bluuebunny/crossref_metadata_2025_split huggingface dataset:
Next-generation of BBQ analogues that selectively target breast cancer
Authors: Baker Jennifer R. , Gilbert Jayne , O’Brien Nicholas S. , Russell Cecilia C. , McCluskey Adam , Sakoff Jennette A. 
Published: June 2024

We previously reported on the interaction of 10-chloro-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one (10-Cl-BBQ) with the Aryl hydrocarbon Receptor (AhR) and selective growth inhibition in breast cancer cell lines. We now report on a library of BBQ analogues with substituents on the phenyl and naphthyl rings for biological screening. Herein, we show that absence of the phenyl Cl of 10-Cl-BBQ to produce the simple BBQ molecule substantially enhanced the growth inhibitory effect with GI50 values of 0.001–2.1 μM in select breast cancer cell lines MCF-7, T47D, ZR-75-1, SKBR3, MDA-MB-468, BT20, BT474 cells, while having modest effects of 2.1–7 μM in other cell lines including HT29, U87, SJ-G2, A2780, DU145, BE2-C, MIA, MDA-MB-231 or normal breast cells, MCF10A (3.2 μM). The most potent growth inhibitory effect of BBQ was observed in the triple negative cell line, MDA-MB-468 with a GI50 value of 0.001 μM, presenting a 3,200-fold greater response than in the normal MCF10A breast cells. Additions of Cl, CH3, CN to the phenyl ring and ring expansion from benzoimidazole to dihydroquinazoline hindered the growth inhibitory potency of the BBQ analogues by blocking potential sites of CYP1 oxidative metabolism, while addition of Cl or NO2 to the naphthyl rings restored potency. In a cell-based reporter assay all analogues induced 1.2 to 10-fold AhR transcription activation. Gene expression analysis confirmed the induction of CYP1 oxygenases by BBQ. The CYP1 inhibitor α-naphthoflavone, and the SULT1A1 inhibitor quercetin significantly reduced the growth inhibitory effect of BBQ, confirming the importance of both phase I and II metabolic activation for growth inhibition. Conventional molecular modelling/docking revealed no significant differences between the binding poses of the most and least active analogues. More detailed DFT analysis at the DSD-PBEP86/Def-TZVPP level of theory could not identify significant geometric or electronic changes which would account for this varied AhR activation. Generation of Fukui functions at the same level of theory showed that CYP1 metabolism will primarily occur at the phenyl head group of the analogues, and substituents within this ring lead to lower cytotoxicity.
Iodine and other factors associated with fertility outcome following oil-soluble contrast medium hysterosalpingography: a prospective cohort study
Authors: Mathews Divya M. , Peart Jane M. , Sim Robert G. , Johnson Neil P. , O’Sullivan Susannah , Derraik José G B , Hofman Paul L. 
Published: June 2024

ObjectiveTo examine factors associated with fertility following hysterosalpingography (HSG) using an oil-soluble contrast medium (OSCM).DesignIn a prospective cohort study on 196 women undergoing OSCM HSG, we showed that iodine excess was almost universal (98%) and mild subclinical hypothyroidism was frequent (38%). Here, we report the analyses of secondary outcomes examining factors associated with the likelihood of pregnancy following the HSG.SettingAuckland, New Zealand (2019–2021).Sample196 women with primary or secondary infertility who underwent OSCM HSG.MethodsBaseline and serial urine iodine concentrations (UIC) and thyroid function tests were measured over six months following the HSG. Pregnancy and treatment with levothyroxine during the study period were documented.ResultsFollowing OSCM HSG, pregnancy rates were 49% in women aged &lt;40 years (77/158) but considerably lower (16%) among those ≥40 years (6/38). Similarly, live birth rates were markedly lower in women ≥40 years (17%; 1/6) versus &lt;40 years (73%; 56/77). 29% of participants were iodine deficient at baseline despite advice recommending iodine fortification. Following HSG, the likelihood of pregnancy in women with moderate iodine deficiency was 64% higher than in women with normal iodine levels (p=0.048). Among women aged &lt;40 years who had subclinical hypothyroidism (n=75), levothyroxine treatment was associated with higher pregnancy rates compared to untreated women [63% (26/48) vs 37% (10/27), respectively; p=0.047].ConclusionOSCM HSG was associated with higher pregnancy rates in women ≤40 than in those aged &gt;40 years. Iodine deficiency was relatively common in this cohort, and increased iodine levels from OSCM exposure may contribute to the improved fertility observed with this procedure. Trial registrationThis study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR: 12620000738921) https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000738921.
The association between weight change patterns and obesity-related complex multimorbidity: evidence from NHANES
Authors: Gong Hong-Jian , Tang Xingyao , Zhou Jian-Bo 
Published: June 2024

ObjectiveObesity is a major risk factor for non-communicable diseases (NCDs), which has been the leading cause of death nowadays. The aim of this study is to examine the association between total changes in body mass index (BMI) across adulthood and the risk of obesity-related complex multimorbidity in elderly, characterizing the capacity of BMI waves in predicting major chronic diseases.MethodsIn this retrospective study, 15,520 participants were analyzed from the National Health and Nutrition Examination Survey (NHANES) from 1999 and 2018. BMI was categorized as obesity (≥30.0 kg/m²), overweight (25.0–29.9 kg/m²), normal weight (18.5–24.9 kg/m²), and underweight (&lt;18.5 kg/m²). Odds ratios (ORs) with 95% confidence interval (CIs) for the relationship between BMI change patterns and major health outcomes included hypertension, cancer, chronic obstructive pulmonary disease, cardiovascular disease, and diabetes, and population attributable fractions (PAFs) of BMI were evaluated.ResultsIn comparison with participants who remained non-obese, those who are stable obese showed the highest risks of developing at least one chronic disease in later life, with odds ratios of 2.76 (95% CI: 2.20 to 3.45) from age 25 years to 10 years before baseline, 2.90 (2.28 to 3.68) from age 25 years to baseline, and 2.49 (2.11 to 2.95) in the 10-year period before baseline. Moving from non-obese to obese weight-change pattern in all periods (from age 25 years to 10 years before baseline: OR = 1.82; 95% CI, 1.57 to 2.11; from age 25 years to baseline: OR = 1.87; 95% CI, 1.59 to 2.19; from 10 years before baseline to baseline: OR = 1.62; 95% CI, 1.26 to 2.08) and moving from obese to non-obese, the 10-year period before baseline (OR = 1.89; 95% CI, 1.39 to 2.57) was associated with increased risk of chronic diseases. Midlife obesity status can explain the 8.6% risk of occurrence of the chronic diseases in elderly.ConclusionsMaintaining a stable healthy weight and losing weight in early adulthood and midlife are important for better life quality during the aging process. More effective strategies and policies to reduce the prevalence of obesity are needed.
Construction of a predictive model of 2–3 cm ground-glass nodules developing into invasive lung adenocarcinoma using high-resolution CT
Authors: Zhang Yifan , Qu Lin , Zhang Haihua , Wang Ying , Gao Guizhou , Wang Xiaodong , Zhang Tao 
Published: June 2024

BackgroundThe purpose of this study was to analyze the imaging risk factors for the development of 2–3 cm ground-glass nodules (GGN) for invasive lung adenocarcinoma and to establish a nomogram prediction model to provide a reference for the pathological prediction of 2–3 cm GGN and the selection of surgical procedures.MethodsWe reviewed the demographic, imaging, and pathological information of 596 adult patients who underwent 2–3 cm GGN resection, between 2018 and 2022, in the Department of Thoracic Surgery, Second Affiliated Hospital of the Air Force Medical University. Based on single factor analysis, the regression method was used to analyze multiple factors, and a nomogram prediction model for 2–3 cm GGN was established.Results(1) The risk factors for the development of 2–3 cm GGN during the invasion stage of the lung adenocarcinoma were pleural depression sign (OR = 1.687, 95%CI: 1.010–2.820), vacuole (OR = 2.334, 95%CI: 1.222–4.460), burr sign (OR = 2.617, 95%CI: 1.008–6.795), lobulated sign (OR = 3.006, 95%CI: 1.098–8.227), bronchial sign (OR = 3.134, 95%CI: 1.556–6.310), diameter of GGN (OR = 3.118, 95%CI: 1.151–8.445), and CTR (OR = 172.517, 95%CI: 48.023–619.745). (2) The 2–3 cm GGN risk prediction model was developed based on the risk factors with an AUC of 0.839; the calibration curve Y was close to the X-line, and the decision curve was drawn in the range of 0.0–1.0.ConclusionWe analyzed the risk factors for the development of 2–3  cm GGN during the invasion stage of the lung adenocarcinoma. The predictive model developed based on the above factors had some clinical significance.
Screening and characterization of a novel linear B-cell epitope on orf virus F1L protein
Authors: Zhang Zhibang , Zhang Xiaoyan , Feng Kang , Ba Shufan , Yang Taotao , Gong Jinxiang , Yang Ziyin , Zhang Hong , Sun Zilong , Li Pengcheng 
Published: June 2024

BackgroundOrf, also known as contagious ecthyma (CE), is an acute, contagious zoonotic disease caused by the orf virus (ORFV). The F1L protein is a major immunodominant protein on the surface of ORFV and can induce the production of neutralizing antibodies.MethodsThe prokaryotic expression system was used to produce the recombinant F1L protein of ORFV, which was subsequently purified and used to immunize mice. Positive hybridoma clones were screened using an indirect enzyme-linked immunosorbent assay (ELISA). The reactivity and specificity of the monoclonal antibody (mAb) were verified through Western blot and indirect immunofluorescence (IFA). The linear antigenic epitope specific to the mAb was identified through Western blot, using truncated F1L proteins expressed in eukaryotic cells. A multiple sequence alignment of the ORFV reference strains was performed to evaluate the degree of conservation of the identified epitope.ResultsAfter three rounds of subcloning, a mAb named Ba-F1L was produced. Ba-F1L was found to react with both the exogenously expressed F1L protein and the native F1L protein from ORFV-infected cells, as confirmed by Western blot and IFA. The mAb recognized the core epitope 103CKSTCPKEM111, which is highly conserved among various ORFV strains, as shown by homologous sequence alignment.ConclusionThe mAb produced in the present study can be used as a diagnostic reagent for detecting ORFV and as a basic tool for exploring the mechanisms of orf pathogenesis. In addition, the identified linear epitope may be valuable for the development of epitope-based vaccines.
Exploring causal correlations of inflammatory biomarkers in idiopathic normal-pressure hydrocephalus: insights from bidirectional Mendelian randomization analysis
Authors: Lu Jianglong , Wang Xianpeng , Xu Fanjie , Rao Changjun , Guo Yuhang , Su Zhipeng , Chen Siyan , Li Qun 
Published: June 2024

Background and objectiveNeuroinflammatory processes have been identified as playing a crucial role in the pathophysiology of various neurodegenerative diseases, including idiopathic normal-pressure hydrocephalus (iNPH). iNPH, defined as a common disease of cognitive impairment in older adults, poses major challenges for therapeutic interventions owing to the stringent methodological requirements of relevant studies, clinical heterogeneity, unclear etiology, and uncertain diagnostic criteria. This study aims to assess the relationship between circulating inflammatory biomarkers and iNPH risk using bidirectional two-sample Mendelian randomization (MR) combined with meta-analysis.MethodsIn our bidirectional MR study, genetic data from a genome-wide association study (GWAS) involving 1,456 iNPH cases and 409,726 controls of European ancestry were employed. Single-nucleotide polymorphisms (SNPs) associated with exposures served as instrumental variables for estimating the causal relationships between iNPH and 132 types of circulating inflammatory biomarkers from corresponding GWAS data. Causal associations were primarily examined using the inverse variance-weighted method, supplemented by MR-Egger, weighted median, simple mode, and weighted mode analyses. In the results, heterogeneity was assessed using the Cochran Q test. Horizontal pleiotropy was evaluated through the MR-Egger intercept test and the MR pleiotropy residual sum and outliers test. Sensitivity analysis was conducted through leave-one-out analysis. Reverse MR analyses were performed to mitigate bias from reverse causality. Meta-analyses of identical inflammatory biomarkers from both data sources strengthened the findings.ResultsResults indicated a genetically predicted association between Interleukin-16 (IL-16) [OR: 1.228, 95% CI: 1.049–1.439, p = 0.011], TNF-related apoptosis ligand (TRAIL) [OR: 1.111, 95% CI: 1.019–1.210, p = 0.017] and Urokinase-type plasminogen activator (uPA) [OR: 1.303, 95% CI: 1.025–1.658, p = 0.031] and the risk of iNPH. Additionally, changes in human Glial cell line-derived neurotrophic factor (hGDNF) [OR: 1.044, 95% CI: 1.006–1.084, p = 0.023], Matrix metalloproteinase-1 (MMP-1) [OR: 1.058, 95% CI: 1.020, 1.098, p = 0.003] and Interleukin-12p70 (IL-12p70) [OR: 0.897, 95% CI: 0.946–0.997, p = 0.037] levels were identified as possible consequences of iNPH.ConclusionOur MR study of inflammatory biomarkers and iNPH, indicated that IL-16, TRAIL, and uPA contribute to iNPH pathogenesis. Furthermore, iNPH may influence the expression of hGDNF, MMP-1, and IL-12p70. Therefore, targeting specific inflammatory biomarkers could be promising strategy for future iNPH treatment and prevention.
CT perfusion for predicting intracranial atherosclerotic middle cerebral artery occlusion
Authors: Wang Zigao , Yasheng Abudoukeyoumu , Ling Yifeng , Zhao Hongchen , Mao Yiting , Yang Shilin , Cao Wenjie 
Published: June 2024

Backgrounds and purposeIdentifying the underlying cause of acute middle cerebral artery occlusion (MCAO) as intracranial atherosclerotic stenosis (ICAS) or embolism is essential for determining the optimal treatment strategy before endovascular thrombectomy. We aimed to evaluate whether baseline computed tomography perfusion (CTP) characteristics could differentiate ICAS-related MCAO from embolic MCAO.MethodsWe conducted a retrospective analysis of the clinical and baseline CTP data from patients who underwent endovascular thrombectomy for acute MCAO between January 2018 and December 2022. Core volume growth rate was defined as core volume on CTP divided by onset to CTP time. Multivariate logistic analysis was utilized to identify independent predictors for ICAS-related acute MCAO, and the diagnostic performance of these predictors was evaluated using receiver operating characteristic curve analysis.ResultsAmong the 97 patients included (median age, 71 years; 60% male), 31 (32%) were diagnosed with ICAS-related MCAO, and 66 (68%) had embolism-related MCAO. The ICAS group was younger (p = 0.002), had a higher proportion of males (p = 0.04) and smokers (p = 0.001), a lower prevalence of atrial fibrillation (AF) (p &lt; 0.001), lower NIHSS score at admission (p = 0.04), smaller core volume (p &lt; 0.001), slower core volume growth rate (p &lt; 0.001), and more frequent core located deep in the brain (p &lt; 0.001) compared to the embolism group. Multivariate logistic analysis identified core volume growth rate (aOR 0.46, 95% CI 0.26–0.83, p = 0.01) as an independent predictor of ICAS-related MCAO. A cutoff value of 2.5 mL/h for core volume growth rate in predicting ICAS-related MCAO was determined from the receiver operating characteristic curve analysis, with a sensitivity of 81%, specificity of 80%, positive predictive value of 66%, and negative predictive value of 90%.ConclusionSlow core volume growth rate identified on baseline CTP can predict ICAS-related MCAO. Further prospective studies are warranted to confirm and validate these findings.
Predictive value of synaptic plasticity for functional decline in patients with multiple sclerosis
Authors: Balloff Carolin , Janßen Lisa Kathleen , Hartmann Christian Johannes , Meuth Sven Günther , Schnitzler Alfons , Penner Iris-Katharina , Albrecht Philipp 
Published: June 2024

BackgroundPrevious research suggested that quadripulse (QPS)-induced synaptic plasticity is associated with both cognitive and motor function in patients with multiple sclerosis (MS) and does not appear to be reduced compared to healthy controls (HCs).ObjectiveThis study aimed to explore the relationship between the degree of QPS-induced plasticity and clinically significant decline in motor and cognitive functions over time. We hypothesized that MS patients experiencing functional decline would exhibit lower levels of baseline plasticity compared to those without decline.MethodsQPS-induced plasticity was evaluated in 80 MS patients (56 with relapsing-remitting MS and 24 with progressive MS), and 69 age-, sex-, and education-matched HCs. Cognitive and motor functions, as well as overall disability status were evaluated annually over a median follow-up period of 2 years. Clinically meaningful change thresholds were predefined for each outcome measure. Linear mixed-effects models, Cox proportional hazard models, logistic regression, and receiver-operating characteristic analysis were applied to analyse the relationship between baseline plasticity and clinical progression in the symbol digit modalities test, brief visuospatial memory test revised (BVMT-R), nine-hole peg test (NHPT), timed 25-foot walk test, and expanded disability status scale.ResultsOverall, the patient cohort showed no clinically relevant change in any functional outcome over time. Variability in performance was observed across time points in both patients and HCs. MS patients who experienced clinically relevant decline in manual dexterity and/or visuospatial learning and memory had significantly lower levels of synaptic plasticity at baseline compared to those without such decline (NHPT: β = −0.25, p = 0.02; BVMT-R: β = −0.50, p = 0.005). Receiver-operating characteristic analysis underscored the predictive utility of baseline synaptic plasticity in discerning between patients experiencing functional decline and those maintaining stability only for visuospatial learning and memory (area under the curve = 0.85).ConclusionOur study suggests that QPS-induced plasticity could be linked to clinically relevant functional decline in patients with MS. However, to solidify these findings, longer follow-up periods are warranted, especially in cohorts with higher prevalences of functional decline. Additionally, the variability in cognitive performance in both patients with MS and HCs underscores the importance of conducting further research on reliable change based on neuropsychological tests.
Frontiers and hotspots in comorbid epilepsy and depression: a bibliometric analysis from 2003 to 2023
Authors: Liu Gui-Yu , Fu Fan-Jia , Chou Ying-Xin , Ye Ming-Sha , Ouyang Yi-Lin , Yan Ming-De , Pan Lei , Li Wei-Peng , Xie Wei 
Published: June 2024

BackgroundEpilepsy ranks among the most common neurological disorders worldwide, frequently accompanied by depression as a prominent comorbidity. This study employs bibliometric analysis to reveal the research of comorbid epilepsy and depression over the past two decades, aiming to explore trends and contribute insights to ongoing investigations.MethodsWe conducted a comprehensive search on the Web of Science Core Collection database and downloaded relevant publications on comorbid epilepsy and depression published from 2003 to 2023. VOSviewer and CiteSpace were mainly used to analyze the authors, institutions, countries, publishing journals, reference co-citation patterns, keyword co-occurrence, keyword clustering, and other aspects to construct a knowledge atlas.ResultsA total of 5,586 publications related to comorbid epilepsy and depression were retrieved, with a general upward trend despite slight fluctuations in annual publications. Publications originated from 121 countries and 636 institutions, with a predominant focus on clinical research. The United States led in productivity (1,529 articles), while Melbourne University emerged as the most productive institution (135 articles). EPILEPSY &amp; BEHAVIOR was the journal with the highest publication output (1,189 articles) and citation count. Keyword analysis highlighted emerging trends, including “recognitive impairment” and “mental health,” indicating potential future research hotspots and trends.ConclusionThis study is one of the first to perform a bibliometric analysis of the 20-year scientific output of comorbid epilepsy and depression. While research has trended upwards, ambiguity in pathogenesis and the absence of standardized diagnostic guidelines remain concerning. Our analysis offers valuable guidance for researchers, informing that this might be a strong area for future collaborations.
Hearing rehabilitation of adults with auditory processing disorder: a systematic review and meta-analysis of current evidence-based interventions
Authors: Crum Rachel , Chowsilpa Sanathorn , Kaski Diego , Giunti Paola , Bamiou Doris-Eva , Koohi Nehzat 
Published: June 2024

BackgroundFor adults with auditory processing disorder (APD), listening and communicating can be difficult, potentially leading to social isolation, depression, employment difficulties and certainly reducing the quality of life. Despite existing practice guidelines suggesting treatments, the efficacy of these interventions remains uncertain due to a lack of comprehensive reviews. This systematic review and meta-analysis aim to establish current evidence on the effectiveness of interventions for APD in adults, addressing the urgent need for clarity in the field.MethodsFollowing the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic search across MEDLINE (Ovid), Embase (Ovid), Web of Science and Scopus, focusing on intervention studies involving adults with APD. Studies that met the inclusion criteria were grouped according to intervention with a meta-analysis only conducted where intervention, study design and outcome measure were comparable.ResultsOut of 1,618 screened records, 13 studies were included, covering auditory training (AT), low-gain hearing aids (LGHA), and personal remote microphone systems (PRMS). Our analysis revealed: AT, Mixed results with some improvements in speech intelligibility and listening ability, indicating potential benefits but highlighting the need for standardized protocols; LGHA, The included studies demonstrated significant improvements in monaural low redundancy speech testing (p &lt; 0.05), suggesting LGHA could enhance speech perception in noisy environments. However, limitations include small sample sizes and potential biases in study design. PRMS, Demonstrated the most consistent evidence of benefit, significantly improving speech testing results, with no additional benefit from combining PRMS with other interventions.DiscussionPRMS presents the most evidence-supported intervention for adults with APD, although further high-quality research is crucial for all intervention types. The establishment and implementation of standardized intervention protocols alongside rigorously validated outcome measures will enable a more evidence-based approach to managing APD in adults.