bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic susceptibility and causal pathway analysis of eye disorders coexisting in multiple sclerosis
Authors: Qiu Xuecheng , Huang Mi Ni , Ping Suning 
Published: February 2024

IntroductionThe comorbidity of optic neuritis with multiple sclerosis has been well recognized. However, the causal association between multiple sclerosis and optic neuritis, as well as other eye disorders, remains incompletely understood. To address these gaps, we investigated the genetically relationship between multiple sclerosis and eye disorders, and explored potential drugs.MethodsIn order to elucidate the genetic susceptibility and causal links between multiple sclerosis and eye disorders, we performed two-sample Mendelian randomization analyses to examine the causality between multiple sclerosis and eye disorders. Additionally, causal single-nucleotide polymorphisms were annotated and searched for expression quantitative trait loci data. Pathway enrichment analysis was performed to identify the possible mechanisms responsible for the eye disorders coexisting with multiple sclerosis. Potential therapeutic chemicals were also explored using the Cytoscape.ResultsMendelian randomization analysis revealed that multiple sclerosis increased the incidence of optic neuritis while reducing the likelihood of concurrent of cataract and macular degeneration. Gene Ontology enrichment analysis implicated that lymphocyte proliferation, activation and antigen processing as potential contributors to the pathogenesis of eye disorders coexisting with multiple sclerosis. Furthermore, pharmaceutical agents traditionally employed for allograft rejection exhibited promising therapeutic potential for the eye disorders coexisting with multiple sclerosis.DiscussionMultiple sclerosis genetically contributes to the development of optic neuritis while mitigating the concurrent occurrence of cataract and macular degeneration. Further research is needed to validate these findings and explore additional mechanisms underlying the comorbidity of multiple sclerosis and eye disorders.
Clinical and microbiological features of host-bacterial interplay in chronic venous ulcers versus other types of chronic skin ulcers
Authors: Mihai Mara Mădălina , Popa Mircea Ioan , Holban Alina Maria , Gheorghe-Barbu Irina , Popa Liliana Gabriela , Chifiriuc Mariana-Carmen , Giurcăneanu Călin , Bleotu Coralia , Cucu Corina Ioana , Lazăr Veronica 
Published: February 2024

IntroductionChronic venous ulcers of the lower limbs develop in the context of advanced venous disease and have a significant impact on the patient’s quality of life, being associated with depression and worrisome suicide rates, as well as with an economic burden caused by increased medical care costs and high epidemiological risks of healthcare associated infections and emergence of strains resistant to multiple classes of antibiotics and/ or antiseptics. Although numerous studies have investigated the composition of the chronic wounds microbiome, either by culture-dependent or independent methods, there are no data on the association between virulence and resistance profiles of strains isolated from venous ulcers and the clinical picture of this pathology. The elucidation of pathogenic mechanisms, at both phenotypic and molecular level, is crucial in the fight against these important human microbial agents, in order to develop novel biomarkers and discover new therapeutic targets.MethodsIn this study we aimed to characterize the phenotypic virulence profiles (including the ability to develop biofilms) of microorganisms isolated from chronic skin wounds and to correlate them with the clinical symptomatology. Considering the high incidence of Staphylococcus aureus infections in chronic ulcers, but also the ability of this species to develop multi-drug resistance, we performed an more in-depth study of the phenotypic and genotypic virulence profiles of methicillin-resistant Staphylococcus.ResultsThe study revealed important differences regarding the clinical evolution and virulence profiles of microorganisms isolated from lower limb wounds, as well as between patients diagnosed with chronic venous ulcers and those with lesions of different etiology.
The prognosis of TP53 and EGFR co-mutation in patients with advanced lung adenocarcinoma and intracranial metastasis treated with EGFR-TKIs
Authors: Gu Weiguo , Liu Penghui , Tang Jiaming , Lai Jianfei , Wang Siya , Zhang Jiaming , Xu Jinbiao , Deng Jianxiong , Yu Feng , Shi Chao , Qiu Feng 
Published: February 2024

BackgroundTP53 mutation is a poor factor for non-small cell lung cancer (NSCLC), while the effect of TP53 on prognosis in epidermal growth factor receptor (EGFR)-mutated lung adenocarcinoma (LUAD) with brain metastasis remains elusive and needs further exploration.MethodsWe retrospectively analyzed 236 patients and tested for TP53- and EGFR-mutant status in metastasis LUAD patients who had received first-line EGFR-tyrosine kinase inhibitor (TKI) treatment. Survival rates were calculated by the Kaplan–Meier method. Furthermore, univariate and multivariate Cox analyses were performed to identify the independent prognostic factors.ResultsThere were 114 patients with confirmed non-brain metastasis (NBM), 74 patients with preliminary diagnosis early brain metastasis (EBM), and 48 patients with late brain metastasis (LBM). TP53 and EGFR co-mutations were found in 35/236 patients (14.8%). The median progression-free survival (PFS) and overall survival (OS) in the EGFR mutation and TP53 wild-type group were significantly longer than those in the EGFR and TP53 co-mutation group in all advanced LUAD or NBM. Concurrently, PFS and OS were found to be not significant in EBM and LBM patients. Subgroup analysis revealed longer median PFS and OS in the TP53 wild-type group compared to the TP53 mutant group in L858R patients and not significant in EGFR Exon 19 deletion patients. In LBM patients, the time to brain metastasis in the EGFR mutation and TP53 wild-type group was longer than that in the EGFR and TP53 co-mutation group, and TP53 mutant status was an independent prognostic factor for brain metastasis. The TP53 wild-type group exhibited a higher objective remission rate (ORR) and disease control rate (DCR) than the TP53 mutant group in NBM, EBM, and LBM patients, irrespective of primary lung and brain metastatic lesions.ConclusionTP53/EGFR co-mutation patients receiving first-line EGFR-TKI treatment had poor prognoses in advanced LUAD, especially with L858R mutation. Moreover, TP53/EGFR co-mutation patients treated with EGFR-TKIs may more easy developed intracranial metastasis.
The role of blood metabolites in oral cancer: insights from a Mendelian randomization approach
Authors: Hu Ziyang , Xu Zhe , Yue Qu , Pan Xuhong , Shi Ping , Zhang Dandan , Zhang Jiexia , Deng Runzhi , Lin Zitong 
Published: February 2024

AimThis research aimed to explore the causal impact of blood metabolites on oral cancer using a two-sample Mendelian randomization (MR) analysis. The study endeavored to identify potential biomarkers for oral cancer’s clinical management.Materials and methodsBased on the large individual-level datasets from UK Biobank as well as GWAS summary datasets, we first constructed genetic risk scores (GRSs) of 486 human blood metabolites and evaluated the effect on oral cancer. Various statistical methods, including inverse variance weighted (IVW), MR-Egger, and weighted median, among others, were employed to analyze the potential causal relationship between blood metabolites and oral cancer. The sensitivity analyses were conducted using Cochran’s Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests.Results29 metabolites met the stringent selection criteria. Out of these, 14 metabolites demonstrated a positive association with oral cancer risk, while 15 metabolites indicated a protective effect against oral cancer. The IVW-derived estimates were significant, and the results were consistent across different statistical methodologies. Both the Cochran Q test and the MR-Egger intercept test indicated no heterogeneity and pleiotropy.ConclusionThis MR study offers evidence of the role specific blood metabolites play in oral cancer, pinpointing several with potential risk or protective effects. These findings could be helpful for new diagnostic tools and treatments for oral cancer. While the results are promising, additional research is necessary to fully validate and refine these conclusions. This study serves as a foundational step towards more comprehensive understandings in the future.
Potential mechanisms for osteopathic manipulative treatment to alleviate migraine-like pain in female rats
Authors: Byrd Katherine , Lund Makayla , Pan Yan , Chung Brandon H. , Child Kaitlyn , Fowler Danny , Burns-Martin Jared , Sanikommu Mythili , Henderson Hallie , Gregory Caroline , Fleming Regina K. , Xie Jennifer Yanhua 
Published: February 2024

IntroductionMigraines are the leading cause of disability in the United States, and the use of non-pharmaceutical treatments like osteopathic manipulative treatment (OMT) has shown promise. Despite its potential, the lack of mechanistic understanding has hindered widespread adoption. This study aims to investigate the efficacy of OMT in treating acute migraines and unravel its underlying mechanisms of action.MethodsFemale rats were subjected to a “two-hit” approach to induce migraine-like pain. This involved bilateral injections of Complete Freund's Adjuvant (CFA) into the trapezius muscle (1st hit) followed by exposure to Umbellulone, a human migraine trigger, on Day 6 post-CFA (2nd hit). Soft tissue and articulatory techniques were applied to the cervical region for acute abortive or repeated prophylactic treatment. Cutaneous allodynia and trigeminal system activation were assessed through behavioral tests and immunohistochemical staining.ResultsFollowing Umbellulone inhalation, CFA-primed rats exhibited periorbital and hind paw allodynia. Immediate application of OMT after Umbellulone inhalation as an abortive treatment partially alleviated cutaneous allodynia. With OMT applied thrice as a prophylactic measure, complete suppression of tactile hypersensitivity was observed. Prophylactic OMT also prevented the increase of c-fos signals in the trigeminal nucleus caudalis and the elevation of calcitonin gene-related peptide expression in trigeminal ganglia induced by CFA and Umbellulone exposure at 2 h post-inhalation.DiscussionThese findings provide mechanistic insights into OMT's migraine-relief potential and underscore its viability as a non-pharmacological avenue for managing migraines.
Effectiveness of anticoagulant therapy using heparin combined with Plavix after Rex shunt
Authors: Zhang JinShan , Li Long 
Published: February 2024

PurposeRex shunt is an optimal surgery for the treatment of extra-hepatic portal venous obstruction (EHPVO) in children. Anticoagulant therapy has been used to keep the patency of the bypass vein in the Rex shunt. This study was to investigate the effectiveness of anticoagulant therapy using heparin combined with Plavix in improving the prognosis and shunt patency of Rex shunt.MethodsFrom January 2010 to September 2019, 51 children with EHPVO underwent a portal cavernoma- Rex shunt. Based on whether using the anticoagulant therapy after the Rex shunt, all patients were divided into two groups: the anticoagulant group and the non-anticoagulant group. The diameter and flow velocity of the bypass vein were measured by the post-operative ultrasound, which was used to calculate the flow volume of the bypass vein (FV) and standard portal venous flow (SPVF). The bypass venous flow index (BVFI) was used to evaluate the ability of portal blood into the liver through the bypass vein after the Rex shunt, which was a ratio of FV to SPVF. The incidence of post-operative re-bleeding, the postoperative patency rate of the bypass vein, the remission rate of postoperative hypersplenism, the remission rate of postoperative esophagogastric varices and the BVFI were compared between the two groups.ResultsOf the 51 patients, 12 patients in the anticoagulant group were treated with heparin combined with Plavix after Rex shunt; 39 patients in the non-anticoagulant group were not treated with any anticoagulant therapy. 8 of 51 patients suffered from postoperative re-bleeding, of whom 6 patients with thrombosis of the bypass vein and 2 patients with anastomotic stenosis of the bypass vein. All 8 patients with re-bleeding belonged to the non-anticoagulant group. The remission rate of hypersplenism was no significant difference between the two groups after surgery (91% vs. 58%, P = 0.100). However, 3 patients without hypersplenism before surgery suffered from hypersplenism after surgery, who belonged to the non-anticoagulant group. There was no significant difference in the remission rate of esophagogastric varices (33% vs. 46%, P = 1.000). The BVFI of the anticoagulant group was significantly higher than that of the non-anticoagulant group (5.71 ± 5.89 vs. 1.1 ± 1.52, P = 0.003).ConclusionsAnticoagulant therapy using heparin combined with Plavix plays an important role in maintaining the patency of the bypass vein, which improved the portal blood flow into the liver through the bypass vein after the Rex shunt.
Concomitant inhibition of PI3K/mTOR signaling pathways boosts antiproliferative effects of lanreotide in bronchopulmonary neuroendocrine tumor cells
Authors: von Hessert-Vaudoncourt Claus , Lelek Sara , Geisler Christina , Hartung Teresa , Bröker Vanessa , Briest Franziska , Mochmann Liliana , Jost-Brinkmann Fabian , Sedding Dagmar , Benecke Joana , Freitag Helma , Wolfshöfer Sebastian , Lammert Hedwig , Nölting Svenja , Hummel Michael , Schrader Jörg , Grabowski Patricia 
Published: February 2024

Introduction: Somatostatin analogues (SSAs) are commonly used in the treatment of hormone hypersecretion in neuroendocrine tumors (NETs), however the extent to which they inhibit proliferation is much discussed.Objective: We studied the antiproliferative effects of novel SSA lanreotide in bronchopulmonary NETs (BP-NETs). We focused on assessing whether pretreating cells with inhibitors for phosphatidylinositol 3-kinase (PI3K) and mammalian target for rapamycin (mTOR) could enhance the antiproliferative effects of lanreotide.Methods: BP-NET cell lines NCI-H720 and NCI-H727 were treated with PI3K inhibitor BYL719 (alpelisib), mTOR inhibitor everolimus and SSA lanreotide to determine the effect on NET differentiation markers, cell survival, proliferation and alterations in cancer-associated pathways. NT-3 cells, previously reported to express somatostatin receptors (SSTRs) natively, were used as control for SSTR expression.Results: SSTR2 was upregulated in NCI-H720 and NT-3 cells upon treatment with BYL719. Additionally, combination treatment consisting of BYL719 and everolimus plus lanreotide tested in NCI-H720 and NCI-H727 led to diminished cell proliferation in a dose-dependent manner. Production of proteins activating cell death mechanisms was also induced. Notably, a multiplexed gene expression analysis performed on NCI-H720 revealed that BYL719 plus lanreotide had a stronger effect on the downregulation of mitogens than lanreotide alone.Discussion/Conclusion: We report a widespread analysis of changes in BP-NET cell lines at the genetic/protein expression level in response to combination of lanreotide with pretreatment consisting of BYL719 and everolimus. Interestingly, SSTR expression reinduction could be exploited in therapeutic and diagnostic applications. The overall results of this study support the evaluation of combination-based therapies using lanreotide in preclinical studies to further increase its antiproliferative effect and ultimately facilitate its use in high-grade tumors.
Mitophagy regulates mitochondrial number following pharmacological induction of mitochondrial biogenesis in renal proximal tubule cells
Authors: Hurtado Kevin A. , Schnellmann Rick G. 
Published: February 2024

Background: Mitochondrial biogenesis (MB) induction through the activation of the 5-Hydroxytriptamine (5-HT) 1F receptor (HTR1F) is a promising mechanism for the treatment of diseases characterized by mitochondrial dysfunction, such as acute kidney injury (AKI). While several studies report pharmacological activation of MB in the proximal tubule, it is unclear how the proximal tubule regulates itself once the pharmacological activation is removed. Mitophagy is the process of selective mitochondria degradation. We hypothesize that mitophagy decreases mitochondrial number after pharmacological stimulation and restore mitochondrial homeostasis.Methods: Renal proximal tubules were treated at time 0hr with LY344864 or vehicle for 24 h and then removed. LY344864, a selective HTR1F agonist, induces MB in renal proximal tubules as previously reported (Gibbs et al., Am J Physiol Renal Physiol, 2018, 314(2), F260–F268). Vehicle and pharmacological reagents were added at the 24 h time point. Electron microscopy was used to assess mitochondrial morphology, number, and autolysosomes. Seahorse Bioscience XF-96 extracellular flux analyzer was used to measure maximal mitochondrial oxygen consumption rates (FCCP-OCR), a functional marker of MB.Results: LY344864 treatment increased FCCP-OCR, phosphorylation of protein kinase B (AKT), peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α), and mitochondrial number after 24 h. These endpoints decreased to baseline 24 h after LY344864 removal. Treatment with ROC-325, an autophagy inhibitor, increased Sequestosome-1 (SQSTM1/P62) and microtubule-associated protein-1 light chain 3 (LC3B) after 24 h of treatment. Also, ROC-325 treatment sustained the elevated mitochondrial number after LY344864 pre-treatment and removal.Conclusion: These data revealed that inhibition of autophagy extends elevated mitochondrial number and function by preventing the lysosomal degradation of mitochondria after the removal of LY344864.
The crucial role of lateral root angle in enhancing drought resilience in cotton
Authors: Guo Congcong , Bao Xiaoyuan , Sun Hongchun , Chen Jing , Zhu Lingxiao , Zhang Jianhong , Zhang Haina , Zhang Yongjiang , Zhang Ke , Bai Zhiying , Li Anchang , Liu Liantao , Li Cundong 
Published: February 2024

IntroductionPlant responses to drought stress are influenced by various factors, including the lateral root angle (LRA), stomatal regulation, canopy temperature, transpiration rate and yield. However, there is a lack of research that quantifies their interactions, especially among different cotton varieties.MethodsThis experiment included two water treatments: well-watered (75 ± 5% soil relative water content) and drought stress (50 ± 5% soil relative water content) starting from the three-leaf growth stage. ResultsThe results revealed that different LRA varieties show genetic variation under drought stress. Among them, varieties with smaller root angles show greater drought tolerance. Varieties with smaller LRAs had significantly increased stomatal opening by 15% to 43%, transpiration rate by 61.24% and 62.00%, aboveground biomass by 54% to 64%, and increased seed cotton yield by 76% to 79%, and decreased canopy temperature by 9% to 12% under drought stress compared to the larger LRAs. Varieties with smaller LRAs had less yield loss under drought stress, which may be due to enhanced access to deeper soil water, compensating for heightened stomatal opening and elevated transpiration rates. The increase in transpiration rate promotes heat dissipation from leaves, thereby reducing leaf temperature and protecting leaves from damage. DiscussionDemonstrating the advantages conferred by the development of a smaller LRA under drought stress conditions holds value in enhancing cotton’s resilience and promoting its sustainable adaptation to abiotic stressors.
Adverse childhood experiences are associated with perceived cognitive difficulties among high school students in the United States
Authors: Iverson Ila A. , Cook Nathan E. , Iverson Grant L. 
Published: February 2024

ObjectiveAdverse childhood experiences (ACEs) are associated with mental health and cognitive problems, and mental health problems are associated with perceived cognitive difficulties among adolescents. The unique contribution of ACEs to cognitive difficulties after adjusting for poor mental health is not well understood and represents the purpose of this study.MethodsThe Adolescent Behaviors and Experiences Survey was conducted in 2021 with high school students in the United States. Cognitive difficulty was assessed with: ‘Because of a physical, mental, or emotional problem, do you have serious difficulty concentrating, remembering, or making decisions?’ Four ACEs were examined: sexual violence (lifetime and past 12 months), parental emotional abuse, and parental physical abuse. Students were asked about feeling sad or hopeless (past year), considering suicide (past year), and having poor mental health (past month). Binary logistic regressions examined the association between ACEs and cognitive problems, adjusting for mental health.ResultsParticipants were 6,945 students. Students reporting poor mental health were very likely to endorse difficulty concentrating, remembering, or making decisions (girls = 81% and boys = 67%). Cognitive difficulty was uncommon among students who denied poor mental health (girls = 17% and boys = 12%). For boys [p &lt; 0.001; R2 = 0.22] and girls [p &lt; 0.001; R2 = 0.31], after adjusting for mental health problems, independent predictors of cognitive difficulties included parental verbal abuse and physical abuse. For girls, lifetime forced sexual intercourse and sexual violence during the past year were also independently associated.ConclusionACEs are associated with perceived cognitive difficulty in both adolescent girls and boys, even after adjusting for poor mental health.