bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative analysis of circadian clock with prognostic and immunological biomarker identification in ovarian cancer
Authors: Zhao Lianfang , Tang Yuqin , Yang Jiayan , Lin Fang , Liu Xiaofang , Zhang Yongqiang , Chen Jianhui 
Published: June 2023

Objective: To identify circadian clock (CC)-related key genes with clinical significance, providing potential biomarkers and novel insights into the CC of ovarian cancer (OC).Methods: Based on the RNA-seq profiles of OC patients in The Cancer Genome Atlas (TCGA), we explored the dysregulation and prognostic power of 12 reported CC-related genes (CCGs), which were used to generate a circadian clock index (CCI). Weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network were used to identify potential hub genes. Downstream analyses including differential and survival validations were comprehensively investigated.Results: Most CCGs are abnormally expressed and significantly associated with the overall survival (OS) of OC. OC patients with a high CCI had lower OS rates. While CCI was positively related to core CCGs such as ARNTL, it also showed significant associations with immune biomarkers including CD8+ T cell infiltration, the expression of PDL1 and CTLA4, and the expression of interleukins (IL-16, NLRP3, IL-1β, and IL-33) and steroid hormones-related genes. WGCNA screened the green gene module to be mostly correlated with CCI and CCI group, which was utilized to construct a PPI network to pick out 15 hub genes (RNF169, EDC4, CHCHD1, MRPL51, UQCC2, USP34, POM121, RPL37, SNRPC, LAMTOR5, MRPL52, LAMTOR4, NDUFB1, NDUFC1, POLR3K) related to CC. Most of them can exert prognostic values for OS of OC, and all of them were significantly associated with immune cell infiltration. Additionally, upstream regulators including transcription factors and miRNAs of key genes were predicted.Conclusion: Collectively, 15 crucial CC genes showing indicative values for prognosis and immune microenvironment of OC were comprehensively identified. These findings provided insight into the further exploration of the molecular mechanisms of OC.
Benefits and risks of antiplatelet therapy for moyamoya disease: a systematic review and meta-analysis
Authors: Liu Tingting , Qin Mingzhen , Xiong Xuejiao , Li Tingting , Feng Luda , Lai Xinxing , Gao Ying 
Published: June 2023

BackgroundMoyamoya disease (MMD) is a leading cause of stroke in children and young adults, whereas no specific drugs are available. Antiplatelet therapy (APT) has been considered a promising treatment option, but its effectiveness remains controversial. Therefore, we aimed to comprehensively evaluate the benefits and risks of APT for MMD.MethodsWe systematically searched PubMed, Embase, and Cochrane Library electronic databases from their inception to 30 June 2022 and conducted a systematic review. All-cause mortality was taken as the primary outcome.ResultsNine studies that enrolled 16,186 patients with MMD were included. The results from a single study showed that APT was associated with lower mortality [hazard ratio (HR) = 0.60; 95% confidence interval (CI) (0.50–0.71); p &lt; 0.01] and improved bypass patency after surgical revascularization [HR = 1.57; 95% CI (1.106–2.235); p &lt; 0.05]. The results of the meta-analysis showed that APT reduced the risk of hemorrhagic stroke [HR = 0.47; 95% CI (0.24–0.94); p &lt; 0.05] but neither reduced the risk of ischemic stroke [HR = 0.80; 95% CI (0.33–1.94); p = 0.63] nor increased the proportion of independent patients [RR = 1.02; 95% CI (0.97–1.06); p = 0.47].ConclusionCurrent evidence showed that APT was associated with a reduced risk of hemorrhagic stroke in MMD patients but did not reduce the risk of ischemic stroke or increase the proportion of independent patients. There was insufficient evidence about the benefit of APT on survival and postoperative bypass patency after surgical revascularization. However, the results should be interpreted cautiously because of the limited number of studies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/.
Linear fine-tuning: a linear transformation based transfer strategy for deep MRI reconstruction
Authors: Bi Wanqing , Xv Jianan , Song Mengdie , Hao Xiaohan , Gao Dayong , Qi Fulang 
Published: June 2023

IntroductionFine-tuning (FT) is a generally adopted transfer learning method for deep learning-based magnetic resonance imaging (MRI) reconstruction. In this approach, the reconstruction model is initialized with pre-trained weights derived from a source domain with ample data and subsequently updated with limited data from the target domain. However, the direct full-weight update strategy can pose the risk of "catastrophic forgetting" and overfitting, hindering its effectiveness. The goal of this study is to develop a zero-weight update transfer strategy to preserve pre-trained generic knowledge and reduce overfitting.MethodsBased on the commonality between the source and target domains, we assume a linear transformation relationship of the optimal model weights from the source domain to the target domain. Accordingly, we propose a novel transfer strategy, linear fine-tuning (LFT), which introduces scaling and shifting (SS) factors into the pre-trained model. In contrast to FT, LFT only updates SS factors in the transfer phase, while the pre-trained weights remain fixed.ResultsTo evaluate the proposed LFT, we designed three different transfer scenarios and conducted a comparative analysis of FT, LFT, and other methods at various sampling rates and data volumes. In the transfer scenario between different contrasts, LFT outperforms typical transfer strategies at various sampling rates and considerably reduces artifacts on reconstructed images. In transfer scenarios between different slice directions or anatomical structures, LFT surpasses the FT method, particularly when the target domain contains a decreasing number of training images, with a maximum improvement of up to 2.06 dB (5.89%) in peak signal-to-noise ratio.DiscussionThe LFT strategy shows great potential to address the issues of "catastrophic forgetting" and overfitting in transfer scenarios for MRI reconstruction, while reducing the reliance on the amount of data in the target domain. Linear fine-tuning is expected to shorten the development cycle of reconstruction models for adapting complicated clinical scenarios, thereby enhancing the clinical applicability of deep MRI reconstruction.
Gender effects on autism spectrum disorder: a multi-site resting-state functional magnetic resonance imaging study of transcriptome-neuroimaging
Authors: Li Yanling , Li Rui , Wang Ning , Gu Jiahe , Gao Jingjing 
Published: June 2023

IntroductionThe gender disparity in autism spectrum disorder (ASD) has been one of the salient features of condition. However, its relationship between the pathogenesis and genetic transcription in patients of different genders has yet to reach a reliable conclusion.MethodsTo address this gap, this study aimed to establish a reliable potential neuro-marker in gender-specific patients, by employing multi-site functional magnetic resonance imaging (fMRI) data, and to further investigate the role of genetic transcription molecules in neurogenetic abnormalities and gender differences in autism at the neuro-transcriptional level. To this end, age was firstly used as a regression covariate, followed by the use of ComBat to remove the site effect from the fMRI data, and abnormal functional activity was subsequently identified. The resulting abnormal functional activity was then correlated by genetic transcription to explore underlying molecular functions and cellular molecular mechanisms.ResultsAbnormal brain functional activities were identified in autism patients of different genders, mainly located in the default model network (DMN) and precuneus-cingulate gyrus-frontal lobe. The correlation analysis of neuroimaging and genetic transcription further found that heterogeneous brain regions were highly correlated with genes involved in signal transmission between neurons’ plasma membranes. Additionally, we further identified different weighted gene expression patterns and specific expression tissues of risk genes in ASD of different genders.DiscussionThus, this work not only identified the mechanism of abnormal brain functional activities caused by gender differences in ASD, but also explored the genetic and molecular characteristics caused by these related changes. Moreover, we further analyzed the genetic basis of sex differences in ASD from a neuro-transcriptional perspective.
Short-term symptom improvement in infants with suspected cow’s milk protein allergy using amino acid formula: a prospective cohort analysis
Authors: Wilsey Michael J. , Baran Jessica V. , Lamos Luke , Beacker Jesse , Florio Jared , Oliveros Lea , Sriaroon Panida , Brown Jerry M. , Vanderhoof Jon A. 
Published: June 2023

BackgroundCow’s milk protein allergy (CMPA) occurs commonly in infants. While the long-term efficacy of amino acid formulas for managing CMPA is well-established, there is limited data on the short-term symptom improvement of using amino acid formula (AAF).ObjectiveThis study aimed to determine the short-term effects of managing suspected CMPA in infants aged 6 months and under using a commercial AAF.MethodsHealthcare providers who treated infants with suspected CMPA aged 6 months or younger (n = 104) provided de-identified survey data in this prospective study. Healthcare providers scored symptoms for severity from 0 to 3 (none, low, moderate, severe) before using a commercial AAF at Visit 1 and at Visit 2 (3–6 weeks later).ResultsGastrointestinal (94%), skin (87%), respiratory (86%), and uncategorized symptoms (89%) improved from AAF initiation, and these findings were consistent across different follow-up visit durations.ConclusionThis study is the most extensive prospective analysis conducted in the United States examining the short-term change in suspected CMPA symptoms using an AAF. These findings suggest that AAF may decrease the severity of suspected CMPA symptoms in infants 6 months or younger, often by the next follow-up visit. Further randomized controlled trials are required to confirm these initial findings.
Factors associated with outcomes of second-line treatment for EGFR-mutant non-small-cell lung cancer patients after progression on first- or second-generation EGFR-tyrosine kinase inhibitor treatment
Authors: Chang Cheng-Yu , Chen Chung-Yu , Chang Shih-Chieh , Chen Ching-Yi , Lai Yi-Chun , Chang Chun-Fu , Wei Yu-Feng 
Published: June 2023

PurposeEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard first-line treatments for advanced EGFR-mutant non-small-cell lung cancer (NSCLC) patients. However, factors associated with outcomes after progression on first-line therapy are seldom investigated.Materials and methodsFrom January 2016 to December 2020, we enrolled 242 EGFR-mutant stage IIIB–IV NSCLC patients who progressed on first- or second-generation EGFR-TKI treatments, and 206 of them receive second-line treatments after disease progression. The factors that predict the survival outcomes of different second-line treatments after disease progression were evaluated. Clinical and demographic characteristics, including metastatic sites, neutrophil-to-lymphocyte ratio (NLR) at first-line progression, and second-line treatment regimens, and whether re-biopsied after disease progression or not, were reviewed for outcome analysis.ResultsThe univariate analysis showed that the PFS was shorted in male patients (p =0.049), patients with ECOG performance state ≥ 2 (p =0.014), former smokers (p =0.003), patients with brain metastasis (p =0.04), second-line chemotherapy or EGFR-TKIs other than osimertinib (p =0.002), and NLR ≥5.0 (p=0.024). In addition, second-line osimertinib was associated with longer OS compared to chemotherapy and other EGFR-TKI treatment (p =0.001). In the multivariate analysis, only second-line osimertinib was an independent predictor of PFS (p =0.023). Re-biopsy after first-line treatment was associated with a trend of better OS. Patients with NLR ≥5.0 at disease progression had shorter OS than patients with NLR &lt;5.0 (p = 0.008).ConclusionThe benefits of osimertinib necessitate that aggressive re-biopsy after progression on first- or second-generation EGFR-TKI treatment is merited for appropriate second-line treatments to provide better outcomes for these patients.
The hydrophilic extract from a new tomato genotype (named DHO) kills cancer cell lines through the modulation of the DNA damage response induced by Campthotecin treatment
Authors: Barone Daniela , Iannuzzi Carmelina Antonella , Forte Iris Maria , Ragosta Maria Carmen , Cuomo Maria , Dell’Aquila Milena , Altieri Angela , Caporaso Antonella , Camerlingo Rosa , Rigano Maria Manuela , Monti Daria Maria , Barone Amalia , Imbimbo Paola , Frusciante Luigi , Monda Marcellino , D’Angelo Margherita , De Laurentiis Michelino , Giordano Antonio , Alfano Luigi 
Published: June 2023

IntroductionDNA double-strand breaks are the most toxic lesions repaired through the non-homologous and joining (NHEJ) or the homologous recombination (HR), which is dependent on the generation of single-strand tails, by the DNA end resection mechanism. The resolution of the HR intermediates leads to error-free repair (Gene Conversion) or the mutagenic pathways (Single Strand Annealing and Alternative End-Joining); the regulation of processes leading to the resolution of the HR intermediates is not fully understood.MethodsHere, we used a hydrophilic extract of a new tomato genotype (named DHO) in order to modulate the Camptothecin (CPT) DNA damage response.ResultsWe demonstrated increased phosphorylation of Replication Protein A 32 Serine 4/8 (RPA32 S4/8) protein in HeLa cells treated with the CPT in combination with DHO extract with respect to CPT alone. Moreover, we pointed out a change in HR intermediates resolution from Gene Conversion to Single Strand Annealing through the modified DNA repair protein RAD52 homolog (RAD52), DNA excision repair protein ERCC-1 (ERCC1) chromatin loading in response to DHO extract, and CPT co-treatment, with respect to the vehicle. Finally, we showed an increased sensitivity of HeLa cell lines to DHO extract and CPT co-treatment suggesting a possible mechanism for increasing the efficiency of cancer therapy.DiscussionWe described the potential role of DHO extract in the modulation of DNA repair, in response to Camptothecin treatment (CPT), favoring an increased sensitivity of HeLa cell lines to topoisomerase inhibitor therapy.
Serum creatinine/cystatin C ratio as a prognostic indicator for patients with colorectal cancer
Authors: Gao Shunhui , Xie Hailun , Wei Lishuang , Liu Mingxiang , Liang Yanren , Wang Qiwen , Tang Shuangyi , Gan Jialiang 
Published: June 2023

BackgroundThis study aimed to explore the relationship between creatinine/cystatin C ratio and progression-free survival (PFS) and overall survival (OS) in colorectal cancer (CRC) patients undergoing surgical treatment.MethodsA retrospective analysis was conducted on 975 CRC patients who underwent surgical resection from January 2012 to 2015. Restricted three-sample curve to display the non-linear relationship between PFS/OS and creatinine-cystatin C ratio. Cox regression model and Kaplan-Meier method were used to evaluate the effect of the creatinine-cystatin C ratio on the survival of CRC patients. Prognostic variables with p-value ≤0.05 in multivariate analysis were used to construct prognostic nomograms. The receiver operator characteristic curve was used to compare the efficacy of prognostic nomograms and the traditional pathological stage.ResultsThere was a negative linear relationship between creatinine/cystatin C ratio and adverse PFS in CRC patients. Patients with low creatinine/cystatin C ratio had significantly lower PFS/OS than those with high creatinine/cystatin C ratio (PFS, 50.8% vs. 63.9%, p = 0.002; OS, 52.5% vs. 68.9%, p &lt; 0.001). Multivariate analysis showed that low creatinine/cystatin C ratio was an independent risk factor for PFS (HR=1.286, 95%CI = 1.007–1.642, p=0.044) and OS (HR=1.410, 95%CI=1.087–1.829, p=0.010) of CRC patients. The creatinine/cystatin C ratio-based prognostic nomograms have good predictive performance, with a concordance index above 0.7, which can predict the 1–5-year prognosis.ConclusionCreatinine/cystatin C ratio may be an effective prognostic marker for predicting PFS and OS in CRC patients, aid in pathological staging, and along with tumour markers help in-depth prognostic stratification in CRC patients.
Expression of OCT4 isoforms is reduced in primary colorectal cancer
Authors: Turyova Eva , Mikolajcik Peter , Grendar Marian , Kudelova Eva , Holubekova Veronika , Kalman Michal , Marcinek Juraj , Hrnciar Matej , Kovac Michal , Miklusica Juraj , Laca Ludovit , Lasabova Zora 
Published: June 2023

IntroductionColorectal cancer (CRC) is one of the most common types of cancer worldwide. The carcinogenesis of CRC is indeed complex, and there are many different mechanisms and pathways that contribute to the development of malignancy and the progression from primary to metastatic tumors. The OCT4A, encoded by the POU5F1 gene, is a transcription factor responsible for the phenotype of stem cells, maintaining pluripotency and regulation of differentiation. The POU5F1 gene is made up of five exons that can create numerous isoforms through alternative promoter or alternative splicing. In addition to OCT4A, other isoforms called OCT4B are also translated into protein; however, their role in cells has been unclear. The aim of our work was to investigate the expression patterns of OCT4 isoforms in primary and metastatic CRC, providing us with useful information about their role in the development and progression of CRC.MethodsSurgical specimens from a total of 78 patients were collected and isolated from primary tumors (n = 47) and metastases (n = 31). The relative gene expression of OCT4 isoforms was investigated using the RT-qPCR method together with the TaqMan probes for particular OCT4 isoforms.ResultsOur results suggest significantly downregulated expression of the OCT4A and OCT4Bs isoforms in both primary (p = 0.0002 and p &lt; 0.0001, respectively) and metastatic tumors (p = 0.0006 and p = 0.00051, respectively) when compared with the control samples. We also observed a correlation between reduced expression of all OCT4 isoforms and both primary and left-sided tumors (p = 0.001 and p = 0.030, respectively). On the other hand, the expression of all OCT4 isoforms was significantly upregulated in metastases compared with primary tumors (p &lt; 0.0001).DiscussionUnlike previous reports, we found out that the expression of OCT4A, OCT4Bs, and all OCT4 isoforms was significantly reduced in primary tumors and metastases compared with control samples. On the other hand, we supposed that the expression rate of all OCT4 isoforms may be related to the cancer type and side, as well as to liver metastases. However, further studies are required to investigate the detailed expression patterns and significance of individual OCT4 isoforms in carcinogenesis.
Secondary post-oncologic vulvar reconstruction – a simplified algorithm
Authors: Caretto Anna Amelia , Servillo Maria , Tagliaferri Luca , Lancellotta Valentina , Fragomeni Simona Maria , Garganese Giorgia , Scambia Giovanni , Gentileschi Stefano 
Published: June 2023

IntroductionSurgical treatment is the gold standard of care for vulvar cancer and is burdened by a high risk of wound complications due to the poor healing typical of the female genital area. Moreover, this malignancy has a high risk of local relapse even after wide excision. For these reasons, secondary reconstruction of the vulvoperineal area is a relevant and challenging scenario for gynecologists and plastic surgeons. The presence of tissue already operated on and undermined, scars, incisions, the possibility of previous radiation therapy, contamination of urinary and fecal pathogens in the dehiscent wound or ulcerated tumor, and the unavailability of some flaps employed during the primary procedure are typical complexities of this surgery. Due to the rarity of this tumor, a rational approach to secondary reconstruction has never been proposed in the literature.MethodsIn this observational retrospective study, we reviewed the clinical data of patients affected by vulvar cancer who underwent secondary reconstruction of the vulvoperineal area in our hospital between 2013 and 2023. Oncological, reconstructive, demographic, and complication data were recorded. The primary outcome measure was the incidence of wound complications. The secondary outcome measure was the indication of the different flaps, according to the defect, to establish an algorithm for decision-making.ResultsSixty-six patients were included; mean age was 71.3 ± 9.4 years, and the mean BMI was 25.1 ± 4.9. The mean size of the defect repaired by secondary vulvar reconstruction was 178 cm2 ± 163 cm2. Vertical rectus abdominis myocutaneous (VRAM), anterolateral thigh (ALT), fasciocutaneous V-Y (VY), and deep inferior epigastric perforator (DIEP) were the flaps more frequently employed. We observed five cases of wound breakdown, one case of marginal necrosis of an ALT flap, and three cases of wound infection. The algorithm we developed considered the geometry and size of the defect and the flaps still available after previous surgery.DiscussionA systematic approach to secondary vulvar reconstruction can provide good surgical results with a low rate of complications. The geometry of the defect and the use of both traditional and perforator flaps should guide the choice of the reconstructive technique.
Comparison of intraoperative radiotherapy as a boost vs. simultaneously integrated boosts after breast-conserving therapy for breast cancer
Authors: Stoian Raluca , Exner Jan-Philipp Harald , Gainey Mark , Erbes Thalia , Gkika Eleni , Popp Ilinca , Spohn Simon K. B. , Krug David , Juhasz-Böss Ingolf , Grosu Anca-Ligia , Sprave Tanja 
Published: June 2023

BackgroundCurrently, there are no data from randomized trials on the use of intraoperative radiotherapy (IORT) as a tumor bed boost in women at high risk of local recurrence. The aim of this retrospective analysis was to compare the toxicity and oncological outcome of IORT or simultaneous integrated boost (SIB) with conventional external beam radiotherapy (WBI) after breast conserving surgery (BCS).MethodsBetween 2009 and 2019, patients were treated with a single dose of 20 Gy IORT with 50 kV photons, followed by WBI 50 Gy in 25 or 40.05 in 15 fractions or WBI 50 Gy with SIB up to 58.80–61.60 Gy in 25–28 fractions. Toxicity was compared after propensity score matching. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan–Meier method.ResultsA 1:1 propensity-score matching resulted in an IORT + WBI and SIB + WBI cohort of 60 patients, respectively. The median follow-up for IORT + WBI was 43.5 vs. 32 months in the SIB + WBI cohort. Most women had a pT1c tumor: IORT group 33 (55%) vs. 31 (51.7%) SIB group (p = 0.972). The luminal-B immunophenotype was most frequently diagnosed in the IORT group 43 (71.6%) vs. 35 (58.3%) in the SIB group (p = 0.283). The most reported acute adverse event in both groups was radiodermatitis. In the IORT cohort, radiodermatitis was grade 1: 23 (38.3%), grade 2: 26 (43.3%), and grade 3: 6 (10%) vs. SIB cohort grade 1: 3 (5.1%), grade 2: 21 (35%), and grade 3: 7 (11.6%) without a meaningful difference (p = 0.309). Fatigue occurred more frequently in the IORT group (grade 1: 21.7% vs. 6.7%; p = 0.041). In addition, intramammary lymphedema grade 1 occurred significantly more often in the IORT group (11.7% vs. 1.7%; p = 0.026). Both groups showed comparable late toxicity. The 3- and 5-year local control (LC) rates were each 98% in the SIB group vs. 98% and 93% in the IORT group (LS: log rank p = 0.717).ConclusionTumor bed boost using IORT and SIB techniques after BCS shows excellent local control and comparable late toxicity, while IORT application exhibits a moderate increase in acute toxicity. These data should be validated by the expected publication of the prospective randomized TARGIT-B study.