bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of iron deficiency anemia with dental caries in the permanent first molars of children aged 7–12 years in Karachi, Sindh, Pakistan: protocol for an analytical cross-sectional study
Authors: Syed Sadaf , Azam Iqbal , Jamalvi Waseem Ahmed , Khan Farhan Raza , Saleem Ali Faisal , Tikmani Shiyam S 
Published: January 2025

IntroductionIron deficiency anaemia (IDA) and dental caries are prevalent diseases among Pakistani children. Limited research has been done to explore their association with permanent teeth. Given the caries susceptibility of permanent first molars and their role in the development of ideal occlusion, this study aimed to estimate caries frequency in these molars and assess its association with IDA in 7–12 year-old children.Methods and analysisThis analytical cross-sectional study will include 141 children aged 7–12 years visiting physicians in the paediatric OPD of Dr. Ruth K.M. Pfau, Civil Hospital Karachi. Using consecutive sampling, children who met initial screening criteria were further evaluated to determine eligibility for the study. Data collection will involve physical examinations (including weight and height), oral examinations (including the relevant oral hygiene and caries assessments) and laboratory examinations (including the prescribed tests). In addition, questions will be asked about sociodemographic characteristics, history of IDA, oral hygiene habits, smokeless tobacco use and the frequency of cariogenic dietary consumption. Exposure variable will include the presence of IDA, assessed using complete blood count, C-reactive protein and ferritin tests and treated as a dichotomous variable. Outcome variable will include dental caries in at least one permanent first molar, assessed using the Decayed, Missing, and Filled Teeth index and also treated as a dichotomous variable. Analysis will include Poisson regression with robust variance, reporting prevalence ratios with 95% CIs for the association of IDA and dental caries in the permanent first molars. Frequency of children with carious permanent first molars with 95% CIs will also be reported.Ethics and disseminationThis research has been approved by ethical review committee of Aga Khan University (Reference number: 2024-9692-30593) and the institutional review board of Dow University of Health Sciences (IRB Reference: IRB-3556/DUHS/Approval/2024/196) before participant recruitment. Results will be disseminated through seminars and peer-reviewed publications.
Durvalumab and tremelimumab in combination with metronomic oral vinorelbine for recurrent advanced cervical cancer: an open-label phase I/II study
Authors: Frenel Jean-Sébastien , Mathiot Laurent , Cropet Claire , Borcoman Edith , Hervieu Alice , Coquan Elodie , De La Motte Rouge Thibault , Saada-Bouzid Esma , Sabatier Renaud , Lavaud Pernelle , Jimenez Marta , Legrand François , Le Saux Olivia , Charafe Emmanuelle , Gonçalves Anthony 
Published: January 2025

BackgroundThe MOVIE phase I/II trial (NCT03518606) evaluated the safety and antitumor activity of durvalumab and tremelimumab combined with metronomic oral vinorelbine in patients with advanced tumors. We present the results of the recurrent advanced cervical cancer cohort.MethodsPatients received tremelimumab (intravenously, 75 mg, every four weeks (Q4W); four cycles max) plus durvalumab (intravenously, 1,500 mg, Q4W; 26 cycles max) and metronomic oral vinorelbine (40 mg, every three weeks (3QW)) until disease progression. The primary efficacy endpoint was the clinical benefit rate (CBR) based on the Response Evaluation Criteria in Solid Tumors V.1.1, which was analyzed using a Bayesian approachResultsA total of 31 patients were enrolled and treated in the cervical cancer cohort. The median number of previous lines of chemotherapy for advanced disease was 2 (0–6), with all (100%) and 12 (38.7%) patients pretreated with cisplatin and bevacizumab, respectively. At the data cut-off, the median follow-up duration was 12.8 (Q1–Q3, 6.1–34.6) months. The CBR was 53.1% (95% CI, 36.0% to 69.8%), using a non-informative prior distribution (beta(1, 1)). The overall response rate was 41.9%, five patients achieved a complete response (16.1%), and eight patients (25.8%) had a partial response irrespective of histological subtype or programmed death-ligand 1 (PD-L1) expression. Of the 31 patients, 28 (90.3%) experienced treatment-related adverse events (TRAEs), 13 (41.9%) reported grade ≥3 immune-related adverse events (AEs), and 13 (41.9%) reported grade ≥3 chemotherapy-related AEs. The definitive discontinuation rate due to TRAEs was 16.1%.ConclusionsDual checkpoint blockade of PD-L1 and cytotoxic T-lymphocyte-associated antigen-4 combined with metronomic oral vinorelbine demonstrated meaningful and durable clinical activity in patients with previously treated advanced cervical cancer. Toxicity was significant but manageable.
Safety and efficacy of the therapeutic DNA-based vaccine VB10.16 in combination with atezolizumab in persistent, recurrent or metastatic HPV16-positive cervical cancer: a multicenter, single-arm phase 2a study
Authors: Hillemanns Peter , Zikan Michal , Forget Frédéric , Denys Hannelore G , Baurain Jean-Francois , Rob Lukas , Woelber Linn , Blecharz Pawel , Bidzinski Mariusz , Chovanec Josef , Marmé Frederik , Link Theresa , Dannecker Christian , Rosholm Anders , Berg Kaja C G , Oliveri Roberto S , Lindemann Kristina 
Published: January 2025

BackgroundSecond-line treatment options for persistent, recurrent or metastatic (r/m) cervical cancer are limited. We investigated the safety, efficacy, and immunogenicity of the therapeutic DNA-based vaccine VB10.16 combined with the immune checkpoint inhibitor atezolizumab in patients with human papillomavirus (HPV)16-positive r/m cervical cancer.Patients and methodsThis multicenter, single-arm, phase 2a study (NCT04405349, registered 26 May 2020) enrolled adult patients with persistent, r/m HPV16-positive cervical cancer. Patients received 3 mg VB10.16 (every 3 weeks (Q3W) for 12 weeks, hereafter every 6 weeks) combined with 1,200 mg atezolizumab (Q3W) for 48 weeks in total with a 12-month follow-up. The primary endpoints were incidence and severity of adverse events (AEs) and objective response rate (ORR; Response Evaluation Criteria in Solid Tumor V.1.1). ORR was assessed in the efficacy population, being all response-evaluable patients who received any administration of VB10.16 and atezolizumab and had at least one post-baseline imaging assessment.ResultsBetween June 16, 2020, and January 25, 2022, 52 patients received at least one administration of study treatment. Of these, 47 patients had a minimum of one post-baseline tumor assessment. The median follow-up time for survival was 11.7 months. AEs related to VB10.16 were non-serious and mainly mild injection site reactions (9 of 52 patients). There were no signs of new toxicities other than what was already described with atezolizumab. ORR was 19.1% (95% CI 9.1% to 33.3%). Median duration of response was not reached (n.r.) (95% CI 2.2 to n.r.), median progression-free survival was 4.1 months (95% CI 2.1 to 6.2), and median overall survival was 21.3 months (95% CI 8.5 to n.r.). In programmed death-ligand 1 (PD-L1)-positive patients (n=24), ORR was 29.2% (95% CI 12.6 to 51.1). HPV16-specific T-cell responses were analyzed in 36 of 47 patients with an increase observed in 22/36 (61%).ConclusionsThe therapeutic DNA-based vaccine VB10.16 combined with atezolizumab was safe and well tolerated showing a promising clinically meaningful efficacy with durable responses in patients with persistent, r/m HPV16-positive cervical cancer, especially if PD-L1-positive.
Extending the European Competence Framework for Quantum Technologies: new proficiency triangle and qualification profiles
Authors: Greinert Franziska , Goorney Simon , Hilfert-Rüppell Dagmar , Ubben Malte S. , Müller Rainer 
Published: January 2025

AbstractWith the increasing industrial relevance of quantum technologies (QTs), a new quantum workforce with special qualification will be needed. Building this workforce requires educational efforts, ranging from short term training to degree programs. In order to plan, map and compare such efforts, personal qualifications or job requirements, standardization is necessary. The European Competence Framework for Quantum Technologies (CFQT) provides a common language for QT education. The 2024 update to version 2.5 extends it by the new proficiency triangle and qualification profiles: The proficiency triangle proposes six proficiency levels for three proficiency areas, specifying knowledge and skills for each level. Nine qualification profiles show prototypical qualifications or job roles relevant to the quantum industry, with the required proficiency, examples, and suggestions. This is an important step towards the standardization of QT education. The CFQT update is based on the results of an analysis of 34 interviews on industry needs. The initial findings from the interviews were complemented by iterative refinement and expert consultation.
Flavonoids of Tetrastigma hemsleyanum Diels et Gilg Against Acute Hepatic Injury by Blocking PI3K/AKT Signaling Pathway
Authors: Li Lingling , Zhan Lianghui , Wu Xiaojun , Jiang Xuechun , Pu Jinbao 
Published: January 2025

Objective: This study aims to investigate the mechanism of Tetrastigma hemsleyanum Diels et Gilg flavonoids (THF) on acute hepatic injury (AHI).Methods: First, high‐performance liquid chromatography (HPLC) fingerprints were established to obtain the main chemical components of THF. According to the network pharmacology databases, collect active targets of AHI and potential targets. Using interaction targets to construct a protein–protein interaction (PPI) network, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, the affinity between the core targets and the main active ingredients was verified by molecular docking. Next, verified network pharmacology predictions with animal experiments. Mice were treated with THF (20, 40, and 80 mg/kg) for 7 days, and then built an acute liver injury model (lipopolysaccharide [LPS], 10 mg/kg). Detecting the liver biochemical indices, observe the liver pathological changes, and verify the key signaling pathway targets.Results: HPLC showed that the main components of THF were quercetin and kaempferol. Seven active ingredients and 193 potential targets were screened, and 259 disease targets related to acute liver injury, quercetin, and kaempferol may be the main active ingredients in THF. PPI network analysis showed that tumor necrosis factor (TNF), interleukin‐6 (IL‐6), and tumor protein 53 (TP53) were potential targets of THF for the treatment of AHI. KEGG analysis showed that the phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT) signaling pathway might be one of the main pathways in the treatment of AHI. The molecular docking results showed that active compounds both have strong binding activity with potential targets in PPI. In vivo experiments showed that THF could reduce the fibrosis and inflammation of liver tissue etc. Meanwhile, it could downregulate the alanine aminotransferase (ALT), aspartate aminotransferase (AST), IL‐6, tumor necrosis factor alpha (TNF‐α), C‐reactive protein (CRP) levels, and the protein expressions of phosphorylated phosphoinositide 3‐kinase (p‐PI3K), phosphorylated protein kinase B (p‐AKT), and the ratio of BCL2‐associated X (BAX)/B‐cell lymphoma‐2 (BCL‐2) in the liver tissue of the mice with acute liver injury and upregulate the level of interleukin‐10 (IL‐10).Conclusion: The treatment of acute liver injury with THF is characterized by multicomponents and multitargets, and its mechanism may be related to the alleviation of the inflammatory response, reduction of apoptosis, and regulation of the PI3K/AKT signaling pathway.
The spatial organization of cDC1 with CD8+ T cells is critical for the response to immune checkpoint inhibitors in melanoma patients
Authors: Gobbini Elisa , Hubert Margaux , Doffin Anne-Claire , Eberhardt Anais , Hermet Léo , Li Danlin , Duplouye Pierre , Ghamry-Barrin Sarah , Berthet Justine , Benboubker Valentin , Grimont Maxime , Sakref Candice , Perrot Jimmy , Tondeur Garance , Harou Olivier , Lopez Jonathan , Dubois Bertrand , Dalle Stephane , Caux Christophe , Caramel Julie , Valladeau-Guilemond Jenny 
Published: January 2025

Abstract
Dendritic cells (DCs) are promising targets for cancer immunotherapies because of their central role in the initiation and control of immune responses. The rare cDC1 population is of particular interest because of its remarkable ability to cross-present antigens (Ag) to CD8+ T cells, to promote Th1 cell polarization and NK cell activation and recruitment. However, the spatial organization and specific functions of cDC1s in response to immunotherapy remain to be clearly characterized in human tumors. Here, we implemented a multiplexed immunofluorescence analysis pipeline coupled with computational image analysis to determine the spatial organization of the cDC1 subset in a cohort of skin lesions from advanced melanoma patients treated with immune checkpoint inhibitors (ICI). For this, we performed a whole-slide image analysis of cDC1 infiltration and distribution as well as their spatial interactions with key immune partners such as CD8+ T cells and pDC according to the response of patients to ICI. We also analyzed LAMP3+-DC, which correspond to a mature subset of tumor-infiltrating DCs. Distance and cell network analyses demonstrated that cDC1s exhibited a scattered distribution compared to tumor-infiltrating pDCs and LAMP3+-DCs, which were preferentially organized in dense areas with high homotypic connections. Interestingly, the proximity and interactions between CD8+ T cells and cDC1s were positively associated with the response to ICI. In conclusion, our study unravels the complex spatial organization of cDC1s and their interactions with CD8+ T cells in melanoma patient lesions, shedding light on their pivotal role in shaping the response to ICI.
Trabectedin enhances the antitumor effects of IL-12 in triple-negative breast cancer
Authors: Schwarz Emily , Savardekar Himanshu , Zelinskas Sara , Mouse Abigail , Lapurga Gabriella , Lyberger Justin , Rivaldi Adithe , Ringwalt Emily M. , Miller Katherine E. , Yu Lianbo , Behbehani Gregory K. , Cripe Timothy P. , Carson William E. 
Published: January 2025

Abstract
Interleukin-12 (IL-12) is a potent NK cell–stimulating cytokine, but the presence of immunosuppressive myeloid cells such as myeloid-derived suppressor cells (MDSC) can inhibit IL 12-induced NK-cell cytotoxicity. Thus, we hypothesized that trabectedin, a myeloid cell–depleting agent, would improve the efficacy of IL-12 in triple-negative breast cancer (TNBC). In vitro treatment of healthy donor NK cells with trabectedin increased expression of the activation marker CD69 and mRNA expression of T BET (Tbx21), the cytotoxic ligands TRAIL (TNFSF10) and Fas ligand (FASLG) and the dendritic cell (DC)–recruiting chemokine lymphotactin (XCL1). The combination of IL-12 and trabectedin increased NK-cell cytotoxicity, activation and production of IFN-γ, TNF-α and granzyme B in the presence of human TNBC cells. Treatment of 4T1 and EMT6 tumor-bearing mice with IL-12 and trabectedin led to a significant reduction in tumor burden compared to single-agent controls, and the highest levels of plasma IFN-γ, intratumoral CD8+ T cells and conventional type 1 DC. MDSC and M2-like macrophages were significantly decreased with combination therapy. NK-cell depletion abrogated the effects of combination therapy, as did elimination of CD8+ T cells. NK-cell depletion led to lower levels of the NK cell–derived chemokine CCL5 and the DC-derived chemokine CXCL10, higher tumor burden, and decreased intratumoral CD8+ T cells. IL 12 and trabectedin also significantly enhanced the response of TNBC to anti-PD-L1 therapy. These data suggest that MDSC depletion augments the ability of IL-12-activated NK cells to drive the infiltration of DC and CD8+ T cells into TNBC for an antitumor effect.
Inhibition of thalamic relay nuclei scales the aperiodic and alpha band oscillations associated with arousal during naturalistic stimulus viewing
Authors: Borah Ritu M. , Pathak Anagh , Banerjee Arpan 
Published: January 2025

Abstract
Existing psychological theories posit valence and arousal as two dimensions along which subjective emotions’ states are represented. The present study sought to determine whether the emotional ratings projected along the valence–arousal axis during naturalistic stimulus viewing are further mapped in the neurodynamical attributes observed from noninvasive electroencephalography (EEG) in humans and their potential biophysical causes. While several studies have explored the periodic features of EEG dynamics of emotion processing, very few studies have previously explored the aperiodic (1/f) components vis-à-vis emotion arousal. Recent signal processing developments have established that segregating EEG time series into aperiodic and periodic components provides fundamental insights underlying neural computations, specifically excitatory–inhibitory balance. In this study, we identified that there is a significant increase in exponent and offset of aperiodic background during arousal. In contrast, there were no discernible variations between the aperiodic components during the differential valence scenarios. Reduction in periodic alpha power was observed with high arousal in line with previous studies. Finally, implementation of a biophysically realistic corticothalamic model of neural field activity allowed us to mechanistically explain that both the empirical observations of heightened arousal represented as higher slope of aperiodic background and decrease in power of the periodic alpha oscillations emerge from an increased inhibitory influence to relay nuclei of the thalamus.
Modelling low-dimensional interacting brain networks reveals organising principle in human cognition
Authors: Perl Yonatan Sanz , Geli Sebastian , Pérez-Ordoyo Eider , Zonca Lou , Idesis Sebastian , Vohryzek Jakub , Jirsa Viktor K. , Kringelbach Morten L. , Tagliazucchi Enzo , Deco Gustavo 
Published: January 2025

Abstract
The discovery of resting-state networks shifted the focus from the role of local regions in cognitive tasks to the ongoing spontaneous dynamics in global networks. Recently, efforts have been invested to reduce the complexity of brain activity recordings through the application of nonlinear dimensionality reduction algorithms. Here, we investigate how the interaction between these networks emerges as an organising principle in human cognition. We combine deep variational autoencoders with computational modelling to construct a dynamical model of brain networks fitted to the whole-brain dynamics measured with functional magnetic resonance imaging (fMRI). Crucially, this allows us to infer the interaction between these networks in resting state and seven different cognitive tasks by determining the effective functional connectivity between networks. We found a high flexible reconfiguration of task-driven network interaction patterns and we demonstrate that it can be used to classify different cognitive tasks. Importantly, compared with using all the nodes in a parcellation, we obtain better results by modelling the dynamics of interacting networks in both model and classification performance. These findings show the key causal role of manifolds as a fundamental organising principle of brain function, providing evidence that interacting networks are the computational engines’ brain during cognitive tasks.
The Danish-Halle Mission from the Perspective of Embodiment: Communication, Ritual, and the Body in Interreligious Contact
Authors: Lind Erki 
Published: January 2025

Abstract
This article studies the role of the body in interreligious contact by looking at the eighteenth-century Danish-Halle mission in South India. The missionaries’ theological arguments were mostly well received by Tamil Hindus, but the bodily lived religion and everyday experience determined the relationship with Christians. It was not only two different theologies that interacted, but two different conceptions of man. The missionaries used verbal communication and sought common ground in concepts, but the article argues that the body also participates in the communication process. The article argues first that the body is a center of relations, and that these relations are created in ritual. Separate rituals not only hold persons in separate networks of relations but create separate worldviews that lay the basis for separate concepts. Second, the body connects the doctrine with ritual and behavior, and the way the body experiences reality forms the basis for lived religion.
Tibetan Remediations: Wax Doubles of Khenpo Jigme Phuntsok
Authors: Brox Trine 
Published: January 2025

Abstract
This article contributes to the study of material religion a discussion on the notion of remediation, by exploring the affordances of the waxwork as a new medium in the Tibetan Buddhist field. It shows how Tibetan waxworks are remediations in two senses of the word. Like the new media forms explored in other studies, they reference older media, blending the popular hyperreal waxwork that we know from Madame Tussauds and the well-established religious mediums of the statue and photo icon. But they can also remediate in the sense of restoration, evoking an experience of bodily copresence with the deceased (or otherwise absent) that can exceed the propinquity afforded by other media used as proxies. Drawing on observations of and interviews with people interacting with waxwork doubles of the Tibetan Buddhist authority Khenpo Jigme Phuntsok (1933–2004), I explore how such remediations can have limited but also unexpected potency and authority.
The Impact of School Support on College Students’ Willingness to Start Their Own Businesses: a Regulated Mediating Effect in Shaanxi
Authors: Yuan Zhaoyang , Chen Wei , Yuan Xiaofei 
Published: January 2025

Abstract
To explore the influence mechanism of school support on college students ‘entrepreneurial willingness, this study conducted a questionnaire survey on 241 college students in three universities in Shaanxi, and the results found that college students’ entrepreneurial willingness, entrepreneurial self-efficacy plays a positive intermediary role; gender not only plays a direct role between the school support and college students ‘entrepreneurial willingness, but also regulates the indirect relationship between school support and college students’ entrepreneurial self-efficacy. These studies found theoretical and practical significance: on the one hand, increasing school support can significantly enhance the entrepreneurial willingness of college students by enhancing the self-efficacy of entrepreneurship; on the other hand, female college students seem to be less sensitive to male college students ‘entrepreneurship support, indicating that the existing school support measures may not take into account the gender differences of students, and need to reflect to develop entrepreneurial support measures suitable for students’ gender characteristics.