bluuebunny/crossref_metadata_2025_split huggingface dataset:
27-hydroxycholesterol and DNA damage repair: implication in prostate cancer
Authors: Galvan Gloria Cecilia , Friedrich Nadine A. , Das Sanjay , Daniels James P. , Pollan Sara , Dambal Shweta , Suzuki Ryusuke , Sanders Sergio E. , You Sungyong , Tanaka Hisashi , Lee Yeon-Joo , Yuan Wei , de Bono Johann S. , Vasilevskaya Irina , Knudsen Karen E. , Freeman Michael R. , Freedland Stephen J. 
Published: December 2023

IntroductionWe previously reported that cholesterol homeostasis in prostate cancer (PC) is regulated by 27-hydroxycholesterol (27HC) and that CYP27A1, the enzyme that converts cholesterol to 27HC, is frequently lost in PCs. We observed that restoring the CYP27A1/27HC axis inhibited PC growth. In this study, we investigated the mechanism of 27HC-mediated anti-PC effects.MethodsWe employed in vitro models and human transcriptomics data to investigate 27HC mechanism of action in PC. LNCaP (AR+) and DU145 (AR-) cells were treated with 27HC or vehicle. Transcriptome profiling was performed using the Affymetrix GeneChip™ microarray system. Differential expression was determined, and gene set enrichment analysis was done using the GSEA software with hallmark gene sets from MSigDB. Key changes were validated at mRNA and protein levels. Human PC transcriptomes from six datasets were analyzed to determine the correlation between CYP27A1 and DNA repair gene expression signatures. DNA damage was assessed via comet assays.ResultsTranscriptome analysis revealed 27HC treatment downregulated Hallmark pathways related to DNA damage repair, decreased expression of FEN1 and RAD51, and induced “BRCAness” by downregulating genes involved in homologous recombination regulation in LNCaP cells. Consistently, we found a correlation between higher CYP27A1 expression (i.e., higher intracellular 27HC) and decreased expression of DNA repair gene signatures in castration-sensitive PC (CSPC) in human PC datasets. However, such correlation was less clear in metastatic castration-resistant PC (mCRPC). 27HC increased expression of DNA damage repair markers in PC cells, notably in AR+ cells, but no consistent effects in AR- cells and decreased expression in non-neoplastic prostate epithelial cells. While testing the clinical implications of this, we noted that 27HC treatment increased DNA damage in LNCaP cells via comet assays. Effects were reversible by adding back cholesterol, but not androgens. Finally, in combination with olaparib, a PARP inhibitor, we showed additive DNA damage effects.DiscussionThese results suggest 27HC induces “BRCAness”, a functional state thought to increase sensitivity to PARP inhibitors, and leads to increased DNA damage, especially in CSPC. Given the emerging appreciation that defective DNA damage repair can drive PC growth, future studies are needed to test whether 27HC creates a synthetic lethality to PARP inhibitors and DNA damaging agents in CSPC.
Use of PIRADS 2.1 to predict capsular invasion in patients with radiologic T3a prostate cancer
Authors: Song Wan , Ko Kwang Jin , Lee Jae Kyung , Kang Minyong , Sung Hyun Hwan , Jeon Hwang Gyun , Jeong Byong Chang , Seo Seong IL. , Jeon Seong Soo , Chung Jae Hoon 
Published: December 2023

ObjectiveUsing multi-parametric magnetic resonance imaging (mpMRI) to identify patients with clinical T3a (cT3a) who were overestimated on mpMRI with final pathological T2 (pT2). To suggest that the neurovascular bundle (NVB) can be preserved by evaluating the characteristics of patients according to their pathological grade among cT3a prostate cancer (PCa) patients using mpMRI.Materials and methodsPatients who underwent robot-assisted laparoscopic radical prostatectomy (RALP) were retrospectively analyzed and those patients with clinical T3aN0M0 were enrolled. These enrolled patients were divided into a localized cancer group with pT2 PCa and a locally advanced group with pT3a or higher. Factors affecting the diagnosis of localized PCa after RALP in patients with cT3a PCa were evaluated.ResultsAmong the preoperative parameters of patients with cT3a PCa, the prostate specific antigen density (PSAD) (OR: 3.76, 95% CI: 1.85–7.64, p&lt;0.001), international society of urological pathology (ISUP) grade (p&lt;0.05), and index lesion size (OR: 1.44, 95% CI: 1.85–7.64, p&lt;0.001) were significantly associated with pathological locally advanced PCa. Optimal cut-off values for prediction of pT3a or higher were 0.36 ng/mL2 for PSAD (sensitivity: 55.7%, specificity: 70.8%), 1.77 cm for index lesion size (sensitivity: 54.3%, specificity: 66.0%), and 2.5 for ISUP grading (sensitivity: 67.6%, specificity: 53.2%). For prediction of pT3a or higher among patients with cT3a PCa, a nomogram was developed using ISUP grade, index lesion size, and PSAD on prostate biopsy (area under the curve: 0.71, 95% CI: 0.670–0.754, p&lt;0.001). PSAD less than 0.36 index lesion size less than 1.77 cm, and biopsy ISUP grade 1–2 are highly likely to indicate that there is no actual extracapsular extension in cT3a PCa patients.ConclusionsPSAD, ISUP, and index lesion size showed significant associations with the classification of pathologic localized and locally advanced PCa in patients with cT3a PCa. A nomogram including these features can predict the diagnosis of locally advanced PCa in patients with cT3a PCa.
Diffusion MRI correlation with p16 status and prediction for tumor progression in locally advanced head and neck cancer
Authors: Cao Yue , Aryal M. , Li P. , Lee C. , Schipper M. , You D. , Jaworski E. , Gharzai L. , Shah J. , Eisbruch A. , Mierzwa Michelle 
Published: December 2023

PurposeTo investigate p16 effects on diffusion image metrics and associations with tumor progression in patients with locally advanced head and neck cancers.MethodsDiffusion images pretreatment and after 20 Gy (2wk) of RT were analyzed in patients with cT4/N3 p16+ oropharynx cancer (OPSCC) (N=51) and locoregionally advanced head and neck squamous cell carcinoma (LAHNSCC) (N=28), enrolled onto a prospective adaptive RT trial. Mean ADC values, subvolumes with ADC &lt;1.2 um2/ms (TVLADC), and peak values of low (µL) and high (µH) components of ADC histograms in primary and total nodal gross tumor volumes were analyzed for prediction of freedom from local, distant, or any progression (FFLP, FFDP or FFLRDP) using multivariate Cox proportional-hazards model with clinical factors. P value with false discovery control &lt;0.05 was considered as significant.ResultsWith a mean follow up of 36 months, 18 of LAHNSCC patients and 16 of p16+ OPSCC patients had progression. After adjusting for p16, small µL and ADC values, and large TVLADC of primary tumors pre-RT were significantly associated with superior FFLRDP, FFLP and FFDP in the LAHNSCC (p&lt;0.05), but no diffusion metrics were significant in p16+ oropharynx cancers. Post ad hoc analysis of the p16+ OPSCC only showed that large TVLADC of the total nodal burden pre-RT was significantly associated with inferior FFDP (p=0.05).ConclusionADC metrics were associated with different progression patterns in the LAHNSCC and p16+ OPSCC, possibly explained by differences in cancer biology and morphology. A deep understanding of ADC metrics is warranted to establish imaging biomarkers for adaptive RT in HNSCC.
Research hotspots and trends on neuropathic pain-related mood disorders: a bibliometric analysis from 2003 to 2023
Authors: Wang Xiaohua , Zhuang Yueyang , Lin Zhigang , Chen Shuijin , Chen Lechun , Huang Hongye , Lin Hui , Wu Shiye 
Published: December 2023

IntroductionNeuropathic Pain (NP) is often accompanied by mood disorders, which seriously affect the quality of life of patients. This study aimed to analyze the hotspots and trends in NP-related mood disorder research using bibliometric methods and to provide valuable predictions for future research in this field.MethodsArticles and review articles on NP-related mood disorders published from January 2003 to May 2023 were retrieved from the Web of Science Core Collection. We used CiteSpace to analyze publications, countries, institutions, authors, cited authors, journals, cited journals, references, cited references, and keywords. We also analyzed collaborative network maps and co-occurrence network maps.ResultsA total of 4,540 studies were collected for analysis. The number of publications concerning NP-related mood disorders every year shows an upward trend. The United States was a major contributor in this field. The University of Toronto was the most productive core institution. C GHELARDINI was the most prolific author, and RH DWORKIN was the most frequently cited author. PAIN was identified as the journal with the highest productivity and citation rate. The current research hotspots mainly included quality of life, efficacy, double-blind methodology, gabapentin, pregabalin, postherpetic neuralgia, and central sensitization. The frontiers in research mainly focused on the mechanisms associated with microglia activation, oxidative stress, neuroinflammation, and NP-related mood disorders.DiscussionIn conclusion, the present study provided insight into the current state and trends in NP-related mood disorder research over the past 20 years. Consequently, researchers will be able to identify new perspectives on potential collaborators and cooperative institutions, hot topics, and research frontiers in this field.
Association between mortality and critical events within 48 hours of transfer to the pediatric intensive care unit
Authors: Liang Huan , Carey Kyle A. , Jani Priti , Gilbert Emily R. , Afshar Majid , Sanchez-Pinto L. Nelson , Churpek Matthew M. , Mayampurath Anoop 
Published: December 2023

IntroductionCritical deterioration in hospitalized children, defined as ward to pediatric intensive care unit (PICU) transfer followed by mechanical ventilation (MV) or vasoactive infusion (VI) within 12 h, has been used as a primary metric to evaluate the effectiveness of clinical interventions or quality improvement initiatives. We explore the association between critical events (CEs), i.e., MV or VI events, within the first 48 h of PICU transfer from the ward or emergency department (ED) and in-hospital mortality.MethodsWe conducted a retrospective study of a cohort of PICU transfers from the ward or the ED at two tertiary-care academic hospitals. We determined the association between mortality and occurrence of CEs within 48 h of PICU transfer after adjusting for age, gender, hospital, and prior comorbidities.ResultsExperiencing a CE within 48 h of PICU transfer was associated with an increased risk of mortality [OR 12.40 (95% CI: 8.12–19.23, P &lt; 0.05)]. The increased risk of mortality was highest in the first 12 h [OR 11.32 (95% CI: 7.51–17.15, P &lt; 0.05)] but persisted in the 12–48 h time interval [OR 2.84 (95% CI: 1.40–5.22, P &lt; 0.05)]. Varying levels of risk were observed when considering ED or ward transfers only, when considering different age groups, and when considering individual 12-h time intervals.DiscussionWe demonstrate that occurrence of a CE within 48 h of PICU transfer was associated with mortality after adjusting for confounders. Studies focusing on the impact of quality improvement efforts may benefit from using CEs within 48 h of PICU transfer as an additional evaluation metric, provided these events could have been influenced by the initiative.
Serum metabolomics characteristics and fatty-acid-related mechanism of cirrhosis with histological response in chronic hepatitis B
Authors: Fan Hai-Na , Zhao Zhi-Min , Huang Kai , Wang Xiao-Ning , Dai Yun-Kai , Liu Cheng-Hai 
Published: December 2023

Background and aims: The serum metabolites changes in patients with hepatitis B virus (HBV)-related cirrhosis as progression. Peroxisome proliferator-activated receptor gamma (PPARγ) is closely related to lipid metabolism in cirrhotic liver. However, the relationship between fatty acids and the expression of hepatic PPARγ during cirrhosis regression remains unknown. In this study, we explored the serum metabolic characteristics and expression of PPARγ in patients with histological response to treatment with entecavir.Methods: Sixty patients with HBV-related cirrhosis were selected as the training cohort with thirty patients each in the regression (R) group and non-regression (NR) group based on their pathological changes after 48-week treatment with entecavir. Another 72 patients with HBV-related cirrhosis and treated with entecavir were collected as the validation cohort. All of the serum samples were tested using ultra-performance liquid chromatography coupled to tandem mass spectrometry. Data were processed through principal component analysis and orthogonal partial least square discriminant analysis. Hepatic PPARγ expression was observed using immunohistochemistry. The relationship between serum fatty acids and PPARγ was calculated using Pearson’s or Spearman’s correlation analysis.Results: A total of 189 metabolites were identified and 13 differential metabolites were screened. Compared to the non-regression group, the serum level of fatty acids was higher in the R group. At baseline, the expression of PPARγ in hepatic stellate cells was positively correlated with adrenic acid (r2 = 0.451, p = 0.046). The expression of PPARγ in both groups increased after treatment, and the expression of PPARγ in the R group was restored in HSCs much more than that in the NR group (p = 0.042). The adrenic acid and arachidonic acid (AA) in the R group also upgraded more than the NR group after treatment (p = 0.037 and 0.014).Conclusion: Baseline serum differential metabolites, especially fatty acids, were identified in patients with HBV-related cirrhosis patients who achieved cirrhosis regression. Upregulation of adrenic acid and arachidonic acid in serum and re-expression of PPARγ in HSCs may play a crucial role in liver fibrosis improvement.
Prophylactic treatments for vestibular migraine: a systematic review and network meta-analysis of randomized clinical trials
Authors: Chu Hongyuan , Wang Yuru , Ling Xia , Li Kangzhi , Yang Xu 
Published: December 2023

Objectives: We compared and ranked the efficacy and tolerability of multiple prophylactic treatments for vestibular migraine (VM), including β-blockers, calcium channel blockers, antiseizure medications, and antidepressants such as tricyclics and serotonin–noradrenaline reuptake inhibitors.Methods: PubMed, Web of Science, Embase, and Cochrane Center for Clinical Trials were systematically searched for relevant randomized clinical trials (RCTs) from March 2023 to May 2023. Studies on the efficacy and tolerability of prophylactic treatments for VM were included. Efficacy was measured using the average vertigo frequency per month and dizziness handicap inventory (DHI) improvement after 3–6 months of treatment. Tolerability was measured by the number of patients reporting at least one adverse event (AE). Network meta-analyses were performed according to a Bayesian framework and a random-effects model based on odds ratios or mean differences (MDs) and 95% confidence intervals (CIs). A sequence of ranking probability was calculated according to the surface under the cumulative ranking (SUCRA) curve. This network meta-analysis was previously registered with PROSPERO (CRD42023422258).Results: Five RCTs comprising 334 patients were analyzed by synthesizing the published evidence. Considering the examined prophylactic therapies, there is significant evidence that valproate acid (VPA) is superior to placebo or abortive treatment alone (MD = −4.12, 95% CI = −8.09, −0.15) in reducing the frequency of vertigo. Flunarizine (MD = 20.00, 95% CI = 10.90, 29.10), valproate acid (MD = 18.88, 95% CI = 10.42, 27.34), and venlafaxine (MD = 11.48, 95% CI = 9.84, 13.12) were significantly more effective than placebo or abortive treatment in reducing DHI. VPA most strongly reduced the frequency of vertigo according to SUCRA, but it ranked third-to-last in tolerability. Flunarizine ranked best in DHI improvement but worst in tolerability. Metoprolol ranked worst for efficacy but best for tolerability.Conclusion: VPA and flunarizine reduced the frequency of vertigo and improved DHI, but they had unfavorable tolerability. The effects of metoprolol on vertigo require further study. Given the low certainty and limited sample, additional head-to-head RCTs are warranted to further confirm efficacy.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/; Identifier CRD42023422258.
A complex regulatory network governs the expression of symbiotic genes in Sinorhizobium fredii HH103
Authors: Navarro-Gómez Pilar , Fuentes-Romero Francisco , Pérez-Montaño Francisco , Jiménez-Guerrero Irene , Alías-Villegas Cynthia , Ayala-García Paula , Almozara Andrés , Medina Carlos , Ollero Francisco-Javier , Rodríguez-Carvajal Miguel-Ángel , Ruiz-Sainz José-Enrique , López-Baena Francisco-Javier , Vinardell José-María , Acosta-Jurado Sebastián 
Published: December 2023

IntroductionThe establishment of the rhizobium-legume nitrogen-fixing symbiosis relies on the interchange of molecular signals between the two symbionts. We have previously studied by RNA-seq the effect of the symbiotic regulators NodD1, SyrM, and TtsI on the expression of the symbiotic genes (the nod regulon) of Sinorhizobium fredii HH103 upon treatment with the isoflavone genistein. In this work we have further investigated this regulatory network by incorporating new RNA-seq data of HH103 mutants in two other regulatory genes, nodD2 and nolR. Both genes code for global regulators with a predominant repressor effect on the nod regulon, although NodD2 acts as an activator of a small number of HH103 symbiotic genes.MethodsBy combining RNA-seq data, qPCR experiments, and b-galactosidase assays of HH103 mutants harbouring a lacZ gene inserted into a regulatory gene, we have analysed the regulatory relations between the nodD1, nodD2, nolR, syrM, and ttsI genes, confirming previous data and discovering previously unknown relations.Results and discussionPreviously we showed that HH103 mutants in the nodD2, nolR, syrM, or ttsI genes gain effective nodulation with Lotus japonicus, a model legume, although with different symbiotic performances. Here we show that the combinations of mutations in these genes led, in most cases, to a decrease in symbiotic effectiveness, although all of them retained the ability to induce the formation of nitrogen-fixing nodules. In fact, the nodD2, nolR, and syrM single and double mutants share a set of Nod factors, either overproduced by them or not generated by the wild-type strain, that might be responsible for gaining effective nodulation with L. japonicus.
How incidental and intentional news exposure in social media relate to political knowledge and voting intentions
Authors: Dreston Jana H. , Neubaum German 
Published: December 2023

BackgroundCitizens are expected to make informed voting decisions. Theoretical approaches suggest that people are most likely to acquire their political knowledge through media. As more people turn to social media as a source of news, the political knowledge gains from using these technologies are called into question. Previous research has shown that rather than increasing objective political knowledge, the use of social media for news only increases people’s metacognitive sense of being knowledgeable (subjective knowledge), which in turn increases their political participation. However, it remains to be understood which particular forms of social media use, e.g., incidental or intentional news exposure, are related to which dimension of political knowledge. The present work examines (a) the extent to which different motivational forms of social media news consumption foster subjective knowledge, and (b) whether this metacognition is related not only to political participation as a broad concept, but also to specific democratic outcomes such as voting intentions.Methods and resultsResults from a pre-registered, pre-election survey (N = 1,223) of social media users show that intentional news seeking, but not incidental news exposure on social media, is directly related to increased subjective knowledge. Subjective knowledge appears to explain the relationship between social media news use and voting.DiscussionBy showing that incidental and intentional social media news use affect subjective knowledge differently, this study provides preliminary and nuanced insights into the ultimate role that social media technologies can play in democratic processes.
Identifying and regulating emotions after acquired brain injury: the role of interoceptive sensibility
Authors: Desdentado Lorena , Miragall Marta , Llorens Roberto , Navarro María Dolores , Baños Rosa M. 
Published: December 2023

IntroductionInteroceptive deficits are associated with difficulties in identifying and regulating emotions. However, research on interoception after acquired brain injury (ABI) is scarce, and its relationship with emotional difficulties in this population is unknown. This study aimed to (1) examine differences in self-reported alexithymia, performance-based emotional awareness, emotion regulation, depression, and interoceptive sensibility between ABI and control individuals; and (2) analyze the role of adaptive interoceptive dimensions in these emotional processes after ABI.MethodsForty-three individuals with ABI and 42 matched control individuals completed the Multidimensional Assessment of Interoceptive Awareness-2, the Toronto Alexithymia Scale, the Levels of Emotional Awareness Scale, the Difficulties in Emotion Regulation Scale, and the Hospital Anxiety and Depression Scale.ResultsCompared to the control group, individuals with ABI showed reduced tendency to ignore unpleasant sensations increased severity of depressive symptoms, as well as tendencies to have greater difficulties in emotion regulation and lower emotional awareness. Additionally, interoceptive dimensions such as trusting, as well as not-distracting from and not-worrying about bodily sensations, played a relevant role in explaining lower alexithymia and difficulties in emotion regulation. Moreover, lower alexithymia and emotion dysregulation were related to less depressive symptoms. These relationships were invariant across ABI and control individuals.DiscussionAlthough individuals with ABI may have different levels of emotional abilities compared to non-ABI individuals, the relationship patterns between interoceptive and emotional processes appear to be similar between the two groups. This study suggests the potential benefit of addressing both interoceptive and emotional difficulties in treatments targeting such prevalent sequelae of ABI as depressive symptoms.