bluuebunny/crossref_metadata_2025_split huggingface dataset:
How effective psychological treatments work: mechanisms of change in cognitive behavioural therapy and beyond
Authors: Salkovskis Paul M. , Sighvatsson Magnus Blondahl , Sigurdsson Jon Fridrik 
Published: January 2024

AbstractBackground:Cognitive behavioural therapy (CBT) has, in the space of 50 years, evolved into the dominant modality in psychological therapy. Mechanism/s of change remain unclear, however.Aims:In this paper, we will describe key features of CBT that account for the pace of past and future developments, with a view to identifying candidates for mechanism of change. We also highlight the distinction between ‘common elements’ and ‘mechanisms of change’ in psychological treatment.Method:The history of how behaviour therapy and cognitive therapy developed are considered, culminating in the wide range of strategies which now fall under the heading of cognitive behavioural therapy (CBT). We consider how the empirical grounding of CBT has led to the massive proliferation of effective treatment strategies. We then consider the relationship between ‘common factors’ and ‘mechanisms of change’, and propose that a particular type of psychological flexibility is the mechanism of change not only in CBT but also effective psychological therapies in general.Conclusion:Good psychological therapies should ultimately involve supporting people experiencing psychological difficulties to understand where and how they have become ‘stuck’ in terms of factors involved in maintaining distress and impairment. A shared understanding is then evaluated and tested with the intention of empowering and enabling them to respond more flexibly and thereby reclaim their life.
Roadmaps to managed competition: to what extent does South Africa meet the preconditions for equity and efficiency?
Authors: van den Heever Alex 
Published: January 2024

Abstract
South Africa offers universal health coverage through large public and private systems. The private system is characterised by a regulated market for health insurance, referred to domestically as medical schemes. From 2000, the private system was undergoing a reform process consistent with theoretical approaches for regulated competition for health insurance. However, from 2008, the reform process was interrupted, leaving in place a partial framework which included open enrolment, community rating and regulated minimum benefits but excluded, inter alia, risk equalisation. The incomplete reform, however, provides an opportunity to examine the system outcomes that result from a partial approach. This paper therefore reviews the system outcomes of the partial reform using a descriptive data analysis. The findings then inform an evaluation of the extent to which the preconditions for regulated competition have been met as indicated by the theory of regulated competition in healthcare. The paper therefore highlights the areas where regulatory interventions need to be prioritised in South Africa to achieve the objectives of regulatory competition that are able to achieve access, fairness and efficiency. The analysis points to significant failures at the level of health insurance competition in South Africa with resulting outcomes consistent with the theory of regulated competition.
Norwegian Adolescents in the Initial Stages of COVID-19 Restrictions
Authors: Hygen Beate W. , Skalicka Vera , Coplan Robert J. , von Soest Tilmann , Fredriksen Eivor , Bekkhus Mona 
Published: January 2024

Abstract: In response to the COVID-19 pandemic outbreak in March 2020, the Norwegian government closed schools and limited leisure activities. In this cross-sectional study, we examined how different types of digital versus in-person social interactions and digital media use were associated with loneliness and mental health problems among adolescents during the initial COVID-19 lockdown. Participants ( N = 703, 79.7% girls , Mage = 17.3 years) completed a questionnaire assessing loneliness, mental health problems, digital media use, and in-person interactions. Both in-person and digital social interaction (texting) with friends were negatively associated with adolescents’ mental health problems and loneliness. By contrast, time spent alone on screen and on social media was positively related to mental health problems. The findings highlight that during the first weeks of the pandemic and of social distancing, increased interactions (either in-person or digital) among adolescents and their friends coincided with lower levels of mental health problems and less loneliness.
A Forecast Test for Reducing Dynamical Dimensionality of Model Emulators
Authors: Xu Tongtong , Newman Matthew , Alexander Michael A. , Capotondi Antonietta 
Published: January 2024

AbstractThe climate system can be numerically represented by a set of physically based dynamical equations whose solution requires substantial computational resources. This makes computationally efficient, low dimensional emulators that simulate trajectories of the underlying dynamical system an attractive alternative for model evaluation and diagnosis. We suggest that since such an emulator must adequately capture anomaly evolution, its construction should employ a grid search technique where maximum forecast skill determines the best reference model. In this study, we demonstrate this approach by testing different bases used to construct a Linear Inverse Model (LIM), a stochastically forced multivariate linear model that has often been used to represent the evolution of coarse‐grained climate anomalies in both models and observations. LIM state vectors are typically represented in a basis of the leading Empirical Orthogonal Functions (EOFs), but while dominant large‐scale climate variations often are captured by a subset of these statistical patterns, key precursor dynamics involving relatively small scales are not. An alternative approach is balanced truncation, where the dynamical system is transformed into its Hankel space, whose modes span both precursors and their subsequent responses. Constructing EOF‐ and Hankel‐based LIMs from monthly observed anomalous Pacific sea surface temperatures, both for the 150‐year observational record and a perfect model study using 600 years of LIM output, we find that no balanced truncation model of any dimension can outperform an EOF‐based LIM whose dimension is chosen to maximize independent skill. However, the dynamics of a high‐dimensional EOF‐based LIM can be efficiently reproduced by far fewer Hankel modes.
Properties of Intense H‐Band Electromagnetic Ion Cyclotron Waves: Implications for Quasi‐Linear, Nonlinear, and Nonresonant Wave‐Particle Interactions
Authors: Shi Xiaofei , Artemyev Anton , Zhang Xiao‐Jia , Mourenas Didier , An Xin , Angelopoulos Vassilis 
Published: January 2024

AbstractResonant interactions between relativistic electrons and electromagnetic ion cyclotron (EMIC) waves provide an effective loss mechanism for this important electron population in the outer radiation belt. The diffusive regime of electron scattering and loss has been well incorporated into radiation belt models within the framework of the quasi‐linear diffusion theory, whereas the nonlinear regime has been mostly studied with test particle simulations. There is also a less investigated, nonresonant regime of electron scattering by EMIC waves. All three regimes should be present, depending on the EMIC waves and ambient plasma properties, but the occurrence rates of these regimes have not been previously quantified. This study provides a statistical investigation of the most important EMIC wave‐packet characteristics for the diffusive, nonlinear, and nonresonant regimes of electron scattering. We utilize 3 years of observations to derive distributions of wave amplitudes, wave‐packet sizes, and rates of frequency variations within individual wave‐packets. We demonstrate that EMIC waves typically propagate as wave‐packets with ∼10 wave periods each, and that ∼3–10% of such wave‐packets can reach the regime of nonlinear resonant interaction with 2–6 MeV electrons. We show that EMIC frequency variations within wave‐packets reach 50–100% of the center frequency, corresponding to a significant high‐frequency tail in their wave power spectrum. We explore the consequences of these wave‐packet characteristics for high and low energy electron precipitation by H‐band EMIC waves and for the relative importance of quasi‐linear and nonlinear regimes of wave‐particle interactions.
Assessing Empirical Components in Wave Breaking and Rollers Through Model Comparison of Radiation Stress and Vortex Force
Authors: Wu Yuefeng , Wu Yongsheng , Zhang Qinghe , Ji Chao 
Published: January 2024

AbstractAs incoming waves approach shallow water, they break and result in nearshore currents. The assessment of the wave‐induced nearshore currents often relies on the application of radiation stress (RS) and vortex force (VF) in circulation models, both of which incorporate empirical components to describe wave breaking and wave rollers. In this study, we compared a recent 3D RS formulation and a VF formulation by assessing the modeled cross‐shore velocities against the measured counterparts from the LIP11D and Duck’94 experiments. The comparison results indicate that the RS model performs better in LIP11D, whereas the VF model exhibits better with respect to Duck’94. Using momentum balance analysis, we found that the cross‐shore velocities were dominated by the breaking term (representing the RS terms and non‐conservative breaking term in the RS and VF models, respectively) and the roller term. The breaking term generates undertow currents across the entire surf zone. The roller term cooperates with the breaking term in the inner surf zone, but counteracts the breaking term and tends to trigger unrealistic offshore currents at the water surface in the outer surf zone. Further analysis reveals that the RS and VF formulations can simulate almost identical velocity results by adjusting the vertical distribution of the breaking and roller terms. Overall, this study indicates that both the RS and VF formulations are effective in evaluating wave effects on the cross‐shore currents, and empirical components in the breaking and roller terms are important for modeling cross‐shore velocities.
Modification of immune cell-derived exosomes for enhanced cancer immunotherapy: current advances and therapeutic applications
Authors: Jung Inseong , Shin Sanghee , Baek Moon-Chang , Yea Kyungmoo 
Published: January 2024

AbstractCancer immunotherapy has revolutionized the approach to cancer treatment of malignant tumors by harnessing the body’s immune system to selectively target cancer cells. Despite remarkable advances, there are still challenges in achieving successful clinical responses. Recent evidence suggests that immune cell-derived exosomes modulate the immune system to generate effective antitumor immune responses, making them a cutting-edge therapeutic strategy. However, natural exosomes are limited in clinical application due to their low drug delivery efficiency and insufficient antitumor capacity. Technological advancements have allowed exosome modifications to magnify their intrinsic functions, load different therapeutic cargoes, and preferentially target tumor sites. These engineered exosomes exert potent antitumor effects and have great potential for cancer immunotherapy. In this review, we describe ingenious modification strategies to attain the desired performance. Moreover, we systematically summarize the tumor-controlling properties of engineered immune cell-derived exosomes in innate and adaptive immunity. Collectively, this review provides a comprehensive and intuitive guide for harnessing the potential of modified immune cell-derived exosome-based approaches, offering valuable strategies to enhance and optimize cancer immunotherapy.
Elevated expression of WSB2 degrades p53 and activates the IGFBP3-AKT-mTOR-dependent pathway to drive hepatocellular carcinoma
Authors: Li Xun , Zhang Cheng-Cheng , Lin Xiao-Tong , Zhang Jie , Zhang Yu-Jun , Yu Hong-Qiang , Liu Ze-Yu , Gong Yi , Zhang Lei-Da , Xie Chuan-Ming 
Published: January 2024

AbstractDysregulation of wild-type p53 turnover is a key cause of hepatocellular carcinoma (HCC), yet its mechanism remains poorly understood. Here, we report that WD repeat and SOCS box containing protein 2 (WSB2), an E3 ubiquitin ligase, is an independent adverse prognostic factor in HCC patients. WSB2 drives HCC tumorigenesis and lung metastasis in vitro and in vivo. Mechanistically, WSB2 is a new p53 destabilizer that promotes K48-linked p53 polyubiquitination at the Lys291 and Lys292 sites in HCC cells, leading to p53 proteasomal degradation. Degradation of p53 causes IGFBP3-dependent AKT/mTOR signaling activation. Furthermore, WSB2 was found to bind to the p53 tetramerization domain via its SOCS box domain. Targeting mTOR with everolimus, an oral drug, significantly blocked WSB2-triggered HCC tumorigenesis and metastasis in vivo. In clinical samples, high expression of WSB2 was associated with low wild-type p53 expression and high p-mTOR expression. These findings demonstrate that WSB2 is overexpressed and degrades wild-type p53 and then activates the IGFBP3-AKT/mTOR axis, leading to HCC tumorigenesis and lung metastasis, which indicates that targeting mTOR could be a new therapeutic strategy for HCC patients with high WSB2 expression and wild-type p53.
Current understanding of the Alzheimer’s disease-associated microbiome and therapeutic strategies
Authors: Seo Dong-oh , Holtzman David M. 
Published: January 2024

AbstractAlzheimer’s disease (AD) is a fatal progressive neurodegenerative disease. Despite tremendous research efforts to understand this complex disease, the exact pathophysiology of the disease is not completely clear. Recently, anti-Aβ antibodies have been shown to remove amyloid from the brain and slow the clinical progression of mild dementia by ~30%. However, exploring alternative strategies is crucial to understanding and developing more effective therapeutic interventions. In recent years, the microbiota-gut-brain axis has received significant attention in the AD field. Numerous studies have suggested that alterations in the gut microbiota composition are associated with the progression of AD, and several underlying mechanisms have been proposed. However, studies in this area are still in their infancy, and many aspects of this field are just beginning to be explored and understood. Gaining a deeper understanding of the intricate interactions and signaling pathways involved in the microbiota-AD interaction is crucial for optimizing therapeutic strategies targeting gut microbiota to positively impact AD. In this review, we aim to summarize the current understanding of the microbiota-gut-brain axis in AD. We will discuss the existing evidence regarding the role of gut microbiota in AD pathogenesis, suggested underlying mechanisms, biological factors influencing the microbiome-gut-brain axis in AD, and remaining questions in the field. Last, we will discuss potential therapeutic approaches to recondition the community of gut microbiota to alleviate disease progression. An ongoing exploration of the gut-brain axis and the development of microbiota-based therapies hold the potential for advancing AD management in the future.
Pathological phenotypes of astrocytes in Alzheimer’s disease
Authors: Kim Junhyung , Yoo Ik Dong , Lim Jaejoon , Moon Jong-Seok 
Published: January 2024

AbstractAstrocytes are involved in various processes in the central nervous system (CNS). As the most abundant cell type in the CNS, astrocytes play an essential role in neuronal maintenance and support, synaptic activity, neuronal metabolism, and amyloid-beta (Aβ) clearance. Alzheimer’s disease (AD) is a neurodegenerative disorder associated with cognitive and behavioral impairment. The transformation of astrocytes is involved in various neurodegenerative diseases, such as AD. Since astrocytes have functional diversity and morphological and physiological heterogeneity in the CNS, AD-related astrocytes might show various pathological phenotypes during AD. Astrocytes developing pathological phenotypes could contribute to AD progression. In this review, we provide an overview of the pathological phenotypes of astrocytes in the context of AD, highlighting recent findings in human and mouse AD.
Astrocytes in the adult dentate gyrus—balance between adult and developmental tasks
Authors: Chalmers Nicholas , Masouti Evangelia , Beckervordersandforth Ruth 
Published: January 2024

AbstractAstrocytes, a major glial cell type in the brain, are indispensable for the integration, maintenance and survival of neurons during development and adulthood. Both life phases make specific demands on the molecular and physiological properties of astrocytes, and most research projects traditionally focus on either developmental or adult astrocyte functions. In most brain regions, the generation of brain cells and the establishment of neural circuits ends with postnatal development. However, few neurogenic niches exist in the adult brain in which new neurons and glial cells are produced lifelong, and the integration of new cells into functional circuits represent a very special form of plasticity. Consequently, in the neurogenic niche, the astrocytes must be equipped to execute both mature and developmental tasks in order to integrate newborn neurons into the circuit and yet maintain overall homeostasis without affecting the preexisting neurons. In this review, we focus on astrocytes of the hippocampal dentate gyrus (DG), and discuss specific features of the astrocytic compartment that may allow the execution of both tasks. Firstly, astrocytes of the adult DG are molecularly, morphologically and functionally diverse, and the distinct astrocytes subtypes are characterized by their localization to DG layers. This spatial separation may lead to a functional specification of astrocytes subtypes according to the neuronal structures they are embedded in, hence a division of labor. Secondly, the astrocytic compartment is not static, but steadily increasing in numbers due to lifelong astrogenesis. Interestingly, astrogenesis can adapt to environmental and behavioral stimuli, revealing an unexpected astrocyte dynamic that allows the niche to adopt to changing demands. The diversity and dynamic of astrocytes in the adult DG implicate a vital contribution to hippocampal plasticity and represent an interesting model to uncover mechanisms how astrocytes simultaneously fulfill developmental and adult tasks.
Elevated CSF angiopoietin-2 correlates with blood-brain barrier leakiness and markers of neuronal injury in early Alzheimer’s disease
Authors: Van Hulle Carol , Ince Selvi , Okonkwo Ozioma C. , Bendlin Barbara B. , Johnson Sterling C. , Carlsson Cynthia M. , Asthana Sanjay , Love Seth , Blennow Kaj , Zetterberg Henrik , Scott Miners J. 
Published: January 2024

AbstractBreakdown of the neurovascular unit is associated with blood-brain barrier (BBB) leakiness contributing to cognitive decline and disease pathology in the early stages of Alzheimer’s disease (AD). Vascular stability depends on angiopoietin-1 (ANGPT-1) signalling, antagonised by angiopoietin-2 (ANGPT-2) expressed upon endothelial injury. We examined the relationship between CSF ANGPT-2 and CSF markers of BBB leakiness and core AD biomarkers across three independent cohorts: (i) 31 AD patients and 33 healthy controls grouped according to their biomarker profile (i.e., AD cases t-tau > 400 pg/mL, p-tau > 60 pg/mL and Aβ42 < 550 pg/mL); (ii) 121 participants in the Wisconsin Registry for Alzheimer’s Prevention or Wisconsin Alzheimer’s Disease Research study (84 participants cognitively unimpaired (CU) enriched for a parental history of AD, 20 participants with mild cognitive impairment (MCI), and 17 with AD); (iii) a neurologically normal cohort aged 23–78 years with paired CSF and serum samples. CSF ANGPT-2, sPDGFRβ, albumin and fibrinogen levels were measured by sandwich ELISA. In cohort (i), CSF ANGPT-2 was elevated in AD and correlated with CSF t-tau and p-tau181 but not Aβ42. ANGPT-2 also correlated positively with CSF sPDGFRβ and fibrinogen – markers of pericyte injury and BBB leakiness. In cohort (ii), CSF ANGPT-2 was highest in MCI and correlated with CSF albumin in the CU and MCI cohorts but not in AD. CSF ANGPT-2 also correlated with CSF t-tau and p-tau and with markers of neuronal injury (neurogranin and α-synuclein) and neuroinflammation (GFAP and YKL-40). In cohort (iii), CSF ANGPT-2 correlated strongly with the CSF/serum albumin ratio. Serum ANGPT-2 showed non-significant positive associations with CSF ANGPT-2 and the CSF/serum albumin ratio. Together, these data indicate that CSF and possibly serum ANGPT-2 is associated with BBB leakiness in early AD and is closely related to tau pathology and neuronal injury. The utility of serum ANGPT-2 as a biomarker of BBB damage in AD requires further study.
Protein tyrosine phosphatase PTPRO represses lung adenocarcinoma progression by inducing mitochondria-dependent apoptosis and restraining tumor metastasis
Authors: Dai Yuan , Shi Shuangshuang , Liu Hongda , Zhou Hong , Ding Wenqiu , Liu Chenyang , Jin Linling , Xie Weiping , Kong Hui , Zhang Qun 
Published: January 2024

AbstractEmerging evidence indicates that protein activities regulated by receptor protein tyrosine phosphatases (RPTPs) are crucial for a variety of cellular processes, such as proliferation, apoptosis, and immunological response. Protein tyrosine phosphatase receptor type O (PTPRO), an RPTP, has been revealed as a putative suppressor in the development of particular tumors. However, the function and the underlying mechanisms of PTPRO in regulating of lung adenocarcinoma (LUAD) are not well understood. In this view, the present work investigated the role of PTPRO in LUAD. Analysis of 90 pairs of clinical LUAD specimens revealed significantly lower PTPRO levels in LUAD compared with adjacent non-tumor tissue, as well as a negative correlation of PTPRO expression with tumor size and TNM stage. Survival analyses demonstrated that PTPRO level can help stratify the prognosis of LUAD patients. Furthermore, PTPRO overexpression was found to suppress the progression of LUAD both in vitro and in vivo by inducing cell death via mitochondria-dependent apoptosis, downregulating protein expression of molecules (Bcl-2, Bax, caspase 3, cleaved-caspase 3/9, cleaved-PARP and Bid) essential in cell survival. Additionally, PTPRO decreased LUAD migration and invasion by regulating proteins involved in the epithelial-to-mesenchymal transition (E-cadherin, N-cadherin, and Snail). Moreover, PTPRO was shown to restrain JAK2/STAT3 signaling pathways. Expression of PTPRO was negatively correlated with p-JAK2, p-STAT3, Bcl-2, and Snail levels in LUAD tumor samples. Furthermore, the anti-tumor effect of PTPRO in LUAD was significant but compromised in STAT3-deficient cells. These data support the remarkable suppressive role of PTPRO in LUAD, which may represent a viable therapeutic target for LUAD patients.