bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combination treatment of radiofrequency ablation and peptide neoantigen vaccination: Promising modality for future cancer immunotherapy
Authors: Shou Jiawei , Mo Fan , Zhang Shanshan , Lu Lantian , Han Ning , Liu Liang , Qiu Min , Li Hongseng , Han Weidong , Ma Dongying , Guo Xiaojie , Guo Qianpeng , Huang Qinxue , Zhang Xiaomeng , Ye Shengli , Pan Hongming , Chen Shuqing , Fang Yong 
Published: September 2022

BackgroundThe safety and immunogenicity of a personalized neoantigen-based peptide vaccine, iNeo-Vac-P01, was reported previously in patients with a variety of cancer types. The current study investigated the synergistic effects of radiofrequency ablation (RFA) and neoantigen vaccination in cancer patients and tumor-bearing mice.MethodsTwenty-eight cancer patients were enrolled in this study, including 10 patients who had received RFA treatment within 6 months before vaccination (Cohort 1), and 18 patients who had not (Cohort 2). Individualized neoantigen peptide vaccines were designed, manufactured, and subcutaneously administrated with GM-CSF as an adjuvant for all patients. Mouse models were employed to validate the synergistic efficacy of combination treatment of RFA and neoantigen vaccination.ResultsLonger median progression free survival (mPFS) and median overall survival (mOS) were observed in patients in Cohort 1 compared to patients in Cohort 2 (4.42 and 20.18 months vs. 2.82 and 10.94 months). The results of ex vivo IFN-γ ELISpot assay showed that patients in Cohort 1 had stronger neoantigen-specific immune responses at baseline and post vaccination. Mice receiving combination treatment of RFA and neoantigen vaccines displayed higher antitumor immune responses than mice receiving single modality. The combination of PD-1 blockage with RFA and neoantigen vaccines further enhanced the antitumor response in mice.ConclusionNeoantigen vaccination after local RFA treatment could improve the clinical and immune response among patients of different cancer types. The synergistic antitumor potentials of these two modalities were also validated in mice, and might be further enhanced by immune checkpoint inhibition. The mechanisms of their synergies require further investigation. Clinical trial registrationhttps://clinicaltrials.gov/, identifier NCT03662815.
Identification and validation of ferroptosis-related lncRNA signature as a prognostic model for skin cutaneous melanoma
Authors: Guo Sen , Chen Jianru , Yi Xiuli , Lu Zifan , Guo Weinan 
Published: September 2022

BackgroundMelanoma is a type of skin cancer, which originates from the malignant transformation of epidermal melanocytes, with extremely high lethality. Ferroptosis has been documented to be highly related to cancer pathogenesis and the effect of immunotherapy. In addition, the dysregulation of lncRNAs is greatly implicated in melanoma progression and ferroptosis regulation. However, the significance of ferroptosis-related lncRNA in melanoma treatment and the prognosis of melanoma patients remains elusive.MethodsVia Least Absolute Shrinkage Selection Operator (LASSO) regression analysis in the TCGA SKCM database, a cutaneous melanoma risk model was established based on differentially-expressed ferroptosis-related lncRNAs (DEfrlncRNAs). The nomogram, receiver operating characteristic (ROC) curves, and calibration plots were conducted to examine the predictive performance of this model. Sequentially, we continued to analyze the differences between the high- and low-risk groups, in terms of clinical characteristics, immune cell infiltration, immune-related functions, and chemotherapy drug sensitivity. Moreover, the expressions of DEfrlncRNAs, PD-L1, and CD8 were also examined by qRT-PCR and immunohistochemical staining in melanoma tissues to further confirm the potential clinical implication of DEfrlncRNAs in melanoma immunotherapy.Results16 DEfrlncRNAs were identified, and a representative risk score for patient survival was constructed based on these 16 genes. The risk score was found to be an independent prognostic factor for the survival of melanoma patients. In addition, the low-risk group of patients had higher immune cell infiltration in the melanoma lesions, higher sensitivity to chemotherapeutic agents, and a better survival prognosis. Besides, the high expression of the identified 5 DEfrlncRNA in the low-risk group might suggest a higher possibility to benefit from immune checkpoint blockade therapy in the treatment of melanoma.ConclusionThe DEfrlncRNA risk prediction model related to ferroptosis genes can independently predict the prognosis of patients with melanoma and provide a basis for evaluating the response of clinical treatment in melanoma.
Assessment of plasma Catestatin in COVID-19 reveals a hitherto unknown inflammatory activity with impact on morbidity-mortality
Authors: Schneider Francis , Le Borgne Pierrick , Herbrecht Jean-Etienne , Danion François , Solis Morgane , Hellé Sophie , Betscha Cosette , Clere-Jehl Raphaël , Lefebvre François , Castelain Vincent , Goumon Yannick , Metz-Boutigue Marie-Hélène 
Published: September 2022

IntroductionNeuroendocrine cells release Catestatin (CST) from Chromogranin A (CgA) to regulate stress responses. As regards COVID-19 patients (COVID+) requiring oxygen supply, to date nobody has studied CST as a potential mediator in the regulation of immunity.Patients &amp; MethodsAdmission plasma CST and CgA - its precursor - concentrations were measured (ELISA test) in 73 COVID+ and 27 controls. Relationships with demographics, comorbidities, disease severity and outcomes were analysed (Mann-Whitney, Spearman correlation tests, ROC curves).ResultsAmong COVID+, 49 required ICU-admission (COVID+ICU+) and 24 standard hospitalization (COVID+ICU-). Controls were either healthy staff (COVID-ICU-, n=11) or (COVID-ICU+, patients n=16). Median plasma CST were higher in COVID+ than in controls (1.6 [1.02; 3.79] vs 0.87 [0.59; 2.21] ng/mL, p&lt;0.03), with no difference between COVID+ and COVID-ICU+. There was no difference between groups in either CgA or CST/CgA ratios, but these parameters were lower in healthy controls (p&lt;0.01). CST did not correlate with either hypoxia- or usual inflammation-related parameters. In-hospital mortality was similar whether COVID+ or not, but COVID+ had longer oxygen support and more complications (p&lt;0.03). CST concentrations and the CST/CgA ratio were associated with in-hospital mortality (p&lt;0.01) in COVID+, whereas CgA was not. CgA correlated with care-related infections (p&lt;0.001).ConclusionRespiratory COVID patients release significant amounts of CST in the plasma making this protein widely available for the neural regulation of immunity. If confirmed prospectively, plasma CST will reliably help in predicting in-hospital mortality, whereas CgA will facilitate the detection of patients prone to care-related infections.
Independent value of serum β-human chorionic gonadotropin in predicting early pregnancy loss risks in IVF/ICSI cycles
Authors: Wang Liyan , Jiang Yanbiao , Shen Haofei , Ma Xiaoling , Gao Mingxia , Jin Panpan , Zhang Rui , Zhao Lihui , Zhang Xuehong 
Published: September 2022

BackgroundEarly pregnancy loss (EPL) is the most prevalent complication, particularly in couples undergoing assisted reproductive technology treatment. The present study aimed to determine whether the serum β-human chorionic gonadotropin (β-hCG) level after 14 days of embryo transfer, either alone or in conjunction with other parameters in IVF/ICSI cycles, could be used to predict subsequent EPL.MethodsThis was a retrospective cohort study of all couples who received clinical pregnancy and underwent fresh IVF/ICSI cycles at a single large reproductive medical center between January 2013 and June 2020. The research involved a total of 6600 cycles. For risk variables, we conducted the least absolute shrinkage and selection operator (LASSO) analysis, and for risk scoring, we used logistic regression coefficients. To analyze relevant risk factors for EPL, univariate and multivariate logistic regression analyses were employed. Areas under the curve (AUC) were determined and compared between β-hCG and other factors using receiver operating characteristic (ROC) curves.Resultsβ-hCG level was considerably lower in women who had EPL than in those who were ongoing pregnancy (564.03 ± 838.16 vs 1139.04 ± 1048.72 IU/L, p&lt; 0.001). Univariable and multivariable logistic regression revealed that β-hCG levels were significantly correlated with the probability of EPL, independent of other risk factors. More importantly, the β-hCG level could independently predict the occurrence of EPL and was comparable to the model that combined other risk factors. The optimal serum β-hCG cut-off value for predicting EPL was 542.45 IU/L.ConclusionsOur results suggest that the serum β-hCG level has a strong independent predictive value for EPL occurrence in fresh IVF/ICSI cycles.
Identification of diagnostic gene biomarkers and immune infiltration in patients with diabetic kidney disease using machine learning strategies and bioinformatic analysis
Authors: Fu Shaojie , Cheng Yanli , Wang Xueyao , Huang Jingda , Su Sensen , Wu Hao , Yu Jinyu , Xu Zhonggao 
Published: September 2022

ObjectiveDiabetic kidney disease (DKD) is the leading cause of chronic kidney disease and end-stage renal disease worldwide. Early diagnosis is critical to prevent its progression. The aim of this study was to identify potential diagnostic biomarkers for DKD, illustrate the biological processes related to the biomarkers and investigate the relationship between them and immune cell infiltration.Materials and methodsGene expression profiles (GSE30528, GSE96804, and GSE99339) for samples obtained from DKD and controls were downloaded from the Gene Expression Omnibus database as a training set, and the gene expression profiles (GSE47185 and GSE30122) were downloaded as a validation set. Differentially expressed genes (DEGs) were identified using the training set, and functional correlation analyses were performed. The least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forests (RF) were performed to identify potential diagnostic biomarkers. To evaluate the diagnostic efficacy of these potential biomarkers, receiver operating characteristic (ROC) curves were plotted separately for the training and validation sets, and immunohistochemical (IHC) staining for biomarkers was performed in the DKD and control kidney tissues. In addition, the CIBERSORT, XCELL and TIMER algorithms were employed to assess the infiltration of immune cells in DKD, and the relationships between the biomarkers and infiltrating immune cells were also investigated.ResultsA total of 95 DEGs were identified. Using three machine learning algorithms, DUSP1 and PRKAR2B were identified as potential biomarker genes for the diagnosis of DKD. The diagnostic efficacy of DUSP1 and PRKAR2B was assessed using the areas under the curves in the ROC analysis of the training set (0.945 and 0.932, respectively) and validation set (0.789 and 0.709, respectively). IHC staining suggested that the expression levels of DUSP1 and PRKAR2B were significantly lower in DKD patients compared to normal. Immune cell infiltration analysis showed that B memory cells, gamma delta T cells, macrophages, and neutrophils may be involved in the development of DKD. Furthermore, both of the candidate genes are associated with these immune cell subtypes to varying extents.ConclusionDUSP1 and PRKAR2B are potential diagnostic markers of DKD, and they are closely associated with immune cell infiltration.
Dropout from a maternal and newborn continuum of care after antenatal care booking and its associated factors in Debre Berhan town, northeast Ethiopia
Authors: Tadese Mesfin , Tessema Saba Desta , Aklilu Dawit , Wake Getu Engida , Mulu Getaneh Baye 
Published: September 2022

BackgroundContinuum of care (CoC) is the continuity of care from the beginning of pregnancy to the postnatal period to improve maternal, neonatal, and child health. Dropout from the maternal CoC remains a public health challenge in Ethiopia. There are limited studies on women who dropped out of the CoC. The available studies have focused on the time dimension of the CoC, and there is a paucity of data on the place dimension of the CoC. Thus, this study aimed to determine the prevalence of dropout from the maternal CoC and its associated factors in Debre Berhan town, northeast Ethiopia.MethodsA community-based cross-sectional study design was conducted among 842 mothers from September to October 2020. A cluster sampling technique was applied, and data were collected through face-to-face interviews using a structured and pre-tested questionnaire. Data were cleaned and entered into EpiData version 4.6 and exported to SPSS version 25 for analysis. Descriptive statistics, and bivariable and multivariable logistic regression analyses were performed to summarize the findings, and a p-value of &lt;0.05 was considered statistically significant.ResultThe overall prevalence of dropout from the maternity continuum of care was 69.1% [95% CI (66.0–72.3)]. The prevalence of dropout from ANC, skilled birth attendant, and PNC visits was 45.4, 0.5, and 48.7%, respectively. Rural residents, partners' level of education, monthly income, the timing of the first ANC visit, antenatal counseling about a continuum of care, and the level of satisfaction with the service delivery were significantly associated with ANC dropout. Maternal age and occupation, partners' age, media exposure, parity, the timing of the first ANC visit, the place of ANC visit, and the time spent for an ANC visit were significantly associated with dropout from PNC visits. Husbands' occupation, monthly income, number of alive children, the timing of the first ANC visit, and the time spent for an ANC visit had a statistically significant association with dropout from the maternity CoC.ConclusionDropout from the CoC in the study area was high. Socioeconomic development, partner involvement, antenatal counseling, efficient service delivery, and media exposure are vital to improving the high dropout rate from the maternal continuum of care.
Timing of glaucoma treatment in patients with MICOF: A retrospective clinical study
Authors: Li Zhao , Wang Qun , Zhang Shi-Feng , Huang Yi-Fei , Wang Li-Qiang 
Published: September 2022

PurposeTo summarize and discuss the treatment and timing of glaucoma in patients with MICOF keratoprosthesis implantation to guide follow-up clinical treatment.MethodsThe data of 39 eyes (39 patients) with the Moscow Eye Microsurgery Complex in Russia (MICOF) keratoprosthesis implantation in our hospital from 1 January 2002 to 31 December 2017 were collected, including patients with preexisting glaucoma and those who developed glaucoma de novo after MICOF. The sex, age, preoperative diagnosis, glaucoma surgery, keratoplasty, times of keratoplasty, best corrected visual acuity (BCVA) and final follow-up corrected visual acuity, visual field (VF) defect, and cup-to-disk ratio (CDR) were statistically analyzed.ResultsAmong 16 eyes with preexisting glaucoma, eight eyes underwent glaucoma surgery before MICOF, 4 eyes underwent glaucoma surgery combined with MICOF, and four eyes were managed medically. Among 23 eyes with de novo glaucoma, seven eyes were treated with surgery and 16 eyes were treated with medication only. A total of 9 (56.3%) eyes had corneal transplants with preexisting glaucoma, which was a higher percentage than that in the patients with de novo glaucoma (n = 5, 21.7%, P = 0.043). In both the preexisting glaucoma group and the de novo glaucoma group, the most common causes were alkali burns (56.3% of preexisting glaucoma and 43.5% of de novo glaucoma). There was no significant difference between the operation and initial visual acuity, postoperative visual acuity, BCVA, CDR, or VF defect. In the de novo glaucoma group, the final follow-up visual acuity of the glaucoma surgery group (1.56 ± 1.07) was worse than that of the mediation group (0.44 ± 0.53) (P &lt; 0.017). Among the complications, the incidence of cornea melting in the patients treated with medications only (n=10) was significantly higher than that in the patients treated with glaucoma surgery (n = 0, P = 0.007), but there was no significant difference in the other complications.ConclusionAmong patients with MICOF, those patients who have undergone keratoplasty are more likely to develop glaucoma before surgery and glaucoma needs to be prevented. Surgical treatment can be selected according to the ocular surface condition in the patients with de novo glaucoma to reduce the occurrence of complications.
PUP-IT2 as an alternative strategy for PUP-IT proximity labeling
Authors: Yue Suyu , Xu Peng , Cao Zhihe , Zhuang Min 
Published: September 2022

PUP-IT is a proximity labeling method based on the prokaryotic enzyme PafA. PafA mediates the ligation of Pup, a small peptide, to the proximal proteins. It is different from other proximity labeling methods, such as BioID and APEX, in that both the enzyme and the labeling tag are proteins, which allows for potential in vivo applications. All proximity labeling involves the genetic fusion of the proximity labeling enzyme with the bait protein. However, PafA is a 55 kDa enzyme which sometimes interferes with the bait function. In this study, we tested an alternative proximity labeling strategy, PUP-IT2, in which only a small 7 kDa protein is fused to the bait protein. We examined the activity of PUP-IT2 in vitro and in cells. We also compared it with the original PUP-IT. Finally, we applied PUP-IT2 coupled mass spectrometry to map protein-protein interactions. Overall, we established a new way to use PUP-IT2 for proximity labeling, and this method may have a broad application.
Two novel bombesin-like neuropeptides from the skin secretion of Pelophylax kl. esculentus: Ex vivo pharmacological characterization on rat smooth muscle types
Authors: Zhang Luyao , Chen Chen , Zou Wanchen , Chen Xiaoling , Zhou Mei , Ma Chengbang , Xi Xinping , Chen Tianbao , Shaw Chris , Liu Mingchun , Wang Lei 
Published: September 2022

Mammalian bombesin-like neuropeptides (BLPs) play an important role in regulation of physiological and pathophysiological processes. Frog skin-derived BLPs, of smaller size and diverse lengths and sequences at their N-terminus, have attracted the attention of many researchers. However, these N-terminal variants and the receptors modulating their pharmacological actions are poorly studied and less understood. In this study, two BLPs, namely, [Asn3, Lys6, Thr10, Phe13]3–14-bombesin and [Asn3, Lys6, Phe13]3–14-bombesin with primary structures NLGKQWATGHFM and NLGKQWAVGHFM were isolated from the skin secretion of hybrid Pelophylax kl. esculentus. Both BLPs share a similar primary structure with only a single amino acid substitution at the eighth position (threonine to valine), while they have quite different myotropic potencies with EC50 values in the range of 22.64 ± 9.7 nM (N = 8) to 83.93 ± 46.9 nM (N = 8). The potency of [Asn3, Lys6, Thr10, Phe13]3–14-bombesin was approximately 3-fold higher than that of [Asn3, Lys6, Phe13]3–14-bombesin. Through the investigation of receptor selectivity using a canonical bombesin receptor antagonist, it was found that [Asn3, Lys6, Thr10, Phe13]3–14-bombesin and [Asn3, Lys6, Phe13]3–14-bombesin had an affinity to both BB1 and BB2 receptors. Their contractile functions are mainly modulated by both BB1 and BB2 receptors on rat urinary bladder and BB2 alone on rat uterus smooth muscle preparations. These data may provide new insights into the design of potent and selective ligands for bombesin receptors. Moreover, [Asn3, Lys6, Thr10, Phe13]3–14-bombesin and [Asn3, Lys6, Phe13]3–14-bombesin did not induce significant hemolysis and toxicity in normal human cells, suggesting that these two natural novel BLPs have great potential for development into new drug candidates.
Gender difference in association between H-type hypertension and subcortical ischemic vascular disease
Authors: Wang Juan , Xi Yuan-Xue , Li Jia-Qi , Zhu Wei-Wen 
Published: September 2022

BackgroundSubcortical ischemic vascular disease (SIVD) is a leading cause of vascular dementia. The present study tries to explore not only the gender-specific association between H-type hypertension and SIVD but also the indirect effects of H-type hypertension on cognition through the ischemic brain injury caused by SIVD.Materials and methodsA total of 601 SIVD patients were included, comprising 322 males and 279 females. H-type hypertension was defined as hypertension accompanied with elevated serum total homocysteine (tHcy) level. The imaging manifestations of ischemic brain injury caused by SIVD were also evaluated, including white matter lesions (WML), lacunar infarction (LI) and brain atrophy (BA). Gender-specific subgroup analyses in association between H-type hypertension and SIVD were conducted, followed by a structural equation model based evaluation of the gender-specific mediating effects of SIVD on the relationship between H-type hypertension and cognition.ResultsFor males, there was no noticeable difference in WML, LI and BA scores among control group, isolated hypertension group, isolated high tHcy group, and H-type hypertension group in most brain regions, but significant difference was found in all brain regions for females. Multiple regression analyses showed that H-type hypertension was significantly associated with WML, LI and BA for females, but not for males. For males, H-type hypertension mainly affected cognition through direct effect, while the H-type hypertension effect was mediated by ischemic brain injury caused by SIVD for females.ConclusionH-type hypertension was more closely related to SIVD for females than males, suggesting a gender-specific difference in association patterns between H-type hypertension and cognition.