex differences in CVB3 myocarditis. We performed enrichment analysis and functional validation to understand sex differences in the transcriptional landscape of myocarditis and identify factors that might drive sex differences in myocarditis.

Results

As expected, the hearts of male and female mice with myocarditis were significantly enriched for pathways related to an innate and adaptive immune response compared to uninfected controls. Unique to this study, we found that males were enriched for inflammatory pathways and gene changes that suggested worse mitochondrial electron transport function while females were enriched for pathways related to mitochondrial homeostasis. Mitochondria isolated from the heart of males were confirmed to have worse mitochondrial respiration than females during myocarditis. Unbiased TRANSFAC analysis identified estrogen-related receptor alpha (ERRα) as a transcription factor that may mediate sex differences in mitochondrial function during myocarditis. Transcript and protein levels of ERRα were confirmed as elevated in females with myocarditis compared to males. Differential binding analysis from chromatin immunoprecipitation (ChIP) sequencing confirmed that ERRα bound highly to select predicted respiratory chain genes in females more than males during myocarditis.

Conclusions

Females with viral myocarditis regulate mitochondrial homeostasis by upregulating master regulators of mitochondrial transcription including ERRα.
Grayken Lessons: a patient who developed opioid use disorder after traumatic brain injury
Authors: Reed Gabriela , Lugo Hansel , Adams Rachel Sayko , Walley Alexander Y.
Published: December 2024

Background

Traumatic brain injury (TBI) is common in people with substance use disorders (SUDs). TBI often results in cognitive deficits which can affect the clinical course of SUD.

Case presentation

Here we present the case of a 34-year-old Spanish-speaking man with severe opioid use disorder and two prior TBIs affecting his cognitive abilities. He was linked to outpatient addiction specialty care at a community health center. After identification of his TBI history, his care team, which included a language-concordant physician and peer recovery coach, worked to develop a treatment plan that accounted for his unique cognitive deficits and behavioral challenges. He was also connected with community resources including a rehabilitation program designed for people with TBI. These individualized aspects of treatment helped to better engage and retain the patient in quality care for his SUD.

Conclusions

By identifying TBI history in people with SUDs, the treatment plan can be tailored to accommodate TBI-related deficits. An effective care plan should incorporate not only medical providers, but also resources such as peer recovery supports and TBI-focused rehabilitation programs when and where they are available, with an emphasis on improving functional capacity.
AtGATA5 acts as a novel regulator in secondary cell wall biosynthesis by modulating NAC-domain transcription factors in Arabidopsis thaliana
Authors: Kim Byeonggyu , Kim Kihwan , Kim Won-Chan
Published: December 2024

The plant cell wall is composed of a primary and secondary cell wall. The secondary cell wall (SCW) plays a crucial role in the movement of nutrients and water and serves as a barrier against pathogens and environmental stresses. However, the biosynthesis of the SCW is complex, involving a network of genes regulated by environmental factors, including light. In this study, we investigated the nuclear localization of AtGATA5 to determine its potential role as a transcription factor and its involvement in SCW formation. To explore changes in leaf phenotypes in overexpression AtGATA5 and the thickening of interfascicular fiber cells, we conducted a transient activity assay using Arabidopsis protoplasts. The results demonstrated that AtGATA5 can up-regulate NAC-domain transcription factors, which are master regulators of the SCW biosynthesis pathway. Furthermore, gene expression analysis in plants confirmed that as AtGATA5 expression increased, the expression levels of NAC-domain transcription factors also increased. These findings suggest that AtGATA5 plays a functional role in SCW formation by up-regulating master regulators in the SCW biosynthesis pathway. Overall, AtGATA5 may act as a novel regulator of SCW biosynthesis, offering insights into potential application.
Data-driven material modeling based on the Constitutive Relation Error
Authors: Ladevèze Pierre , Chamoin Ludovic
Published: December 2024

Prior to any numerical development, the paper objective is to answer first to a fundamental question: what is the mathematical form of the most general data-driven constitutive model for stable materials, taking maximum account of knowledge from physics and materials science? Here we restrict ourselves to elasto-(visco-)plastic materials under the small displacement assumption. The experimental data consists of full-field measurements from a family of tested mechanical structures. In this framework, a general data-driven approach is proposed to learn the constitutive model (in terms of thermodynamic potentials) from data. A key element that defines the proposed data-driven approach is a tool: the Constitutive Relation Error (CRE); the data-driven model is then the minimizer of the CRE. A notable aspect of this procedure is that it leads to quasi-explicit formulations of the optimal constitutive model. Eventually, a modified Constitutive Relation Error is introduced to take measurement noise into account.
AXL in myeloid malignancies – an elusive target?
Authors: Aehnlich Pia , Leuchte Katharina , Schöllkopf Claudia , Salo Sara Fresnillo , Seremet Tina J. , Høgdall Estrid , Met Özcan , Grønbaek Kirsten , Straten Per thor
Published: December 2024

The TAM receptor tyrosine kinase family member AXL plays critical roles in tissue homeostasis, survival, chemoresistance, and motility. This study investigates the receptor expression in six AML cell lines and bone marrow myeloblasts from 25 patients with myeloid neoplasms. We found that AXL expression was generally absent or very low in AML myeloblasts. These findings suggest that the efficacy of AXL inhibitors may not depend on AXL positivity but rather on alternative therapeutic mechanisms, such as inducing significant immune responses.
Atomic oxygen ion retrieval from 630.0 nm airglow during geomagnetically quiet periods: a mid-latitude case study near Irkutsk
Authors: Duann Y. , Chang L. C. , Chiu Y.-C. , Salinas C. C. J. H. , Dmitriev A. V. , Ratovsky K. G. , Medvedeva I. V. , Vasilyev R. , Mikhalev A. V. , Liu J. Y. , Lin C. H. , Fang T.-W.
Published: December 2024

This study develops and validates three photochemical inversion models to retrieve atomic oxygen ion density ([O+]) profiles from 630.0 nm airglow emissions in the mid-latitude ionosphere during geomagnetically quiet period. Using passive ground-based instruments and empirical models, the models were tested and compared against electron density data from FORMOSAT-3/COSMIC (F3/C) and DPS-4 digisonde at Irkutsk. Among the models, Inversion Model 3 showed the strongest agreement with observations, particularly in capturing seasonal variations such as the June–July peak and a secondary March–April peak, which were absent in IRI-2012 predictions. These results highlight the potential of Inversion Model 3 for accurate [O+] retrieval, offering a novel approach for monitoring ionospheric variability using passive photometric observations.
Effect of El Niño on summer extreme ocean waves over East Asian regions
Authors: Bayhaqi Ahmad , Yoo Jeseon
Published: December 2024

Extreme wave events have had devastating impacts on East Asian (EA) coastal regions. However, despite being a prominent region for extreme waves due to the influence of anomalous seasonal atmospheric and remote climate variability, the investigation of EA extreme wave characteristics, such as duration and intensity, and their relation to the climate variability remains unclear. By applying the peaks-over-threshold (POT) method with a fixed threshold set at the 99th percentile, this study aims to quantify the duration and intensity of EA extreme wave events in boreal summer from 1980–2021 and investigates the influence of warm phase of El Niño-Southern Oscillation (ENSO, El Niño) and Pacific Decadal Oscillation (PDO) as the main climate mode in the Pacific Ocean. Spatially, the findings demonstrate that extreme waves have occurred with an intensity (the wave height above threshold) of up to 1.5 m, persisting for 8 to 35 h across the study area and revealing the significant area in the southern part of the region, impacting the southern coast of Korea. The area-averaged, calculated specifically for this significant area, indicate that the occurrence of El Niño induces longer (averaging 85 h) and more intense summer extreme waves, with a maximum intensity of 2 m. Furthermore, a positive PDO tends to strengthen the El Niño effect, with the almost doubled in duration, through strong anomalous anticyclonic formation in the Philippine Sea. The study findings enhance our understanding of the link between ENSO and TS activity with respect to extreme wave duration and intensity; these factors can be relevant in formulating plans for mitigating the impact of extreme wave events on coastal environments.
ZWDX: a global zenith wet delay forecasting model using XGBoost
Authors: Crocetti Laura , Schartner Matthias , Wareyka-Glaner Marcus Franz , Schindler Konrad , Soja Benedikt
Published: December 2024

Tropospheric delays play a crucial role for Global Navigation Satellite Systems (GNSS). They are a major error source in GNSS positioning and, at the same time, also a variable of interest in GNSS meteorology. Regardless of whether the delay shall be eliminated or inverted to atmospheric parameters, and no matter how this is done, it is of utmost importance to accurately determine tropospheric delays. In this study, we present a global zenith wet delay (ZWD) model, called ZWDX, that offers accurate spatial and temporal ZWD predictions at any desired location on Earth. ZWDX is based on the XGBoost algorithm and uses ZWDs measured at over 19,000 GNSS stations as reference. The inputs of ZWDX are the geographical location, observation time, and specific humidity at nine atmospheric pressure levels. For our study, we train the model on the years 2010 to 2021 and then test it for the year 2022. While ZWDX is trained to predict ZWD values based on specific humidity values from the ERA5 reanalysis, we show that it also delivers good predictions when applied to HRES specific humidity forecasts, making it suitable for (short-term) ZWD forecasting. The ZWDX model predictions are evaluated at 2500 globally distributed, spatio-temporally independent GNSS stations, with forecasting horizons ranging from 0 h to 48 h, and achieve root mean squared errors (RMSE) between 10.1 mm and 16.2 mm. To independently evaluate ZWDX’s performance and to demonstrate its potential for a real-world downstream task, we use its predictions as a-priori values for a precise point positioning (PPP) analysis and compare the results with those obtained using ZWD values from VMF1 or VMF3. We find that the highest accuracy and fastest convergence are indeed achieved with ZWDX.

Graphical Abstract
Formation of a magnetic duct by the compressional component of ULF oscillation: a ray tracing study of whistler-mode wave propagation
Authors: Tachi Kohki , Katoh Yuto
Published: December 2024

We investigate the propagation of whistler-mode waves in ultralow frequency (ULF) wave-derived magnetic ducts using ray tracing simulations in a two-dimensional dipole coordinate system on the meridian plane. The refractive index modulation caused by the ULF wave affects whistler-mode wave propagation. In this study, a magnetic duct structure at an L value (magnetic shell) of 6 is considered by a waveform of the fundamental mode with compressional and poloidal components. The total magnetic field strength increases depending on the ULF wave phase, forming duct structures that correspond to a decrease in the refractive index and vice versa. We model the refractive index distribution and compute the ray paths of whistler-mode waves under the settings of each ULF wave phase. We assume whistler-mode waves with a frequency of 20 or 70% of the electron gyrofrequency at the equator. The initial wave normal angle is 0 degrees at the equator. The results show duct propagation, while the frequency at which the ducting of whistler-mode waves switches with the duct structure varies with the ULF wave phase. The present study depicts the duct propagation caused by the ULF wave and suggests that ULF waves should cause spatial and temporal modulation of the whistler-mode wave via the duct propagation process. These features could help in the study of inner magnetospheric processes and aurora physics.

Graphical Abstract
A snapshot of cancer in Chile II: an update on research, strategies and analytical frameworks for equity, innovation and national development
Authors: Vacarezza Cristóbal , Araneda Julieta , Gonzalez Pamela , Arteaga Oscar , Marcelain Katherine , Castellon Enrique A. , Periera Ana , Khoury Maroun , Müller Bettina , Lecaros Juan Alberto , Salas Sofia P. , Riquelme Arnoldo , Corvalan Alejandro H. , de la Jara Jorge Jiménez , Ferreccio Catterina , Goic Carolina , Nervi Bruno , Roa Juan Carlos , Owen Gareth I.
Published: December 2024

Introduction

Chile has achieved developed nation status and boasts a life expectancy of 81 + years; however, the healthcare and research systems are unprepared for the social and economic burden of cancer. One decade ago, the authors put forward a comprehensive analysis of cancer infrastructure, together with a series of suggestions on research orientated political policy.

Objectives

Provide an update and comment on policy, infrastructure, gender equality, stakeholder participation and new challenges in national oncology. Assess the funding and distribution of cancer investigation. Present actions for the development of oncology research, innovation and patient care.

Methods

Triangulating objective system metrics of economic, epidemiological, private and public sector resources together with policy analysis, we assessed cancer burden, infrastructure, and investigation. We analyzed governmental and private-sector cancer databases, complemented by interviews with cancer stakeholders.

Results

Governmental policy and patient advocacy have led to the recognition of cancer burden, a cancer law, and a national cancer plan. Cancer has become the leading cause of death in Chile (59,876 cases and 31,440 cancer deaths in 2022), yet only 0.36% gross domestic product (GDP) is directed to research and development. Inequalities in treatment regimens persist. Prevention policy has lowered tobacco consumption, sugar intake via soft drinks and offered a high coverage of HPV vaccines. A high-quality cancer research community is expanding, and internationally sponsored clinical oncology trials are increasing.

Conclusions

The cancer law has facilitated advancement in policy. Prevention policies have impacted tobacco and sugar intake, while gender equality and care inequality have entered the public forum. Cancer research is stagnated by the lack of investment. Implementation of a cancer registry and biobanking, reinforcement of prevention strategies, development of human resources, promotion of clinical trial infrastructure and investment in new technologies must be placed as a priority to permit advancements in innovation and equitable cancer care.
Effects of pore water and pore air pressure on the slope failure mechanisms due to rainfall in centrifuge investigation
Authors: Cho May Than Thar , Sato Tomotaka , Saito Hirotaka , Izumi Akira , Kohgo Yuji
Published: December 2024

Background

The slope failures triggered by heavy rainfall are challenging to predict. However, their severe impact and potential for extensive damage emphasize the urgent need for effective strategies to mitigate these risks. This study aimed to investigate the effects of pore water pressures (PWPs) and pore air pressures (PAPs) on slope failure during heavy rainfall under centrifuge condition. Three centrifuge rainfall model tests were conducted with varying rainfall intensities (I) and relative densities (Dr). In this experiment, the slope model was subjected to a centrifugal acceleration of 30 G.

Results

In all cases, slope failures started at the slope toes when the PWPs became positive and phreatic surfaces appeared on the slope surface. In the Toyoura sand case, the PAPs increased slightly at the slope crest, hardly changed at the slope toe, and oscillated at the slope shoulder due to rainwater infiltration. The entire slope failure was observed in this case. In the Silica sand cases, only localized slope toe failures were observed. The PAPs slightly oscillated with small changes in the silica sand case with a relative density of Dr = 50%. However, in the case with a Dr = 25%, the PAPs at the slope toe significantly increased compared to the other parts, and the oscillations were comparatively large. After the first failure occurred at the slope toe in the silica sand case with a Dr = 25%, cracks and slip lines appeared at the slope crest.

Conclusions

The three cases illustrated the complex relationship between soil properties, rainfall intensity, and the dynamics of pore water and pore air pressure on slope stability during heavy rainfall. From the behaviour of PAPs and PWPs in all cases, it was found that the transition from air to water occurred smoothly, and the isolation of air was not observed even during heavy rainfall. Changes in PAPs were far smaller than those in PWPs, indicating a smaller impact on slope stability than PWPs.
Role of PD-1/PD-L1 signaling axis in oncogenesis and its targeting by bioactive natural compounds for cancer immunotherapy
Authors: Godiyal Yogesh , Maheshwari Drishti , Taniguchi Hiroaki , Zinzuwadia Shweta S. , Morera-Díaz Yanelys , Tewari Devesh , Bishayee Anupam
Published: December 2024

Cancer is a global health problem and one of the leading causes of mortality. Immune checkpoint inhibitors have revolutionized the field of oncology, emerging as a powerful treatment strategy. A key pathway that has garnered considerable attention is programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1). The interaction between PD-L1 expressed on tumor cells and PD-1 reduces the innate immune response and thus compromises the capability of the body’s immune system. Furthermore, it controls the phenotype and functionality of innate and adaptive immune components. A range of monoclonal antibodies, including avelumab, atezolizumab, camrelizumab, dostarlimab, durvalumab, sinitilimab, toripalimab, and zimberelimab, have been developed for targeting the interaction between PD-1 and PD-L1. These agents can induce a broad spectrum of autoimmune-like complications that may affect any organ system. Recent studies have focused on the effect of various natural compounds that inhibit immune checkpoints. This could contribute to the existing arsenal of anticancer drugs. Several bioactive natural agents have been shown to affect the PD-1/PD-L1 signaling axis, promoting tumor cell apoptosis, influencing cell proliferation, and eventually leading to tumor cell death and inhibiting cancer progression. However, there is a substantial knowledge gap regarding the role of different natural compounds targeting PD-1 in the context of cancer. Hence, this review aims to provide a common connection between PD-1/PD-L1 blockade and the anticancer effects of distinct natural molecules. Moreover, the primary focus will be on the underlying mechanism of action as well as the clinical efficacy of bioactive molecules. Current challenges along with the scope of future research directions targeting PD-1/PD-L1 interactions through natural substances are also discussed.
Clinical characteristics of patients requiring emergency hospitalization due to immune-related adverse events: a retrospective study
Authors: Ikeda Tatsuki , Nihei Satoru , Saito Kazuki , Asaka Junichi , Kudo Kenzo
Published: December 2024

Background

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, offering hope for various malignancies by enhancing the immune response against tumors. However, ICIs are associated with unique immune-related adverse events (irAEs), which differ significantly from conventional chemotherapy-induced toxicities. These irAEs, which affect more than 70% of patients and often escalate to severe grades, present substantial clinical management challenges and frequently necessitate emergency hospitalization. Therefore, this study aimed to investigate the clinical characteristics of patients requiring emergency hospitalization due to irAEs during ICI therapy to enhance understanding and improve management strategies.

Methods

This retrospective study evaluated patients who received ICIs at Iwate Medical University Hospital between August 1, 2016, and December 31, 2022, and required emergency hospitalization due to irAEs. Clinical data were extracted from the medical records, including patient demographics, presenting complaints, time from ICI initiation to hospitalization, irAE diagnoses, and treatment outcomes. The Spearman rank correlation coefficient was used to analyze the associations between the chief complaints and irAE diagnoses.

Results

Of 1009 ICI-treated patients, 96 required emergency hospitalization for irAEs. The cohort's mean age was 73 years, with 75.0% of patients being male. Among patients who required emergency hospitalization, a high proportion were undergoing treatment for lung cancer (41.7%). The median hospitalization duration was 87 days. The chief complaints included dyspnea (34.4%) and fatigue (34.4%), with gastrointestinal and respiratory disorders being the most frequent irAEs (35.4%). Significant correlations were observed between dyspnea and respiratory diseases (Rs = 0.66), skin diseases and disorders (Rs = 0.81), pain and musculoskeletal disorders (Rs = 0.59), and diarrhea and gastrointestinal disorders (Rs = 0.49). Corticosteroids were administered to 64.6% of the patients. Despite emergency interventions, 8.3% of patients succumbed to irAEs, while 33.3% resumed ICI therapy after hospitalization.

Conclusions

Emergency hospitalization due to irAEs is a considerable concern in ICI therapy, occurring in 9.5% of treated patients. The high incidence of severe irAEs within the first 3 months of treatment underscores the need for early and vigilant monitoring. This study highlights the importance of recognizing and promptly managing irAEs to improve patient outcomes. Future strategies should focus on developing comprehensive management frameworks and enhancing patient and caregiver education to recognize symptoms that warrant immediate medical attention.
From shared experiences of gendered racism to converging interpretations? Exploring the formation of a decolonial standpoint by women of Moroccan descent in postcolonial France
Authors: Sahraoui Nina
Published: December 2024

This article invites a dialogue between decolonial perspectives on diasporas and feminist standpoint theories by exploring processes of standpoint formation by women of Moroccan descent who grew up in postcolonial France. The article draws on 18 interviews with women aged in their 20s to their 40s, as well as a long-term engagement with these questions through ‘patchwork ethnography’. While emphasising that these women were neither exposed to identical experiences nor have the same worldviews, the article shows that they have navigated a set of shared experiences that pertain to their social position and that they are thus aware of the manifestations in their everyday lives and of the workings of gendered and racialised social hierarchies that affect them. The article explores participants’ experiences of racism and of its gendered inflections; the formation of ‘shared angles of visions’ (Hill Collins, 1997) around specific issues as a result; and finally, participants’ assessments of the different terms used to describe them in public and in everyday discourses. The article seeks to contribute to thinking through empirically the formation of an epistemological standpoint at the crossroads of feminist and decolonial approaches.