bluuebunny/crossref_metadata_2025_split huggingface dataset:
Response to primary chemoradiotherapy of locally advanced oropharyngeal carcinoma is determined by the degree of cytotoxic T cell infiltration within tumor cell aggregates
Authors: Haist Maximilian , Kaufmann Justus , Kur Ivan-Maximiliano , Zimmer Stefanie , Grabbe Stephan , Schmidberger Heinz , Weigert Andreas , Mayer Arnulf 
Published: April 2023

BackgroundEffective anti-tumor immune responses are mediated by T cells and require organized, spatially coordinated interactions within the tumor microenvironment (TME). Understanding coordinated T-cell-behavior and deciphering mechanisms of radiotherapy resistance mediated by tumor stem cells will advance risk stratification of oropharyngeal cancer (OPSCC) patients treated with primary chemoradiotherapy (RCTx).MethodsTo determine the role of CD8 T cells (CTL) and tumor stem cells for response to RCTx, we employed multiplex immunofluorescence stains on pre-treatment biopsy specimens from 86 advanced OPSCC patients and correlated these quantitative data with clinical parameters. Multiplex stains were analyzed at the single-cell level using QuPath and spatial coordination of immune cells within the TME was explored using the R-package Spatstat.ResultsOur observations demonstrate that a strong CTL-infiltration into the epithelial tumor compartment (HR for overall survival, OS: 0.35; p&lt;0.001) and the expression of PD-L1 on CTL (HR: 0.36; p&lt;0.001) were both associated with a significantly better response and survival upon RCTx. As expected, p16 expression was a strong predictor of improved OS (HR: 0.38; p=0.002) and correlated with overall CTL infiltration (r: 0.358, p&lt;0.001). By contrast, tumor cell proliferative activity, expression of the tumor stem cell marker CD271 and overall CTL infiltration, regardless of the affected compartment, were not associated with response or survival.ConclusionIn this study, we could demonstrate the clinical relevance of the spatial organization and the phenotype of CD8 T cells within the TME. In particular, we found that the infiltration of CD8 T cells specifically into the tumor cell compartment was an independent predictive marker for response to chemoradiotherapy, which was strongly associated with p16 expression. Meanwhile, tumor cell proliferation and the expression of stem cell markers showed no independent prognostic effect for patients with primary RCTx and thus requires further study.
Interplay among differential exposure to Mycobacterium leprae and TLR4 polymorphism impacts the immune response in household contacts of leprosy patients
Authors: Cunha Eloisa Helena Medeiros , Marçal Pedro Henrique Ferreira , Gama Rafael Silva , de Oliveira Lorena Bruna Pereira , Pinheiro Roberta Olmo , Sarno Euzenir Nunes , Brito-de-Sousa Joaquim Pedro , de Souza Márcio Luís Moreira , Fairley Jessica Kathleen , Valente Thaisa Netto Souza , Velloso-Rodrigues Cibele , Martins-Filho Olindo Assis , de Oliveira Dirce Ribeiro , Fraga Lucia Alves de Oliveira 
Published: April 2023

IntroductionThe aim of the present study was to investigate the association between the single nucleotide polymorphism (SNP) rs1927914 A/G in TLR4 gene and the immunological profile of household contacts (HHC) of leprosy patients. Leprosy classification is usually complex and requires the assessment of several clinical and laboratorial features.MethodsHerein, we have applied distinct models of descriptive analysis to explore qualitative/quantitative changes in chemokine and cytokine production in HHC further categorized according to operational classification [HHC(PB) and HHC(MB)] and according to TLR4SNP.Results and discussionOur results showed that M. leprae stimuli induced an outstanding production of chemokines (CXCL8;CCL2; CXCL9; CXCL10) by HHC(PB), while increase levels of pro-inflammatory cytokines (IL-6; TNF; IFN-γ; IL-17) were observed for HHC(MB). Moreover, the analysis of chemokine and cytokine signatures demonstrated that A allele was associated with a prominent soluble mediator secretion (CXCL8; CXCL9; IL-6; TNF; IFN-γ). Data analysis according to TLR4 SNP genotypes further demonstrated that AA and AG were associated with a more prominent secretion of soluble mediators as compared to GG, supporting the clustering of AA and AG genotypes into dominant genetic model. CXCL8, IL-6, TNF and IL-17 displayed distinct profiles in HHC(PB) vs HHC(MB) or AA+AG vs GG genotype. In general, chemokine/cytokine networks analysis showed an overall profile of AA+GA-selective (CXCL9–CXCL10) and GG-selective (CXCL10–IL-6) axis regardless of the operational classification. However, mirrored inverted CCL2–IL-10 axis and a (IFN-γ–IL-2)-selective axis were identified in HHC(MB). CXCL8 presented outstanding performance to classify AA+AG from GG genotypes and HHC(PB) from HHC(MB). TNF and IL-17 presented elevated accuracy to classify AA+AG from GG genotypes and HHC(PB) (low levels) from HHC(MB) (high levels), respectively. Our results highlighted that both factors: i) differential exposure to M. leprae and ii) TLR4 rs1927914 genetic background impact the immune response of HHC. Our main results reinforce the relevance of integrated studies of immunological and genetic biomarkers that may have implications to improve the classification and monitoring of HHC in future studies.
Treatment of condylomata acuminata caused by low-risk human papillomavirus with chloroquine phosphate gel
Authors: Li Xiangling , Guan Zhisheng , Liu Qi , Yang Wei , Huang Jie , Yuan Manli , Yu Junlong 
Published: April 2023

ObjectiveTo observe the stability and therapeutic effect of chloroquine phosphate gel on human condylomata acuminata (CA) caused by low-risk human papillomavirus (HPV).MethodsThe appearance, viscosity, pH, chloroquine concentration, deethylchloroquine concentration and content uniformity of chloroquine phosphate gel were examined for 24 months, the gel met the quality standards throughout the 24-month observation. A nude mouse model harboring CA xenografts was used to observe the therapeutic effect of this gel on CAin vivo.ResultsAfter 14 days of gel administration, compared with the control group, the treatment group had significantly smaller warts and significantly reduced DNA copy numbers of HPV6 and HPV11 in the wart tissues. Immunohistochemistry analysis of p53 protein expression in the wart tissues of the treatment group was significantly increased.ConclusionChloroquine phosphate gel was stable and effective against CA, possibly through the promotion of p53 protein expression to induce apoptosis, leading to the involution of warts.
Mapping of exogenous choline uptake and metabolism in rat glioblastoma using deuterium metabolic imaging (DMI)
Authors: Ip Kevan L. , Thomas Monique A. , Behar Kevin L. , de Graaf Robin A. , De Feyter Henk M. 
Published: April 2023

IntroductionThere is a lack of robust metabolic imaging techniques that can be routinely applied to characterize lesions in patients with brain tumors. Here we explore in an animal model of glioblastoma the feasibility to detect uptake and metabolism of deuterated choline and describe the tumor-to-brain image contrast.MethodsRG2 cells were incubated with choline and the level of intracellular choline and its metabolites measured in cell extracts using high resolution 1H NMR. In rats with orthotopically implanted RG2 tumors deuterium metabolic imaging (DMI) was applied in vivo during, as well as 1 day after, intravenous infusion of 2H9-choline. In parallel experiments, RG2-bearing rats were infused with [1,1′,2,2′-2H4]-choline and tissue metabolite extracts analyzed with high resolution 2H NMR to identify molecule-specific 2H-labeling in choline and its metabolites.ResultsIn vitro experiments indicated high uptake and fast phosphorylation of exogenous choline in RG2 cells. In vivo DMI studies revealed a high signal from the 2H-labeled pool of choline + metabolites (total choline, 2H-tCho) in the tumor lesion but not in normal brain. Quantitative DMI-based metabolic maps of 2H-tCho showed high tumor-to-brain image contrast in maps acquired both during, and 24 h after deuterated choline infusion. High resolution 2H NMR revealed that DMI data acquired during 2H-choline infusion consists of free choline and phosphocholine, while the data acquired 24 h later represent phosphocholine and glycerophosphocholine.DiscussionUptake and metabolism of exogenous choline was high in RG2 tumors compared to normal brain, resulting in high tumor-to-brain image contrast on DMI-based metabolic maps. By varying the timing of DMI data acquisition relative to the start of the deuterated choline infusion, the metabolic maps can be weighted toward detection of choline uptake or choline metabolism. These proof-of-principle experiments highlight the potential of using deuterated choline combined with DMI to metabolically characterize brain tumors.
Radiomic and clinical nomogram for cognitive impairment prediction in Wilson’s disease
Authors: Tian Liwei , Dong Ting , Hu Sheng , Zhao Chenling , Yu Guofang , Hu Huibing , Yang Wenming 
Published: April 2023

ObjectiveTo investigate potential biomarkers for the early detection of cognitive impairment in patients with Wilson’s disease (WD), we developed a computer-assisted radiomics model to distinguish between WD and WD cognitive impairment.MethodsOverall, 136 T1-weighted MR images were retrieved from the First Affiliated Hospital of Anhui University of Chinese Medicine, including 77 from patients with WD and 59 from patients with WD cognitive impairment. The images were divided into training and test groups at a ratio of 70:30. The radiomic features of each T1-weighted image were extracted using 3D Slicer software. R software was used to establish clinical and radiomic models based on clinical characteristics and radiomic features, respectively. The receiver operating characteristic profiles of the three models were evaluated to assess their diagnostic accuracy and reliability in distinguishing between WD and WD cognitive impairment. We combined relevant neuropsychological test scores of prospective memory to construct an integrated predictive model and visual nomogram to effectively assess the risk of cognitive decline in patients with WD.ResultsThe area under the curve values for distinguishing WD and WD cognitive impairment for the clinical, radiomic, and integrated models were 0.863, 0.922, and 0.935 respectively, indicative of excellent performance. The nomogram based on the integrated model successfully differentiated between WD and WD cognitive impairment.ConclusionThe nomogram developed in the current study may assist clinicians in the early identification of cognitive impairment in patients with WD. Early intervention following such identification may help improve long-term prognosis and quality of life of these patients.
Personality traits and pattern of beliefs of near-death(-like) experiencers
Authors: Bicego Aminata , Cassol Héléna , Simon Jessica , Fritz Pauline , Abagnale Simona , Vanhaudenhuyse Audrey , Laureys Steven , Martial Charlotte 
Published: April 2023

IntroductionLittle is known about the potential personality and psychological predictors of near-death experiences (NDEs), and fewer yet those of near-death-like experiences (NDEs-like; similar phenomenology reported after a non-life-threatening context). This study investigated whether personality traits (Openness, Extraversion, Pleasantness, Conscientiousness, and Neuroticism), dissociative experiences, Fantasy proneness, disposition toward auditory hallucinations, absorption trait, and endorsement of paranormal and spiritual beliefs could be associated with the recall of NDEs(-like).MethodsTo this aim, we invited four groups of people to retrospectively fill in questionnaires assessing the following factors: NDE experiencers (n = 63), NDE(-like) experiencers (n = 31), controls with a life-threatening situation but no NDE(-like) (n = 43), and controls without a life-threatening situation or an NDE(-like) (n = 44). We carried out univariate analyses for each factor and then performed a multiple regression analysis and a discriminant analysis.ResultsThe multivariate logistic regression analysis revealed that the endorsement of spiritual beliefs was associated with the recall of NDEs-like while Openness and Fantasy proneness were associated with the recall of NDEs. The discriminant analysis showed that these variables produce 35% of correct classification.DiscussionAlbeit retrospective, these results pave the way for future research on psychological predictors of NDEs(-like) by highlighting the influence of Spirituality, Openness, and Fantasy proneness on these phenomena.
The association between oxidative balance score and periodontitis in adults: a population-based study
Authors: Qu Haitao 
Published: April 2023

IntroductionThe pathogenesis between oxidative stress and periodontitis was correlated. The Oxidative Balance Score (OBS) is a systematic tool to assess the effects of diet and lifestyle in relation to oxidative stress. However, the association between OBS and periodontitis has not been reported previously.MethodsSixteen dietary factors and four lifestyle factors were selected to score the OBS. Multivariate logistic regression and sensitivity analysis were used to investigate the relationship between OBS and periodontitis based on data from the National Health and Nutrition Examination Survey (NHANES) 1999–2018. Subgroup analysis and interaction tests were used to investigate whether this association was stable across populations.ResultsThis study included 3,706 participants. There was a negative linear association between OBS and periodontitis in all participants [0.89 (0.80, 0.97)], and after converting OBS to a quartile variable, participants with OBS in the highest quartile had a 29% lower risk of periodontitis than those with OBS in the lowest quartile [0.71 (0.42, 0.98)]. This negative association differed with respect to age and diabetes.ConclusionThere is a negative association between OBS and periodontitis in US adults. Our results suggest that OBS may be used as a biomarker for measuring periodontitis.
Incremental value of radiomics with machine learning to the existing prognostic models for predicting outcome in renal cell carcinoma
Authors: Xing Jiajun , Liu Yiyang , Wang Zhongyuan , Xu Aiming , Su Shifeng , Shen Sipeng , Wang Zengjun 
Published: April 2023

PurposeTo systematically evaluate the potential of radiomics coupled with machine-learning algorithms to improve the predictive power for overall survival (OS) of renal cell carcinoma (RCC).MethodsA total of 689 RCC patients (281 in the training cohort, 225 in the validation cohort 1 and 183 in the validation cohort 2) who underwent preoperative contrast-enhanced CT and surgical treatment were recruited from three independent databases and one institution. 851 radiomics features were screened using machine-learning algorithm, including Random Forest and Lasso-COX Regression, to establish radiomics signature. The clinical and radiomics nomogram were built by multivariate COX regression. The models were further assessed by Time-dependent receiver operator characteristic, concordance index, calibration curve, clinical impact curve and decision curve analysis.ResultThe radiomics signature comprised 11 prognosis-related features and was significantly correlated with OS in the training and two validation cohorts (Hazard Ratios: 2.718 (2.246,3.291)). Based on radiomics signature, WHOISUP, SSIGN, TNM Stage and clinical score, the radiomics nomogram has been developed. Compared with the existing prognostic models, the AUCs of 5 years OS prediction of the radiomics nomogram were superior to the TNM, WHOISUP and SSIGN model in the training cohort (0.841 vs 0.734, 0.707, 0.644) and validation cohort2 (0.917 vs 0.707, 0.773, 0.771). Stratification analysis suggested that the sensitivity of some drugs and pathways in cancer were observed different for RCC patients with high-and low-radiomics scores.ConclusionThis study showed the application of contrast-enhanced CT-based radiomics in RCC patients, creating novel radiomics nomogram that could be used to predict OS. Radiomics provided incremental prognostic value to the existing models and significantly improved the predictive power. The radiomics nomogram might be helpful for clinicians to evaluate the benefit of surgery or adjuvant therapy and make individualized therapeutic regimens for patients with renal cell carcinoma.
Why is advance care planning underused in oncology settings? A systematic overview of reviews to identify the benefits, barriers, enablers, and interventions to improve uptake
Authors: Guccione Lisa , Fullerton Sonia , Gough Karla , Hyatt Amelia , Tew Michelle , Aranda Sanchia , Francis Jill 
Published: April 2023

BackgroundAdvance care planning (ACP) centres on supporting people to define and discuss their individual goals and preferences for future medical care, and to record and review these as appropriate. Despite recommendations from guidelines, rates of documentation for people with cancer are considerably low.AimTo systematically clarify and consolidate the evidence base of ACP in cancer care by exploring how it is defined; identifying benefits, and known barriers and enablers across patient, clinical and healthcare services levels; as well as interventions that improve advance care planning and are their effectiveness.MethodsA systematic overview of reviews was conducted and was prospectively registered on PROSPERO. PubMed, Medline, PsycInfo, CINAHL, and EMBASE were searched for review related to ACP in cancer. Content analysis and narrative synthesis were used for data analysis. The Theoretical Domains Framework (TDF) was used to code barriers and enablers of ACP as well as the implied barriers targeted by each of the interventions.ResultsEighteen reviews met the inclusion criteria. Definitions were inconsistent across reviews that defined ACP (n=16). Proposed benefits identified in 15/18 reviews were rarely empirically supported. Interventions reported in seven reviews tended to target the patient, even though more barriers were associated with healthcare providers (n=40 versus n=60, respectively).ConclusionTo improve ACP uptake in oncology settings; the definition should include key categories that clarify the utility and benefits. Interventions need to target healthcare providers and empirically identified barriers to be most effective in improving uptake.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?, identifier CRD42021288825.
Histogram analysis of multi-model high-resolution diffusion-weighted MRI in breast cancer: correlations with molecular prognostic factors and subtypes
Authors: Qin Yanjin , Wu Feng , Hu Qilan , He Litong , Huo Min , Tang Caili , Yi Jingru , Zhang Huiting , Yin Ting , Ai Tao 
Published: April 2023

ObjectiveTo investigate the correlations between quantitative diffusion parameters and prognostic factors and molecular subtypes of breast cancer, based on a single fast high-resolution diffusion-weighted imaging (DWI) sequence with mono-exponential (Mono), intravoxel incoherent motion (IVIM), diffusion kurtosis imaging (DKI) models.Materials and MethodsA total of 143 patients with histopathologically verified breast cancer were included in this retrospective study. The multi-model DWI-derived parameters were quantitatively measured, including Mono-ADC, IVIM-D, IVIM-D*, IVIM-f, DKI-Dapp, and DKI-Kapp. In addition, the morphologic characteristics of the lesions (shape, margin, and internal signal characteristics) were visually assessed on DWI images. Next, Kolmogorov–Smirnov test, Mann-Whitney U test, Spearman’s rank correlation, logistic regression, receiver operating characteristic (ROC) curve, and Chi-squared test were utilized for statistical evaluations.ResultsThe histogram metrics of Mono-ADC, IVIM-D, DKI-Dapp, and DKI-Kapp were significantly different between estrogen receptor (ER)-positive vs. ER-negative groups, progesterone receptor (PR)-positive vs. PR-negative groups, Luminal vs. non-Luminal subtypes, and human epidermal receptor factor-2 (HER2)-positive vs. non-HER2-positive subtypes. The histogram metrics of Mono-ADC, DKI-Dapp, and DKI-Kapp were also significantly different between triple-negative (TN) vs. non-TN subtypes. The ROC analysis revealed that the area under the curve considerably improved when the three diffusion models were combined compared with every single model, except for distinguishing lymph node metastasis (LNM) status. For the morphologic characteristics of the tumor, the margin showed substantial differences between ER-positive and ER-negative groups.ConclusionsQuantitative multi-model analysis of DWI showed improved diagnostic performance for determining the prognostic factors and molecular subtypes of breast lesions. The morphologic characteristics obtained from high-resolution DWI can be identifying ER statuses of breast cancer.
HOPE (SOLTI-1903) breast cancer study: real-world, patient-centric, clinical practice study to assess the impact of genomic data on next treatment decision-choice in patients with locally advanced or metastatic breast cancer
Authors: Olivera-Salguero Rubén , Seguí Elia , Cejalvo Juan Miguel , Oliveira Mafalda , Tolosa Pablo , Vidal Maria , Malumbres Marcos , Gavilá Joaquín , Saura Cristina , Pernas Sonia , López Rafael , Margelí Mireia , Balmaña Judith , Muñoz Montserrat , Blancas Isabel , Boni Valentina , Ciruelos Eva , Galve Elena , Perelló Antonia , Sánchez-Bayona Rodrigo , de la Cruz Susana , de la Hoya Miguel , Galván Patricia , Sanfeliu Esther , Gonzalez-Farre Blanca , Sirenko Valeria , Blanch-Torras Aura , Canes Jordi , Masanas Helena , Olmos Rosa , Forns Margarita , Prat Aleix , Casas Ana , Pascual Tomás 
Published: April 2023

BackgroundMetastatic breast cancer (mBC) causes nearly all BC-related deaths. Next-generation sequencing (NGS) technologies allow for the application of personalized medicine using targeted therapies that could improve patients’ outcomes. However, NGS is not routinely used in the clinical practice and its cost induces access-inequity among patients. We hypothesized that promoting active patient participation in the management of their disease offering access to NGS testing and to the subsequent medical interpretation and recommendations provided by a multidisciplinary molecular advisory board (MAB) could contribute to progressively overcome this challenge. We designed HOPE (SOLTI-1903) breast cancer trial, a study where patients voluntarily lead their inclusion through a digital tool (DT). The main objectives of HOPE study are to empower mBC patients, gather real-world data on the use of molecular information in the management of mBC and to generate evidence to assess the clinical utility for healthcare systems.Trial designAfter self-registration through the DT, the study team validates eligibility criteria and assists patients with mBC in the subsequent steps. Patients get access to the information sheet and sign the informed consent form through an advanced digital signature. Afterwards, they provide the most recent (preferably) metastatic archival tumor sample for DNA-sequencing and a blood sample obtained at the time of disease progression for ctDNA analysis. Paired results are reviewed by the MAB, considering patient’s medical history. The MAB provides a further interpretation of molecular results and potential treatment recommendations, including ongoing clinical trials and further (germline) genetic testing. Participants self-document their treatment and disease evolution for the next 2 years. Patients are encouraged to involve their physicians in the study. HOPE also includes a patient empowerment program with educational workshops and videos about mBC and precision medicine in oncology. The primary endpoint of the study was to describe the feasibility of a patient-centric precision oncology program in mBC patients when a comprehensive genomic profile is available to decide on a subsequent line of treatment.Clinical trial registrationwww.soltihope.com, identifier NCT04497285.