bluuebunny/crossref_metadata_2025 huggingface dataset:
Dual-Nuclide Biodistribution and Therapeutic Evaluation of a Novel Antibody-Based Radiopharmaceutical in Anaplastic Thyroid Cancer Xenografts
Authors: Lundgren Mortensen Anja Charlotte. , Berglund Hanna , Jha Preeti , Stenman Adam , Selvaraju Ram Kumar , Lundqvist Hans , Hofström Camilla , Persson Helena , Juhlin C. Christofer , Zedenius Jan , Frejd Fredrik Y. , Nestor Marika
Published: February 2025

Anaplastic thyroid cancer (ATC) is a rare but severe form of thyroid cancer responsible for approximately 50% of thyroid cancer deaths. Consequently, the identification of innovative therapies remains crucial for the effective treatment of ATC. Molecular radiotherapy is a rapidly growing field within oncology and the cell surface antigen CD44v6, which is overexpressed in several cancers, is a plausible target for molecular radiotherapy of ATC. Immunohistochemistry (IHC) of 39 ATC patient samples were evaluated for CD44v6 expression. Biodistribution and dosimetry of 125I/177Lu-labeled UU-40, a CD44v6 specific antibody, followed by in vivo efficacy in two ATC xenograft models with varying target expression levels (ACT-1 and BHT-101) accompanied by SPECT-imaging evaluated radiolabeled UU-40 for therapeutic efficiency in ATC xenografts. The IHC revealed CD44v6 immunoreactivity in 46% of ATC patient samples. The biodistribution favored 177LuUU-40 over the 125I-labeled antibody and confirmed in vivo specificity of both radioconjugates. The in vivo efficacy and accompanied SPECT imaging of a moderate CD44v6-expressing xenograft model (BHT-101) verified the tumor specificity as well as the target-specific effect of 177Lu -UU-40 on tumor growth and survival. A 100% complete response rate was demonstrated as a result of therapy using a single dose of 16 MBq 177Lu -UU-40 in a high CD44v6-expressing xenograft model (ACT-1), and SPECT-imaging revealed excellent tumor uptake of the radioconjugate at 14 days post-injection. This study verifies the expression of CD44v6 in ATC and cements the superiority and promise of 177Lu -UU-40 over 131I-UU-40 for antibody-based molecular radiotherapy of CD44v6-positive ATC.
A checkpoint reversal receptor mediates bipartite activation and enhances
CAR T-cell function
Authors: Landi Daniel , Navai Shoba A. , Brock Rebecca M. , Fousek Kristen , Nawas Zeid , Sanber Khaled , Chauvin-Fleurence Cynthia , Bhat Raksha R. , Xu Shuo , Krishnamurthy Purna , Choe Michelle , Campbell Matthew , Morris Jessica S. , Gad Ahmed Z. , Shree Ankita , Echeandia Alesandra , Saadeldin Amr , Matthew Pretty R. , Mullikin Dolores , Bielamowicz Kevin , Kurenbekova Lyazat , Major Angela M. , Salsman Vita S. , Byrd Tiara T. , Hicks M. John , Zhang Yi Jonathan. , Yustein Jason , Carisey Alexandre F. , Joseph Sujith K. , Ahmed Nabil , Hegde Meenakshi
Published: February 2025

The efficacy of CAR T-cells (CART) in solid tumors is limited by immune inhibition. In our study, we observed that effector cytokines mediated the upregulation of the PD-L1 immune-checkpoint in primary glioblastoma (GBM). To offset the PD-L1 inhibitory signal, we engineered PD-1 checkpoint reversal receptors (CPR) with a CD28 or 41BB co-stimulatory endodomain and co-expressed them with a first-generation or a CD28-containing second-generation HER2-specific CAR (CPR/CART) using bicistronic vectors. We found that bipartite T-cell activation, by CAR-generated signal 1 and CPR co-stimulation (signal 2), fine-tuned pro-inflammatory cytokine release and sustained antitumor activity. While both CPR28 and CPR41BB effectively counteracted the PD-1 signal in vitro, CPR41BB, when co-expressed with a first-generation CAR (CARζ/CPR41BB), promoted central memory differentiation following repeat antigenic stimulation. CARζ/CPR41BB T-cells formed a robust immune synapse with tumor targets, similar to a 4-1BB-containing second-generation CART, maintained the favorable metabolic parameters associated with 4-1BB co-stimulation, and demonstrated superior antitumor function after adoptive transfer in xenograft models of GBM and metastatic osteosarcoma. Thus, a CPR molecule with 4-1BB co-stimulation that curtails PD-1 inhibition and complements CAR signaling to optimize T-cell activation could enhance CART efficacy against solid tumors.
TRPV4 Promotes Vascular Calcification by Directly Associating With and Activating β-Catenin
Authors: Yuan Menglu , Li Qi , Wang Zhiwei , Liu Liangju , Wen Chengyuan , Liu Guizhu , Yu Fan , Feng Lei , Yang Liu
Published: February 2025

BACKGROUND:

Vascular calcification contributes to increased cardiovascular morbidity and mortality in patients with chronic kidney disease, diabetes, and atherosclerosis. Currently, there are no effective therapeutic strategies to prevent or reverse vascular calcification. TRPV4 (transient receptor potential channel V4), a key Ca
2+
-permeable channel, plays an important role in various diseases. However, the role and mechanism of TRPV4 in vascular calcification have not yet been elucidated.

METHODS:

The effects of TRPV4 on vascular calcification were explored in vitro and in vivo. TRPV4 interactome assessment and molecular docking were performed to investigate the mechanism and specific therapeutic strategy for vascular calcification.

RESULTS:

TRPV4 was substantially upregulated in high inorganic phosphate–induced calcified vascular smooth muscle cells (SMCs) and calcified aortas from cholecalciferol (vitamin D3)-overloaded mice. TRPV4 overexpression increased the expression of the osteochondrogenic markers Runx2 (runt-related transcription factor 2), Msx2 (Msh homeobox 2), and Sox9 (SRY-box transcription factor 9) and exacerbated high inorganic phosphate–induced vascular SMC calcification in a Ca
2+
influx–dependent manner. In contrast, TRPV4 deficiency or inactivation significantly inhibited vascular SMC calcification under high inorganic phosphate conditions. Moreover, compared with that in control littermates, SMC-specific TRPV4 deficiency in mice alleviated vitamin D3–induced and 5/6 nephrectomy–induced vascular calcification. Mechanistically, TRPV4 interacted with β-catenin and activated β-catenin/TCF (T-cell factor) transcriptional activity via Ca
2+
/ASK1 (apoptosis signal regulating kinase 1)/p38 signaling. β-Catenin knockdown abolished the effects of TRPV4 overexpression on vascular SMC calcification. TRPV4/β-catenin interaction is pivotal for maintaining TRPV4/Ca
2+
-induced ASK1/p38/β-catenin activation. Hesperidin, a natural product found in citrus fruits, effectively disrupted TRPV4/β-catenin interaction, thereby inhibiting ASK1/p38/β-catenin activity and preventing vascular calcification.

CONCLUSIONS:

Our study identified TRPV4 as a new pathogenic factor for vascular calcification that directly associates with and activates β-catenin. Blocking the TRPV4/β-catenin interaction through hesperidin suppressed the progression of vascular calcification and may be an effective precision strategy to address vascular calcification.
SRSF4-Associated ca-circFOXP1 Regulates Hypoxia-Induced PASMC Proliferation by the Formation of R Loop With Host Gene
Authors: Song Xinyue , Xu Ya , Li Mengnan , Guan Xiaoyu , Liu Huiyu , Zhang Jingya , Sun Hanliang , Ma Cui , Zhang Lixin , Zhao Xijuan , Zheng Xiaodong , Zhu Daling
Published: February 2025

BACKGROUND:

Pulmonary hypertension (PH) is a rare and fatal disease, the pathological changes of which include pulmonary arterial smooth muscle cell (PASMC) proliferation, which is the pathological basis of pulmonary vascular remodeling. Studies have demonstrated that chromatin-associated circRNA can regulate a variety of biological processes, including PASMC proliferation in patients with hypoxic PH. However, the role of chromatin-associated circRNA in the proliferation of PH remains largely unexplored. In this study, we aimed to identify the function and mechanism of chromatin-associated circRNA in PASMC proliferation in PH.

METHODS:

The role of ca-circFOXP1 was investigated in hypoxic mouse PASMCs and SuHX (Sugen5416+hypoxia) model mice through the use of antisense oligonucleotide knockdown and adeno-associated virus–mediated knockdown. Through bioinformatic sequence alignment, chromatin isolation by RNA purification, Cell Counting Kit 8, 5-ethynyl-2-deoxyuridine, Western blot, and other experiments, the function and mechanism of ca-circFOXP1 were verified.

RESULTS:

The expression of ca-circFOXP1 was found to be significantly increased in SuHX model mice and hypoxic mouse PASMCs. Moreover, ca-circFOXP1 was found to regulate the level of the host protein FOXP1 (forkhead box protein 1) through the R loop, thereby influencing the phosphorylation activity of SMAD2 (SMAD family member 2) and, consequently, the proliferation of mouse PASMCs. It is noteworthy that the m6A modification was found to promote the formation of the R loop between ca-circFOXP1 and the host gene
FOXP1
, thereby regulating the expression of the host protein. Furthermore, we have identified that the splicing factor SRSF4 (serine/arginine rich splicing factor 4) can upregulate the expression of ca-circFOXP1 by splicing exons 6 and 9 of FOXP1 pre-mRNA.

CONCLUSIONS:

The results demonstrated that the splicing factor SRSF4 upregulated the expression of ca-circFOXP1, and m6A methylation promoted R-loop formation between ca-circFOXP1 and host genes, regulated the level of host protein FOXP1, and then affected the phosphorylation activity of SMAD2, mediating PASMC proliferation, leading to pulmonary vascular remodeling. These results provide a theoretical basis for further study of the pathological mechanisms of hypoxic PH and may provide certain insights.
Independent External Evaluation of Pediatric Hypertrophic Cardiomyopathy Risk Scores in Predicting Severe Ventricular Arrhythmias
Authors: Wilkin Marie , Khraiche Diala , Panaioli Elena , Pontailler Margaux , Raisky Olivier , Marijon Eloi , Bonnet Damien , Waldmann Victor
Published: February 2025

BACKGROUND:

Sudden cardiac death is the most common cause of death in childhood hypertrophic cardiomyopathy (HCM). Recently, 2 risk scores have been developed to estimate the 5-year risk of sudden cardiac death. We aimed to assess their respective performances in an independent cohort.

METHODS:

All patients with HCM aged <18 years from a single center were retrospectively included between 2003 and 2023. HCM Risk-Kids and PRIMaCY risk scores were calculated at diagnosis and during follow-up. The primary composite outcome included sustained ventricular arrhythmia, appropriate implantable cardioverter defibrillator (ICD) therapy, aborted cardiac arrest, or sudden cardiac death.

RESULTS:

A total of 100 primary prevention children were included (7.1±5.6 years, 59.0% males), with a mean follow-up of 8.6±5.5 years. Overall, 13 (13.0%) patients experienced the primary composite outcome. When only considering events during the 5 first years, Harrel C index was 0.52 (95% CI, 0.27–0.77) for HCM Risk-Kids (≥6%) and 0.70 (95% CI, 0.59–0.80) for PRIMaCY (>8.3%), with 1 patient potentially treated by ICD for every 25 ICDs implanted for HCM Risk-Kids and 1 for every 14 ICDs implanted for PRIMaCY. When risk scores were repeated and all primary outcomes during follow-up were considered, 12 of 13 (92.3%) events were correctly identified using both risk scores, with 1 patient potentially treated by ICD for every 5.6 ICDs implanted for HCM Risk-Kids and 1 for every 5.3 ICDs implanted for PRIMaCY. Among 44 (44.0%) patients implanted with an ICD, all primary prevention patients who had ≥1 appropriate ICD therapy during follow-up had an HCM Risk-Kids ≥6% and PRIMaCY >8.3% at implantation.

CONCLUSIONS:

In this independent evaluation, our findings suggest imperfect discrimination between low and high-risk patients using the HCM Risk-Kids and PRIMaCY risk scores, with predicted risks tending to be overestimated compared with the actual observed events. The performance or risk scores was substantially improved by periodic reassessment during follow-up.
P-NP instance decomposition based on the Fourier transform for solving the Linear Ordering Problem
Authors: Benavides Xabier , Hernando Leticia , Ceberio Josu , Lozano Jose A.
Published: February 2025

The Fourier transform over finite groups has proved to be a useful tool for analyzing combinatorial optimization problems. However, few heuristic and meta-heuristic algorithms have been proposed in the literature that utilize the information provided by this technique to guide the search process. In this work, we attempt to address this research gap by considering the case study of the Linear Ordering Problem (LOP).

Based on the Fourier transform, we propose an instance decomposition strategy that divides any LOP instance into the sum of two LOP instances associated with a P and an NP-Hard optimization problem. By linearly aggregating the instances obtained from the decomposition, it is possible to create artificial instances with modified proportions of the P and NP-Hard components. Conducted experiments show that increasing the weight of the P component leads to a less rugged fitness landscape suitable for local search-based optimization. We take advantage of this phenomenon by presenting a new meta-heuristic algorithm called P-Descent Search (PDS). The proposed method, first, optimizes a surrogate instance with a high proportion of the P component, and then, gradually increases the weight of the NP-Hard component until the original instance is reached. The multi-start version of PDS shows a promising and predictable performance that appears to be correlated to specific characteristics of the problem, which could open the door to an automatic tuning of its hyper-parameters.
Impacts of Climate Change and Population Pressure on Food Consumption Patterns and Economic Consequence
Authors: Lakew Hermela , Bahta Yonas , Ogundeji Abiodun , Sebastian Yong
Published: February 2025

There are discernible trends in severe food insecurity prevalence among the adult population in sub-Saharan Africa. This study delves into the complex interactions of climate change impacts, agricultural factor productivity and changes in population growth, which together exacerbate the issue of food insecurity. To comprehend these intertwined effects on rural and urban food insecurity, we employed the Rural Investment and Policy Analysis data and Computable General Equilibrium modelling system developed by the International Food Policy Research Institute. Our findings revealed a decline in urban food consumption associated with increased urban population and decreased agricultural total factor productivity. However, we observed a slight increase in real consumption for rural households. Our analysis indicates a contraction in the economy and a disruption in the volume of international trade. This research contributes valuable insights into the multifaceted challenges sub-Saharan Africa faces in its pursuit of food security, enabling policymakers to construct informed decisions and design effective interventions.
The Kitāb al-Aṣl of Muḥammad b. al-Ḥasan al-Shaybānī (d. 189/805) and its Riwāyas (Recensions)
Authors: Tsafrir Nurit
Published: February 2025

This essay is a preliminary study of some aspects of the transmission of Kitāb al-Aṣl by Muḥammad b. al-Ḥasan al-Shaybānī. The essay examines information, preserved in later, mainly Ḥanafī works, about two major riwāyas of al-Aṣl, and analyses some points of doctrine on which they differ. These differences are shown to be substantial, as emerges from biographical sources. Given the divergence from each other and also, in one instance, from a third riwāya, I propose that the two riwāyas do not represent the content of a single original text. They may reflect either different stages in the development of a text that was still fluid, or else doctrinal changes that were introduced into a fixed text by its transmitters. The disparity between the riwāyas must be taken into consideration in any attempt to reconstruct the teachings and history of Kitāb al-Aṣl.
“Overcoming the Slumps in Performance”: Metacognition, Grit and Self-Efficacy in Sports among Athletes
Authors: Pandey Kashish , K Khusboo
Published: February 2025

Predictably, millions of dollars get invested in sport science by the federation for impeccable performance of an athlete. However, there is a gap which exist to understand the nature of cognitive-motion nexus in sports with regard to performance. Hence, this systematic review synthesized evidence on the influence of metacognition, grit and self-efficacy on performance in sport domain using PRISMA guidelines. A search of Web of Science, PubMed, Google Scholar, PsycINFO and Scopus databases reaped 26 eligible studies. Findings were classified into three domains namely metacognitive inferences, feedback for grit and role of self-efficacy. Grit is positively correlated with metacognition and self-efficacy. We conclude by encouraging the sports system to foster the skills of these constructs.
From an Object to a Tool: On Possible Transformations of Analysis of the Border Problem
Authors: Zaporowski Andrzej
Published: February 2025

The article addresses the border as an object and yet a tool found in the cultural realm, where the object is approached in three stages. Firstly, the border problem is given the form of an assembled representation, and which becomes an object of one’s reflection. Secondly, this object turns into an obstacle as one faces both the abstract and the concrete references of the representation in question. Thirdly, this obstacle requires some steps to cope with it by one; one becomes a user of the assembled representation, where the object becomes a tool. The divisions suggested by the representation are conditioned by means of the cultural actions. Culture as a set of particular attitudes like belief, intention and assessment allows of approaching the border as both an object and a tool, where not only manipulation but also responsibility and creativity is crucial.
Metaphysics of Soul, Universal Spirit, and Consciousness
Authors: Holsapple Ryan J.
Published: February 2025

Jon Mills’ and Erik Goodwyn’s (2023) work Archetypal Origins establishes a foundation for ongoing dialogue about metaphysical origins for Jungian Psychology. This article explores tensions within their work, particularly concerning consciousness, agency, and the ontological status of matter. Examining Goodwyn’s cosmopsychism, it problematizes its treatment of matter and suggests an alternative framework. Retaining some of Goodwyn’s key themes of holism and formal cause, this variation of ontological idealism gives consciousness more primacy. The proposal suggests Universal Spirit as non-local absolute consciousness and Soul as a localized projection within the appearance of spacetime.
Innovative Capacity in Triple Helix Partnerships: an Assessment of Conditions for Social Learning
Authors: Mudde Huub L. M. , Chekole Alemfrie Derese , Lauer Madeleine
Published: February 2025

The Triple Helix (3H) model has attracted considerable attention in both developed and emerging economies as a tool to enhance innovation for economic development (Etzkowitz and Leydesdorff, 2000). This article examines the assumption underlying the triple helix that the exchange of diverse knowledge between academia, industry, and government stimulates innovativeness. The research underlying this article investigates whether and how learning is facilitated by triple helix based on a case study of three partnerships established by the Bright Future in Agriculture project in Ethiopia. Data was gathered from 57 respondents through in-depth interviews and surveys. The findings show that participant’s learning has taken place due to a more diverse and relevant network, but that 3H partnerships are not by default catalysts for innovation. The authors argue that this would need purposeful orchestration. This study further supports the plea in literature for quadruple or even quintuple helix models, being more apt as inclusive networks for learning and innovation.
New Histories of the Old Left
Authors: Wald Alan M.
Published: February 2025

The United States Communist Party (cp-USA) is a subject rooted in an ample storehouse of research; one chock-full of many confirmable facts amassed by several cohorts of competent academics. At the same time, three new histories demonstrate that polarizing divergencies in perspective and evaluation have never been quelled and continue to emerge. Maurice Isserman’s Reds: The Tragedy of American Communism is a substantially sobering work because the problems in cp-USA history it aspires to tackle are disturbingly real. The other two books, by Robert Cherny and Denise Lynn, are more upbeat, depicting a movement full of charismatic activists who express a resolute political commitment and a willingness to devote themselves to admirable causes. Nevertheless, what stands out after a close, comparative reading of all three volumes is how each historian can curate the archive according to his or her individualized needs; all three smooth contradictions, diminish some aspects and valorize others, and implicitly assign a politically motivated cognitive frame to structure the reader’s perception.
An Act of Infinite Love
Authors: Umbelino Luís António
Published: February 2025

To what extent do we depend on ourselves? The crucial point of this question, constantly asked by Maine de Biran, is that from the point of view of “spiritual life” an “explicit” answer is not really needed: the mystery of what supports us will be solved by a vertical dimension of feeling that welcomes, at the limit of a radical kind of passivity, an act of infinite love – as if one were connected to a divine Presence. In this paper I will try to show in what sense “love” is, according to Biran, the fundamental principle of “spiritual life” and to what extent such a concept can help us understand the fundamental coherence of Maine de Biran’s philosophical path.
On the Body as a Site of Inscription of Colonial Domination: a Visualisation of Colonial Hierarchy in Labour and Porter Scenes in German Cameroon
Authors: Nkouda Sopgui Romuald Valentin
Published: February 2025

The main argument underpinning this reflection is that the German colonies were increasingly present in the media, photographically, during the Empire. Pictures showed what they looked like, what was growing there, what the living conditions were like and what the colonial administration seemed to be achieving. The aim of this article is to examine the visual mediatisation of colonial relations of domination. My interest is to examine colonial practices of domination as they can be seen in colonial images. Using the example of German colonial images in Cameroon that have labour and porter scenes as their motif, the article shows that the body of the colonised was a place where colonial power was expressed or inscribed. In so doing, colonial labour and porter scenes locate colonialism as hegemonic inscription of Foucauldian power/knowledge on the colonised body.
Declining Labour and Strengthening Capital: an Analysis of the ilo Wage Report and ituc Rights Index
Authors: Bellucci Stefano
Published: February 2025

The Global Wage Report and the Global Rights Index are published by the International Labour Organization (ilo) in Geneva and the International Trade Union Confederation (ituc) in Brussels. This article analyses the global data and results presented by these publications and explains how they portray the ineluctable deterioration of workers’ wages and labour rights within the capitalist mode of production. Capitalism implies a tendency towards the dissolution of labour rights and super-exploitation (with wages closer to and below subsistence level). Trade unions’ struggle for labour rights and the improvement of workers’ material conditions and wages only makes sense in relation to a struggle against absolute capitalism.
Is There a (Pre)Trial Penalty? Assessing the Joint Impacts of Pretrial Detention and Trial Conviction on Sentencing
Authors: St. Louis Stacie , Bolton Marlena G. , Petersen Nick
Published: February 2025

This study examines the joint sentencing penalty experienced by defendants detained pretrial and convicted via jury trial. The focal concerns and cumulative disadvantage frameworks suggest these defendants are sentenced most severely because early case decisions make them appear especially culpable, dangerous, and irredeemable during later case decisions. We use propensity-score regression analyses to test this hypothesis, analyzing data on defendants processed in urban jurisdictions over two decades. Findings provide evidence of a (pre)trial penalty. Detained defendants convicted via jury trials have the highest probability of being sentenced to prison and are sentenced to the longest prison and jail terms, net of numerous controls. Moreover, detained defendants’ guilty plea discounts are generally similar in magnitude to released defendants’ trial penalties.
Short Horizon for Audit Partner and Audit Quality: Evidence From a Dual-Rotation Regime
Authors: Mazza Tatiana , Azzali Stefano , Reichelt Kenneth J. , Fornaciari Luca
Published: February 2025

Our study examines how a short audit partner horizon affects audit quality. A short audit partner horizon originates from the joint requirement of mandatory audit firm rotation and mandatory audit partner rotation. We study a unique setting in Italy where a 9-year mandatory firm rotation term and a 7-year mandatory partner rotation term are jointly imposed. The outcome is at least two partner horizons, where one partner horizon is shorter than the other. We predict that the partner with the shorter horizon will likely invest less effort in acquiring client knowledge. Namely, the expected payoffs are fewer, tacit knowledge is not sufficiently transferred from the previous partner, and monitoring by the successor partner is insufficient. We find that clients whose auditors have a shorter partner horizon are associated with lower audit quality. Our findings provide insights for academics, audit firms, and regulators in evaluating auditor rotation strategies in their countries, especially in the European Union, where member states have mandatory audit partner and audit firm rotation.

JEL codes: M42 and M48
Benefits of a physics-driven interdisciplinary final project for mechanical engineering undergraduates
Authors: Persano Adorno Dominique , Pizzolato Nicola
Published: February 2025

In the context of higher education, the call for interdisciplinary learning is becoming increasingly imperative. This holds especially true for fields like Mechanical Engineering, where complex challenges often transcend the boundaries of traditional disciplines. On the other hand, active learning activities promote curiosity, enjoyment, and interest. An interdisciplinary final project with an 'active' approach creates an opportunity for students to integrate and apply knowledge across multiple subject areas. In this contribution, we discuss the results obtained in the Bachelor of Mechanical Engineering of the University of Palermo (Italy) in the last three years, since the Bachelor's degree candidates have had the possibility to choose an interdisciplinary final project, showing that it offers a myriad of advantages that not only prepare students for real-world scenarios but also foster innovation and holistic problem-solving skills. By exposing students to interdisciplinary challenges, these projects ensure that graduates are equipped to navigate the complexities of emerging technologies and adapt to changing industry dynamics. The challenges and possibilities of these self-directed thinking are also discussed.
A Mendelian randomization approach for advancing healthcare innovation: From pregnancy hypertension to schizophrenia
Authors: Peng Wenjie , Ran Qingqi , Wu Fang , Hu Zhangxue
Published: February 2025

Background

Schizophrenia, a severe mental disorder, is strongly associated with perinatal factors, including pregnancy hypertension, which affects fetal neurodevelopment. The causal relationship between pregnancy hypertension and schizophrenia remains unclear.

Objective

To investigate the causal relationship between pregnancy hypertension and schizophrenia using a two-sample Mendelian randomization (MR) study.

Methods

Pregnancy hypertension (cases/controls: 7686/115,8993) was considered as exposure and schizophrenia (cases/controls: 76755/243,649) as outcome. A two-sample MR study genetically estimated associations, with the inverse variance-weighted method as primary analysis. A two-step MR study explored potential mediators. Sensitivity tests assessed pleiotropy, heterogeneity, and stability.

Results

Four single nucleotide polymorphisms (SNPs) were identified as genetic instruments for pregnancy hypertension (P < 5 × 10-8, r² < 0.001). Pregnancy hypertension increased the risk of schizophrenia (odds ratio = 1.098, 95% CI = 1.025–1.173, P = 0.007), while reverse MR analysis found no significant link (odds ratio = 1.03, 95% CI = 0.980–1.082, P = 0.235). The two-step study revealed pregnancy hypertension elevated levels of 1,4-Dihydroxy-2-naphthoic acid (odds ratio = 1.351, 95% CI = 1.097–1.664, P = 0.004), which decreased schizophrenia risk (odds ratio = 0.97, 95% CI = 0.942–0.998, P = 0.040).

Conclusion

Pregnancy hypertension is a high-risk factor for schizophrenia, with 1,4-Dihydroxy-2-naphthoic acid potentially mitigating this effect. These findings offer insights for the prophylaxis of schizophrenia and highlight the need for further research into underlying mechanisms.
Efficacy of a Combined Aerobic Exercise and Mindfulness Intervention on Depressive Symptoms: A Pilot Randomized Controlled Trial
Authors: Wei Xiaoqi , Li Hehui , Jia Yuncheng , Qu Diyang , Chen Sitong , Huang Liuyue , Chen Shiyun , Bu He , LeMoult Joelle , Zieff Gabriel , Lin Li , Chi Xinli
Published: February 2025

Purpose: The current study aimed to preliminarily examine the effectiveness and acceptability of a combined exercise + mindfulness intervention on depressive symptoms among healthy Chinese university students (study 1) and those with subthreshold depression (study 2). Methods: Two 2 (intervention group vs. control group) × 2 (pretest vs. posttest) randomized controlled trials were conducted in healthy students without subthreshold depression and students with subthreshold depression, respectively. Description analysis, linear mixed-effects models, and qualitative analysis were used in both studies. Results: Results of both studies showed that the combined intervention was acceptable and effective in preventing and reducing depressive symptoms, with small effect sizes for healthy students ( d = −0.47) and large effect sizes for subthreshold depression students ( d = −1.51), respectively. Conclusions: The aerobic exercise plus mindfulness intervention was evidenced to be a preventive and therapeutic measure of depressive symptoms among university students.
Assessment of the quality and reliability of Turkish YouTube videos on frozen shoulder exercises
Authors: Tuna Mustafa , Ay Bilgehan Kolutek
Published: February 2025

Purpose

This study aimed to evaluate the reliability and quality of Turkish videos about frozen shoulder exercises published on the Youtube platform.

Material-Method

54 videos were included in the study as a result of searches and evaluations made on the YouTube platform using the keywords “frozen shoulder exercises” and “adhesive capsulitis exercises”. The included videos were evaluated by two independent observers and a final independent 3rd observer, and the given modified DISCERN (mDISCERN), Global Quality Scale (GQS) and JAMA scores were compared with other video parameters. Differences between groups were examined.

Result

Exercises were detected in 10 different categories in the 54 videos included in the study. In the examination made according to GQS scoring, a statistically significant relationship was found between the viewing rate, mDISCERN and JAMA scores, the number of exercise types included in the video and the GQS quality grouping (p < 0.05). In the examination conducted in terms of reliability, a statistically significant relationship was found between mDISCERN scores and the number of exercise types included in the videos, JAMA and GQS scores (p < 0.05).

Conclusion

In our study, more than half of the frozen shoulder exercise videos on the Youtube platform were found to be low in reliability and quality. Due to the variety of content in the videos and the lack of individualized exercises, YouTube does not appear to be a suitable resource for frozen shoulder exercises. Considering all these, we believe that videos with informative content should be created by physicians or should be audited.
“RIP TOP G:” Rhetoric, Responses, and Realities Surrounding the Social Media Ban of Andrew Tate
Authors: Smith Camden R. , Brammer Sydney E. , Cloudy Joshua , Essary Ch’Ree , Pérez Carolina
Published: February 2025

This study explores the rhetoric used by Andrew Tate, known as a ‘misogyny influencer’, and its impact on his followers. Tate released a vlog in response to his ban from social media. This vlog was analyzed along with his followers’ comments ( n = 300) on the video. Through hegemonic masculinity and social identity frameworks, we offer a thematic analysis of Tate's rhetoric. Results contribute to the growing body of literature on online manospheric communities and why followers may be drawn to Tate's leadership styles. Findings also extend literature regarding themes that may appear in other radicalized spaces.
Mapping contextual data
Authors: Tatari Maryam
Published: February 2025

The proliferating platformization and digital transformation require designing and deploying suitable research methods and approaches to address the hybrid nature of actors, relations, practices, and the growing importance of the context. This paper explores the design of such a tailored methodology for investigating the value-driven development of online public service media platforms in Germany. While qualitative methodologies are time- and resource-consuming and digital methods leave out less context to the field, this mixed methodology emphasizes the context and invests in collecting thick data. It encompasses multiple stages of recording and mapping that employ qualitative and quantitative approaches to bring together various vignettes, unveiling complementary context and contradictory accounts with the help of visualization. In each mapping and visualization stage, the paper investigates actors and relationships heuristically and emphasizes the work-in-progress nature of mapping regarding platforms.
Privacy protection technology in e-commerce based on dilated convolution network model
Authors: Huang Furong
Published: February 2025

This paper aims to investigate and advance the privacy protection techniques within the e-commerce domain by leveraging the dilated convolutional network (DCN) model. It endeavors to elevate the safeguarding of user data privacy to a higher level of security. The study introduces a privacy protection methodology grounded on the DCN model. Firstly, it delves into an analysis of the threats and attack vectors concerning privacy security in e-commerce settings. Subsequently, it devises a network model integrating DCN, attention mechanism, and gating mechanism, tailored to fortify the privacy of user data. Additionally, the paper incorporates advanced technologies such as differential privacy and encryption algorithms to augment the data’s privacy protection capabilities. Finally, this paper uses the actual e-commerce dataset for experimental evaluation and compares the method proposed in this paper with other common privacy protection methods. The experimental results show that (1) the privacy protection technology based on the DCN model proposed in this paper has obvious advantages in reconstruction error, information utilization efficiency, and model efficiency. (2) The overall performance (accuracy, recall, and F1 value) of the privacy protection technology based on the DCN model proposed in this paper is better than that of the comparison method. The experimental findings outlined above underscore the promising potential and advantages of the DCN model in enhancing privacy protection within e-commerce platforms. This paper presents a robust privacy protection technology tailored for e-commerce platforms, which serves to bolster user trust and elevate the overall level of data privacy protection.
Researching With Young Nigerian Girls Trafficked Into Commercial Sex Exploitation in Northern Ghana: Reflections on Methodological and Ethical Challenges and Mitigation Strategies
Authors: Musah Baba Iddrisu , Mohammed Abdul-Rahim , Mahmoud Bayan
Published: February 2025

There have been calls for researchers, especially within the qualitative paradigm, to document and discuss the challenges they experience on the field while researching sensitive topics or with vulnerable groups, as failure to do so creates a missed opportunity for researchers to learn from one another. Accordingly, in this article, we reflect on the several layers of fieldwork challenges we experienced while researching with a vulnerable group (young Nigerian girls trafficked into northern Ghana) on a sensitive topic (commercial sexual exploitation). The reflections on the methodological and ethical challenges in this paper are drawn from a wider qualitative study conducted by the authors to explore the factors predicting the trafficking of young Nigerian girls into commercial sexual exploitation in Ghana’s Tamale Metropolitan area. The sensitive nature of the topic, coupled with the “invisible” manner in which the victims operate in Tamale, naturally raises many ethical and methodological challenges for researchers. The article discusses four main challenges the authors encountered in the field: (i) Accessing Hard-to-Reach Participants, (ii) Ethical Dilemmas in Consent: Demands for Payment, (iii) Trust-Building Strategies, and (iv) Researching in Risky Environments. The paper also discusses the approaches used to surmount these challenges.
The Essential Oils of Litsea cubeba (Lour.) Pers. Fruit Extracted from Different Temperature Ranges Exhibit Distinct Chemical Compositions and Biologic Activities
Authors: Chung Jeng-Der , Chang Chao Lin , Kung Fang-Xian , Guo Jia-You , Huang Yu-Ping , Wang Heng-Long , Pai Hsiu-Hua
Published: February 2025

Objective: This study presents a stepwise-heating hydrodistillation to collect the fruit of Litsea cubeba essential oil (EO) from different temperature ranges. The differences between the qualitative and quantitative properties of these EOs and the effects of these differences on the antioxidant and antibacterial activity of the EOs were investigated. Methods: The chemical composition of EOs was analysed by means of Gas Chromatography-Mass Spectroscopy analysis (GC-MS); moreover, 2,2-diphenyl-1-picrylhydrazyl (DPPH) was made to evaluate the antioxidant activity. In addition, disk diffusion method and minimum inhibitory concentration (MIC) were employed to evaluate the antimicrobial activities against Staphylococcus aureus and Escherichia coli. Results: The total yield of EO was 4.95% (v/w), with the EO collected at 95 °C to 98 °C (LCF-1), 98 °C to 99 °C (LCF-2), and 99 °C to 100 °C (LCF-3) accounting for 8.60%, 84.83%, and 6.53% of this yield, respectively. A total of 14, 17, and 19 compounds were identified, representing 98.17%, 98.69%, and 97.52% of the total oil content of LCF-1, LCF-2, and LCF-3, respectively. These fractions primarily contained limonene (11.46%−31.57%), neral (19.75%−33.57%), and geranial (24.63%−40.38%). LCF-3 had the highest 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, LCF-2 had the strongest inhibitory effect on S. aureus growth, and LCF-1 and LCF-2 had a stronger ability to inhibit E. coli than did LCF-3. In addition to the 3 main ingredients aforementioned, some minor components, such as verbenol, β-caryophyllene, and α-pinene that may also affect the antibacterial and antioxidant activities of these EO fractions. Conclusion: The study demonstrated that the different in the qualitative and quantitative components of EOs of Litsea cubeba fruit extracted from three temperature ranges, resulting in exhibiting the distinct expression of antioxidative and antibacterial activities of three EO fractions. Therefore, this paper provides an innovative extraction strategy for EOs to recover the EO in specific temperature range according to the biological activity required.
Interlocutors for decolonial logics
Authors: Barrera de la Torre Gerónimo
Published: February 2025

In this commentary, I respond to Gibson's paper, calling for a thorough and robust engagement across political ecologies with the idea of interlocution-dialogues. Drawing on the work critiques from decolonial and postcolonial geographies, I argue that our focus on dialogues represents a significant epistemic move away from the logical, analytical enclosure explored by Gibson in her article. This shift becomes pivotal in questioning the practices and unremembering that pervades the participatory turn. Furthermore, paying attention to the immaterial actors and the representational aporia has become critical within the interlocution/dialogue framework, evidencing the need to expand methodological approaches to unmap the paths shaped by coloniality.
Sleep as a window of cardiometabolic health: The potential of digital sleep and circadian biomarkers
Authors: van den Brink Willem J , Oosterman Johanneke E , Smid Dagmar J , de Vries Herman J , Atsma Douwe E , Overeem Sebastiaan , Wopereis Suzan
Published: February 2025

Digital biomarkers are quantifiable and objective indicators of a person's physiological function, behavioral state or treatment response, that can be captured using connected sensor technologies such as wearable devices and mobile apps. We envision that continuous and 24-h monitoring of the underlying physiological and behavioral processes through digital biomarkers can enhance early diagnostics, disease management, and self-care of cardiometabolic diseases. Cardiometabolic diseases, which include a combination of cardiovascular and metabolic disorders, represent an emerging global health threat. The prevention potential of cardiometabolic diseases is around 80%, indicating a promising role for interventions in the lifestyle and/or the environmental context. Disruption of sleep and circadian rhythms are increasingly recognized as risk factors for cardiometabolic disease. Digital biomarkers can be used to measure around the clock, that is, day and night, to quantify not only sleep patterns but also diurnal fluctuations of certain biomarkers and processes. In this way, digital biomarkers can support the delivery of optimal timed medical care. Night-time cardiometabolic patterns, such as blood pressure dipping, are predictive of cardiometabolic health outcomes. In addition, the sleep period provides an opportunity for digital cardiometabolic health monitoring with relatively low influence of artifacts, such as physical activity and eating. Digital biomarkers that utilize sleep as a window of health can be used during daily life to enable early diagnosis of cardiometabolic diseases, facilitate remote patient monitoring, and support self-management in people with cardiometabolic diseases. This review describes the influence of sleep and circadian rhythms on cardiometabolic disease and highlights the state-of-the-art sleep and circadian digital biomarkers which could be of benefit in the prevention of cardiometabolic disease.
Percutaneous Transluminal Renal Artery Stenting in Takayasu Arteritis: A Reversible Cause of Young Hypertension
Authors: Kumar Basant , Bose Arghadip , Nema Rahul
Published: February 2025

Renal artery involvement is commonly seen in Takayasu arteritis (TA) and patients often present with renovascular hypertension resistant to conventional antihypertensive therapy. Early initiation of immunosuppressive therapy with corticosteroids is the mainstay of treatment during active disease. Percutaneous transluminal renal angioplasty has emerged as a preferred mode of revascularization for renal artery stenosis during inactive disease primarily due to its safety, efficacy, and promising long-term outcomes. This report describes a young girl with TA with right atretic renal artery and severe stenosis of the ostial left renal artery who presented with uncontrolled hypertension and was successfully treated with percutaneous angioplasty. The utility of fractional flow reserve in TA-induced renal artery stenosis has also been emphasized.
Surface pTα expression predicts LCK activation and preclinical synergy of LCK and JAK coinhibition in adult T-ALL
Authors: Courtois Lucien , Pinton Antoine , Cabannes-Hamy Aurelie , Simonin Mathieu , Andrieu Guillaume P. , Queri Mélodie , Smith Charlotte , Charbonnier Guillaume , Dourthe Marie-Emilie , Courgeon Marianne , Huré Grégoire , Gaidot Nicolas , Macintyre Elizabeth A. , Dombret Hervé , Baruchel André , Boissel Nicolas , Touzart Aurore , Lhermitte Ludovic , Rousselot Philippe , Asnafi Vahid
Published: February 2025

Refractory and/or relapsing T-cell acute lymphoblastic leukemia (T-ALL) remains a major therapeutic challenge. The pre-TCR pathway has recently emerged as a therapeutic target via LCK inhibition in this context. However, there is a need for simple and quickly assessable biomarkers to predict sensitivity to LCK inhibitors. Moreover, targeting LCK alone by tyrosine kinase inhibitors, such as Dasatinib, often results in transient clinical responses, emphasizing the need for efficient combination strategies. Here, we assessed pre-TCR alpha chain (pTα) surface expression by flow cytometry in a unique series of 50 adult T-ALL patient-derived xenografts (PDX). We show that cases displaying a cortical phenotype often express high levels of surface pTα (pre-TCR+ T-ALL) and that the latter associates with LCK activation. Furthermore, we show that ectopic interleukin-7 receptor (IL-7R) expression can rescue pre-TCR+ T-ALL from Dasatinib cytotoxicity (5 PDX). We tested whether co-inhibition of pre-TCR and IL-7R signaling pathways could be synergetic in pre-TCR+ IL-7R+ T-ALL (11 PDX). Combination of JAK-inhibitors, Ruxolitinib or Tofacitinib, with Dasatinib elicited strong and specific synergy in IL-7R+ pre-TCR+ T-ALL in vitro, including in the relapse setting (4/28 patient-derived primary samples). Using 3 adult-PDX models, we show that in vivo treatment with this combination significantly delayed leukemic progression and prolonged survival compared to either monotherapy. This preclinical study thus proposes the use of pTα as a biomarker of LCK-inhibitor sensitivity in T-ALL, and suggests that dual targeting of IL-7R and pre-TCR signaling pathways may be a relevant therapeutic strategy in a substantial proportion of adult T-ALL.
Radiation symptoms resemble laminopathies and the physical underlying cause may sit at the lamin A C-terminus
Authors: Waldherr Alexandra , Fogtman Anna
Published: February 2025

Ionizing radiation causes three divergent effects in the human body: On one side, tissue death (= deterministic effects) sets on, on the other side, mutations and cancer growth (= stochastic effects) can occur. In recent years, the additional phenomenon of accelerated aging has come to light. In the following, we argue that these seemingly contradictory radiation responses namely: (i) increased cancer growth, (ii) ablation of cancer tissue or (iii) deterministic senescence, share an underlying cause from damage at the lamin A C-terminus. In other words, besides the typically described genomic radiation impact, we propose an additional destabilization pathway via oxidation at the nuclear envelope. We propose five concrete hypotheses that draw a direct mechanistic model from radiation damage and cellular oxidative stress, to micronuclei and clinical symptoms. In conjunction with lamin B compensation, we might be able to explain why deterministic or stochastic responses dominate. If our model holds true, a novel target for radiotherapeutics and radiooncology arises, and a rationale to closer connect laminopathy and radioprotection research.

Graphical Abstract