bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of fibrosis, inflammation, and congestion biomarkers for outcome prediction in candidates to cardiac resynchronization therapy: is “response” the right answer?
Authors: Beltrami Matteo , Galluzzo Alessandro , Brocci Riccardo Tappa , Paoletti Perini Alessandro , Pieragnoli Paolo , Garofalo Manuel , Halasz Geza , Milli Massimo , Barilli Maria , Palazzuoli Alberto 
Published: June 2023

BackgroundCardiac resynchronization therapy (CRT) is an established treatment in selected patients suffering from heart failure with reduced ejection fraction (HFrEF). It has been proposed that myocardial fibrosis and inflammation could influence CRT “response” and outcome. Our study investigated the long-term prognostic significance of cardiac biomarkers in HFrEF patients with an indication for CRT.MethodsConsecutive patients referred for CRT implantation were retrospectively evaluated. The soluble suppression of tumorigenicity 2 (sST2), galectin-3 (Gal-3), N-terminal portion of the B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR) were measured at baseline and after 1 year of follow-up. Multivariate analyses were performed to evaluate their correlation with the primary composite outcome of cardiovascular mortality and heart failure hospitalizations at a mean follow-up of 9 ± 2 years.ResultsAmong the 86 patients enrolled, 44% experienced the primary outcome. In this group, the mean baseline values of NT-proBNP, Gal-3, and sST2 were significantly higher compared with the patients without cardiovascular events. At the multivariate analyses, baseline Gal-3 [cut-off: 16.6 ng/ml, AUC: 0.91, p &lt; 0.001, HR 8.33 (1.88–33.33), p = 0.005] and sST2 [cut-off: 35.6 ng/ml AUC: 0.91, p &lt; 0.001, HR 333 (250–1,000), p = 0.003] significantly correlated with the composite outcome in the prediction models with high likelihood. Among the parameters evaluated at 1-year follow-up, sST2, eGFR, and the variation from baseline to 1-year of Gal-3 levels showed a strong association with the primary outcome [HR 1.15 (1.08–1.22), p &lt; 0.001; HR: 0.84 (0.74–0.91), p = 0.04; HR: 1.26 (1.10–1.43), p ≤ 0.001, respectively]. Conversely, the echocardiographic definition of CRT response did not correlate with any outcome.ConclusionIn HFrEF patients with CRT, sST2, Gal-3, and renal function were associated with the combined endpoint of cardiovascular death and HF hospitalizations at long-term follow-up, while the echocardiographic CRT response did not seem to influence the outcome of the patients.
Cluster analysis of carboniferous gas reservoirs and application of recovery prediction model
Authors: Zhang Kai , Peng Xian , Chen Yingli , Yan Yuhan , Mei Qingyan , Chen Yu , Zhang Dongming 
Published: June 2023

Since the discovery of the Carboniferous gas reservoirs in East Sichuan in 1977, after more than 40 years of development, most of the gas reservoirs have entered the middle and late stages of development. The gas reservoir is characterized by strong heterogeneity, large difference in permeability, and serious impact of water invasion in some blocks. Therefore, how to make a correct decision on gas field development and deployment is of vital importance. Combined with system clustering, BP neural network, correlation analysis and other methods, this paper first analyzes and calculates the static indicators of the Carboniferous gas reservoirs, and then divides the gas reservoirs into four categories using ward clustering method according to the calculated weight value, and determines the characteristics of each type of gas reservoirs using correlation coefficient analysis method. Finally, the recovery prediction model of each type of gas reservoir is established according to the BP neural network. The results indicate that: (1) The recovery rate prediction model can predict the trend of cumulative gas production changes, thereby obtaining the space for improving recovery rate, and the accuracy of the prediction results is high, which can be used as a reference for gas field planning. (2) The sub-active gas reservoirs with strong heterogeneous water bodies and the inactive gas reservoirs with low permeability water bodies have a certain space for enhanced oil recovery.
WeChat official accounts’ posts on medication use of 251 community healthcare centers in Shanghai, China: content analysis and quality assessment
Authors: Liang Xujian , Yan Ming , Li Haixin , Deng Zhiling , Lu Yiting , Lu Panpan , Cai Songtao , Li Wanchao , Fang Lizheng , Xu Zhijie 
Published: June 2023

BackgroundThe dissemination of online health information (OHI) on medication use via WeChat Official Accounts (WOAs) is an effective way to help primary care practitioners (PCPs) address drug-related problems (DRPs) in the community. Although an increasing number of primary care institutions in China have published WOA posts on medication use, their content and quality have not yet been assessed.ObjectiveThis study aimed to explore the general features and content of WOA posts on medication use published by community healthcare centers (CHCs) in Shanghai, China and to assess their quality of content. It also aimed to explore the factors associated with the number of post views.MethodsFrom June 1 to October 31, 2022, two coauthors independently screened WOA posts on medication use published throughout 2021 by the CHCs in Shanghai. Content analysis was performed to analyze their general features (format, length, and source, etc.) and content (types of medicines and diseases). The QUEST tool was used to assess the quality of the posts. We compared the differences among posts published by CHCs in central urban areas and suburban areas, and used multiple linear regression to explore the factors associated with the number of post views.ResultsA total of 236 WOAs of interest published 37,147 posts in 2021, and 275 (0.74%) of them were included in the study. The median number of post views was 152. Thirty percent of the posts were reviewed by the CHCs’ staff before publication and only 6% provided information on PCPs’ consultations. The most commonly mentioned medicines and diseases in the posts were Chinese patent medicines (37.1%) and respiratory diseases (29.5%). The posts frequently provided information on indications (77%) and usage (56%) but rarely on follow-up (13%) and storage (11%). Of the posts, 94.9% had a total QUEST score &lt; 17 (full score = 28). The median number of post views and total post quality scores did not significantly differ among the CHCs in central urban and suburban areas. In the multiple linear regression model, the number of post views was associated with scores of complementarity (B = 56.47, 95% CI 3.05, 109.89) and conflict of interest (B = −46.40, 95% CI -56.21, −36.60).ConclusionThe quantity and quality of WOA posts on medication use published by CHCs in China need improvement. The quality of posts may partially impact the dissemination effect, but intrinsic causal associations merit further exploration.
Chemo-radiotherapy with 177Lu-PLGA(RGF)-CXCR4L for the targeted treatment of colorectal cancer
Authors: Cruz-Nova Pedro , Gibbens-Bandala Brenda , Ancira-Cortez Alejandra , Ramírez-Nava Gerardo , Santos-Cuevas Clara , Luna-Gutiérrez Myrna , Ocampo-García Blanca 
Published: June 2023

IntroductionMore than 1.9 million new cases of colorectal cancer and 935,000 deaths were estimated to have occurred worldwide in 2020. Therapies for metastatic colorectal cancer include cytotoxic chemotherapy and targeted therapies in multiple lines of treatment. Nevertheless, the optimal use of these agents has not yet been resolved. Regorafenib (RGF) is an Food and Drug Administration (FDA)-authorized multikinase inhibitor indicated for patients with metastatic colorectal cancer, non-responding to priority lines of chemotherapy and immunotherapy. Nanoparticles have been used in specific applications, such as site-specific drug delivery systems, cancer therapy, and clinical bioanalytical diagnostics. C-X-C Chemokine receptor type 4 (CXCR4) is the most widely-expressed chemokine receptor in more than 23 human cancer types, including colorectal cancer. This research aimed to synthesize and preclinically evaluate a targeted nanosystem for colorectal cancer chemo-radiotherapy using RGF encapsulated in Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles coated with a CXCR4 ligand (CXCR4L) and 177Lu as a therapeutic β-emitter.MethodsEmpty PLGA and PLGA(RGF) nanoparticles were prepared using the microfluidic method, followed by the DOTA and CXCR4L functionalization and nanoparticle radiolabeling with 177Lu. The final nanosystem gave a particle size of 280 nm with a polydispersity index of 0.347. In vitro and in vivo toxicity effects were assessed using the HCT116 colorectal cancer cell line.Results177Lu-PLGA(RGF)-CXCR4L nanoparticles decreased cell viability and proliferation by inhibiting Erk and Akt phosphorylation and promoting apoptosis. Moreover, in vivo administration of 177Lu-PLGA(RGF)-CXCR4L significantly reduced tumor growth in an HCT116 colorectal cancer xenograft model. The biokinetic profile showed hepatic and renal elimination.DiscussionData obtained in this research justify additional preclinical safety trials and the clinical evaluation of 177Lu-PLGA(RGF)-CXCR4L as a potential combined treatment of colorectal cancer.
Tailoring the secretome composition of mesenchymal stem cells to augment specific functions of epidermal regeneration: an in vitro diabetic model
Authors: Hodge Jacob G. , Robinson Jennifer L. , Mellott Adam J. 
Published: June 2023

IntroductionWound healing consists of a dynamic series of events that are highly dependent on paracrine factors for proper progression through the phases of wound healing. Inappropriate progression through the phases is associated with insufficient epidermal regeneration (i.e., re-epithelialization) of wounds and subsequent propagation of chronic wounds, such as diabetic ulcers, which are associated with increased patient morbidity. Recently, investigation into the dynamic secretome of Adipose-derived Mesenchymal Stem Cells (ASCs), have shown promise in augmenting the wound healing response of chronic diabetic wounds. However, currently utilized 2D culture techniques are known to drastically alter the regenerative phenotype of ASCs. In this study a novel tissue-mimetic 3D system was utilized as a means to culture ASCs.MethodsThe capacity for the ASC secretome to augment epidermal regeneration activity was then evaluated after exposure of ASCs to “wound priming stimuli” in 2D and 3D. The priming stimuli consisted of coating the 2D and 3D systems with the wound matrix proteins, collagen type I, fibronectin, and fibrin. To understand the potential benefit of the ASC secretome in the context of diabetic wounds, keratinocytes (KCs) were exposed to super-physiological glucose levels to induce a diabetic-like phenotype (idKCs).ResultsRelative to KCs, idKC exhibited a 52% and 23% decline in proliferation and migration, respectively. Subsequently, analyses of the ASC secretome were performed. ASC conditioned media (ASC-CM) from tissue-mimetic culture demonstrated a &gt; 50% increase secretion of proteins and a 2-fold increase in secreted EVs, relative to 2D culture. Interestingly, the different priming stimuli did not alter the total amount of protein or EVs secreted within the tissue-mimetic system. However, evaluation of specific soluble proteins via ELISA revealed significant differences in key epidermal regeneration factors, such as EGF, IGF-1, FGF-2, MMP-1, TIMP-1, and TGFβ-1. Additionally, the relative effect of ASC-EVs from the 2D and 3D system on idKCs epidermal regeneration functionality varied significantly, with EVs from 3D-Collagen culture providing the most significant benefit on idKC activity.DiscussionTogether, these data support the utilization of tissue-mimetic culture system to enhance the adaptability and secretory activity of MSC-like populations in order to generate tailored biologics, via priming stimuli, for specific wound healing applications.
Identification of immunosuppressive signature subtypes and prognostic risk signatures in triple-negative breast cancer
Authors: Ding Ran , Wang Yuhan , Fan Jinyan , Tian Ziyue , Wang Shuang , Qin Xiujuan , Su Wei , Wang Yanbo 
Published: June 2023

PurposeImmune checkpoint blockade (ICB) therapy has transformed the treatment of triple-negative breast cancer (TNBC) in recent years. However, some TNBC patients with high programmed death-ligand 1 (PD-L1) expression levels develop immune checkpoint resistance. Hence, there is an urgent need to characterize the immunosuppressive tumor microenvironment and identify biomarkers to construct prognostic models of patient survival outcomes in order to understand biological mechanisms operating within the tumor microenvironment.Patients and methodsRNA sequence (RNA-seq) data from 303 TNBC samples were analyzed using an unsupervised cluster analysis approach to reveal distinctive cellular gene expression patterns within the TNBC tumor microenvironment (TME). A panel of T cell exhaustion signatures, immunosuppressive cell subtypes and clinical features were correlated with the immunotherapeutic response, as assessed according to gene expression patterns. The test dataset was then used to confirm the occurrence of immune depletion status and prognostic features and to formulate clinical treatment recommendations. Concurrently, a reliable risk prediction model and clinical treatment strategy were proposed based on TME immunosuppressive signature differences between TNBC patients with good versus poor survival status and other clinical prognostic factors.ResultsSignificantly enriched TNBC microenvironment T cell depletion signatures were detected in the analyzed RNA-seq data. A high proportion of certain immunosuppressive cell subtypes, 9 inhibitory checkpoints and enhanced anti-inflammatory cytokine expression profiles were noted in 21.4% of TNBC patients that led to the designation of this group of immunosuppressed patients as the immune depletion class (IDC). Although IDC group TNBC samples contained tumor-infiltrating lymphocytes present at high densities, IDC patient prognosis was poor. Notably, PD-L1 expression was relatively elevated in IDC patients that indicated their cancers were resistant to ICB treatment. Based on these findings, a set of gene expression signatures predicting IDC group PD-L1 resistance was identified then used to develop risk models for use in predicting clinical therapeutic outcomes.ConclusionA novel TNBC immunosuppressive tumor microenvironment subtype associated with strong PD-L1 expression and possible resistance to ICB treatment was identified. This comprehensive gene expression pattern may provide fresh insights into drug resistance mechanisms for use in optimizing immunotherapeutic approaches for TNBC patients.
The role of MRI after neochemoradiotherapy in predicting pathological tumor regression grade and clinical outcome in patients with locally advanced rectal adenocarcinoma
Authors: Niu Shaoqing , Chen Yan , Peng Fang , Wen Jie , Xiong Jianqi , Yang Zhuangzhuang , Peng Jianjun , Bao Yong , Ding Li 
Published: June 2023

ObjectiveTo evaluate the predictive value of tumor regression grade assessed by MRI (mr-TRG) after neoadjuvant chemoradiotherapy (neo-CRT) for postoperative pathological TRG (pTRG) and prognosis in patients with locally advanced rectal adenocarcinoma (LARC).Materials and methodsThis was a retrospective study from a single center experience. The patients who were diagnosed with LARC and received neo-CRT in our department between January 2016 and July 2021 were enrolled. The agreement between mrTRG and pTRG was assessed with the weighted κ test. Overall survival (OS), progress-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were calculated by Kaplan-Meier analysis and log-rank test.ResultsFrom January 2016 to July 2021, 121 LARC patients received neo-CRT in our department. Among them, 54 patients had complete clinical data, including MRI of pre- and post-neo-CRT, postoperative tumor samples, and follow-up. The median follow-up time was 34.6 months (range: 4.4-70.6 months). The estimated 3-year OS, PFS, LRFS and DMFS were 78.5%, 70.7%, 89.0%, and 75.2%, respectively. The median time from the completion of neo-CRT to preoperative MRI and surgery was 7.1 weeks and 9.7 weeks, respectively. Out of 54 patients, 5 patients achieved mrTRG1 (9.3%), 37 achieved mrTRG2 (68.5%), 8 achieved mrTRG3 (14.8%), 4 achieved mrTRG4 (7.4%), and no patient achieved mrTRG5 after neo-CRT. Regarding pTRG, 12 patients achieved pTRG0 (22.2%), 10 achieved pTRG1 (18.5%), 26 achieved pTRG2 (48.1%), and 6 achieved pTRG3 (11.1%). The agreement between three-tier mrTRG (mrTRG1 vs. mrTRG2-3 vs. mrTRG4-5) and pTRG (pTRG0 vs. pTRG1-2 vs. pTRG3) was fair (weighted kappa=0.287). In a dichotomous classification, the agreement between mrTRG(mrTRG1 vs. mrTRG2-5)and pTRG(pTRG0 vs. pTRG1-3) also resulted in fair agreement (weighted kappa=0.391). The sensitivity, specificity, positive, and negative predictive values of favorable mrTRG (mrTRG 1-2) for pathological complete response (PCR) were 75.0%, 21.4%, 21.4%, and 75.0%, respectively. In univariate analysis, favorable mrTRG (mrTRG1-2) and downstaging N were significantly associated with better OS, while favorable mrTRG (mrTRG1-2), downstaging T, and downstaging N were significantly associated with superior PFS (p&lt;0.05). In multivariate analysis, downstaging N was an independent prognostic factor for OS. Meanwhile, downstaging T and downstaging N remained independent prognostic factors for PFS.ConclusionsAlthough the consistency between mrTRG and pTRG is only fair, favorable mrTRG after neo-CRT may be used as a potential prognostic factor for LARC patients.
A meta-analysis: the clinical value of PD-1 inhibitor or protein tyrosine kinase inhibitors in the treatment of advanced osteosarcoma
Authors: Shi Binhao , Chang Junli , Sun Xingyuan , Ma Xiaoping , Zhao Peng , Zhou Chujie , Wang Yongjun , Yang Yanping 
Published: June 2023

BackgroundsPD-1 inhibitors and TKIs have been used to treat advanced osteosarcoma, but there is still a lack of intuitive data for the comparison of their efficacy. We conducted a meta-analysis to evaluate their therapeutic benefits.MethodsA systematic methodological search of five primary electronic databases was performed. Studies with a randomized design of any type about PD-1 inhibitors or TKIs for the treatment of advanced osteosarcoma were included. The primary outcomes mainly included CBR, PFS, OS and ORR, The CR, PR, SD and AEs were the secondary outcomes. The survival period (months) of patients was taken as the main analysis data. Random-effects models were used for meta-analysis.ResultsEight immunocheckpoint inhibitors in 327 patients from 10 clinical trials were finally evaluated. For OS, TKIs [11.67 months (95% CI, 9.32-14.01)] show more obvious advantages than PD-1 inhibitors [6.37 months (95% CI, 3.96-8.78)]. For PFS, TKIs [4.79 months (95% CI, 3.33-6.24)] are longer than PD-1 inhibitors [1.46 months (95% CI, 1.23-1.69)]. Although there was no fatal event, attention should still be paid, especially during the combined application of PD-1 inhibitors with TKIs since their obvious AEs.ConclusionsThe findings of this study suggest that patients with advanced osteosarcoma, TKIs may be more beneficial than PD-1 inhibitors. TKIs combined with PD-1 inhibitors has a bright future in the treatment of advanced osteosarcoma, but we should always pay attention to the strong side effects.
Facial nerve outcome score: a new score to predict long-term facial nerve function after vestibular schwannoma surgery
Authors: Di Perna Giuseppe , De Marco Raffaele , Baldassarre Bianca Maria , Lo Bue Enrico , Cofano Fabio , Zeppa Pietro , Ceroni Luca , Penner Federica , Melcarne Antonio , Garbossa Diego , Lanotte Michele Maria , Zenga Francesco 
Published: June 2023

IntroductionPatients’ quality of life (QoL), facial nerve (FN), and cochlear nerve (CN) (if conserved) functions should be pursued as final outcomes of vestibular schwannoma (VS) surgery. In regard to FN function, different morphologic and neurophysiological factors have been related to postoperative outcomes. The aim of the current retrospective study was to investigate the impact of these factors on the short- and long-term FN function after VS resection. The combination of preoperative and intraoperative factors resulted in designing and validating a multiparametric score to predict short- and long-term FN function.MethodsA single-center retrospective analysis was performed for patients harboring non-syndromic VS who underwent surgical resection in the period 2015–2020. A minimum follow-up period of 12 months was considered among the inclusion criteria. Morphological tumor characteristics, intraoperative neurophysiological parameters, and postoperative clinical factors, namely, House–Brackmann (HB) scale, were retrieved in the study. A statistical analysis was conducted to investigate any relationships with FN outcome and to assess the reliability of the score.ResultsSeventy-two patients with solitary primary VS were treated in the period of the study. A total of 59.8% of patients showed an HB value &lt; 3 in the immediate postoperative period (T1), reaching to 76.4% at the last follow-up evaluation. A multiparametric score, Facial Nerve Outcome Score (FNOS), was built. The totality of patients with FNOS grade A showed an HB value &lt; 3 at 12 months, decreasing to 70% for those with FNOS grade B, whereas 100% of patients with FNOS grade C showed an HB value ≥ 3. The ordinal logistic regression showed three times increasing probability to see an HB value ≥ 3 at 3-month follow-up for each worsening point in FNOS score [Exp(B), 2,999; p &lt; 0.001] that was even more probable [Exp(B), 5.486; p &lt; 0.001] at 12 months.ConclusionThe FNOS score resulted to be a reliable score, showing high associations with FN function both at short- and long-term follow-up. Although multicenter studies would be able to increase its reproducibility, it could be used to predict the FN damage after surgery and the potential of restoring its function on the long-term period.
Phenotypes, bedside examination, and video head impulse test in vestibular migraine of childhood compared with probable vestibular migraine and recurrent vertigo in childhood
Authors: Teggi Roberto , Colombo Bruno , Familiari Marco , Cangiano Iacopo , Bussi Mario , Filippi Massimo 
Published: June 2023

IntroductionVestibular impairment and vertigo in the pediatric population have an estimated prevalence ranging between 0.4% and 5.6% and are a topic of interest in recent years. The Bárány Society has recently reclassified migraine-related vertigo syndromes as vestibular migraine of childhood (VMC), probable vestibular migraine of childhood (probable VMC), and recurrent vertigo of childhood (RVC).MethodsApplying the criteria established by the Bárány Society, we retrospectively analyzed data on 95 pediatric patients suffering from episodic vertigo that were recruited from 2018 to 2022. In applying the revised criteria, 28 patients had VMC, 38 had probable VMC, and 29 had RVC.ResultsVisuo-vestibular symptoms (external vertigo) or internal vertigo were reported by 20 of 28 VMC patients (71.4%) compared to 8 of 38 probable VMC patients (21%) (P &lt; .001). None of the RVC patients reported external vertigo. Duration of vertigo was demonstrably longer in the VMC patients than in the probable VMC (P &lt; .001) and RVC (P &lt; .001) patients. Cochlear symptoms were reported by 28.6% of VMC patients and by 13.1% of probable VMC patients. No cochlear symptoms were reported by any RVC patients. Familial cases for headache and episodic vertigo showed no significant difference between groups.DiscussionThe most frequent finding during bedside examination in all three groups was central positional nystagmus. Differences in the duration of attacks and in accompanying symptoms may underline different pathophysiological mechanisms.