bluuebunny/crossref_metadata_2025 huggingface dataset:
Stimulatory effect of fluoxetine and desipramine, but not mirtazapine on C26 colon carcinoma hepatic metastases formation: association with cytokines
Authors: Kubera Marta , Arteta Beatriz , Grygier Beata , Curzytek Katarzyna , Malicki Stanisław , Maes Michael
Published: June 2023

Due to the high prevalence of depression among cancer patients, antidepressant medications are frequently administered as adjuvant treatment. However, the safety of such medications in the development of metastasis is unclear. In this study, we investigated the effects of fluoxetine, desipramine, and mirtazapine on the liver metastasis of murine C26 colon carcinoma (cc). Balb/c male mice were administered these antidepressants intraperitoneally (i.p.) for 14 days following intrasplenic injections of C26 colon carcinoma cells. Desipramine and fluoxetine, but not mirtazapine, significantly increased the number of tumor foci and total volume of the tumor in liver tissue. This effect was associated with a decrease in the ability of splenocytes to produce interleukin (IL)-1β and interferon (IFN)-γ and an increase in their ability to produce interleukin (IL)-10. Similar changes were observed in plasma IL-1β, IFN-γ, and IL-10 levels. The current study demonstrates that the stimulatory effect of desipramine and fluoxetine, but not mirtazapine, on experimental colon cancer liver metastasis is associated with a suppression of immune defenses against the tumor.
The soluble receptor for advanced glycation end products is potentially predictive of pulmonary arterial hypertension in systemic sclerosis
Authors: Atzeni Isabella M. , Al-Adwi Yehya , Doornbos-van der Meer Berber , Roozendaal Caroline , Stel Alja , van Goor Harry , Gan C. Tji , Dickinson Michael , Timens Wim , Smit Andries J. , Westra Johanna , Mulder Douwe J.
Published: June 2023

Introduction

Pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) are the leading causes of death in systemic sclerosis (SSc). Until now, no prospective biomarker to predict new onset of SSc-ILD or SSc-PAH in patients with SSc has reached clinical application. In homeostasis, the receptor for advanced glycation end products (RAGE) is expressed in lung tissue and involved in cell-matrix adhesion, proliferation and migration of alveolar epithelial cells, and remodeling of the pulmonary vasculature. Several studies have shown that sRAGE levels in serum and pulmonary tissue vary according to the type of lung-related complication. Therefore, we investigated levels of soluble RAGE (sRAGE) and its ligand high mobility group box 1 (HMGB1) in SSc and their abilities to predict SSc-related pulmonary complications.

Methods

One hundred eighty-eight SSc patients were followed retrospectively for the development of ILD, PAH, and mortality for 8 years. Levels of sRAGE and HMGB1 were measured in serum by ELISA. Kaplan-Meier survival curves were performed to predict lung events and mortality and event rates were compared with a log-rank test. Multiple linear regression analysis was performed to examine the association between sRAGE and important clinical determinants.

Results

At baseline, levels of sRAGE were significantly higher in SSc-PAH-patients (median 4099.0 pg/ml [936.3-6365.3], p = 0.011) and lower in SSc-ILD-patients (735.0 pg/ml [IQR 525.5-1988.5], p = 0.001) compared to SSc patients without pulmonary involvement (1444.5 pg/ml [966.8-2276.0]). Levels of HMGB1 were not different between groups. After adjusting for age, gender, ILD, chronic obstructive pulmonary disease, anti-centromere antibodies, the presence of puffy fingers or sclerodactyly, use of immunosuppression, antifibrotic therapy, or glucocorticoids, and use of vasodilators, higher sRAGE levels remained independently associated with PAH. After a median follow-up of 50 months (25-81) of patients without pulmonary involvement, baseline sRAGE levels in the highest quartile were predictive of development of PAH (log-rank p = 0.01) and of PAH-related mortality (p = 0.001).

Conclusions

High systemic sRAGE at baseline might be used as a prospective biomarker for patients with SSc at high risk to develop new onset of PAH. Moreover, high sRAGE levels could predict lower survival rates due to PAH in patients with SSc.
Novel microRNAs modulating ecto-5′-nucleotidase expression
Authors: Kordaß Theresa , Chao Tsu-Yang , Osen Wolfram , Eichmüller Stefan B.
Published: June 2023

Introduction

The expression of immune checkpoint molecules (ICMs) by cancer cells is known to counteract tumor-reactive immune responses, thereby promoting tumor immune escape. For example, upregulated expression of ecto-5′-nucleotidase (NT5E), also designated as CD73, increases extracellular levels of immunosuppressive adenosine, which inhibits tumor attack by activated T cells. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level. Thus, the binding of miRNAs to the 3′-untranslated region of target mRNAs either blocks translation or induces degradation of the targeted mRNA. Cancer cells often exhibit aberrant miRNA expression profiles; hence, tumor-derived miRNAs have been used as biomarkers for early tumor detection.

Methods

In this study, we screened a human miRNA library and identified miRNAs affecting the expression of ICMs NT5E, ENTPD1, and CD274 in the human tumor cell lines SK-Mel-28 (melanoma) and MDA-MB-231 (breast cancer). Thereby, a set of potential tumor-suppressor miRNAs that decreased ICM expression in these cell lines was defined. Notably, this study also introduces a group of potential oncogenic miRNAs that cause increased ICM expression and presents the possible underlying mechanisms. The results of high-throughput screening of miRNAs affecting NT5E expression were validated in vitro in 12 cell lines of various tumor entities.

Results

As result, miR-1285-5p, miR-155-5p, and miR-3134 were found to be the most potent inhibitors of NT5E expression, while miR-134-3p, miR-6859-3p, miR-6514-3p, and miR-224-3p were identified as miRNAs that strongly enhanced NT5E expression levels.

Discussion

The miRNAs identified might have clinical relevance as potential therapeutic agents and biomarkers or therapeutic targets, respectively.
MR1 deficiency enhances IL-17-mediated allergic contact dermatitis
Authors: Imahashi Naoya , Satoh Masashi , Clemente Emanuela , Yoshino Kazuhisa , Di Gioacchino Mario , Iwabuchi Kazuya
Published: June 2023

Major histocompatibility complex (MHC) class Ib molecules present antigens to subsets of T cells primarily involved in host defense against pathogenic microbes and influence the development of immune-mediated diseases. The MHC class Ib molecule MHC-related protein 1 (MR1) functions as a platform to select MR1-restricted T cells, including mucosal-associated invariant T (MAIT) cells in the thymus, and presents ligands to them in the periphery. MAIT cells constitute an innate-like T-cell subset that recognizes microbial vitamin B2 metabolites and plays a defensive role against microbes. In this study, we investigated the function of MR1 in allergic contact dermatitis (ACD) by examining wild-type (WT) and MR1-deficient (MR1-/-) mice in which ACD was induced with 2,4-dinitrofluorobenzene (DNFB). MR1-/- mice exhibited exaggerated ACD lesions compared with WT mice. More neutrophils were recruited in the lesions in MR1-/- mice than in WT mice. WT mice contained fewer MAIT cells in their skin lesions following elicitation with DNFB, and MR1-/- mice lacking MAIT cells exhibited a significant increase in IL-17-producing αβ and γδ T cells in the skin. Collectively, MR1-/- mice displayed exacerbated ACD from an early phase with an enhanced type 3 immune response, although the precise mechanism of this enhancement remains elusive.
Physiological condition of the warty venus (Venus verrucosa L. 1758) larvae modulates response to pile driving and drilling underwater sounds
Authors: Gigot Mathilde , Tremblay Réjean , Bonnel Julien , Chauvaud Laurent , Olivier Frédéric
Published: June 2023

Noise is now recognized as a new form of pollution in marine coastal habitats. The development of marine renewable energies has introduced new sonorous perturbations, as the wind farm installation requires pile driving and drilling operations producing low frequency sounds at high sound pressure levels. Exponential expansion of offshore wind farms is occurring worldwide, making impact studies, particularly on benthic species highly abundant and diverse in the coastal area used for wind farming, a necessity. As larval recruitment is the basis for establishing a population, we conducted an experimental study to assess the interactive effects of pile driving or drilling sounds and larval rearing temperature on the endobenthic bivalve Venus verrucosa. In ectothermic animals, temperature modifies the organism’s physiology, resulting in performance variability. We hypothesize that temperature modulation could change larval responses to noise and explore the potential interacting effects of temperature and noise. Using two distinct rearing temperatures, physiologically different batches of larvae were produced with contrasting fatty acid content and composition in the neutral and polar lipid fractions. Without defining any absolute audition threshold for the larvae, we demonstrate that the effects of temperature and noise were ontogenic-dependent and modulated larval performance at the peri-metamorphic stage, acting on the metamorphosis dynamic. At the pediveligers stage, a strong interaction between both factors indicated that the response to noise was highly related to the physiological condition of the larvae. Finally, we suggest that underwater noise reduces the compensatory mechanisms established to balance the temperature increase.
Management of keratoconus: an updated review
Authors: Deshmukh Rashmi , Ong Zun Zheng , Rampat Radhika , Alió del Barrio Jorge L. , Barua Ankur , Ang Marcus , Mehta Jodhbir S. , Said Dalia G. , Dua Harminder S. , Ambrósio Renato , Ting Darren Shu Jeng
Published: June 2023

Keratoconus is the most common corneal ectatic disorder. It is characterized by progressive corneal thinning with resultant irregular astigmatism and myopia. Its prevalence has been estimated at 1:375 to 1:2,000 people globally, with a considerably higher rate in the younger populations. Over the past two decades, there was a paradigm shift in the management of keratoconus. The treatment has expanded significantly from conservative management (e.g., spectacles and contact lenses wear) and penetrating keratoplasty to many other therapeutic and refractive modalities, including corneal cross-linking (with various protocols/techniques), combined CXL-keratorefractive surgeries, intracorneal ring segments, anterior lamellar keratoplasty, and more recently, Bowman’s layer transplantation, stromal keratophakia, and stromal regeneration. Several recent large genome-wide association studies (GWAS) have identified important genetic mutations relevant to keratoconus, facilitating the development of potential gene therapy targeting keratoconus and halting the disease progression. In addition, attempts have been made to leverage the power of artificial intelligence-assisted algorithms in enabling earlier detection and progression prediction in keratoconus. In this review, we provide a comprehensive overview of the current and emerging treatment of keratoconus and propose a treatment algorithm for systematically guiding the management of this common clinical entity.
16S rRNA gene sequencing reveals the correlation between the gut microbiota and the susceptibility to pathological scars
Authors: Li Ming , Li Minghao , Dai Yingting , Li Dang , Yu Han , Liu Jian , Gao Hangqi , Zhong Yi , Huang Mingquan , Lin Jing , Xie Yide , Guo Zhihui , Chen Xiaosong
Published: June 2023

The gut microbiome profile in patients with pathological scars remains rarely known, especially those patients who are susceptible to pathological scars. Previous studies demonstrated that gut microbial dysbiosis can promote the development of a series of diseases via the interaction between gut microbiota and host. The current study aimed to explore the gut microbiota of patients who are prone to suffer from pathological scars. 35 patients with pathological scars (PS group) and 40 patients with normal scars (NS group) were recruited for collection of fecal samples to sequence the 16S ribosomal RNA (16S rRNA) V3-V4 region of gut microbiota. Alpha diversity of gut microbiota showed a significant difference between NS group and PS group, and beta diversity indicated that the composition of gut microbiota in NS and PS participants was different, which implied that dysbiosis exhibits in patients who are susceptible to pathological scars. Based on phylum, genus, species levels, we demonstrated that the changing in some gut microbiota (Firmicutes; Bacteroides; Escherichia coli, etc.) may contribute to the occurrence or development of pathological scars. Moreover, the interaction network of gut microbiota in NS and PS group clearly revealed the different interaction model of each group. Our study has preliminary confirmed that dysbiosis exhibits in patients who are susceptible to pathological scars, and provide a new insight regarding the role of the gut microbiome in PS development and progression.
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

Background

Moyamoya 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.

Methods

We 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.

Results

Nine 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 < 0.01] and improved bypass patency after surgical revascularization [HR = 1.57; 95% CI (1.106–2.235); p < 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 < 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].

Conclusion

Current 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 registration

https://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

Introduction

Fine-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.

Methods

Based 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.

Results

To 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.

Discussion

The 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

Introduction

The 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.

Methods

To 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.

Results

Abnormal 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.

Discussion

Thus, 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

Background

Cow’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).

Objective

This study aimed to determine the short-term effects of managing suspected CMPA in infants aged 6 months and under using a commercial AAF.

Methods

Healthcare 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).

Results

Gastrointestinal (94%), skin (87%), respiratory (86%), and uncategorized symptoms (89%) improved from AAF initiation, and these findings were consistent across different follow-up visit durations.

Conclusion

This 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

Purpose

Epidermal 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 methods

From 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.

Results

The 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 <5.0 (p = 0.008).

Conclusion

The 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

Introduction

DNA 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.

Methods

Here, we used a hydrophilic extract of a new tomato genotype (named DHO) in order to modulate the Camptothecin (CPT) DNA damage response.

Results

We 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.

Discussion

We 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

Background

This 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.

Methods

A 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.

Results

There 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 < 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.

Conclusion

Creatinine/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

Introduction

Colorectal 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.

Methods

Surgical 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.

Results

Our results suggest significantly downregulated expression of the OCT4A and OCT4Bs isoforms in both primary (p = 0.0002 and p < 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 < 0.0001).

Discussion

Unlike 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.
Multidisciplinary Taiwan consensus for the use of conventional TACE in hepatocellular carcinoma treatment
Authors: Chang Pi-Yi , Lee Rheun-Chuan , Liang Po-Chin , Liu Yi-Sheng , Chuang Vicent P. , Wu Ding-Kwo , Cheng Yu-Fan , Huang Jen-I. , Tseng Hsiuo-Shan , Hung Chien-Fu , Wu Reng-Hong , Chern Ming-Chih , Cheng Hua-Ming , Wu Chih-Horng , Cheng She-Meng , Chiang Chia-Ling , Liang Huei-Lung
Published: June 2023

Developed in early 1980s, transarterial chemoembolization (TACE) with Lipiodol was adopted globally after large-scale randomized control trials and meta-analyses proving its effectiveness were completed. Also known as “conventional TACE” (cTACE), TACE is currently the first-line treatment for patients with unresectable intermediate stage hepatocellular carcinoma (HCC) and delivers both ischemic and cytotoxic effects to targeted tumors. Although new technology and clinical studies have contributed to a more comprehensive understanding of when and how to apply this widely-adopted therapeutic modality, some of these new findings and techniques have yet to be incorporated into a guideline appropriate for Taiwan. In addition, differences in the underlying liver pathologies and treatment practices for transcatheter embolization between Taiwan and other Asian or Western populations have not been adequately addressed, with significant variations in the cTACE protocols adopted in different parts of the world. These mainly revolve around the amount and type of chemotherapeutic agents used, the type of embolic materials, reliance on Lipiodol, and the degree of selectiveness in catheter positioning. Subsequently, interpreting and comparing results obtained from different centers in a systematic fashion remain difficult, even for experienced practitioners. To address these concerns, we convened a panel of experts specializing in different aspects of HCC treatment to devise modernized recommendations that reflect recent clinical experiences, as well as cTACE protocols which are tailored for use in Taiwan. The conclusions of this expert panel are described herein.
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

Introduction

Surgical 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.

Methods

In 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.

Results

Sixty-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.

Discussion

A 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

Background

Currently, 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).

Methods

Between 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.

Results

A 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).

Conclusion

Tumor 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.
Targeted genome editing in polyploids: lessons from Brassica
Authors: Ahmad Niaz , Fatima Samia , Mehmood Muhammad Aamer , Zaman Qamar U. , Atif Rana Muhammad , Zhou Weijun , Rahman Mehboob-ur , Gill Rafaqat Ali
Published: June 2023

CRISPR-mediated genome editing has emerged as a powerful tool for creating targeted mutations in the genome for various applications, including studying gene functions, engineering resilience against biotic and abiotic stresses, and increasing yield and quality. However, its utilization is limited to model crops for which well-annotated genome sequences are available. Many crops of dietary and economic importance, such as wheat, cotton, rapeseed-mustard, and potato, are polyploids with complex genomes. Therefore, progress in these crops has been hampered due to genome complexity. Excellent work has been conducted on some species of Brassica for its improvement through genome editing. Although excellent work has been conducted on some species of Brassica for genome improvement through editing, work on polyploid crops, including U’s triangle species, holds numerous implications for improving other polyploid crops. In this review, we summarize key examples from genome editing work done on Brassica and discuss important considerations for deploying CRISPR-mediated genome editing more efficiently in other polyploid crops for improvement.
Insight into biodiversity of the recently rearranged genus Dickeya
Authors: Hugouvieux-Cotte-Pattat Nicole , Pédron Jacques , Van Gijsegem Frédérique
Published: June 2023

The genus Dickeya includes plant pathogenic bacteria attacking a wide range of crops and ornamentals as well as a few environmental isolates from water. Defined on the basis of six species in 2005, this genus now includes 12 recognized species. Despite the description of several new species in recent years, the diversity of the genus Dickeya is not yet fully explored. Many strains have been analyzed for species causing diseases on economically important crops, such as for the potato pathogens D. dianthicola and D. solani. In contrast, only a few strains have been characterized for species of environmental origin or isolated from plants in understudied countries. To gain insights in the Dickeya diversity, recent extensive analyzes were performed on environmental isolates and poorly characterized strains from old collections. Phylogenetic and phenotypic analyzes led to the reclassification of D. paradisiaca (containing strains from tropical or subtropical regions) in the new genus, Musicola, the identification of three water species D. aquatica, D. lacustris and D. undicola, the description of a new species D. poaceaphila including Australian strains isolated from grasses, and the characterization of the new species D. oryzae and D. parazeae, resulting from the subdivision of the species D. zeae. Traits distinguishing each new species were identified from genomic and phenotypic comparisons. The high heterogeneity observed in some species, notably for D. zeae, indicates that additional species still need to be defined. The objective of this study was to clarify the present taxonomy of the genus Dickeya and to reassign the correct species to several Dickeya strains isolated before the current classification.
Impact of the COVID-19 pandemic on obsessive-compulsive symptoms in the Swiss general population
Authors: Otte Johanna , Schicktanz Nathalie , Bentz Dorothée
Published: June 2023

Background

In the early stages of the COVID-19 pandemic, mental-health experts called attention to a possible deterioration of obsessive-compulsive symptoms (OCSs). In particular, people suffering from a fear of contamination were considered a vulnerable population.

Aim

The aim of this study was to investigate the change in OCSs from before to during the pandemic within the Swiss general population, and to examine a possible relationship of OCSs to stress and anxiety.

Methods

This cross-sectional study was implemented as an anonymized online survey (N = 3,486). The Obsessive-Compulsive Inventory-Revised (OCI-R) was used to assess global OCS severity (range: 0–72, clinical cut-off > 18) and specific OCS dimensions (range: 0–12) during the second wave of the pandemic and retrospectively for before the pandemic. Participants were asked to report stress and anxiety in the previous 2 weeks before the survey.

Results

Participants reported significantly higher OCI-R total scores during (12.73) compared to before the pandemic (9.04, mean delta increase: 3.69). Significantly more individuals reported an OCI-R total score exceeding the clinical cut-off during (24%) than before the pandemic (13%). OCS severity increased on all symptom dimensions, but was most pronounced on the washing dimension (all with p < 0.001). Self-reported stress and anxiety were weakly associated with differences in severity in total score and symptom dimensions (with R2 < 0.1 and p < 0.001).

Conclusion

Our results indicate that the full spectrum of people with OCS should be considered as risk groups for symptom deterioration during a pandemic and when assessing its possible long-term effects of such.
Objective and subjective career success: individual, structural, and behavioral determinants on European hybrid workers
Authors: Hildred Kiall , Piteira Margarida , Cervai Sara , Pinto Joana Carneiro
Published: June 2023

Introduction

In the current worldwide labor context, where a disruption took place and employees experience.

Methods

Participated in this study 739 European hybrid workers who fulfilled an online assessment protocol.

Results

Results indicate that higher ages, higher educational levels, being married, having children, working.

Discussion

This study makes a unique contribution to the extant research on hybrid workers’ careers, specifically.
Association of maternal mental health and drinking/smoking with adolescents’ mental health based on the Korea National Health and Nutrition Examination Survey
Authors: Lee Junghan , Song Kyungchul , Jeon Soyoung , Lee Hye Sun , Lee San , Kim Ho-Seong , Chae Hyun Wook
Published: June 2023

Introduction

Depression is one of the major concerns in adolescence, with a global prevalence of approximately 5%. Diverse environmental factors can affect the development of depression depending on the individual developmental stage.

Methods

Using data from the Korea National Health and Nutrition Examination Survey (KNHANES), we aimed to investigate the association between socioeconomic factors and mental health in a population of non-clinically ill adolescents in Korea totaling 6,261 adolescents aged 12–18 years.

Results

Drinking, smoking, stress, depressed mood, suicidal ideation in adolescents, and stress, depressed mood, and suicidal ideation in mothers were identified as factors associated with adolescent depression. In addition to depressed mood and suicidal ideation, the higher perception of stress in mothers was related to higher stress perception, depressed mood, and suicidal ideation in adolescents. The association of adolescents’ mental health with fathers’ mental health was weaker than that with mothers’ mental health. Additionally, increased smoking and drinking were commonly reported in adolescents with higher stress perception, depressed mood, and suicidal ideation.

Discussion

We conclude that close monitoring of mental health is required for adolescents with drinking and smoking habits and mothers with mental health problems.