bluuebunny/crossref_metadata_2025_split huggingface dataset:
In situ gelling hydrogel loaded with berberine liposome for the treatment of biofilm-infected wounds
Authors: Li Sipan , Wang Yongan , Wang Siting , Xie Jianjun , Fu Tingming , Li Shaoguang 
Published: May 2023

Background: In recent years, the impact of bacterial biofilms on traumatic wounds and the means to combat them have become a major research topic in the field of medicine. The eradication of biofilms formed by bacterial infections in wounds has always been a huge challenge. Herein, we developed a hydrogel with the active ingredient berberine hydrochloride liposomes to disrupt the biofilm and thereby accelerate the healing of infected wounds in mice.Methods: We determined the ability of berberine hydrochloride liposomes to eradicate the biofilm by means of studies such as crystalline violet staining, measuring the inhibition circle, and dilution coating plate method. Encouraged by the in vitro efficacy, we chose to coat the berberine hydrochloride liposomes on the Poloxamer range of in-situ thermosensitive hydrogels to allow fuller contact with the wound surface and sustained efficacy. Eventually, relevant pathological and immunological analyses were carried out on wound tissue from mice treated for 14 days.Results: The final results show that the number of wound tissue biofilms decreases abruptly after treatment and that the various inflammatory factors in them are significantly reduced within a short period. In the meantime, the number of collagen fibers in the treated wound tissue, as well as the proteins involved in healing in the wound tissue, showed significant differences compared to the model group.Conclusion: From the results, we found that berberine liposome gel can accelerate wound healing in Staphylococcus aureus infections by inhibiting the inflammatory response and promoting re-epithelialization as well as vascular regeneration. Our work exemplifies the efficacy of liposomal isolation of toxins. This innovative antimicrobial strategy opens up new perspectives for tackling drug resistance and fighting wound infections.
Prevalence and trend of atrial fibrillation and its associated risk factors among the population from nationwide health check-up centers in China, 2012–2017
Authors: Sun Tao , Ye Mao , Lei Fang , Qin Juan-Juan , Liu Ye-Mao , Chen Ze , Chen Ming-Ming , Yang Chengzhang , Zhang Peng , Ji Yan-Xiao , Zhang Xiao-Jing , She Zhi-Gang , Cai Jingjing , Jin Zhao-Xia , Li Hongliang 
Published: May 2023

BackgroundAtrial fibrillation (AF) is the most prevalent cardiac arrhythmia, which poses huge disease burdens in China. A study was conducted to systematically analyze the recent prevalence trend of AF and age-related disparities in AF risk among the nationwide healthy check-up population.MethodWe conducted a nationwide cross-sectional study involving 3,049,178 individuals ≥35 years from health check-up centers to explore the prevalence and trend of AF by age, sex, and region from 2012 to 2017. Additionally, we analyzed risk factors associated with AF among the overall population and different age groups via the Boruta algorithm, the LASSO regression, and the Logistic regression.ResultThe age-, sex-. and regional-standardized prevalence of AF kept stable between 0.4%–0.45% among national physical examination individuals from 2012 to 2017. However, the prevalence of AF showed an undesirable upward trend in the 35–44-year age group (annual percentage changes (APC): 15.16 [95%CI: 6.42,24.62]). With increasing age, the risk of AF associated with the overweight or obesity gradually exceeds that associated with diabetes and hypertension. In addition to traditional leading risk factors such as age≥65 and coronary heart disease, elevated uric acid and impaired renal function were tightly correlated with AF in the population.ConclusionThe significant rise in the prevalence of AF in the 35–44 age group reminds us that in addition to the elderly (the high-risk group), younger people seem to be in more urgent need of attention. Age-related disparities in AF risk also exist. This updated information may provide references for the national prevention and control of AF.
Effects of PCSK9 inhibition on glucose metabolism and β-cell function in humans: a pilot study
Authors: Moffa Simona , Mezza Teresa , Ferraro Pietro Manuel , Di Giuseppe Gianfranco , Cefalo Chiara M. A. , Cinti Francesca , Impronta Flavia , Capece Umberto , Ciccarelli Gea , Mari Andrea , Pontecorvi Alfredo , Giaccari Andrea 
Published: May 2023

BackgroundAnti-PCSK9 monoclonal antibodies are effective in reducing LDL-C and cardiovascular events by neutralizing circulating PCSK9. PCSK9, however, is also expressed in tissues, including the pancreas, and studies on PCSK9 KO mice have shown impaired insulin secretion. Statin treatment is already known to affect insulin secretion. Our aim was to conduct a pilot study to evaluate the effect of anti-PCSK9 mAb on glucose metabolism and β-cell function in humans.MethodsFifteen non-diabetic subjects, candidates for anti-PCSK9 mAb therapy, were enrolled. All underwent OGTT at baseline and after 6 months of therapy. During OGTT, insulin secretion parameters were derived from C-peptide by deconvolution (β cell glucose sensitivity). Surrogate insulin sensitivity indices were also obtained from OGTT (Matsuda).ResultsGlucose levels during OGTT were unchanged after 6 months of anti-PCSK9 mAb treatment, as well as insulin and C-peptide levels. The Matsuda index remained unchanged, while β-cell glucose sensitivity improved post-therapy (before: 85.3 ± 65.4; after: 118.6 ± 70.9 pmol min-1m-2mM-1; p&lt;0.05). Using linear regression, we found a significant correlation between βCGS changes and BMI (p=0.004). Thus, we compared subjects with values above and below the median (27.6 kg/m2) and found that those with higher BMI had a greater increase in βCGS after therapy (before: 85.37 ± 24.73; after: 118.62 ± 26.83 pmol min-1m-2mM-1; p=0.007). There was also a significant correlation between βCGS change and Matsuda index through linear regression (p=0.04), so we analyzed subjects who had values above and below the median (3.8). This subgroup analysis showed a slight though not significant improvement in βCGS in more insulin resistant patients, (before: 131.4 ± 69.8; after: 170.8 ± 92.7 pmol min-1m-2mM-1; p=0.066).ConclusionsOur pilot study demonstrates that six-month treatment with anti-PCSK9 mAb improves β-cell function, and does not alter glucose tolerance. This improvement is more evident in patients with greater insulin-resistance (low Matsuda) and higher BMI.
Case Report: A novel mutation in TNFAIP3 in a patient with type 1 diabetes mellitus and haploinsufficiency of A20
Authors: Cao Conghui , Fu Xue , Wang Xiaoli 
Published: May 2023

BackgroundHaploinsufficiency of A20 (HA20) is a monogenic autosomal-dominant genetic autoinflammatory disease caused by loss of function mutations in the TNFAIP3 gene. The predominant autoimmune phenotype associated with HA20 varies significantly, presenting with fever, recurrent oral and genital ulcers, skin rash, gastrointestinal and musculoskeletal symptoms, and other clinical manifestations, all of which indicate an early-onset of autoinflammatory disorder. Genetic linkage between TNFAIP3 and T1DM was reported in GWAS studies. However, only a few cases of HA20 combined with T1DM have been reported.Case descriptionA 39-year-old man with a history of type 1 diabetes mellitus since 19 years was admitted to the Department of Endocrinology and Metabolism, First Affiliated Hospital of China Medical University. He also suffered from recurring and minor mouth ulcers since early childhood. His laboratory evaluation results revealed reduced islet function, normal lipid profile, HbA1c of 7%, elevated glutamate decarboxylase antibodies, elevated hepatic transaminases, and elevated thyroid-related antibodies with normal thyroid function. Notably, the patient was diagnosed in adolescence and never had ketoacidosis, the islets were functioning despite the long disease duration, his abnormal liver function could not be reasonably explained, and he had early onset Behcet’s-like disease symptom. Hence, although he was on routine follow-up for diabetes, we communicated with him and obtained consent for genetic testing. Whole-exome sequencing revealed a novel c.1467_1468delinsAT heterozygous mutation in the gene TNFAIP3, which is located in exon 7, resulting in a stop-gained type mutation p.Q490*. With good but mild fluctuating glycemic control, the patient received intensive insulin therapy with long-acting and short-acting insulin. The liver function was improved by using ursodeoxycholic acid 0.75 mg/d during the follow-up.ConclusionWe report a novel pathogenic mutation in TNFAIP3 that results in HA20 in a patient with T1DM. In addition, we analyzed the clinical feathers of such patients and summarized the cases of five patients with HA20 co-presented with T1DM. When T1DM co-occurs with autoimmune diseases or other clinical manifestations, such as oral and/or genital ulcers and chronic liver damage, the possibility of an HA20 must be considered. Early and definitive diagnosis of HA20 in such patients may inhibit the progression of late-onset autoimmune diseases, including T1DM.
Patient decision aids for patients with differentiated thyroid carcinoma: development process and alpha and beta testing
Authors: Koot Anna , Hermens Rosella , Ottevanger Petronella , Netea-Maier Romana , Stalmeier Peep ,   the COMBO study group
Published: May 2023

BackgroundPatient decision aids (PtDAs) are structured clinical tools that facilitate shared decision-making. Two important treatment decisions for patients with differentiated thyroid cancer (DTC), which could benefit from PtDAs, are as follows (1): the extent of surgery decision in patients with low-risk DTC and (2) the decision to start or delay starting the treatment with tyrosine kinase inhibitors (TKIs) in patients with advanced tumors.Material and methodsPtDAs for these two decisions were developed using the International Patient Decision Aids Standards (IPDAS) quality criteria in an iterative process of prototype development via alpha and beta testing by patients and physicians. The information content of the PtDAs was based on the available literature, current guidelines, and patient’s needs, preferences, and values.ResultsThe web-based PtDAs underwent two rounds of alpha testing, revisions, and beta testing. The PtDAs have the same structure, consisting of six steps: a general introduction, information about the treatment options, comparing the treatment options, knowledge questions, a values clarification exercise, and saving the information. The alpha testing (n = 8 patients, n = 10 physicians) showed that the PtDAs were highly acceptable and usable for decision-making. Results of the beta testing in 20 patients showed that two patients did not use the PtDA; the other 18 patients found that the PtDAs were readable (n = 17) and helpful (n = 14) for decision-making. All patients recommend using the PtDAs.ConclusionsEvidence-based PtDAs were created for patients with DTC for two different treatment decisions. Our final version was judged to be clear, balanced, and helpful in decision-making.
Keratinocytes use FPR2 to detect Staphylococcus aureus and initiate antimicrobial skin defense
Authors: Lebtig Marco , Scheurer Jasmin , Muenkel Marie , Becker Janna , Bastounis Effie , Peschel Andreas , Kretschmer Dorothee 
Published: May 2023

IntroductionKeratinocytes form a multilayer barrier that protects the skin from invaders or injuries. The barrier function of keratinocytes is in part mediated by the production of inflammatory modulators that promote immune responses and wound healing. Skin commensals and pathogens such as Staphylococcus aureus secrete high amounts of phenol-soluble modulin (PSM) peptides, agonists of formyl-peptide receptor 2 (FPR2). FPR2 is crucial for the recruitment of neutrophils to the sites of infection, and it can influence inflammation. FPR1 and FPR2 are also expressed by keratinocytes but the consequences of FPR activation in skin cells have remained unknown.MethodsSince an inflammatory environment influences S. aureus colonization, e. g. in patients with atopic dermatitis (AD), we hypothesized that interference with FPRs may alter keratinocyte-induced inflammation, proliferation, and bacterial colonization of the skin. To assess this hypothesis, we investigated the effects of FPR activation and inhibition in keratinocytes with respect to chemokine and cytokine release as well as proliferation and skin wound gap closure.ResultsWe observed that FPR activation induces the release of IL-8, IL-1α and promotes keratinocyte proliferation in a FPR-dependent manner. To elucidate the consequence of FPR modulation on skin colonization, we used an AD-simulating S. aureus skin colonization mouse model using wild-type (WT) or Fpr2-/- mice and demonstrate that inflammation enhances the eradication of S. aureus from the skin in a FPR2-dependent way. Consistently, inhibition of FPR2 in the mouse model or in human keratinocytes as well as human skin explants promoted S. aureus colonization.DiscussionOur data indicate that FPR2 ligands promote inflammation and keratinocyte proliferation in a FPR2-dependent manner, which is necessary for eliminating S. aureus during skin colonization.
Sintilimab as maintenance treatment for local/regional recurrent esophageal squamous carcinoma after concurrent chemoradiotherapy: a single-arm Ib/II phase study
Authors: Liu Chengxin , Sun Hongfu , Huang Wei , Wang Zhongtang , Fu Chengrui , Han Dan , Zhao Qian , Wu Xue , Li Baosheng 
Published: May 2023

BackgroundEsophageal cancer (EC) is an aggressive neoplasm of the gastrointestinal tract that is usually treated with a combination of chemotherapy, radiotherapy (RT), and/or surgery, according to disease status. Despite the availability of multimodal therapeutic strategies, local recurrence is frequently observed. However, there is no standard treatment or promising therapeutic approach for local recurrence or metastatic esophageal carcinoma after the RT. This study tended to investigate the efficacy and safety of sintilimab maintenance after concurrent chemoradiotherapy (CCRT) for local/regional recurrent esophageal squamous carcinoma.MethodsThis study was a single-arm, phase Ib/II trial conducted in a single site in China. Patients previously radically treated (surgery or CCRT), histologically confirmed, local or regional recurrence esophageal squamous carcinoma, qualified for the study design, were treated with 25–28 times radiotherapy plus raltitrexed once every 3 weeks for up to two cycles. Patients who have not progressed after CCRT received sintilimab as maintenance once every 3 weeks up to 1 year. Primary endpoints were overall survival (OS) and safety. Secondary endpoints were progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR).ResultsBetween September 2019 and March 2022, in a total of 36 enrolled patients, 34 pts completed CCRT. Three patients excluded due to violation of the exclusion criteria (1 pt) and consent withdrawal (2 pts). Finally, 33 pts were included in the final analysis, in which 3 pts had disease progression, and the remaining 30 entered maintenance therapy with sintilimab. The median follow-up time was 12.3 months. Median OS was 20.6 months (95%CI 10.5–NA) and the 1-year OS rate was 64%. Median PFS was 11.5 months (95%CI 5.29–21.3) and the 1-year PFS rate was 43.6%. The ORR was 63.6% (95%CI 44.6–77.8), including 2 cases of CR and 19 cases of PR. The DCR was 19.9%, the median DOR was 19.5 months, and the median TTR was 2.4 months. The rate of any grade TRAEs was 96.7%; ≥Grade 3 TRAE was 23.4%. The incidence of immune-related AE was 60%, most of which were grade 1–2, and only one case of thyroid-stimulating hormone increased was irAE with grade 3 or above.ConclusionSintilimab has shown promising clinical efficacy and a manageable safety profile as maintenance therapy after CCRT for local/regional recurrent esophageal squamous carcinoma. In addition, further confirmation from a large-scale real-world study is still needed.
A plasmatic score using a miRNA signature and CXCL-10 for accurate prediction and diagnosis of liver allograft rejection
Authors: Millán Olga , Ruiz Pablo , Julian Judit , Lizana Ana , Fundora Yiliam , Crespo Gonzalo , Colmenero Jordi , Navasa Miquel , Brunet Mercè 
Published: May 2023

IntroductionThe use of noninvasive biomarkers may avoid the need for liver biopsy (LB) and could guide immunosuppression adjustment in liver transplantation (LT). The aims of this study were: to confirm the predictive and diagnostic capacity of plasmatic expression of miR-155-5p, miR-181a-5p, miR-122-5p and CXCL-10 for assessing T-cell mediated rejection (TCMR) risk; to develop a score based on a panel of noninvasive biomarkers to predict graft rejection risk and to validate this score in a separate cohort.MethodsA prospective, observational study was conducted with a cohort of 79 patients followed during the first year after LT. Plasma samples were collected at predetermined time points for the analysis of miRNAs and the CXCL-10. Patients with LFTs abnormalities were submitted to a LB to rule out rejection, assessing previous and concurrent expression of the biomarkers to evaluate their predictive and diagnostic ability. Information from 86 patients included in a previous study was collected and used as a validation cohort.ResultsTwenty-four rejection episodes were diagnosed in 22 patients. Plasmatic CXCL-10 concentration and the expression of the three miRNAs were significantly elevated prior to and at the moment of the diagnosis of rejection. We developed a logistic model for rejection prediction and diagnosis, which included CXCL-10, miR-155-5p and miR-181a-5p. The area under the ROC curve (AUROC) for rejection prediction was 0.975 (79.6% sensitivity, 99.1% specificity, 90,7% PPV; 97.7% NPV; 97.1% correctly classified) and 0.99 for diagnosis (87.5% sensitivity, 99.5% specificity, 91.3% PPV; 99.3% NPV; 98.9% correctly classified). In the validation cohort (n=86; 14 rejections), the same cut-off points were used obtaining AUROCs for rejection prediction and diagnosis of 0.89 and 0.92 respectively. In patients with graft dysfunction in both cohorts the score could discriminate those with rejection regarding other causes with an AUROC of 0.98 (97.3% sensitivity, 94.1%specificity).ConclusionThese results suggest that the clinical implementation of the monitoring of this noninvasive plasmatic score may allow the prediction and diagnosis of rejection and identify patients with graft dysfunction due to rejection, helping with a more efficient guide for immunosuppressive therapy adjustment. This finding warrants the development of prospective biomarker-guided clinical trials.
A novel signature predicts prognosis and immunotherapy in lung adenocarcinoma based on cancer-associated fibroblasts
Authors: Ren Qianhe , Zhang Pengpeng , Lin Haoran , Feng Yanlong , Chi Hao , Zhang Xiao , Xia Zhijia , Cai Huabao , Yu Yue 
Published: May 2023

BackgroundExtensive research has established the significant correlations between cancer-associated fibroblasts (CAFs) and various stages of cancer development, including initiation, angiogenesis, progression, and resistance to therapy. In this study, we aimed to investigate the characteristics of CAFs in lung adenocarcinoma (LUAD) and develop a risk signature to predict the prognosis of patients with LUAD.MethodsWe obtained single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from the public database. The Seurat R package was used to process the scRNA-seq data and identify CAF clusters based on several biomarkers. CAF-related prognostic genes were further identified using univariate Cox regression analysis. To reduce the number of genes, Lasso regression was performed, and a risk signature was established. A novel nomogram that incorporated the risk signature and clinicopathological features was developed to predict the clinical applicability of the model. Additionally, we conducted immune landscape and immunotherapy responsiveness analyses. Finally, we performed in vitro experiments to verify the functions of EXO1 in LUAD.ResultsWe identified 5 CAF clusters in LUAD using scRNA-seq data, of which 3 clusters were significantly associated with prognosis in LUAD. A total of 492 genes were found to be significantly linked to CAF clusters from 1731 DEGs and were used to construct a risk signature. Moreover, our immune landscape exploration revealed that the risk signature was significantly related to immune scores, and its ability to predict responsiveness to immunotherapy was confirmed. Furthermore, a novel nomogram incorporating the risk signature and clinicopathological features showed excellent clinical applicability. Finally, we verified the functions of EXP1 in LUAD through in vitro experiments.ConclusionsThe risk signature has proven to be an excellent predictor of LUAD prognosis, stratifying patients more appropriately and precisely predicting immunotherapy responsiveness. The comprehensive characterization of LUAD based on the CAF signature can predict the response of LUAD to immunotherapy, thus offering fresh perspectives into the management of LUAD patients. Our study ultimately confirms the role of EXP1 in facilitating the invasion and growth of tumor cells in LUAD. Nevertheless, further validation can be achieved by conducting in vivo experiments.
Minimally invasive surgery vs. open thoracotomy for non-small-cell lung cancer with N2 disease: a systematic review and meta-analysis
Authors: Liu Songlin , Li Shaopeng , Tang Yong , Chen Rixin , Qiao Guibin 
Published: May 2023

BackgroundThis meta-analysis aimed to investigate the effectiveness and safety of minimally invasive surgery [MIS, including robotic-assisted thoracoscopic surgery (RATS) and video-assisted thoracoscopic surgery (VATS)] and open thoracotomy (OT) for non-small cell lung cancer (NSCLC) patients with N2 disease.MethodsWe searched online databases and studies from the creation of the database to August 2022, comparing the MIS group to the OT group for NSCLC with N2 disease. Study endpoints included intraoperative outcomes [e.g., conversion, estimated blood loss (EBL), surgery time (ST), total lymph nodes (TLN), and R0 resection], postoperative outcomes [e.g., length of stay (LOS) and complication], and survival outcomes [e.g., 30-day mortality, overall survival (OS), and disease-free survival (DFS)]. We estimated outcomes using random effects meta-analysis to account for studies with high heterogeneity (I2 &gt; 50 or p &lt; 0.05). Otherwise, we used a fixed-effect model. We calculated odds ratios (ORs) for binary outcomes and standard mean differences (SMDs) for continuous outcomes. Treatment effects on OS and DFS were described by hazard ratio (HR).ResultsThis systematic review and meta-analysis of 15 studies on MIS vs. OT for NSCLC with N2 disease included 8,374 patients. Compared to OT, patients that underwent MIS had less estimated blood loss (EBL) (SMD = – 64.82, p &lt; 0.01), shorter length of stay (LOS) (SMD = −0.15, p &lt; 0.01), higher R0 resection rate (OR = 1.22, p = 0.049), lower 30-day mortality (OR = 0.67, p = 0.03), and longer overall survival (OS) (HR = 0.61, P &lt; 0.01). The results showed no statistically significant differences in surgical time (ST), total lymph nodes (TLN), complications, and disease-free survival (DFS) between the two groups.ConclusionCurrent data suggest that minimally invasive surgery may provide satisfying outcomes, a higher R0 resection rate, and better short-term and long-term survival than open thoracotomy.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022355712.