bluuebunny/crossref_metadata_2025_split huggingface dataset:
An interactive course program on nutrition for medical students: interdisciplinary development and mixed-methods evaluation
Authors: Ngoumou Gonza B. , Koppold Daniela A. , Wenzel Laetitia , Schirmaier Anne , Breinlinger Carolin , Pörtner Lisa M. , Jordan Stefan , Schiele Julia K. , Hanslian Etienne , Koppold Annika , Stock-Schröer Beate , Varvarezou Dimitra M. , Jeitler Michael , Ortiz Miriam , Michalsen Andreas , Stritter Wiebke , Seifert Georg , Kessler Christian S. 
Published: January 2025

Abstract
Nutrition plays a crucial role in human and planetary health, as prevailing nutritional patterns significantly contribute to the global non-communicable disease pandemic. Moreover, the global food system is inextricably linked to planetary health deterioration. The relevance of nutrition for individual and planetary health is insufficiently addressed in German medical schools. Here, we present a two-week course for medical students in the 8th semester at Charité - Universitätsmedizin Berlin on nutrition and fasting in the context of human and planetary health. The course was developed iteratively along the Kern cycle for medical curricula and underwent evaluation through a mixed-methods design spanning across two consecutive semesters. Assessment involved quantitative questionnaires and qualitative interviews. The main exploratory outcome was the overall module rating. Further outcomes encompassed in-depth evaluations of specific aspects, including content, teaching methods, instructor performance, and subjective experiential aspects. The conceptualisation resulted in a highly participative two-week course of 37.5 h. The main learning objectives aimed at the acquisition of technical competences and personal competencies in four areas: (1) the role of nutrition in health and disease; (2) the exploration of global food systems; (3) communication on subjects of nutrition; (4) culinary medicine. Various interactive didactic methodologies were used. 77.8% (n = 27) of the participants rated the course as very good or good. The conviction that nutrition influences health and disease increased over the course (Wilcoxon signed rank test, z = -2.82, p = 0.005, r = 0.57). In the qualitative interviews (n = 8) the course content, its didactical diversity and the positive group experience were appreciated. Our results indicate that it could be worthwhile to further incorporate nutrition curricula in medical education.
Effects of genetic ablation and pharmacological inhibition of HuR on gene expression, iron metabolism, and hormone levels
Authors: Idlin Nathalie , Krishnamoorthy Sivakumar , Wolczyk Magdalena , Fakhri Mouad , Lechowski Michal , Stec Natalia , Milek Jacek , Mandal Pratik Kumar , Cendrowski Jaroslaw , Spanos Christos , Dziembowska Magdalena , Mleczko-Sanecka Katarzyna , Rappsilber Juri , Michlewski Gracjan 
Published: January 2025

Abstract

Background
HuR/ELAV1, a ubiquitous RNA-binding protein, belongs to the RNA-binding protein family and is crucial for stabilizing and regulating the translation of various mRNA targets, influencing gene expression. Elevated HuR levels are associated with multiple disorders, including cancer and neurodegenerative diseases. Despite the identification of small molecule inhibitors targeting HuR, their detailed characterization remains limited. Recently, Eltrombopag, an FDA-approved drug for immune thrombocytopenic purpura and chemotherapy-induced thrombocytopenia, emerged as a potential HuR inhibitor. However, the specific molecular pathways influenced by both HuR and Eltrombopag are not fully understood.

Results
Our study demonstrates that Eltrombopag operates via HuR inhibition, affecting gene expression regulation at the posttranscriptional level. We show that both HuR knockout and Eltrombopag treatment modulate iron metabolism by decreasing ferritin heavy chain (FTH1) and light chain (FTL) synthesis while increasing the expression of iron-regulatory protein 2 (IRP2), a key regulator of ferritin translation. Additionally, HuR inhibition reduces the levels of glycoprotein hormones, alpha polypeptide (CGA), a marker associated with hormone-induced tumors, suggesting a potential use of Eltrombopag in treatment of cancers overexpressing CGA. We observed that the main of control is manifested at the level of translation inhibition, with proteasome-mediated regulation also playing an important role.

Conclusions
These findings uncover novel posttranscriptional mechanisms governed by HuR and its inhibitor, elucidating pathways relevant to HuR-mediated regulation and molecular therapies aimed at targeting this protein.
Selective arm-usage of pre-miR-1307 dysregulates angiogenesis and affects breast cancer aggressiveness
Authors: Sumer Oyku Ece , Schelzig Korbinian , Jung Janine , Li Xiaoya , Moros Janina , Schwarzmüller Luisa , Sen Ezgi , Karolus Sabine , Wörner Angelika , de Melo Costa Verônica Rodrigues , Nataraj Nishanth Belugali , Vlachavas Efstathios-Iason , Gerhäuser Clarissa , Müller-Decker Karin , Helm Dominic , Yarden Yosef , Michels Birgitta Elisabeth , Körner Cindy 
Published: January 2025

Abstract

Background
Breast cancer is the leading cause of cancer-related mortality in women. Deregulation of miRNAs is frequently observed in breast cancer and affects tumor biology. A pre-miRNA, such as pre-miR-1307, gives rise to several mature miRNA molecules with distinct functions. However, the impact of global deregulation of pre-miR-1307 and its individual mature miRNAs in breast cancer has not been investigated in breast cancer, yet.

Results
Here, we found significant upregulation of three mature miRNA species derived from pre-miR-1307 in human breast cancer tissue. Surprisingly, the overexpression of pre-miR-1307 in breast cancer cell lines resulted in reduced xenograft growth and impaired angiogenesis. Mechanistically, overexpression of miR-1307-5p altered the secretome of breast cancer cells and reduced endothelial cell sprouting. Consistently, expression of miR-1307-5p was inversely correlated with endothelial cell fractions in human breast tumors pointing at an anti-angiogenic role of miR-1307-5p. Importantly, the arm usage of miR-1307 and other miRNAs was highly correlated, which suggests an undefined common regulatory mechanism.

Conclusions
In summary, miR-1307-5p reduces angiogenesis in breast cancer, thereby antagonizing the oncogenic effects of miR-1307-3p. Our results emphasize the importance of future research on the regulation of miRNA arm selection in cancer. The underlying mechanisms might inspire new therapeutic strategies aimed at shifting the balance towards tumor-suppressive miRNA species.

Graphical Abstract
Optimising patient engagement for assessing total joint arthroplasty outcomes – a randomised controlled trial
Authors: Tyndall Wyatt , Kuljic Nebojsa , Thatcher Michael , Nickol Michaela , van der Merwe Johannes M. 
Published: January 2025

Abstract

Introduction
Patient satisfaction is a critical outcome in total joint arthroplasty (TJA), yet assessing it effectively remains a challenge due to limitations in patient-reported outcome measures (PROMS). While these measures are commonly gathered in clinical settings, additional contact through mail or phone is often needed, and low response rates can affect the validity and reliability of collected data. To improve response rates, this study evaluated various methods of incentivizing patient participation in a randomized trial format, focusing on postal questionnaires.

Patients and methods
The study investigated three methods to improve response rates: including a gift card with the questionnaire, promising a gift card upon questionnaire completion, and offering no incentive. It also examined whether different monetary values and the inclusion of the surgeon’s name on materials impacted response rates. We tried to determine factors that could improve follow up telephone response rates in the group of patients that failed to return their questionnaires.

Results
Higher response rates were observed with monetary incentives (P = 0.056), larger amounts of money offered (P = 0.3839) for filling out the questionnaire, and if the surgeon’s details were on the cover letter or questionnaire (P = 0.632). There was no correlation between age and sex and participation. We did find a statistically significant difference in total participation and poorer total knee arthroplasty outcomes scores (P < 0.001).

Conclusion
Our study supports findings from prior research indicating that monetary incentives and personalized materials can improve response rates, although in this cohort, results were modest. Follow-up calls further boosted response rates, suggesting that multi-modal engagement may be beneficial. Although the response improvements were limited and lacked statistical significance, the study highlights the importance of refining strategies to ensure reliable PROMS data, which is vital for understanding patient outcomes in TJA. Future studies might consider demographic factors and other outreach methods to enhance PROMs data collection.
Stochastic demethylation and redundant epigenetic suppressive mechanisms generate highly heterogeneous responses to pharmacological DNA methyltransferase inhibition
Authors: Jakobsen Mie K. , Traynor Sofie , Nielsen Aaraby Y. , Dahl Christina , Staehr Mette , Jakobsen Simon T. , Madsen Maria S. , Siersbaek Rasmus , Terp Mikkel G. , Jensen Josefine B. , Pedersen Christina B. , Shrestha Anup , Brewer Jonathan R. , Duijf Pascal H. G. , Gammelgaard Odd L. , Ditzel Henrik J. , Kirkin Alexei F. , Guldberg Per , Gjerstorff Morten F. 
Published: January 2025

Abstract

Background
Despite promising preclinical studies, the application of DNA methyltransferase inhibitors in treating patients with solid cancers has thus far produced only modest outcomes. The presence of intratumoral heterogeneity in response to DNA methyltransferase inhibitors could significantly influence clinical efficacy, yet our understanding of the single-cell response to these drugs in solid tumors remains very limited.

Methods
In this study, we used cancer/testis antigen genes as a model for methylation-dependent gene expression to examine the activity of DNA methyltransferase inhibitors and their potential synergistic effect with histone deacetylase inhibitors at the single-cancer cell level. The analysis was performed on breast cancer patient-derived xenograft tumors and cell lines, employing a comprehensive set of techniques, including targeted single-cell mRNA sequencing. Mechanistic insights were further gained through DNA methylation profiling and chromatin structure analysis.

Results
We show that breast cancer tumors and cell cultures exhibit a highly heterogenous response to DNA methyltransferase inhibitors, persisting even under high drug concentrations and efficient DNA methyltransferase depletion. The observed variability in response to DNA methyltransferase inhibitors was independent of cancer-associated aberrations and clonal genetic diversity. Instead, these variations were attributed to stochastic demethylation of regulatory CpG sites and the DNA methylation-independent suppressive function of histone deacetylases.

Conclusions
Our findings point to intratumoral heterogeneity as a limiting factor in the use of DNA methyltransferase inhibitors as single agents in treatment of solid cancers and highlight histone deacetylase inhibitors as essential partners to DNA methyltransferase inhibitors in the clinic.
High-sensitive cardiac troponin T and NT-proBNP are associated with the left ventricular apical thickness in apical hypertrophic cardiomyopathy
Authors: Zhang Meng , Gao Wei , Cui Xiaotong , Han Xueting , Xu Yamei , Zhou Jingmin , Ge Junbo 
Published: January 2025

Abstract

Background
Apical hypertrophic cardiomyopathy (AHCM) is a subtype of hypertrophic cardiomyopathy (HCM). The expression level of high-sensitive cardiac troponin T (hs-cTNT) and N-terminal pro-BNP (NT-proBNP) in AHCM patients, and these relationships between echocardiography parameters were still unclear.

Methods
We retrospectively screened AHCM patients between January 2019 and December 2021 in Zhongshan Hospital Fudan University. The relationship between the level of hs-cTNT, NT-proBNP and echocardiography parameters were analyzed. The risk factors for elevated hs-cTNT and NT-proBNP level were investigated with linear regression analysis.

Results
A total of 267 AHCM patients were enrolled. They were divided into hs-cTNT normal (129, 48.3%) and abnormal (138, 51.7%) group. Compared with hs-cTNT normal group, hs-cTNT abnormal group were elder (68.3 ± 11.6 vs. 63.8 ± 10.6, P = 0.001); with higher rate of atrial fibrillation (AF) (41.3% vs. 17.8%, P < 0.001) and higher level of NT-proBNP concentration (752.0 [343.8–1345.5] vs. 249.0 [104.0–541.0], P < 0.001). For echocardiography parameters, hs-cTNT abnormal patients have thicker interventricular septum (IVS) (11.6 ± 2.0 vs. 11.0 ± 1.7, P = 0.02), thicker left ventricular apical (LVA) (16.9 ± 3.0 vs. 14.9 ± 2.3, P < 0.001) and larger left atrium diameter (LAD) (45.9 ± 6.6 vs. 42.4 ± 5.1, P < 0.001). LVA was independently correlated with both the level of hs-cTNT and NT-proBNP (hs-cTNT r = 0.224, P = 0.143; NT-proBNP r = 0.370, P < 0.001). Linear regression analysis revealed that LVA was independent risk factor of both the elevated hs-cTNT and NT-proBNP level.

Conclusions
More than half of AHCM patients had abnormal hs-cTNT level. LVA was positively and independently correlated with the level of hs-cTNT and NT-proBNP.
Slowly digestible starch impairs growth performance of broiler chickens offered low-protein diet supplemental higher amino acid densities by inhibiting the utilization of intestinal amino acid
Authors: Luo Caiwei , Yu Yao , Meng Gang , Yuan Jianmin 
Published: January 2025

Abstract

Background
The synchronized absorption of amino acids (AAs) and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body. The study investigated how the starch digestion rate and AA levels impact intestinal AA digestion, transport and metabolism, breast muscle protein metabolism, and growth in grower broilers. A total of 720 21-day-old healthy male Arbor Acres Plus broilers were randomly assigned to 12 treatments, each with 6 replicates of 10 birds. The treatments comprised 3 different starch [corn: control, cassava: rapidly digestible starch (RDS), and pea: slowly digestible starch (SDS)] with 4 different AA levels [based on standardized ileal digestible lysine (SID Lys), 0.92%, 1.02% (as the standard), 1.12% and 1.22%].

Results
An interaction between dietary starch sources and SID Lys levels significantly affected breast muscle yield (P = 0.033). RDS and SDS diets, or SID Lys levels of 0.92%, 1.02%, or 1.22%, significantly decreased the breast muscle yield of broilers in contrast to the corn starch diet with 1.12% SID Lys (P = 0.033). The SID Lys levels of 1.12% and 1.22% markedly improved body weight (BW), body weight gain (BWG) from 22 to 42 days of age, and mRNA expression of y
+
LAT1 and mTOR while reducing feed intake (FI) and feed/gain ratio (F/G) compared to the 0.92% SID Lys level (P < 0.05). The SDS diet significantly decreased BW and BWG of broilers from 22 to 42 days of age, distal ileal starch digestibility, jejunal amylase and chymotrypsin activities, and mRNA expression of GLUT2 and y
+
LAT1 compared to the corn starch diet (P < 0.05). The RDS diet suppressed the breast muscle mass by down-regulating expression of mTOR, S6K1, and eIF4E and up-regulating expression of MuRF, CathepsinB, Atrogin-1, and M-calpain compared to the corn starch diet (P < 0.05). Targeted metabolomics analysis revealed that the SDS diet significantly increased acetyl-CoA and α-ketoglutaric acid levels in the tricarboxylic acid (TCA) cycle (P < 0.05) but decreased the ileal digestibility of Lys, Tyr, Leu, Asp, Ser, Gly, Pro, Arg, Ile, and Val compared to the corn starch group (P < 0.05).

Conclusion
The SDS diet impaired broiler growth by reducing intestinal starch digestibility, which inhibited intestinal AA and glucose absorption and utilization, increased AA oxidation for energy supply, and lowered the efficiency of protein synthesis. Although the RDS diet resulted in growth performance similar to the corn starch diet, it reduced breast muscle mass by inhibiting protein synthesis and promoting degradation.

Graphical Abstract
Innovative approach for modelling gravity-induced signal path variations of VLBI radio telescopes
Authors: Lösler Michael , Eschelbach Cornelia , Greiwe Ansgar , Zhou Boye , McCallum Lucia 
Published: January 2025

Abstract
Gravitationally induced deformation of the receiving unit of radio telescopes used for Very Long Baseline Interferometry (VLBI) distorts the observations and biases the deduced products. As this deformation acts systematically and is individual for each radio telescope, the International VLBI Service for Geodesy and Astrometry (IVS) calls for gravitational deformation investigations to be able to correct VLBI data on the observation level. The most commonly used approach for modelling signal path variations was developed in 1988 during investigations at the 26-m VLBI radio telescope in Fairbanks (Alaska). This approach considers only homologous deformation of the receiving unit and takes into account three main deformation patterns affecting the signal path. For this reason, the measuring and modelling effort can be greatly simplified because the original spatial problem is reduced to a two-dimensional problem. However, more recent investigations refute the assumption of homogeneous deformation, because the receiver unit can be affected by arbitrary deformation patterns. Hence, identification and modelling as well as considering all deformation patterns that can be parameterised in a corresponding correction function require specific and more complex analysis approaches. In this contribution an innovative approach for modelling signal path variations is presented, based on Zernike polynomials. In contrast to the conventional approach, the proposed approach models the entire receiving unit spatially, and is not restricted to a homologous deformation pattern. This new approach has been successfully exercised on the 26-m radio telescope at the Mount Pleasant Radio Observatory Hobart (Tasmania, Australia). Despite the large dimensions of this radio telescope, the detected deformation is unexpectedly small, and leads to signal path variations of less than 2 mm.

Graphical Abstract
An efficient decoupled 3-D axial anisotropic resistivity inversion for magnetotelluric data with OpenMP parallelization
Authors: Thongyoy Wisart , Siripunvaraporn Weerachai , Amatayakul Puwis , Rung-Arunwan Tawat , Baba Kiyoshi 
Published: January 2025

Abstract
We have developed two novel axial anisotropic inversion codes for magnetotelluric (MT) data: a full axial inversion and a decoupled axial inversion. Both codes are based on the data space Gauss–Newton inversion method used in the WSINV3DMT code, enhanced with OpenMP parallelization and Intel MKL PARDISO direct solver for improved computational efficiency. The full axial inversion searches for three axial anisotropic resistivity elements

$${\rho }_{xx}$$

ρ

xx

,

$${\rho }_{yy}$$

ρ

yy

, and

$${\rho }_{zz}$$

ρ

zz

. Based on our prior influence studies, we identified contrasting influence patterns:

$${\rho }_{xx}$$

ρ

xx

has a strong influence on Z

xy
and Z

yy
, whereas

$${\rho }_{yy}$$

ρ

yy

has a strong influence on Z

yx
and Z

xx
, while

$${\rho }_{zz}$$

ρ

zz

has negligible impact on all responses. We, therefore, proposed a decoupled axial inversion. This novel technique splits the full axial inversion into two independent modes:

$${\rho }_{xx}$$

ρ

xx

- and

$${\rho }_{yy}$$

ρ

yy

-modes. The

$${\rho }_{xx}$$

ρ

xx

-mode requires just the Z

xy
and Z

yy
responses to recover

$${\rho }_{xx}$$

ρ

xx

, while the

$${\rho }_{yy}$$

ρ

yy

-mode requires the other two responses. By splitting the inversion, each mode requires half the data parameters and reduces model parameters to one-third compared to the full axial inversion. The substantial parameter reduction is the key factor leading to significantly faster processing times and lower memory requirements. Both codes were validated with the synthetic model. Utilizing OpenMP and direct solvers, the full axial inversion processed 256 MT stations in 65 min per iteration or a total of 195 min for three iterations to converge. The decoupled inversion achieved significantly faster processing, requiring just 32 min per iteration or a total of 96 min to finish the inversion. In addition, the decoupled inversion requires just a fraction of the memory used in the full axial inversion. This makes it practical to operate even on the standard personal computers of current technology. We further applied the decoupled inversion to real MT data acquired in the Northwestern Pacific Ocean. The resulting 3-D inverted

$${\rho }_{xx}$$

ρ

xx

and

$${\rho }_{yy}$$

ρ

yy

models support the existence of the anisotropy occurring at 60–120 km depth beneath the ocean floor, in agreement with previous studies.

Graphical abstract
First-principles study of the matrix alloying effect of X (X = Cr, Mo, W, V, Ti, Si) on the bonding characteristics and mechanical properties of the NbC/Fe interface
Authors: Yu Yutong , Zhong Lisheng , Han Enci , Shi Ke , Hu Kaiyuan , Zhang Chengwen , Xu Yunhua , Peng Jianhong , Hu Xu 
Published: January 2025

Abstract
Matrix alloying is currently the most commonly used means to improve the interfacial bonding strength. To explore the influence of different alloying elements on the interfacial bonding characteristics and mechanical properties of NbC/Fe, this study investigates the influence of the alloying element X (X = Cr, Mo, W, V, Ti, Si) on the properties of the NbC/Fe surface by using first principles and analyzes the segregation behavior, work of adhesion, electronic structure, and tensile strength of the interface before and after doping with the aforementioned alloying elements. The results demonstrate that the segregation energies of Cr, V, and Ti are less than 0, indicating that these alloy elements tend to segregate at the interface. Other alloying elements have positive segregation energies and are solids dissolved in the Fe matrix. When Si is doped at the interface, the adhesion work of the interface is reduced, and the binding property of the interface is destroyed. The charge density difference and population analyses demonstrated that the charge transfer between Cr, V, Ti, Mo, and W was localized, and there was a charge depletion region, presenting covalent characteristics. After doping, the Si atom demonstrated a charge state of loss, and the charge transfer had no clear direction, indicating the characteristics of an ionic bond. According to the theoretical tensile strength analysis, the addition of Mo, W, Si, and Cu will destroy the critical tensile strain at the interface. The tensile strength and strain of the interface significantly improved after the matrix alloying of Fe by Cr, V and Ti, the microstructure evolved during the tensile deformation, and a new phase was formed. A correlation between the atomic calculations and mechanical properties can be determined using first principles, as well as a reference for practical engineering applications.