bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 30-year bibliometric analysis of the literature in the disciplines of orthopedics, surgery, or oncology on chondrosarcoma from 1993 to 2023
Authors: Yilmaz Selçuk , Kurt Mehmet 
Published: February 2024

Background:
A thorough bibliometric analysis of publications published in the field of chondrosarcoma research has not yet been performed using the Web of Science database, especially for publications published between 1993 and 2023. This study, with a focus on the fields of orthopedics, surgery, and oncology, aims to fill this knowledge gap by providing a thorough analysis of current knowledge in the field of chondrosarcoma.

Methods:
In this bibliometric study, a literature search was performed using the Web of Science database to find all publications on chondrosarcoma. A bibliometric software program was used for data visualization and analysis (opensource visualization application, Vosviewer). The Web of Science Core Collection data used for this retrospective bibliometric study, which covers the period from January 1993 to September 2023, revealed interesting trends in chondrosarcoma research.

Results:
As the most popular fields of study, orthopedics, surgery, and oncology account for a sizable portion of publications. A noteworthy increase in research output from 2014 to 2023, accounting for 41.74% of the papers, reflects the thriving research environment. The leading countries for publication were China, Japan, and the United States, demonstrating cross-border cooperation in chondrosarcoma research. Their contributions were highlighted by their important affiliations with institutions such as Harvard University, Leiden University, and China Medical University Taiwan. A thorough keyword mapping analysis also highlighted research priorities and encouraged interdisciplinary cooperation. The field’s scholarly importance and ongoing relevance are highlighted by the study’s high citation count (30,076) and highly cited articles.

Conclusion:
Overall, this study offers crucial insights into the development and collaborative nature of the chondrosarcoma research landscape and its long-lasting influence on academic research and clinical practice.
Signaling networks guiding erythropoiesis
Authors: Kuttikrishnan Shilpa , Prabhu Kirti S. , Khan Abdul Q. , Uddin Shahab 
Published: February 2024

Purpose of review
Cytokine-mediated signaling pathways, including JAK/STAT, PI3K/AKT, and Ras/MAPK pathways, play an important role in the process of erythropoiesis. These pathways are involved in the survival, proliferation, and differentiation function of erythropoiesis.

Recent findings
The JAK/STAT pathway controls erythroid progenitor differentiation, proliferation, and survival. The PI3K/AKT signaling cascade facilitates erythroid progenitor survival, proliferation, and final differentiation. During erythroid maturation, MAPK, triggered by EPO, suppresses myeloid genes, while PI3K is essential for differentiation. Pro-inflammatory cytokines activate signaling pathways that can alter erythropoiesis like EPOR-triggered signaling, including survival, differentiation, and proliferation.

Summary
A comprehensive understanding of signaling networks is crucial for the formulation of treatment approaches for hematologic disorders. Further investigation is required to fully understand the mechanisms and interactions of these signaling pathways in erythropoiesis.
Detection and significance of anti-Mycobacterium tuberculosis specific IgG antibody response for the diagnosis of pulmonary tuberculosis using enzyme-linked immunosorbent assay.
Authors: Chaudhary Pooja , Mohanty Keshar K. , Kumar Santosh , Sikarwar Arun P. , Patil Shripad A 
Published: February 2024

Objective: For rapid serodiagnosis of pulmonary tuberculosis (PTB), the clinical usefulness of IgG antibody response against the in-house prepared Mycobacterium tuberculosis soluble extract (MTSE) antigen using the ELISA test was evaluated.
Methods: In this study, a total of 758 pulmonary TB patients (652 AFB-positive and 106 AFB-negative), 276 healthy controls, and 43 pulmonary infectious disease controls other than TB were recruited. IgG antibody level against MTB soluble extract was measured in sera samples of all study groups using an ELISA test. The level of IgG antibody responses was compared among groups by the Kruskal-Wallis test. The pairwise comparison was made by the Mann-Whitney test, A positive score was represented by optical density above the cut–off value which was calculated from OD values of healthy controls. The evaluation of diagnostic value was considered based on sensitivity and specificity.
Results: Significantly higher levels of IgG antibody response were observed in PTB patients compared to healthy control and non-TB other pulmonary infectious disease control groups (p value<0.0001). The percent positivity for the IgG antibody response was higher in AFB-positive 574/652 (88.04%) and 79/106 (74.53%) AFB-negative PTB patients as compared to healthy control 9/276 (3.26%) and non-TB other pulmonary infectious disease control 3/43 (6.97%). The sensitivity of the test in PTB patients (AFB-positive and AFB-negative) was 86.15% (95% CI; 83.48-88.53), and the specificity was 96.74% (95% CI; 93.90-98.50).

Conclusion: This developed immunological test could be much more efficient in detecting IgG antibody response in PTB patients. Further, this test could be useful for diagnosing AFB-negative presumptive TB cases.
PRMT5 deficiency disturbs Nur77 methylation to inhibit endometrial stromal cell differentiation in recurrent implantation failure
Authors: Cao Zhiwen , Wang Xiaoying , Liu Yang , Tang Xinyi , Wu Min , Zhen Xin , Kang Nannan , Ding Lijun , Sun Jianxin , Cai Xinyu , Sun Haixiang , Yan Guijun , Jiang Ruiwei 
Published: February 2024

AbstractVarious posttranslational modifications (PTMs) have been implicated in endometrial stromal cell (EnSC) differentiation, but the potential role of PTM crosstalk has not been identified. Here, we report that protein arginine methyltransferase 5 (PRMT5) is indispensable for human endometrial decidualization, functioning as a key regulator of decidualization defect in recurrent implantation failure (RIF) patients. Uterine-selective deletion ofPrmt5led to defective embryo implantation in mice due to impaired EnSC decidualization. Mechanistically, we find that PRMT5 catalyzes symmetric dimethylation of orphan nuclear receptor Nur77 at arginine 346, which in turn promotes Nur77 nuclear localization and increases its transcriptional activity in EnSC. Moreover, we demonstrate that PRMT5-mediated Nur77 methylation antagonizes AKT-induced phosphorylation of Nur77 at serine 351 in the transition from proliferation to differentiation of EnSC and disruption of the balance between methylation and phosphorylation of Nur77 is essentially involved in the endometrium of RIF patients. Furthermore, by modulating the methylation-phosphorylation of Nur77 and its transcriptional activity, we rescued impaired decidualization in RIF, further highlighting the critical role of the PRMT5/AKT/Nur77 complex in uterine receptivity to embryo implantation.
Longitudinal Fragility Phenotyping Predicts Lifespan and Age-Associated Morbidity in C57BL/6 and Diversity Outbred Mice
Authors: Luciano Alison , Robinson Laura , Garland Gaven , Lyons Bonnie , Korstanje Ron , Di Francesco Andrea , Churchill Gary A. 
Published: February 2024

AbstractAging studies in mammalian models often depend on natural lifespan data as a primary outcome. Tools for lifespan prediction could accelerate these studies and reduce the need for veterinary intervention. Here, we leveraged large-scale longitudinal frailty and lifespan data on two genetically distinct mouse cohorts to evaluate noninvasive strategies to predict life expectancy in mice. We applied a modified frailty assessment, the Fragility Index, derived from existing frailty indices with additional deficits selected by veterinarians. We developed an ensemble machine learning classifier to predict imminent mortality (95% proportion of life lived [95PLL]). Our algorithm represented improvement over previous predictive criteria but fell short of the level of reliability that would be needed to make advanced prediction of lifespan and thus accelerate lifespan studies. Highly sensitive and specific frailty-based predictive endpoint criteria for aged mice remain elusive. While frailty-based prediction falls short as a surrogate for lifespan, it did demonstrate significant predictive power and as such must contain information that could be used to inform the conclusion of aging experiments. We propose a frailty-based measure of healthspan as an alternative target for aging research and demonstrate that lifespan and healthspan criteria reveal distinct aspects of aging in mice.
Morroniside promotes skin wound re-epithelialization by facilitating epidermal stem cell proliferation through GLP-1R-mediated upregulation of β-catenin expression
Authors: Yu Chenghao , Yu Siyuan , Liu Zuohua , Xu Lei , Zhang Zhiqiang , Wan Jiaming , Ji Pengxiang , Zhang Ping , Fu Yi , Le Yingying , Hou Ruixing 
Published: February 2024

AbstractEpidermal stem cells (EpSCs) play a vital role in skin wound healing through re-epithelialization. Identifying chemicals that can promote EpSC proliferation is helpful for treating skin wounds. This study investigates the effect of morroniside on cutaneous wound healing in mice and explores the underlying mechanisms. Application of 10-50 μg/mL of morroniside to the skin wound promotes wound healing in mice. In vitro studies demonstrate that morroniside stimulates the proliferation of mouse and human EpSCs in a time- and dose-dependent manner. Mechanistic studies reveal that morroniside promotes the proliferation of EpSCs by facilitating the cell cycle transition from the G1 to S phase. Morroniside increases the expression of β-catenin via the glucagon-like peptide-1 receptor (GLP-1R)-mediated PKA, PKA/PI3K/AKT and PKA/ERK signalling pathways, resulting in the increase of cyclin D1 and cyclin E1 expression, either directly or by upregulating c-Myc expression. This process ultimately leads to EpSC proliferation. Administration of morroniside to mouse skin wounds increases the phosphorylation of AKT and ERK, the expression of β-catenin, c-Myc, cyclin D1, and cyclin E1, as well as the proliferation of EpSCs, in periwound skin tissue, and accelerates wound re-epithelialization. These effects of morroniside are mediated by the GLP-1R. Overall, these results indicate that morroniside promotes skin wound healing by stimulating the proliferation of EpSCs via increasing β-catenin expression and subsequent upregulation of c-Myc, cyclin D1, and cyclin E1 expression through GLP-1R signalling pathways. Morroniside has clinical potential for treating skin wounds.
Recognition ofChlamydia trachomatisby Toll-Like Receptor 9 is altered during persistence
Authors: Diallo Aissata , Overman Grace , Sah Prakash , Liechti George W. 
Published: February 2024

ABSTRACTToll-like receptor 9 (TLR9) is an innate immune receptor that localizes to endosomes in antigen presenting cells and recognizes single stranded unmethylated CpG sites on bacterial genomic DNA. Previous bioinformatic studies have indicated that the genome of the human pathogenChlamydia trachomatiscontains TLR9 stimulatory motifs, and correlative studies have implied a link between human TLR9 (hTLR9) genotype variants and susceptibility to infection. Here we present our evaluation of the stimulatory potential ofC. trachomatisgDNA and its recognition by hTLR9– and murine TLR9 (mTLR9)-expressing cells. We confirm that hTLR9 colocalizes with chlamydial inclusions in the pro-monocytic cell line, U937. Utilizing HEK293 reporter cell lines, we demonstrate that purified genomic DNA fromC. trachomatiscan stimulate hTLR9 signaling, albeit at lower levels than gDNA prepared from other Gram-negative bacteria. Interestingly, we found that whileC. trachomatisis capable of signaling through hTLR9 and mTLR9 during live infections in non-phagocytic HEK293 reporter cell lines, signaling only occurs at later developmental time points. Chlamydia-specific induction of hTLR9 is blocked when protein synthesis is inhibited prior to the RB-to-EB conversion and exacerbated by the inhibition of lipooligosaccharide biosynthesis. The induction of aberrance / persistence also significantly alters Chlamydia-specific TLR9 signaling. Our observations support the hypothesis that chlamydial gDNA is released at appreciable levels by the bacterium during the conversion between its replicative and infectious forms and during treatment with antibiotics targeting peptidoglycan assembly.
Dominant suppressor genes of p53-induced apoptosis inDrosophila melanogaster
Authors: Lukacsovich Tamás , Szlanka Tamás , Bálint Éva , Szabó Kornélia , Hajdu Ildikó , Molnár Enikő , Virágh Erika , Lin Yu-Hsien , Méhi Orsolya , Zvara Ágnes , Török István , Hegedűs Zoltán , Kiss Brigitta , Ramasz Beáta , Magdalena Laura M. , Puskás László , Mechler Bernard M. , Fónagy Adrien , Asztalos Zoltán , Žurovec Michal , Boros Imre , Kiss István 
Published: February 2024

SummaryApoptosis, the programmed cell death, is responsible for the removal of cells seriously damaged or unwanted in development. A major function of apoptosis is the removal of cells which suffered oncogenic mutations, thereby preventing cancerous transformation.By making use of theDEPtransposon, aPelement derivative made in our laboratory, we made an insertional mutagenesis screen inDrosophila melanogasterto identify genes which, when overexpressed, suppress thep53-activated apoptosis. TheDEPelement has Gal4-activatable, outward-directedUAS-promoters at both ends which can be deleted separatelyin vivo. In theDEPinsertion mutants, we used theGMR-Gal4driver to induce transcription from bothUAS-promoters and tested the suppression effect on the apoptotic rough eye phenotype generated by an activatedUAS-p53transgene.ByDEPinsertions, seven genes were identified which suppressed thep53-induced apoptosis. In four mutants, the suppression effect was resulted by single genes activated by oneUAS-promoter (Pka-R2, Rga, crol, Spt5). In the other three (Orct2, Polr2M, stg), deleting eitherUAS-promoter eliminated the suppression effect. In qPCR experiments we found that the genes in the vicinity of theDEPinsertion also showed an elevated expression level. This suggested an additive effect of the nearby genes on suppressing apoptosis.In the eucaryotic genomes there are co-expressed gene clusters. Three of theDEPinsertion mutants are included and two are in close vicinity of separate co-expressed gene clusters. This raises the possibility that the activity of some of the genes in these clusters may help the suppression of the apoptotic cell death.
Optimizing genomics pipeline execution with integer linear programming
Authors: Melnichenko Olesya , Malladi Venkat S. 
Published: February 2024

AbstractIn the field of genomics, bioinformatics pipelines play a crucial role in processing and analyzing vast biological datasets. These pipelines, consisting of interconnected tasks, can be optimized for efficiency and scalability by leveraging cloud platforms such as Microsoft Azure. The choice of compute resources introduces a trade-off between cost and time. This paper introduces an approach that uses Linear Programming (LP) to optimize pipeline execution. We consider optimizing two competing cases: minimizing cost with a run duration restriction and minimizing duration with a cost restriction. Our results showcase the utility of using LP in guiding researchers to make informed compute decisions based on specific data sets, cost and time requirements, and resource constraints.
Interplay Between FoxM1 and Dab2 Promotes Endothelial Cell Responses in Diabetic Wound Healing
Authors: Bhattacharjee Sudarshan , Gao Jianing , Lu Yao Wei , Eisa-Beygi Shahram , Wu Hao , Li Kathryn , Birsner Amy E. , Wong Scott , Song Yudong , Shyy John Y-J. , Cowan Douglas B. , Wei Wenyi , Aikawa Masanori , Shi Jinjun , Chen Hong 
Published: February 2024

AbstractDiabetes mellitus can cause impaired and delayed wound healing, leading to lower extremity amputations; however, the mechanisms underlying the regulation of vascular endothelial growth factor (VEGF)-dependent angiogenesis remain uncertain and could reveal new therapeutic targets. In our study, the molecular underpinnings of endothelial dysfunction in diabetes were investigated, focusing on the roles of Disabled-2 (Dab2) and Forkhead Box M1 (FoxM1) in VEGF receptor 2 (VEGFR2) signaling and endothelial cell (EC) function. Bulk RNA-sequencing analysis identified significant downregulation of Dab2 in high concentrations glucose treated primary mouse skin ECs, simulating hyperglycemic conditions in diabetes mellitus. In diabetic mice with a genetic EC deficiency of Dab2 angiogenesis was reducedin vivoandin vitrowhen compared with wild-type mice. Restoration of Dab2 expression by injected mRNA-containing lipid nanoparticles rescued impaired angiogenesis and wound healing in diabetic mice. At the same time, FoxM1 was downregulated in skin ECs subjected to high glucose conditions as determined by RNA-sequencing analysis. FoxM1 was found to bind to the Dab2 promoter, regulating its expression and influencing VEGFR2 signaling. The FoxM1 inhibitor FDI-6 reduced Dab2 expression and phosphorylation of VEGFR2. These findings indicate that restoring Dab2 expression through targeted therapies can enhance angiogenesis and wound repair in diabetes. To explore this therapeutic potential, we tested LyP-1-conjugated lipid nanoparticles (LNPs) containing Dab2 or control mRNAs to target ECs and found the former significantly improved wound healing and angiogenesis in diabetic mice. This study provides evidence of the crucial roles of Dab2 and FoxM1 in diabetic endothelial dysfunction and establishes targeted delivery as a promising treatment for diabetic vascular complications.
Zebrafish models of candidate human epilepsy-associated genes provide evidence of hyperexcitability
Authors: LaCoursiere Christopher Mark , Ullmann Jeremy F.P. , Koh Hyun Yong , Turner Laura , Baker Cristina M. , Robens Barbara , Shao Wanqing , Rotenberg Alexander , McGraw Christopher M. , Poduri Annapurna 
Published: February 2024

SummaryHundreds of novel candidate human epilepsy-associated genes have been identified thanks to advancements in next-generation sequencing and large genome-wide association studies, but establishing genetic etiology requires functional validation. We generated a list of >2200 candidate epilepsy-associated genes, of which 81 were determined suitable for the generation of loss-of-function zebrafish models via CRISPR/Cas9 gene editing. Of those 81 crispants, 48 were successfully established as stable mutant lines and assessed for seizure-like swim patterns in a primary F2screen. Evidence of seizure-like behavior was present in 5 (arfgef1, kcnd2, kcnv1, ubr5, wnt8b) of the 48 mutant lines assessed. Further characterization of those 5 lines provided evidence for epileptiform activity via electrophysiology inkcnd2andwnt8bmutants. Additionally,arfgef1andwnt8bmutants showed a decrease in the number of inhibitory interneurons in the optic tectum of larval animals. Furthermore, RNAseq revealed convergent transcriptional abnormalities between mutant lines, consistent with their developmental defects and hyperexcitable phenotypes. These zebrafish models provide strongest experimental evidence supporting the role ofARFGEF1, KCND2, andWNT8Bin human epilepsy and further demonstrate the utility of this model system for evaluating candidate human epilepsy genes.HighlightsZebrafish models generated by CRISPR/Cas9 gene editing display seizure-like swim patterns in five candidate human epilepsy genes:arfgef1, kcnd2, kcnv1, ubr5, wnt8b.Local field potential abnormalities recorded fromkcnd2andwnt8bcrispants provide additional evidence of hyperexcitability.Arfgef1andwnt8bmutant larvae have fewer inhibitory interneurons than wild type in the optic tectum.CRISPR-generated mutants of epilepsy genes displayed convergent transcriptional dysregulation, consistent with developmental abnormalities and their hyperexcitability phenotype.
A meta-analysis of the gut microbiome in inflammatory bowel disease patients identifies disease-associated small molecules
Authors: Elmassry Moamen M. , Sugihara Kohei , Chankhamjon Pranatchareeya , Camacho Francine R. , Wang Shuo , Sugimoto Yuki , Chatterjee Seema , Chen Lea Ann , Kamada Nobuhiko , Donia Mohamed S. 
Published: February 2024

AbstractChanges in the gut microbiome have been associated with several human diseases, but the molecular and functional details underlying these associations remain largely unknown. Here, we performed a multi-cohort analysis of small molecule biosynthetic gene clusters (BGCs) in 5,306 metagenomic samples of the gut microbiome from 2,033 Inflammatory Bowel Disease (IBD) patients and 833 matched healthy subjects and identified a group of Clostridia-derived BGCs that are significantly associated with IBD. Using synthetic biology, we discovered and solved the structures of six fatty acid amides as the products of the IBD-enriched BGCs. Using two mouse models of colitis, we show that the discovered small molecules disrupt gut permeability and exacerbate inflammation in chemically and genetically susceptible mice. These findings suggest that microbiome-derived small molecules may play a role in the etiology of IBD and represent a generalizable approach for discovering molecular mediators of microbiome-host interactions in the context of microbiome-associated diseases.