bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone Density Distribution Pattern in the Lateral Wall of the Femoral Intercondylar Notch: Implications for the Direct Insertion of the Femoral ACL Attachment
Authors: Sugawara Yutaro , Iwasaki Koji , Suzuki Yuki , Hishimura Ryosuke , Matsubara Shinji , Matsuoka Masatake , Onodera Tomohiro , Kondo Eiji , Iwasaki Norimasa 
Published: April 2024

Background: The ideal position of the femoral bone tunnel in the anterior cruciate ligament (ACL) is controversial. The functional importance of the ACL fiber varies depending on where it is attached to the femur. Functionally important fibers can cause high mechanical stress on the bone, and the Wolff law predicts that bone mineral density will increase at high mechanical stress sites. Purpose/Hypothesis: The purpose of this study was to use computed tomography imaging to determine the distribution pattern of bone density in the lateral intercondylar wall. It was hypothesized that the high-density area (HDA) of the lateral intercondylar wall would reflect the functional insertion of the ACL as reported in previous anatomic studies. Study Design: Descriptive epidemiology study. Methods: Data from 39 knees without ACL injuries were retrospectively collected. The HDA of the lateral intercondylar wall was defined as the region containing the top 10% of the radiodensity values. The shape of the HDA was approximated as an ellipse, and the quadrant method was used to determine the center of the ellipse. The association between the ratio of the minor axis to the major axis of the ellipse and background characteristics was investigated. Results: According to the quadrant method, the center of the HDA ellipse was 33.6% in the deep-shallow direction and 23.4% in the high-low direction. The center of the ellipse was comparable to the anatomic center of the ACL footprint, as previously reported. The ratio of the minor axis to the major axis of the ellipse was 0.58 (95% CI, 0.54-0.62). There was a significant negative correlation between the ratio of the minor axis to the major axis of the HDA ellipse and the posterior tibial slope ( r = −0.38, P = .02). Conclusion: The center of the HDA ellipse was found to be similar to the anatomic center of the ACL footprint. Considering the mechanical stress responses in bone, the HDA of the lateral intercondylar wall has the potential to represent the ACL insertion, especially functional insertion.
Proton Pump Inhibitors in Germany: Status Quo of a Growing Market
Authors: Plehhova Kate , Häring Monika , Wray Joshua , Coyle Cathal , Kostev Karel 
Published: April 2024

Introduction The volume of prescriptions for proton pump inhibitors (PPIs) remains high, although the literature increasingly points to excessive prescribing in relation to guideline recommendations. No very recent data is available on the specific situation in Germany, particularly on the proportion of PPI consumption from over-the-counter (OTC) sales and self-selection, following PPI down-scheduling. The aim of this study was to determine the actual amount of prescribed and OTC PPIs in Germany. Methods For this retrospective study, several IQVIA databases were used, representing all prescriptions billed to statutory and private health insurers in Germany, as well as OTC sales. Analyses were performed for the period November 2020 to October 2021 or partially November 2018 to October 2021 and were descriptive in nature. Mainly, data were collected from IQVIATM PharmaScope National® as well as IQVIA TM DPM® databases. Results A total of 2.87 billion PPI tablets were shown to have been sold between November 2020 and October 2021, with most drugs prescribed in the largest packages and strengths. In addition, the OTC PPI market increased by an average of 14% per year over a 3-year period. Conclusions The results of this study suggest the substantial size of the PPI market in Germany is based on prescriptions, a consistent increase in OTC PPI purchases and a recent increase in prescriptions.
Exploratory study of blood biomarkers in patients with post-stroke epilepsy
Authors: Abraira Laura , López-Maza Samuel , Quintana Manuel , Fonseca Elena , Toledo Manuel , Campos-Fernández Daniel , Lallana Sofía , Grau-López Laia , Ciurans Jordi , Jiménez Marta , Becerra Juan Luis , Bustamante Alejandro , Rubiera Marta , Penalba Anna , Montaner Joan , Álvarez Sabin José , Santamarina Estevo 
Published: April 2024

Introduction: In addition to clinical factors, blood-based biomarkers can provide useful information on the risk of developing post-stroke epilepsy (PSE). Our aim was to identify serum biomarkers at stroke onset that could contribute to predicting patients at higher risk of PSE. Patients and methods: From a previous study in which 895 acute stroke patients were followed-up, 51 patients developed PSE. We selected 15 patients with PSE and 15 controls without epilepsy. In a biomarker discovery setting, 5 Olink panels of 96 proteins each, were used to determine protein levels. Biomarkers that were down-regulated and overexpressed in PSE patients, and those that showed the strongest interactions with other proteins were validated using an enzyme-linked immunosorbent assay in samples from 50 PSE patients and 50 controls. A ROC curve analysis was used to evaluate the predictive ability of significant biomarkers to develop PSE. Results: Mean age of the PSE discovery cohort was 68.56 ± 15.1, 40% women and baseline NIHSS 12 [IQR 1–25]. Nine proteins were down-expressed: CASP-8, TNFSF-14, STAMBP, ENRAGE, EDA2R, SIRT2, TGF-alpha, OSM and CLEC1B. VEGFa, CD40 and CCL4 showed greatest interactions with the remaining proteins. In the validation analysis, TNFSF-14 was the single biomarker showing statistically significant downregulated levels in PSE patients ( p = 0.006) and it showed a good predictive capability to develop PSE (AUC 0.733, 95% CI 0.601–0.865). Discussion and conclusion: Protein expression in PSE patients differs from that of non-epileptic stroke patients, suggesting the involvement of several different proteins in post-stroke epileptogenesis. TNFSF-14 emerges as a potential biomarker for predicting PSE.
A review on properties and variability of Pinus Pinaster Ait. ssp. Atlantica existing in the Landes of Gascogne
Authors: Chevalier Romain , Catapano Anita , Pommier Régis , Montemurro Marco 
Published: April 2024

AbstractPinus Pinaster Ait. is a softwood species indigenous of the South West of Europe, broadly spread alongside the Mediterranean Sea and present worldwide. Pinus Pinaster Ait. (ssp. Atlantica) is largely used in industrial applications including construction and buildings in the Southwest of France as it has widely grown across the whole area. However, very often, Pinus Pinaster Ait.-based product design strategies make use of properties of generic softwood species due to the lack of a proper database (or review) on the topic. This review article aims to exhaustively present the consistent scientific literature on Pinus Pinaster Ait. properties focusing on its physical, hygrical, thermal and mechanical properties. Indeed, a vast literature exists, laid out across a wide range of years and countries.
Sialylation on vesicular integrin β1 determined endocytic entry of small extracellular vesicles into recipient cells
Authors: Lin Meixuan , Xu Xiaoqiang , Zhou Xiaoman , Feng Hui , Wang Ruili , Yang Yunyun , Li Jing , Fan Ning , Jiang Yazhuo , Li Xiang , Guan Feng , Tan Zengqi 
Published: April 2024

Abstract
Background
Small extracellular vesicles (sEV) are closely associated with the development and metastasis of many types of mammalian cancer. Glycoconjugates are highly expressed on sEV and play important roles in sEV biogenesis and their interaction with other cells. However, the study on vesicular glycoconjugates are far behind proteins and nucleic acids. Especially, the functions of sialic acids which are the terminal components of glycoconjugates, are poorly understood in sEV.

Methods
Sialic acid levels on sEV from plasma and bladder cancer cells were determined by ELISA and lectin blotting. Effects of sialylation on sEV uptake were determined by flow cytometry. Vesicular glycoproteins bearing sialic acids responsible for sEV uptake was identified by proteomics and density gradient centrifugation, and their site-specific sialylation functions were assayed by N-glycosylation site mutation. Effects of integrin β1 bearing sialic acids on the pro-metastatic function of sEV in vivo were explored using Balb/c nu/nu mice.

Results
(1) Increased sialic acid levels were observed in sEV from malignant bladder cancer cells. (2) Elimination of sialic acids on sEV impaired sEV uptake by recipient cells. (3) Vesicular integrin β1 bearing sialic acids was identified to play a key role in sEV uptake. (4) Desialylation of the hybrid domain of vesicular integrin β1 inhibited its binding to matrix fibronectin, and reduced sEV entry into recipient cells. (5) Sialylation on integrin β1 affected pro-metastatic function of sEV in Balb/c nu/nu mice.

Conclusions
Taken together, our findings indicate important functional roles of sialic acids in sEV uptake and reprogramming plasticity of surrounding normal epithelial cells.

Graphical Abstract
Negative regulation of thyroid adenoma-associated protein (THADA) in the cardiac glycoside-induced anti-cancer effect
Authors: Katoh Mizuki , Fujii Takuto , Tabuchi Yoshiaki , Shimizu Takahiro , Sakai Hideki 
Published: April 2024

AbstractCardiac glycosides, known as inhibitors of Na+,K+-ATPase, have anti-cancer effects such as suppression of cancer cell proliferation and induction of cancer cell death. Here, we examined the signaling pathway elicited by cardiac glycosides in the human hepatocellular carcinoma HepG2 cells and human epidermoid carcinoma KB cells. Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA). Interestingly, the knockdown of THADA inhibited cancer cell proliferation, and the proliferation was significantly rescued by re-expression of THADA in the THADA-knockdown cells. In addition, the THADA-knockdown markedly decreased the expression level of L-type amino acid transporter LAT1. Cardiac glycosides also reduced the LAT1 expression. The LAT1 inhibitor, JPH203, significantly weakened the cancer cell proliferation. These results suggest that the binding of cardiac glycosides to Na+,K+-ATPase negatively regulates the THADA-LAT1 pathway, exerting the anti-proliferative effect in cancer cells.
MFSynDCP: multi-source feature collaborative interactive learning for drug combination synergy prediction
Authors: Dong Yunyun , Chang Yunqing , Wang Yuxiang , Han Qixuan , Wen Xiaoyuan , Yang Ziting , Zhang Yan , Qiang Yan , Wu Kun , Fan Xiaole , Ren Xiaoqiang 
Published: April 2024

AbstractDrug combination therapy is generally more effective than monotherapy in the field of cancer treatment. However, screening for effective synergistic combinations from a wide range of drug combinations is particularly important given the increase in the number of available drug classes and potential drug-drug interactions. Existing methods for predicting the synergistic effects of drug combinations primarily focus on extracting structural features of drug molecules and cell lines, but neglect the interaction mechanisms between cell lines and drug combinations. Consequently, there is a deficiency in comprehensive understanding of the synergistic effects of drug combinations. To address this issue, we propose a drug combination synergy prediction model based on multi-source feature interaction learning, named MFSynDCP, aiming to predict the synergistic effects of anti-tumor drug combinations. This model includes a graph aggregation module with an adaptive attention mechanism for learning drug interactions and a multi-source feature interaction learning controller for managing information transfer between different data sources, accommodating both drug and cell line features. Comparative studies with benchmark datasets demonstrate MFSynDCP's superiority over existing methods. Additionally, its adaptive attention mechanism graph aggregation module identifies drug chemical substructures crucial to the synergy mechanism. Overall, MFSynDCP is a robust tool for predicting synergistic drug combinations. The source code is available from GitHub at https://github.com/kkioplkg/MFSynDCP.
The nature and distribution of putative non-functional alleles suggest only two independent events at the origins of Astyanax mexicanus cavefish populations
Authors: Policarpo Maxime , Legendre Laurent , Germon Isabelle , Lafargeas Philippe , Espinasa Luis , Rétaux Sylvie , Casane Didier 
Published: April 2024

AbstractBackgroundSeveral studies suggested that cavefish populations ofAstyanax mexicanussettled during the Late Pleistocene. This implies that the cavefish’s most conspicuous phenotypic changes, blindness and depigmentation, and more cryptic characters important for cave life, evolved rapidly.ResultsUsing the published genomes of 47Astyanaxcavefish from la Cueva de El Pachón, El Sótano de la Tinaja, La Cueva Chica and El Sótano de Molino, we searched for putative loss-of-function mutations in previously defined sets of genes,i.e., vision, circadian clock and pigmentation genes. Putative non-functional alleles for four vision genes were identified. Then, we searched genome-wide for putative non-functional alleles in these four cave populations. Among 512 genes with segregating putative non-functional alleles in cavefish that are absent in surface fish, we found an enrichment in visual perception genes. Among cavefish populations, different levels of shared putative non-functional alleles were found. Using a subset of 12 genes for which putative loss-of-function mutations were found, we extend the analysis of shared pseudogenes to 11 cave populations. Using a subset of six genes for which putative loss-of-function mutations were found in the El Sótano del Toro population, where extensive hybridization with surface fish occurs, we found a correlation between the level of eye regression and the amount of putative non-functional alleles.ConclusionsWe confirm that very few putative non-functional alleles are present in a large set of vision genes, in accordance with the recent origin ofAstyanax mexicanuscavefish. Furthermore, the genome-wide analysis indicates an enrichment of putative loss-of-function alleles in genes with vision-related GO-terms, suggesting that visual perception may be the function chiefly impacted by gene losses related to the shift from a surface to a cave environment.The geographic distribution of putative loss-of-function alleles newly suggests that cave populations from Sierra de Guatemala and Sierra de El Abra share a common origin, albeit followed by independent evolution for a long period. It also supports that populations from the Micos area have an independent origin. In El Sótano del Toro, the troglomorphic phenotype is maintained despite massive introgression of the surface genome.
Protein profile analysis of Jilin white goose testicles at different stages of the laying cycle by DIA strategy
Authors: Song Yupu , Ma Jingyun , Liu Qiuyuan , Mabrouk Ichraf , Zhou Yuxuan , Yu Jin , Liu Fengshuo , Wang Jingbo , Yu Zhiye , Hu Jingtao , Sun Yongfeng 
Published: April 2024

Abstract
Background
Jilin white goose is an excellent local breed in China, with a high annual egg production and laying eggs mainly from February to July each year. The testis, as the only organ that can produce sperm, can affect the sexual maturity and fecundity of male animals. Its growth and development are affected and regulated by a variety of factors. Proteomics is generally applied to identify and quantify proteins in cells and tissues in order to understand the physiological or pathological changes that occur in tissues or cells under specific conditions. Currently, the female poultry reproductive system has been extensively studied, while few related studies focusing on the regulatory mechanism of the reproductive system of male poultry have been conducted.

Results
A total of 1753 differentially expressed proteins (DEPs) were generated in which there were 594, 391 and 768 different proteins showing differential expression in three stages, Initial of Laying Cycle (ILC), Peak of Laying Cycle (PLC) and End of Laying Cycle (ELC). Furthermore, bioinformatics was used to analyze the DEPs. Gene ontology (GO) enrichment, Clusters of Orthologous Groups (COG), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analysis were adopted. All DEPs were found to be implicated in multiple biological processes and pathways associated with testicular development, such as renin secretion, Lysosomes, SNARE interactions in vesicle trafficking, the p53 signaling pathway and pathways related to metabolism. Additionally, the reliability of transcriptome results was verified by real-time quantitative PCR by selecting the transcript abundance of 6 selected DEPs at the three stages of the laying cycle.

Conclusions
The funding in this study will provide critical insight into the complex molecular mechanisms and breeding practices underlying the developmental characteristics of testicles in Jilin white goose.
Transcriptomic changes in the microsporidia proliferation and host responses in congenitally infected embryos and larvae
Authors: Shen Zigang , Ke Zhuojun , Yang Qiong , Ghebremichael Samson Teweldeberhan , Li Tangxin , Li Tian , Chen Jie , Meng Xianzhi , Xiang Heng , Li Chunfeng , Zhou Zeyang , Pan Guoqing , Chen Ping 
Published: April 2024

AbstractCongenital infection caused by vertical transmission of microsporidia N. bombycis can result in severe economic losses in the silkworm-rearing industry. Whole-transcriptome analyses have revealed non-coding RNAs and their regulatory networks in N. bombycis infected embryos and larvae. However, transcriptomic changes in the microsporidia proliferation and host responses in congenitally infected embryos and larvae remains unclear. Here, we simultaneously compared the transcriptomes of N. bombycis and its host B. mori embryos of 5-day and larvae of 1-, 5- and 10-day during congenital infection. For the transcriptome of N. bombycis, a comparison of parasite expression patterns between congenital-infected embryos and larva showed most genes related to parasite central carbon metabolism were down-regulated in larvae during infection, whereas the majority of genes involved in parasite proliferation and growth were up-regulated. Interestingly, a large number of distinct or shared differentially expressed genes (DEGs) were revealed by the Venn diagram and heat map, many of them were connected to infection related factors such as Ricin B lectin, spore wall protein, polar tube protein, and polysaccharide deacetylase. For the transcriptome of B. mori infected with N. bombycis, beyond numerous DEGs related to DNA replication and repair, mRNA surveillance pathway, RNA transport, protein biosynthesis, and proteolysis, with the progression of infection, a large number of DEGs related to immune and infection pathways, including phagocytosis, apoptosis, TNF, Toll-like receptor, NF-kappa B, Fc epsilon RI, and some diseases, were successively identified. In contrast, most genes associated with the insulin signaling pathway, 2-oxacarboxylic acid metabolism, amino acid biosynthesis, and lipid metabolisms were up-regulated in larvae compared to those in embryos. Furthermore, dozens of distinct and three shared DEGs that were involved in the epigenetic regulations, such as polycomb, histone-lysine-specific demethylases, and histone-lysine-N-methyltransferases, were identified via the Venn diagram and heat maps. Notably, many DEGs of host and parasite associated with lipid-related metabolisms were verified by RT-qPCR. Taken together, simultaneous transcriptomic analyses of both host and parasite genes lead to a better understanding of changes in the microsporidia proliferation and host responses in embryos and larvae in N. bombycis congenital infection.
Detection and classification of the integrative conjugative elements of Lactococcus lactis
Authors: van der Els Simon , Sheombarsing Reshtrie , van Kempen Thijn , Wels Michiel , Boekhorst Jos , Bron Peter A. , Kleerebezem Michiel 
Published: April 2024

AbstractLactococcus lactis is widely applied by the dairy industry for the fermentation of milk into products such as cheese. Adaptation of L. lactis to the dairy environment often depends on functions encoded by mobile genetic elements (MGEs) such as plasmids. Other L. lactis MGEs that contribute to industrially relevant traits like antimicrobial production and carbohydrate utilization capacities belong to the integrative conjugative elements (ICE). Here we investigate the prevalence of ICEs in L. lactis using an automated search engine that detects colocalized, ICE-associated core-functions (involved in conjugation or mobilization) in lactococcal genomes. This approach enabled the detection of 36 candidate-ICEs in 69 L. lactis genomes. By phylogenetic analysis of conserved protein functions encoded in all lactococcal ICEs, these 36 ICEs could be classified in three main ICE-families that encompass 7 distinguishable ICE-integrases and are characterized by apparent modular-exchangeability and plasticity. Finally, we demonstrate that phylogenetic analysis of the conjugation-associated VirB4 ATPase function differentiates ICE- and plasmid-derived conjugation systems, indicating that conjugal transfer of lactococcal ICEs and plasmids involves genetically distinct machineries. Our genomic analysis and sequence-based classification of lactococcal ICEs creates a comprehensive overview of the conserved functional repertoires encoded by this family of MGEs in L. lactis, which can facilitate the future exploitation of the functional traits they encode by ICE mobilization to appropriate starter culture strains.
CmDOF18 positively regulates salinity tolerance in Chrysanthemum morifolium by activating the oxidoreductase system
Authors: Li Peiling , Fang Tingting , Chong Xinran , Chen Juanjuan , Yue Jianhua , Wang Zhiyong 
Published: April 2024

Abstract
Background
Chrysanthemum, one of the four major cut flowers all over the world, is very sensitive to salinity during cultivation. DNA binding with one finger (DOF) transcription factors play important roles in biological processes in plants. The response mechanism of CmDOF18 from chrysanthemum to salt stress remains unclear.

Results
In this study, CmDOF18 was cloned from Chrysanthemum morifolium, and its expression was induced by salinity stress. The gene encodes a 291-amino acid protein with a typical DOF domain. CmDOF18 was localized to the nucleus in onion epidermal cells and showed transcriptional activation in yeast. CmDOF18 transgenic plants were generated to identify the role of this gene in resistance to salinity treatment. Chrysanthemum plants overexpressing CmDOF18 were more resistant to salinity stress than wild-type plants. Under salinity stress, the malondialdehyde content and leaf electrolyte conductivity in CmDOF18-overexpressing transgenic plants were lower than those in wild-type plants, while the proline content, chlorophyll content, superoxide dismutase activity and peroxidase activity were higher than those in wild-type plants. The opposite findings were observed in gene-silenced plants compared with wild-type plants. The gene expression levels of oxidoreductase increased in CmDOF18-overexpressing transgenic plants but decreased in CmDOF18-SRDX gene-silenced transgenic plants.

Conclusion
In summary, we analyzed the function of CmDOF18 from chrysanthemum, which may regulate salinity stress in plants, possibly due to its role in the regulation of oxidoreductase.