bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value and immune landscapes of TERT promoter methylation in triple negative breast cancer
Authors: Lin Fei , Huang Jiajia , Zhu Wancui , Jiang Tongchao , Guo Jia , Xia Wen , Chen Miao , Guo Ling , Deng Wuguo , Lin Huanxin 
Published: July 2023

BackgroundTreatment options for patients with triple-negative breast cancer (TNBC) remain limited to mainstay therapies owing to a lack of efficacious therapeutic targets. Accordingly, there is an urgent need to discover and identify novel molecular targets for the treatment and diagnosis of this disease. In this study, we analyzed the correlation of telomerase reverse transcriptase (TERT) methylation status with TERT expression, prognosis, and immune infiltration in TNBC and identified the role of TERT methylation in the regulation TNBC prognosis and immunotherapy.MethodsData relating to the transcriptome, clinicopathological characteristics and methylation of TNBC patients were obtained from The Cancer Genome Atlas (TCGA) database. TERT expression levels and differential methylation sites (DMSs) were detected. The correlations between TERT expression and DMSs were calculated. Kaplan–Meier curves was plotted to analyze the relationship between the survival of TNBC patients and the DMSs. The correlations of DMSs and TERT expression with several immunological characteristics of immune microenvironment (immune cell infiltration, immunomodulators, immune-related biological pathways, and immune checkpoints) were assessed. The results were validated using 40 TNBC patients from Sun Yat-sen University Cancer Center (SYSUCC).ResultsSix DMSs were identified. Among them, four sites (cg11625005, cg07380026, cg17166338, and cg26006951) were within the TERT promoter, in which two sites (cg07380026 and cg26006951) were significantly related to the prognosis of patients with TNBC. Further validation using 40 TNBC samples from SYSUCC showed that the high methylation of the cg26006951 CpG site was associated with poor survival prognosis (P=0.0022). TERT expression was significantly correlated with pathological N stage and clinical stage, and cg07380026 were significantly associated with pathological T and N stages in the TCGA cohort. Moreover, the methylation site cg26006951, cg07380026 and TERT expression were significantly correlated with immune cell infiltration, common immunomodulators, and the level of the immune checkpoint receptor lymphocyte activation gene 3 (LAG-3) in TNBC patients.ConclusionTERT promotertypermethylation plays an important role in TERT expression regulation and tumor microenvironment in TNBC. It is associated with overall survival and LAG-3 expression. TERT promoter hypermethylation may be a potential molecular biomarker for predicting response to the TERT inhibitors and immune checkpoint inhibitors in TNBC.
Lipedema stage affects adipocyte hypertrophy, subcutaneous adipose tissue inflammation and interstitial fibrosis
Authors: Kruppa Philipp , Gohlke Sabrina , Łapiński Kamila , Garcia-Carrizo Francisco , Soultoukis George A. , Infanger Manfred , Schulz Tim J. , Ghods Mojtaba 
Published: July 2023

IntroductionLipedema is a painful subcutaneous adipose tissue (SAT) disease characterized by adipocyte hypertrophy, immune cell recruitment, and fibrosis in the affected areas. These features are thought to contribute to the development and progression of the condition. However, the relationship between lipedema disease stage and the associated adipose tissue changes has not been determined so far.MethodsSAT biopsies of 32 lipedema patients, ranging across the pathological stages I to III, and 14 BMI- and age-matched controls were harvested from lipedema-affected thighs and non-symptomatic lower abdominal regions. Histological and immunohistochemical (IHC) staining and expression analysis of markers for adipogenesis, immunomodulation, and fibrosis were performed on the tissue biopsies.ResultsLipedema patients showed increased adipocyte areas and a stage-dependent shift towards larger cell sizes in the thighs. Lipedema SAT was linked with increased interstitial collagen accumulation in the thighs, but not the lower abdominal region when compared to controls. There was a trend toward progressive SAT fibrosis of the affected thighs with increasing lipedema stage. Elevated gene expression levels of macrophage markers were found for thigh SAT biopsies, but not in the abdominal region. IHC staining of lipedema thigh biopsies confirmed a transiently elevated macrophage polarization towards an M2-like (anti-inflammatory) phenotype.ConclusionsIn summary, lipedema SAT is associated with stage-dependent adipocyte hypertrophy, stage-progressive interstitial fibrosis and elevated proportion of M2-like macrophages. The character of the inflammatory response differs from primary obesity and may possess an essential role in the development of lipedema.
Bibliometric and visualized analysis of myopic corneal refractive surgery research: from 1979 to 2022
Authors: Yang Fang , Dong Yi , Bai Chen , Alzogool Mohammad , Wang Yan 
Published: July 2023

BackgroundMyopic corneal refractive surgery is one of the most prevalent ophthalmic procedures for correcting ametropia. This study aimed to perform a bibliometric analysis of research in the field of corneal refractive surgery over the past 40 years in order to describe the current international status and to identify most influential factors, while highlighting research hotspots.MethodsA bibliometric analysis based on the Web of Science Core Collection (WoSCC) was used to analyze the publication trends in research related to myopic corneal refractive surgery. VOSviewer v.1.6.10 was used to construct the knowledge map in order to visualize the publications, distribution of countries, international collaborations, author productivity, source journals, cited references, keywords, and research hotspots in this field.ResultsA total of 4,680 publications on myopic corneal refractive surgery published between 1979 and 2022 were retrieved. The United States has published the most papers, with Emory University contributing to the most citations. The Journal of Cataract and Refractive Surgery published the greatest number of articles, and the top 10 cited references mainly focused on outcomes and wound healing in refractive surgery. Previous research emphasized “radial keratotomy (RK)” and excimer laser-associated operation methods. The keywords containing femtosecond (FS) laser associated with “small incision lenticule extraction (SMILE)” and its “safety” had higher burst strength, indicating a shift of operation methods and coinciding with the global trends in refractive surgery. The document citation network was clustered into five groups: (1) outcomes of refractive surgery: (2) preoperative examinations for refractive surgery were as follows: (3) complications of myopic corneal refractive surgery; (4) corneal wound healing and cytobiology research related to photorefractive laser keratotomy; and (5) biomechanics of myopic corneal refractive surgery.ConclusionThe bibliometric analysis in this study may provide scholars with valuable to information and help them better understand the global trends in myopic corneal refractive surgery research frontiers. Two stages of rapid development occurred around 1991 and 2013, shortly after the innovation of PRK and SMILE surgical techniques. The most cited articles mainly focused on corneal wound healing, clinical outcomes, ocular aberration, corneal ectasia, and corneal topography, representing the safety of the new techniques.
Uric acid and glaucoma: a systematic review and meta-analysis
Authors: Mohammadi Mohammad , Yarmohammadi Adeleh , Salehi-Abargouei Amin , Ghasemirad Hamidreza , Shirvani Mohammad , Ghoshouni Hamed 
Published: July 2023

BackgroundGlaucoma, the leading cause of irreversible blindness, is a common disorder that contributes to gradual optic nerve degeneration. The beneficial impacts of uric acid (UA) have been reported in some neurodegenerative conditions such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. But the results of current studies about the association between serum UA level and glaucoma are conflicting. The present meta-analysis was conducted to provide a better understanding of the association between serum UA level and glaucoma.MethodsWe searched the databases of PubMed, Scopus, Web of Science, and Google Scholar systematically until November 20, 2022 to identify case-control studies, comparing the serum UA concentrations of the patients with glaucoma and controls. The mean ± standard division difference was used to assess the difference in serum UA concentrations between the glaucoma patients and controls.ResultsSix studies involving 1,221 glaucoma patients and 1,342 control group were included in the present meta-analysis. This meta-analysis using a random effect model indicated that the mean UA level in glaucoma patients was 0.13 (I2 = 91.92%, 95% CI = −0.42 to 0.68) higher than the controls; however, it was not statistically significant.ConclusionsOur findings provide evidence that glaucoma patients have a higher serum UA level compared to the controls, but this difference is not statistically significant. Prospective studies are needed to determine the possible association between increased UA and glaucoma pathogenesis.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022364055, identifier: CRD42022364055.
Virtual brain simulations reveal network-specific parameters in neurodegenerative dementias
Authors: Monteverdi Anita , Palesi Fulvia , Schirner Michael , Argentino Francesca , Merante Mariateresa , Redolfi Alberto , Conca Francesca , Mazzocchi Laura , Cappa Stefano F. , Cotta Ramusino Matteo , Costa Alfredo , Pichiecchio Anna , Farina Lisa M. , Jirsa Viktor , Ritter Petra , Gandini Wheeler-Kingshott Claudia A. M. , D’Angelo Egidio 
Published: July 2023

IntroductionNeural circuit alterations lay at the core of brain physiopathology, and yet are hard to unveil in living subjects. The Virtual Brain (TVB) modeling, by exploiting structural and functional magnetic resonance imaging (MRI), yields mesoscopic parameters of connectivity and synaptic transmission.MethodsWe used TVB to simulate brain networks, which are key for human brain function, in Alzheimer’s disease (AD) and frontotemporal dementia (FTD) patients, whose connectivity and synaptic parameters remain largely unknown; we then compared them to healthy controls, to reveal novel in vivo pathological hallmarks.ResultsThe pattern of simulated parameter differed between AD and FTD, shedding light on disease-specific alterations in brain networks. Individual subjects displayed subtle differences in network parameter patterns that significantly correlated with their individual neuropsychological, clinical, and pharmacological profiles.DiscussionThese TVB simulations, by informing about a new personalized set of networks parameters, open new perspectives for understanding dementias mechanisms and design personalized therapeutic approaches.
Abnormal brain activity in lumbar disc herniation patients with chronic pain is associated with their clinical symptoms
Authors: Tang Cheng , Guo Guangxin , Fang Sitong , Yao Chongjie , Zhu Bowen , Kong Lingjun , Pan Xuanjin , Li Xinrong , He Weibin , Wu Zhiwei , Fang Min 
Published: July 2023

IntroductionLumbar disc herniation, a chronic degenerative disease, is one of the major contributors to chronic low back pain and disability. Although many studies have been conducted in the past on brain function in chronic low back pain, most of these studies did not classify chronic low back pain (cLBP) patients according to their etiology. The lack of etiologic classification may lead to inconsistencies between findings, and the correlation between differences in brain activation and clinical symptoms in patients with cLBP was less studied in the past.MethodsIn this study, 36 lumbar disc herniation patients with chronic low back pain (LDHCP) and 36 healthy controls (HCs) were included to study brain activity abnormalities in LDHCP. Visual analogue scale (VAS), oswestry disability index (ODI), self-rating anxiety scale (SAS), self-rating depression scale (SDS) were used to assess clinical symptoms.ResultsThe results showed that LDHCP patients exhibited abnormally increased and diminished activation of brain regions compared to HCs. Correlation analysis showed that the amplitude of low frequency fluctuations (ALFF) in the left middle frontal gyrus is negatively correlated with SAS and VAS, while the right superior temporal gyrus is positively correlated with SAS and VAS, the dorsolateral left superior frontal gyrus and the right middle frontal gyrus are negatively correlated with VAS and SAS, respectively.ConclusionLDHCP patients have brain regions with abnormally increased and abnormally decreased activation compared to healthy controls. Furthermore, some of the abnormally activated brain regions were correlated with clinical pain or emotional symptoms.
Maternal dietary fiber intake during pregnancy and child development: the Japan Environment and Children's Study
Authors: Miyake Kunio , Horiuchi Sayaka , Shinohara Ryoji , Kushima Megumi , Otawa Sanae , Yui Hideki , Akiyama Yuka , Ooka Tadao , Kojima Reiji , Yokomichi Hiroshi , Mochizuki Kazuki , Yamagata Zentaro ,   The Japan Environment Children's Study Group
Published: July 2023

BackgroundAnimal studies have shown that maternal low-fiber diets during pregnancy may impair brain development and function in offspring, but this has not been validated by epidemiological studies. The aim of this study was to investigate the link between maternal dietary fiber intake during pregnancy and neurodevelopmental delay in offspring using a large birth cohort.MethodsA total of 76,207 mother-infant pairs were analyzed using data from the Japan Environment and Children's Study, a nationwide prospective cohort study. Maternal dietary fiber intake was estimated using the food frequency questionnaire in mid-pregnancy. Maternal dietary fiber intake was adjusted for energy and classified into quintiles. Developmental delay was assessed in five domains using the Japanese version of the Ages and Stages Questionnaire, Third Edition at the age of 3 years. The logistic regression analysis was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) for the link between dietary fiber intake during pregnancy and developmental delay at the age of 3 years.ResultsThe lowest intake group of total dietary fiber had a higher risk of delayed communication [adjusted OR (aOR), 1.51; 95% CI, 1.32–1.74], fine motor (aOR, 1.45; 95% CI, 1.32–1.61), problem-solving (aOR, 1.46; 95% CI, 1.32–1.61), and personal-social skills (aOR, 1.30; 95% CI, 1.12–1.50) than did the highest intake group. An analysis that excluded the effects of insufficient folic acid intake during pregnancy also showed a similar trend.ConclusionThis study showed that maternal dietary fiber deficiency during pregnancy might influence an increased risk of neurodevelopmental delay in offspring.
Telmisartan versus metformin in downregulating myostatin gene expression and enhancing insulin sensitivity in the skeletal muscles of type 2 diabetic rat model
Authors: Abd-Eltawab Tammam Ahmed , Rizg Waleed Y. , Fakhry Boushra Amy , Alhelf Maha , Alissa Mohammed , Soliman Ghada F. , Nady Ouais Ghada , Hosny Khaled M. , Alkhalidi Hala M. , Elebiary Ahmed Magdy 
Published: July 2023

Objective: Telmisartan is an angiotensin receptor blocker (ARB) that specifically blocks angiotensin II type-1 receptors (AT1R). Telmisartan has been proven to have antidiabetic effects via a variety of mechanisms, and it can be utilized in some diabetic patients due to its dual benefit for hypertensive patients with type 2 DM (T2DM) and when the other oral antidiabetic medications are intolerable or contraindicated. However, its precise underlying hypoglycemic mechanism is still obscure.Aim of work: We sought to establish a link between telmisartan administration and myostatin expression in skeletal muscles of T2DM rat model as a potential hypoglycemic mechanism of telmisartan.Materials and Methods: 32 male albino rats were included in the study; 8 rats served as controls (group I). T2DM was inducted in the other 24 rats, which were then randomly subdivided into 3 groups (8 in each): (group II) the Diabetic group and (groups III and IV) which were treated with either telmisartan (8 mg/kg/day) or metformin (250 mg/kg/day) respectively via oral gavage for a 4-week period.Results: Telmisartan administration resulted in a significant improvement in OGTT, HOMA-IR, glucose uptake, and muscle mass/body ratios in Telmisartan group as compared to Diabetic group (p &lt; 0.05). Additionally, telmisartan induced a significant boost in adiponectin and IL-10 serum levels with a substantial drop in TNF-α and IL-6 levels in Telmisartan group compared to diabetic rats (p &lt; 0.05). Moreover, telmisartan significantly boosted SOD and GSH, and decreased MDA levels in the skeletal muscles of telmisartan group. Furthermore, a significant downregulation of myostatin and upregulation of insulin receptor, IRS-1, and IRS-3 genes in the skeletal muscles of Telmisartan group were also detected. Histologically, telmisartan attenuated the morphological damage in the skeletal muscle fibers compared to diabetic rats, as evidenced by a considerable decrease in the collagen deposition area percentage and a reduction in NF-kB expression in the muscle tissues of group III.Conclusion: Telmisartan administration dramatically reduced myostatin and NF-kB expressions in skeletal muscles, which improved insulin resistance and glucose uptake in these muscles, highlighting a novel antidiabetic mechanism of telmisartan in treating T2DM.
Feasibility study of nuclear excitation by electron capture using an electron beam ion trap
Authors: Wang Yumiao , Ma Zhiguo , Yang Yi , Fu Changbo , He Wanbing , Ma Yugang 
Published: July 2023

The nuclear excitation by electron capture (NEEC) mechanism is considered to be one of the most effective ways to excite nuclear isomers. Despite being proposed over 50 years ago, direct experimental evidence of NEEC is yet elusive. In this study, we propose an experimental scheme to examine the NEEC process using an electron beam ion trap (EBIT). In an EBIT, highly charged ions are bombarded by an electron beam, which can result in excitation of the nuclei in the trap through mechanisms such as NEEC and Coulomb excitation (CE), etc. Our calculations show that the total rates of NEEC production for some nuclei can reach over 0.1/s, which is higher than these from other mechanisms like CE. The proposed scheme may result in the confirmation of the existence of NEEC, and can also be used to study atomic nuclear excitation related processes.
Plasma polymers as targets for laser-driven proton-boron fusion
Authors: Tosca Marco , Molloy Daniel , McNamee Aaron , Pleskunov Pavel , Protsak Mariia , Biliak Kateryna , Nikitin Daniil , Kousal Jaroslav , Krtouš Zdeněk , Hanyková Lenka , Hanuš Jan , Biederman Hynek , Foster Temour , Nersisyan Gagik , Martin Philip , Ho Chloe , Macková Anna , Mikšová Romana , Borghesi Marco , Kar Satyabrata , Istokskaia Valeriia , Levy Yoann , Picciotto Antonino , Giuffrida Lorenzo , Margarone Daniele , Choukourov Andrei 
Published: July 2023

Laser-driven proton-boron (pB) fusion has been gaining significant interest for energetic alpha particles production because of its neutron-less nature. This approach requires the use of B- and H-rich materials as targets, and common practice is the use of BN and conventional polymers. In this work, we chose plasma-assisted vapour phase deposition to prepare films of oligoethylenes (plasma polymers) on Boron Nitride BN substrates as an advanced alternative. The r.f. power delivered to the plasma was varied between 0 and 50 W to produce coatings with different crosslink density and hydrogen content, while maintaining the constant thickness of 1 μm. The chemical composition, including the hydrogen concentration, was investigated using XPS and RBS/ERDA, whereas the surface topography was analyzed using SEM and AFM. We triggered the pB nuclear fusion reaction focusing laser pulses from two different systems (i.e., the TARANIS multi-TW laser at the Queen’s University Belfast (United Kingdom) and the PERLA B 10-GW laser system at the HiLASE center in Prague (Czech Republic)) directly onto these targets. We achieved a yield up to 108 and 104 alpha particles/sr using the TARANIS and PERLA B lasers, respectively. Radiative-hydrodynamic and particle-in-cell PIC simulations were performed to understand the laser-target interaction and retrieve the energy spectra of the protons. The nuclear collisional algorithm implemented in the WarpX PIC code was used to identify the region where pB fusion occurs. Taken together, the results suggest a complex relationship between the hydrogen content, target morphology, and structure of the plasma polymer, which play a crucial role in laser absorption, target expansion, proton acceleration and ultimately nuclear fusion reactions in the plasma.
Phylotranscriptomics supports numerous polyploidization events and phylogenetic relationships in Nicotiana
Authors: Wang Shuaibin , Gao Junping , Li Zhaowu , Chen Kai , Pu Wenxuan , Feng Chen 
Published: July 2023

IntroductionNicotiana L. (Solanaceae) is of great scientific and economic importance, and polyploidization has been pivotal in shaping this genus. Despite many previous studies on the Nicotiana phylogenetic relationship and hybridization, evidence from whole genome data is still lacking.MethodsIn this study, we obtained 995 low-copy genes and plastid transcript fragments from the transcriptome datasets of 26 Nicotiana species, including all sections. We reconstructed the phylogenetic relationship and phylogenetic network of diploid species.ResultsThe incongruence among gene trees showed that the formation of N. sylvestris involved incomplete lineage sorting. The nuclear–plastid discordance and nuclear introgression absence indicated that organelle capture from section Trigonophyllae was involved in forming section Petunioides. Furthermore, we analyzed the evolutionary origin of polyploid species and dated the time of hybridization events based on the analysis of PhyloNet, sequence similarity search, and phylogeny of subgenome approaches. Our results highly evidenced the hybrid origins of five polyploid sections, including sections Nicotiana, Repandae, Rusticae, Polydicliae, and Suaveolentes. Notably, we provide novel insights into the hybridization event of section Polydicliae and Suaveolentes. The section Polydicliae formed from a single hybridization event between maternal progenitor N. attenuata and paternal progenitor N. undulata; the N. sylvestris (paternal progenitor) and the N. glauca (maternal progenitor) were involved in the formation of section Suaveolentes.DiscussionThis study represents the first exploration of Nicotiana polyploidization events and phylogenetic relationships using the high-throughput RNA-seq approach. It will provide guidance for further studies in molecular systematics, population genetics, and ecological adaption studies in Nicotiana and other related species.