bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiomics profiling of DNA methylation, microRNA, and mRNA in skeletal muscle from monozygotic twin pairs discordant for type 2 diabetes identifies dysregulated genes controlling metabolism
Authors: Ling Charlotte , Vavakova Magdalena , Ahmad Mir Bilal , Säll Johanna , Perfilyev Alexander , Martin Melina , Jansson Per-Anders , Davegårdh Cajsa , Asplund Olof , Hansson Ola , Vaag Allan , Nilsson Emma 
Published: December 2024

Abstract
Background
A large proportion of skeletal muscle insulin resistance in type 2 diabetes (T2D) is caused by environmental factors.

Methods
By applying multiomics mRNA, microRNA (miRNA), and DNA methylation platforms in biopsies from 20 monozygotic twin pairs discordant for T2D, we aimed to delineate the epigenetic and transcriptional machinery underlying non-genetic muscle insulin resistance in T2D.

Results
Using gene set enrichment analysis (GSEA), we found decreased mRNA expression of genes involved in extracellular matrix organization, branched-chain amino acid catabolism, metabolism of vitamins and cofactors, lipid metabolism, muscle contraction, signaling by receptor tyrosine kinases pathways, and translocation of glucose transporter 4 (GLUT4) to the plasma membrane in muscle from twins with T2D. Differential expression levels of one or more predicted target relevant miRNA(s) were identified for approximately 35% of the dysregulated GSEA pathways. These include miRNAs with a significant overrepresentation of targets involved in GLUT4 translocation (miR-4643 and miR-548z), signaling by receptor tyrosine kinases pathways (miR-607), and muscle contraction (miR-4658). Acquired DNA methylation changes in skeletal muscle were quantitatively small in twins with T2D compared with the co-twins without T2D. Key methylation and expression results were validated in muscle, myotubes, and/or myoblasts from unrelated subjects with T2D and controls. Finally, mimicking T2D-associated changes by overexpressing miR-548 and miR-607 in cultured myotubes decreased expression of target genes, GLUT4 and FGFR4, respectively, and impaired insulin-stimulated phosphorylation of Akt (Ser473) and TBC1D4.

Conclusions
Together, we show that T2D is associated with non- and epigenetically determined differential transcriptional regulation of pathways regulating skeletal muscle metabolism and contraction.
Green space visits among Turkish and South Asian Surinamese women with a high cardiometabolic risk living in disadvantaged neighborhoods in the Netherlands: motives, means and prerequisites
Authors: van den Brekel Lieke , Voogdt-Pruis Helene R. , Wispelweij Lian , Jawalapershad Laxmie , Narain Soerinder , Klipstein-Grobusch Kerstin , Grobbee Diederick E. , Lenters Virissa , Mackenbach Joreintje D. , Vaartjes Ilonca 
Published: December 2024

Abstract
Background
The use of urban green spaces differs by social characteristics, including gender, ethnicity, and socioeconomic position. We examined motives, means and prerequisites to visit green space of marginalised populations with high cardiometabolic risk in the Netherlands, namely women with a Turkish or South Asian Surinamese background residing in disadvantaged neighbourhoods.

Methods
We conducted six focus group discussions in two Dutch cities. The study was performed in collaboration with social workers from the local communities with similar ethnic backgrounds as the participants. A thematic analysis was carried out.

Results
Sixteen Turkish women and 30 South Asian Surinamese women participated. Motives, means and prerequisites that emerged covered four themes: social, personal, environmental characteristics and undertaking activities. Socializing was an important motive to visit green space. Personal motives mainly consisted of positive effects on mental and physical well-being. Activities undertaken in green space were often a means to socialize or improve well-being. Many environmental factors, including safety, aesthetics, and (sanitary) facilities, influenced motivation to visit green space. Except for environmental characteristics, motives, means and prerequisites largely overlapped between ethnic groups. There were notable interactions between the themes.

Conclusion
Motives, means and prerequisites to visit green space of women with a Turkish or South Asian Surinamese background who live in disadvantaged neighborhoods span multiple interacting themes. Future studies examining the relationship between green space and health should consider interactions between motives, means, prerequisites and ethnicity. The possibility of expanding the multifunctionality of green spaces to provide marginalized populations with more equitable access and activities should be further explored.
Research utilization competency development in the health workforce pipeline: Design and formative evaluation of learning objectives for health professions students
Authors: Yini Karway Olive W. , Wleh Jeremiah , Kpatakolee Yamah , Sieka Joseph , Candy Neima , Talbert-Slagle Kristina , Dahn Bernice T. , Harmon-Gray Wahdae-Mai , Skrip Laura A. 
Published: December 2024

Abstract
Background
It is widely recognized that use of research evidence to guide health policy and practice could lead to adoption of life-saving interventions and more effective resource allocation. However, the skills around research utilization are often assumed and rarely taught, particularly in low- and middle-income country contexts. Here we present a set of competency areas and learning objectives developed for institutionalization of research utilization across health professions schools in Liberia. Ahead of implementation and to gauge their perceived value and utility, a participatory formative evaluation was undertaken.

Methods
Focus group discussions were held to gain feedback on a set of research utilization learning objectives and the proposed implementation approach. Focus group participants were drawn from faculty and students at the University of Liberia College of Health Sciences (ULCHS), which houses the country’s only medical and pharmacy schools, along with schools of public health and nursing and midwifery. ULCHS serves an essential role in the health workforce pipeline.

Results
Findings from the focus group discussions identified a limited understanding of research utilization at the ULCHS but a demand for stronger understanding of research methodology and evidence. Participants identified clear examples of how the skills represented in the learning objectives could help specifically their personal careers as well as more broadly the health sector of Liberia. Potential challenges were noted around the incorporation of research utilization learning objectives into existing courses and tended to be logistical (for example, poor internet connectivity and low digital literacy) or around lack of foundational understanding and skills (for example, lack of experience with literature searches and reviews). However, the approach was generally perceived as contextually aware since it would not add new courses, which come with credit fees and extra time commitment, and would focus on practical skills-building rather than theoretical content.

Conclusions
Integrating research utilization learning objectives into existing curricula in health professions schools is expected to enhance uptake and application of research evidence in the Liberian health sector, as students emerge from the workforce pipeline to fill positions in clinical and policy settings. The success of the approach will warrant ongoing evaluation, along with mentorship of faculty, to increasingly incorporate skills and content of local relevance into courses.
Combining immunoscore and tumor budding in colon cancer: an insightful prognostication based on the tumor-host interface
Authors: Haddad T. S. , Bokhorst J. M. , Berger M. D. , Dobbelsteen L. v. d. , Simmer F. , Ciompi F. , Galon J. , Laak J. v. d. , Pagès F. , Zlobec I. , Lugli A. , Nagtegaal I. D. 
Published: December 2024

Abstract
Background
Tumor Budding (TB) and Immunoscore are independent prognostic markers in colon cancer (CC). Given their respective representation of tumor aggressiveness and immune response, we examined their combination in association with patient disease-free survival (DFS) in pTNM stage I-III CC.

Methods
In a series of pTNM stage I-III CCs (n = 654), the Immunoscore was computed and TB detected automatically using a deep learning network. Two-tiered systems for both biomarkers were used with cut-offs of 25% and ten buds for Immunoscore and TB according to clinical guidelines, respectively. Associations of Immunoscore with TB with 5-year DFS were examined using Kaplan–Meier survival analysis in addition to multivariable modeling and relative contribution analysis using Cox regression.

Results
Immunoscore and TB independently are prognostic with hazard ratio (HR) = 2.0, 95% confidence interval (CI) 1.4–2.8 and HR 2.5, with 95% CI 1.4–4.5, respectively; P value < 0.0001. By combining Immunoscore with TB, patients with Immunoscore Low, TB High tumors had a significantly poorer DFS (HR 5.6, 95% CI 2.6–12.0; P value < 0.0001) than those with Immunoscore High, TB Low tumors. The combined Immunoscore with TB score was independently prognostic (P value = 0.009) in comparison to N-stage, T-stage, and MSI. Immunoscore with TB had the highest relative contribution (35%) to DFS in pTNM stage I-II CCs.

Conclusions
The association of Immunoscore and TB with patient survival suggests that both biomarkers are complementary and should be interpreted in combination to identify high-risk Stage I-II patients who should be considered for adjuvant therapy or further diagnostic testing.
Prevalence and clinical characteristics of incontinentia pigmenti: a nationwide population-based study
Authors: Herlin Laura Krogh , Schmidt Sigrun Alba Johannesdottir , Mogensen Trine H. , Sommerlund Mette 
Published: December 2024

Abstract
Background
Incontinentia pigmenti (IP) is an X-linked dominant multisystemic disorder caused by pathogenic variants in the IKBKG gene. Population-based research into the epidemiology of IP is lacking.

Methods
This nationwide cross-sectional study from Jan 1st, 1995 to August 25th, 2021, searched the Danish National Patient Registry (DNPR), the Danish National Database of Rare Genetic Diseases (RareDis) and the Danish Genodermatosis Database to identify patients recorded with a diagnosis of IP. This search was followed by diagnosis validation and collection of clinical data from patient medical records. We investigated the clinical characteristics and genetics of the final cohort of validated IP cases. We estimated the point prevalence in the Danish population, based on non-deceased IP patients currently living in Denmark. Furthermore, we estimated the birth prevalence from 1995 to 2020, assuming a diagnostic delay of up to six months.

Results
We identified a validated cohort of 75 IP patients, including 71 (94.7%) females and 4 (5.3%) males. We estimated a birth prevalence of 2.37 (95% CI: 1.74–3.25) per 100,000 or 1 in 42,194. A total of 54 (72%) patients had a genetic diagnosis, including 39 (72.2%) with the recurrent exon 4–10 deletion and 10 (18.5%) with point mutations in IKBKG. A positive family history was reported in 53.3%. Besides the recognizable blaschkolinear skin lesions reported in 70 (93.3%) of the patients, commonly reported manifestations included the involvement of the teeth (58.7%), the central nervous system (30.7%), hair (26.7%), and eyes (22.6%), as well as nail dystrophy (16.0%).

Conclusions
We identified and characterized a nationwide population-based cohort of IP patients and report a birth prevalence of 2.37 per 100,000 live births, which is twice as high as previous estimates.
Nocardia farcinica pneumonia complicated by pneumocystis jiroveci infection in children with Neuromyelitis Optica Spectrum Disorders: a case report and literature review
Authors: Liu LingLing , Huang Yuan , Shu SaiNan , Zhou Hua , Fang Feng , Liu Xinglou 
Published: December 2024

Abstract
Background
Nocardiosis is an opportunistic infection that has a low prevalence rate, its clinical manifestations are atypical and can be easily misdiagnosed as other diseases. The correct diagnosis and treatment are frequently delayed by various factors. In this case report, we present a pediatric patient with Neuromyelitis Optica Spectrum Disorders who developed Nocardia farcinica pneumonia complicated by pneumocystis jiroveci infection.

Case presentation
An 8-year-old girl with chest pain and cough was admitted to the hospital. She suffered from Neuromyelitis Optica Spectrum Disorders and had been taking methylprednisolone and tacrolimus orally for 3 years. She was admitted to the hospital for tests and was diagnosed with acute pneumonia. Despite empiric antibiotic treatment, her condition gradually worsened. Respiratory distress developed, and she needed to use a ventilator for breathing. The symptoms she exhibited led us to suspect the presence of a tumor. Etiological tests later confirmed the co-infection of Nocardia farcinica and Pneumocystis jiroveci. After treatment, the child’s lung infection eventually resolved.

Conclusion
The Nocardia bacteria and Pneumocystis jiroveci are widely distributed in the environment, possess the capability of systemic dissemination, and exhibit significant resistance to specific treatments. Invasive sampling is frequently necessary for confirming their presence. Timely and accurate diagnosis as well as treatment play a crucial role in patient survival.
NF-κB associated markers of prognosis in early and metastatic triple negative breast cancer
Authors: De La Cruz Payton , McAdams Julia , Morales Aquino Melanie , Fernandez Aileen I. , Elliott Andrew , Lustberg Maryam , Schorl Christoph , Ribeiro Jennifer R. , James Nicole E. 
Published: December 2024

Abstract
Background
Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. While PD-1 based immunotherapies overall have led to improved treatment outcomes for this disease, a diverse response to frontline chemotherapy and immunotherapy still exist in TNBC, highlighting the need for more robust prognostic markers.

Methods
Tumor-intrinsic immunotranscriptomics, serum cytokine profiling, and tumor burden studies were conducted in two syngeneic mouse models to assess differential effects in both the early-stage and metastatic setting. Bioinformatic analyses of both early and metastatic TNBC patient data were performed to assess if identified NF-κB-associated factors are associated with improved patient clinical outcomes.

Results
NF-κB signaling driven by lymphotoxin beta expression is associated with tumor regression in TNBC mouse models. Furthermore, lymphotoxin beta expression in patient TNBC cohorts is prognostic of improved survival outcomes.

Conclusions
This study highlights the potential role for NF-κB-associated factors, specifically lymphotoxin beta to be used as prognostic markers in TNBC, which could ultimately provide insight for improved targeted treatment approaches in the clinic.
Variants of LSTM cells for single-channel speaker-conditioned target speaker extraction
Authors: Sinha Ragini , Rollwage Christian , Doclo Simon 
Published: December 2024

AbstractSpeaker-conditioned target speaker extraction aims at estimating the target speaker from a mixture of speakers utilizing auxiliary information about the target speaker. In this paper, we consider a single-channel target speaker extraction system consisting of a speaker embedder network and a speaker separator network. Instead of using standard long short-term memory (LSTM) cells in the separator network, we propose two variants of LSTM cells that are customized for speaker-conditioned target speaker extraction. The first variant customizes both the forget gate and input gate of the LSTM cell, aiming at retaining only relevant features related to target speaker and disregarding the interfering speakers by simultaneously resetting and updating the cell state using the speaker embedding. For the second variant, we introduce a new gate within the LSTM cell, referred to as auxiliary-modulation gate. This gate modulates the information processing during cell state reset, aiming at learning the long-term and short-term discriminative features of the target speaker. Both in unidirectional and bidirectional mode, experimental results on 2-speaker mixtures, 3-speaker mixtures, and noisy mixtures (containing 1, 2, or 3 speakers) show that both proposed variants of LSTM cells outperform the standard LSTM cells for target speaker extraction, where the best performance is obtained using the auxiliary-gated LSTM cells.
A provenance study on the ceramics excavated at the Varzaneh Plain, central Iran
Authors: Holakooei Parviz , Rafiei-Alavi Babak , Shojaee-Esfahani Ali , Jebreili Yaser , Bahadori Sepehr , Piovesan Rebecca , Maritan Lara 
Published: December 2024

Abstract
Forty-six ceramic shards from the Early Bronze Age (EBA) archaeological site of Tappeh Gabri (the archaeological site 013), dated back to the latter half of the third millennium BCE and located at the Varzaneh Plain, central Iran, were studied using micro energy dispersive X-ray fluorescence (µ-EDXRF) and petrographic analysis. The precision and accuracy of quantitative data obtained by µ-EDXRF were tested using a series of geological certified reference materials (CRM). The expanded uncertainty and the Mantel test on data obtained by µ-EDXRF showed accurate and precise quantitative µ-EDXRF estimation of elements present in the CRMs above their quantification limit. We show that the majority of the ceramics at the Varzaneh Plain is most probably local product. Discussions prompted collecting further compositional data and performing petrographic investigation from the ceramic shards from southern and south-western Iran in order to shed light on the origin of the ceramic shards excavated at the Varzaneh Plain.
The effect of maxillary premolar distalization with different designed clear aligners: a 4D finite element study with staging simulation
Authors: Mao Bochun , Tian Yajing , Liu Dawei , Zhou Yanheng , Wang Shuo 
Published: December 2024

Abstract
Background
Molar distalization with clear aligners (CAs) is a common treatment. However, when the molars reach their target position and the distal movement of premolars begins, the mesial movement of molars might reduce the overall efficiency of molar distalization. This study aimed to investigate tooth movement patterns under different CA designs in the premolar distalization stage using a four-dimensional mechanical simulation method.

Methods
A finite element method (FEM) model encompassing the maxillary dentition, periodontal ligaments, attachments, and associated CAs was constructed. The simulation aimed to replicate a premolar distalization of 2 mm within 10 sequential steps. Buccal interradicular mini-implants were used. Three groups of CAs were designed: the conventional CA design group (Con group), the second molar half-wrap group (SMHW group) and the all-molar half-wrap group (MHW group). An iterative computational approach was employed to simulate prolonged tooth movement resulting from orthodontic forces. Additionally, morphological alterations in the CA throughout the staging process were simulated utilizing the thermal expansion method.

Results
Compared with the Con and SMHW groups, the MHW group presented significantly reduced mesial movement of the first and second molars. However, the MHW group presented the greatest displacement of canines and incisors. The distalization efficiency of premolars in the MHW group reached 95.5–96.5%, which was substantially greater than that in the Con group (84.5–85%) and the SMHW group (75–75.5%).

Conclusions
The four-dimensional mechanical simulation results indicate that during the process of premolar distalization with CA, removing the distal portion of the aligner covering the first and second molars (MHW group) can effectively reduce the mesial movement of molars. Consequently, this approach can increase the overall efficiency of molar distalization.
Electrochemical nucleation and growth model of MoS2 for hydrogen evolution reaction
Authors: Reddy Venumbaka Maneesh , Chandra Marepally Bhanu , Gengan Saravanan , Duraisamy Selvakumar 
Published: December 2024

AbstractThe electrochemical nucleation of MoS2 from a mixture of sodium molybdate dihydrate (Na2MoO4·2H2O) and sodium sulphide (Na2S·xH2O) aqueous solution on Cu substrate has been investigated. The nucleation and formation of molybdenum sulphide were investigated employing cyclic voltammetry and chronoamperometry studies. The experimental i–t curves observed at various overpotentials were compared to theoretical curves derived for the two limiting situations of the 3D instantaneous/progressive nucleation and growth model, as reported by Scharifker and Hills. The outcome of electrodeposition potential on nucleation rate (A) and nucleation density (N) was calculated from the current–time transients and SEM morphology obtained at − 1.1 V (5.75 × 1014 and 1.86 × 1015) was compared with − 0.9 V, − 1.0 V, and − 1.2 V, respectively. The investigation of the initial stages of the transient current–time relationships developed for MoS2 electrodeposition specified that film formation occurred progressively initially and instantaneous nucleation during the course of time. A HPMoS2 with an average size of 5–65 nm was obtained at -1.1 V and exhibited superior performance towards the hydrogen evolution reaction compared to samples obtained at − 0.9 V, − 1.0 V, and − 1.2 V.
Investigating the use of chatGPT as a tool for enhancing critical thinking and argumentation skills in international relations debates among undergraduate students
Authors: de la Puente Mario , Torres Jose , Troncoso Ana Laura Blanco , Meza Yuraima Yuliza Hernández , Carrascal Jenny Xiomara Marquez 
Published: December 2024

AbstractThis study investigated the effectiveness of using ChatGPT, a large language model (LLM), to enhance critical thinking and argumentation skills among undergraduate students studying international relations in a developing nation context. A total of 95 participants were randomly assigned to an experimental group (n = 48) and a control group (n = 47). The experimental group engaged in debate sessions using ChatGPT, while the control group participated in traditional debate sessions. Pre-test and post-test assessments were conducted to measure the participants’ critical thinking and argumentation skills. The results revealed that the use of ChatGPT significantly improved students' understanding of complex concepts, critical thinking, and argumentation skills compared to traditional debate methods. The findings suggest that integrating LLMs into existing educational curricula may be an effective strategy for enhancing students’ critical thinking and argumentation skills in resource-constrained settings. However, the challenges and limitations associated with the use of LLMs in developing nations should be carefully considered. The study contributes to the growing body of research on the application of AI-powered tools in education and informs the development of evidence-based practices and policies for integrating LLMs into educational curricula.