bluuebunny/crossref_metadata_2025_split huggingface dataset:
Type distribution of human papillomaviruses in ThinPrep cytology samples and HPV16/18 E6 gene variations in FFPE cervical cancer specimens in Fars province, Iran
Authors: Farhadi Ali , Abuei Haniyeh , Okhovat Mohammad Ali , Geramizadeh Bita , Behzad-Behbahani Abbas , Chong Pei Pei , Nikouyan Negin , Namdari Sepide 
Published: August 2023

Abstract
Background
There exists strong evidence that human papillomavirus (HPV) is associated with cervical cancer (CC). HPV E6 is a major oncogene whose sequence variations may be associated with the development of CC. There is not sufficient data on the distribution of HPV types in ThinPrep cytology specimens and HPV 16/18 E6 gene variations among CC patients in the southwest of Iran. This study was conducted to contribute to HPV screening and vaccination in Iran.

Methods
A total of 648 women screened for cervicitis, intraepithelial neoplasia or CC were included in the study. All participants underwent ThinPrep cytology testing, single-step HPV DNA detection and allele-specific reverse hybridization assays. Moreover, a total of 96 specimens previously tested positive for single infection with HPV16 or 18 were included for variant analysis. HPV16/18 lineages and sublineages were determined by PCR assays followed by sequencing the E6 gene and the construction of neighbor-joining phylogenetic trees.

Results
Overall, HPV DNA was detected in 62.19% of all the screened subjects. The detection rates of HPV DNA among individuals with normal, ASC-US, ASC-H, LSIL, and HSIL cervical cytology were 48.9%, 93.6%, 100%, 100%, and 100%, respectively. Low-risk HPVs were detected more frequently (46.9%) than high-risk (38.9%) and possible high-risk types (11.1%). Of 403 HPV-positive subjects, 172 (42.7%) had single HPV infections while the remaining 231 (57.3%) were infected with multiple types of HPV. Our results indicated a remarkable growth of high-risk HPV66 and 68 and low-risk HPV81 which have rarely been reported in Iran and HPV90 and 87 that are reported for the first time in the country. In addition, 3 lineages (A, D, and C) and 6 sublineages (A1, A2, A4, C1, D1, and D2) of HPV16, and one lineage and 4 sublineages (A1, A3, A4, and A5) of HPV18 were identified. The studied HPV16 and 18 variants mainly belonged to the D1 and A4 sublineages, respectively.

Conclusion
The present study suggests that the prevalence of HPV infection in women of all age groups with or without premalignant lesions in the southwestern Iran is high and the predominant HPV types in the southwest of Iran may differ from those detected in other parts of the country. This study also highlights the necessity of not only initiating HPV vaccination for the general population but also developing new vaccines that confer immunity against the prevalent HPV types in the area and national cervical screening programs using a combination of thinPrep cytology test and HPV detection assays in order to improve the accuracy of the screening.
Triple negative breast cancer metastasis is hindered by a peptide antagonist of F11R/JAM‑A protein
Authors: Bednarek Radosław , Wojkowska Dagmara W. , Braun Marcin , Watala Cezary , Salifu Moro O. , Swiatkowska Maria , Babinska Anna 
Published: August 2023

Abstract
Background
The F11R/JAM-A cell adhesion protein was examined as the therapeutic target in triple negative breast cancer (TNBC) with the use of the peptide antagonist to F11R/JAM-A, that previously inhibited the early stages of breast cancer metastasis in vitro.

Methods
The online in silico analysis was performed by TNMPlot, UALCAN, and KM plotter. The in vitro experiments were performed to verify the effect of peptide 4D (P4D) on human endothelial cell lines EA.hy926 and HMEC-1 as well as on human TNBC cell line MDA-MB-231. The cell morphology upon P4D treatment was verified by light microscopy, while the cell functions were assessed by colony forming assay, MTT cell viability assay, BrdU cell proliferation assay, and Transepithelial/Endothelial Electrical Resistance measurements. The in vivo experiments on 4T1 murine breast cancer model were followed by histopathological analysis and a series of quantitative analyses of murine tissues.

Results
By in silico analysis we have found the elevated gene expression in breast cancer with particular emphasis on TNBC. The elevated F11R expression in TNBC was related with poorer survival prognosis. Peptide 4D has altered the morphology and increased the permeability of endothelial monolayers. The colony formation, viability, and proliferation of MDA-MB-231 cells were decreased. P4D inhibited the metastasis in 4T1 breast cancer murine model in a statistically significant manner that was demonstrated by the resampling bootstrap technique.

Conclusions
The P4D peptide antagonist to F11R/JAM-A is able to hinder the metastasis in TNBC. This assumption needs to be confirmed by additional 4T1 mouse model study performed on larger group size, before making the decision on human clinical trials.
Identification of allergens in Artocarpus heterophyllus, Moringa oleifera, Trianthema portulacastrum and Syzygium samarangense
Authors: Iddagoda Janitha , Gunasekara Peshala , Handunnetti Shiroma , Jeewandara Chandima , Karunatilake Chandima , Malavige Gathsaurie Neelika , de Silva Rajiva , Dasanayake Dhanushka 
Published: August 2023

Abstract
Background
It is clinically important to identify allergens in Artocarpus heterophyllus (jackfruit), Moringa oleifera (moringa), Trianthema portulacastrum (horse purslane) and Syzygium samarangense (rose apple). This study included 7 patients who developed anaphylaxis to jackfruit (1), moringa (2), horse purslane (3) and rose apple (1). We sought to determine allergens in the edible ripening stages of jackfruit (tender, mature, and ripened jackfruit) and seeds, edible parts of moringa (seeds, seedpod, flesh inside seedpod, and leaves), horse purslane leaves and ripened rose apple fruit. The persistence of the allergens after cooking was also investigated.

Methods
Allergens were identified by clinical history followed by a skin prick test. Protein profiles of plant/fruit crude protein extracts were determined by SDS-PAGE. Molecular weights of the allergens were determined by immunoblotting with patient sera.

Results
A heat-stable allergen of 114 kDa in A. heterophyllus which is shared among different ripening stages and seeds was identified. Additionally, 101 kDa allergen in boiled tender jackfruit, 86 kDa allergen in boiled seeds and 80 kDa allergen in boiled mature jackfruit were identified. Five heat-stable allergens of 14, 23, 35, 43, and 48 kDa in M. oleifera, 1 heat-stable allergen of 97 kDa in T. portulacastrum, and 4 allergens of 26, 31. 60, and 82 kDa in S. samarangense were identified.

Conclusion
Novel IgE-sensitive proteins of A. heterophyllus, M. oleifera, T. portulacastrum and S. samarangense were identified which would be especially useful in the diagnosis of food allergies. The identified allergens can be used in Component Resolved Diagnostics (CRD).
Nano drug delivery systems: a promising approach to scar prevention and treatment
Authors: Ding Jia-Ying , Sun Lu , Zhu Zhi-Heng , Wu Xi-Chen , Xu Xiao-Ling , Xiang Yan-Wei 
Published: August 2023

AbstractScar formation is a common physiological process that occurs after injury, but in some cases, pathological scars can develop, leading to serious physiological and psychological effects. Unfortunately, there are currently no effective means to intervene in scar formation, and the structural features of scars and their unclear mechanisms make prevention and treatment even more challenging. However, the emergence of nanotechnology in drug delivery systems offers a promising avenue for the prevention and treatment of scars. Nanomaterials possess unique properties that make them well suited for addressing issues related to transdermal drug delivery, drug solubility, and controlled release. Herein, we summarize the recent progress made in the use of nanotechnology for the prevention and treatment of scars. We examine the mechanisms involved and the advantages offered by various types of nanomaterials. We also highlight the outstanding challenges and questions that need to be addressed to maximize the potential of nanotechnology in scar intervention. Overall, with further development, nanotechnology could significantly improve the prevention and treatment of pathological scars, providing a brighter outlook for those affected by this condition.
Relationship between cancer stem cell-related SNPs and survival outcomes in patients with primary lung cancer
Authors: Xu Xinying , Liu Yuhang , Hu Huiyi , Wang Jinshen , Cai Yuxin , Xie Jun , Kang Mingqiang , He Fei 
Published: August 2023

Abstract
Background
Cancer stem cells may be the source of cancer-causing mutant cells and are closely related to the prognosis of cancer. Our study aimed to investigate the potential association between single-nucleotide polymorphisms (SNPs) of cancer stem cell-related genes and the prognosis of lung cancer patients.

Methods
The SNP loci were genotyped by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF–MS), and the overall survival of subjects was analyzed by log-rank test after stratifying and adjusting their demographic data, clinical data, and genotypes. The correlation between survival time and quality of life of lung cancer under codominant, dominant, recessive, and additive genetic models was analyzed by the Cox regression model. The association between SNP polymorphism and the prognosis of lung cancer was analyzed by Stata16.0 software, and their heterogeneity was tested. Interaction analysis was performed using R software (version 4.2.0).

Results
Stratified analysis unveiled that rs3740535 had recessive AA genotype and additive GG genotype; Rs3130932 dominant GT + GG genotype, additive TT genotype; Rs13409 additive TT genotype; Rs6815391 recessive CC genotype and additional TT genotype were associated with increased risk of lung cancer death. Rs3130932 recessive GG genotype was associated with a reduced risk of lung cancer death.

Conclusion
Rs3740535, rs3130932, rs13409, and rs6815391 are associated with the overall survival of lung cancer patients and may be valuable for the prognosis of lung cancer patients.
A new and effective method to induce infection of Phyllachora maydis into corn for tar spot studies in controlled environments
Authors: Solórzano José E. , Issendorf Shea E. , Drott Milton T. , Check Jill C. , Roggenkamp Emily M. , Cruz C. D. , Kleczewski Nathan M. , Gongóra-Canul Carlos C. , Malvick Dean K. 
Published: August 2023

Abstract
Background
Tar spot of corn is a significant and spreading disease in the continental U.S. and Canada caused by the obligate biotrophic fungus Phyllachora maydis. As of 2023, tar spot had been reported in 18 U.S. states and one Canadian Province. The symptoms of tar spot include chlorotic flecking followed by the formation of black stromata where conidia and ascospores are produced. Advancements in research and management for tar spot have been limited by a need for a reliable method to inoculate plants to enable the study of the disease. The goal of this study was to develop a reliable method to induce tar spot in controlled conditions.

Results
We induced infection of corn by P. maydis in 100% of inoculated plants with a new inoculation method. This method includes the use of vacuum-collection tools to extract ascospores from field-infected corn leaves, application of spores to leaves, and induction of the disease in the dark at high humidity and moderate temperatures. Infection and disease development were consistently achieved in four independent experiments on different corn hybrids and under different environmental conditions in a greenhouse and growth chamber. Disease induction was impacted by the source and storage conditions of spores, as tar spot was not induced with ascospores from leaves stored dry at 25 ºC for 5 months but was induced using ascospores from infected leaves stored at -20 ºC for 5 months. The time from inoculation to stromata formation was 10 to 12 days and ascospores were present 19 days after inoculation throughout our experiments. In addition to providing techniques that enable in-vitro experimentation, our research also provides fundamental insights into the conditions that favor tar spot epidemics.

Conclusions
We developed a method to reliably inoculate corn with P. maydis. The method was validated by multiple independent experiments in which infection was induced in 100% of the plants, demonstrating its consistency in controlled conditions. This new method facilitates research on tar spot and provides opportunities to study the biology of P. maydis, the epidemiology of tar spot, and for identifying host resistance.
Prevalence and risk factors for retropharyngeal and retro-styloid lymph node metastasis in hypopharyngeal carcinoma
Authors: Toya Ryo , Matsuyama Tomohiko , Saito Tetsuo , Fukugawa Yoshiyuki , Watakabe Takahiro , Shiraishi Shinya , Murakami Daizo , Orita Yorihisa , Hirai Toshinori , Oya Natsuo 
Published: August 2023

Abstract
Background
We evaluated the prevalence and identified the risk factors for retropharyngeal and retro-styloid lymph node metastasis (LNM) in patients with hypopharyngeal carcinoma (HPC). This was achieved using a combination of magnetic resonance (MR) and [18 F]-fluoro-2-deoxy-D-glucose (FDG)–positron emission tomography (PET)/computed tomography (CT) images.

Methods
Two board-certified radiation oncologists retrospectively reviewed pretreatment FDG–PET/CT images and contrast-enhanced thin-slice CT and MR images of 155 patients with HPC who underwent radiotherapy. Fisher’s exact tests and logistic regression analyses were performed to assess the risk factors for LNM.

Results
Retropharyngeal LNM (RPLNM) was confirmed in 20 (13%) patients. Posterior wall (PW) tumors (odds ratio [OR]: 4.128, 95% confidence interval [CI]: 1.339–12.727; p = 0.014) and bilateral or contralateral cervical LNM (OR: 11.577, 95% CI: 2.135–62.789; p = 0.005) were significantly correlated with RPLNM. The RPLNM was found in 9 (32%) of the 28 patients with PW tumors. Of these 9 patients, 2 (7%) had ipsilateral RPLNM, 3 (11%) had contralateral RPLNM, and 4 (14%) had bilateral RPLNM. The PW tumors were significantly associated with contralateral RPLNM (p < 0.001). Retro-styloid LNM (RSLNM) was confirmed in two (1%) patients, both of whom had ipsilateral RSLNM with lymph nodes (LNs) of ≥ 15 mm in the upper limit of ipsilateral level II. A significant association was found between LNs of ≥ 15 mm in the upper limit of ipsilateral level II and ipsilateral RSLNM (p = 0.001).

Conclusions
The RPLNM was identified in 13% of patients with HPC. The PW tumors and bilateral or contralateral cervical LNM were risk factors for RPLNM; particularly, PW tumors were a specific risk factor for contralateral RPLNM. Although the RSLNM was rare, LNs of ≥ 15 mm in the upper limit of ipsilateral level II were a risk factor for ipsilateral RSLNM.
A mannitol-modified emodin nano-drug restores the intestinal barrier function and alleviates inflammation in a mouse model of DSS-induced ulcerative colitis
Authors: Xu Yin-Yue , Zhu Min , Wu Jiang , Luo Long-Biao , Dong Si-jing , Zhang Meng-Gai , Liu Xue , Wang Ke , Luo Hua , Jing Wang-Hui , Wang Lin , Wang Si-Cen 
Published: August 2023

Abstract
Background
Ulcerative colitis (UC) is an inflammatory disease of the colon that is characterized by mucosal ulcers. Given its increasing prevalence worldwide, it is imperative to develop safe and effective drugs for treating UC. Emodin, a natural anthraquinone derivative present in various medicinal herbs, has demonstrated therapeutic effects against UC. However, low bioavailability due to poor water solubility limits its clinical applications.

Methods
Emodin-borate nanoparticles (EmB) were synthesized to improve drug solubility, and they modified with oligomeric mannitol into microgels (EmB-MO) for targeted delivery to intestinal macrophages that express mannose receptors. UC was induced in a mouse model using dextran sulfate sodium (DSS), and different drug formulations were administered to the mice via drinking water. The levels of inflammation-related factors in the colon tissues and fecal matter were measured using enzyme-linked immunosorbent assay. Intestinal permeability was evaluated using fluorescein isothiocyanate dextran. HE staining, in vivo imaging, real-time PCR, and western blotting were performed to assess intestinal barrier dysfunction.

Results
Both EmB and EmB-MO markedly alleviated the symptoms of UC, including body weight loss, stool inconsistency, and bloody stools and restored the levels of pro- and anti-inflammatory cytokines. However, the therapeutic effects of EmB-MO on the macroscopic and immunological indices were stronger than those of EmB and similar to those of 5-aminosalicylic acid. Furthermore, EmB-MO selectively accumulated in the inflamed colon epithelium and restored the levels of the gut barrier proteins such as ZO-1 and Occludin.

Conclusions
EmB-MO encapsulation significantly improved water solubility, which translated to greater therapeutic effects on the immune balance and gut barrier function in mice with DSS-induced UC. Our findings provide novel insights into developing emodin-derived drugs for the management of UC.
Attachment disorder symptoms in foster children: development and associations with attachment security
Authors: Kliewer-Neumann Josephine D. , Zimmermann Janin , Bovenschen Ina , Gabler Sandra , Lang Katrin , Spangler Gottfried , Nowacki Katja 
Published: August 2023

Abstract
Background
Children in foster care constitute a risk population for developing symptoms of attachment disorders. However, little is known about the longitudinal course of attachment disorders and their association with attachment security in foster children.

Method
This longitudinal study assessed attachment disorder symptoms in a sample of foster children (n = 55) aged 12 to 82 months. Foster parents with a newly placed foster child were assessed at three points during the first year of placement. At all assessment points, the Disturbance of Attachment Interview (DAI; Smyke and Zeanah in Disturbances of attachment interview, Tulane University, New Orleans, 1999) and the Attachment Q-sort (AQS; Waters and Deane in Monogr Soc Res Child Dev 50:41–65, 1985 German version as reported
(Schölmerich and Leyendecker in Deutsche Übersetzung des attachment behavior Q-Set, revision 3.2. Unpublished manual, Ruhr University
Bochum, Bochum, 1999) were used to investigate the interplay between disorder symptoms and attachment security.

Results
The results revealed that the symptoms of attachment disorders decreased. The decrease was more pronounced for the inhibited than for the disinhibited symptoms with marked changes in the first 6 months of placement. There was a noticeable gender difference in the development with boys showing a more pronounced decrease in inhibited attachment disorder symptoms and a stronger increase of attachment security. After 12 months, no significant gender effects were found. Regarding the association between symptoms of attachment disorders and attachment security, a significant negative correlation between the inhibited attachment disorder symptoms and attachment security was found 12 months after placement.

Conclusions
Attachment disorder symptoms decreased in the stable foster care environment. Thus, foster care seems to be an effective placement option regarding children’s attachment development.
Predicting response to immunotherapy in gastric cancer via assessing perineural invasion-mediated inflammation in tumor microenvironment
Authors: Li Xunjun , Wang Yiyun , Zhai ZhongYa , Mao Qingyi , Chen Dianjie , Xiao Luxi , Xu Shuai , Wu Qilin , Chen Keming , Hou Qiantong , He Qinglie , Shen Yuyang , Yang Manchun , Peng Zishan , He Siqing , Zhou Xuanhui , Tan Haoyang , Luo Shengwei , Fang Chuanfa , Li Guoxin , Chen Tao 
Published: August 2023

Abstract
Background
The perineural invasion (PNI)-mediated inflammation of the tumor microenvironment (TME) varies among gastric cancer (GC) patients and exhibits a close relationship with prognosis and immunotherapy. Assessing the neuroinflammation of TME is important in predicting the response to immunotherapy in GC patients.

Methods
Fifteen independent cohorts were enrolled in this study. An inflammatory score was developed and validated in GC. Based on PNI-related prognostic inflammatory signatures, patients were divided into Clusters A and B using unsupervised clustering. The characteristics of clusters and the potential regulatory mechanism of key genes were verified by RT-PCR, western-blot, immunohistochemistry and immunofluorescence in cell and tumor tissue samples.The neuroinflammation infiltration (NII) scoring system was developed based on principal component analysis (PCA) and visualized in a nomogram together with other clinical characteristics.

Results
Inflammatory scores were higher in GC patients with PNI compared with those without PNI (P < 0.001). NII.clusterB patients with PNI had abundant immune cell infiltration in the TME but worse prognosis compared with patients in the NII.clusterA patients with PNI and non-PNI subgroups. Higher immune checkpoint expression was noted in NII.clusterB-PNI. VCAM1 is a specific signature of NII.clusterB-PNI, which regulates PD-L1 expression by affecting the phosphorylation of STAT3 in GC cells. Patients with PNI and high NII scores may benefit from immunotherapy. Patients with low nomogram scores had a better prognosis than those with high nomogram scores.

Conclusions
Inflammation mediated by PNI is one of the results of tumor-nerve crosstalk, but its impact on the tumor immune microenvironment is complex. Assessing the inflammation features of PNI is a potential method in predicting the response of immunotherapy effectively.
Factors affecting adherence to a high-risk surveillance protocol among patients with Li-Fraumeni syndrome
Authors: Underkofler Kaylee A. , Thomas Martha H. , Taylor Christina J. , Mazur Christa L. , Erickson Sarah H. , Ring Kari L. 
Published: August 2023

Abstract
Background
High-risk surveillance for patients with Li-Fraumeni syndrome (LFS) has shown a stage shift and improved overall survival, but is demanding. Our objective was to evaluate surveillance adherence in a population of patients with LFS presenting for high-risk care.

Methods
A retrospective analysis of surveillance adherence of adult patients with LFS at a single institution was performed. Adherence was defined by the duration from initial University of Virginia (UVA) LFS clinic visit to the time of first missed surveillance test. Two-sample t-tests and ANOVA tests were used to identify factors associated with duration of adherence.

Results
A total of 42 patients were evaluated in the UVA LFS clinic between 2017 and 2021. Of these, 21 patients met inclusion criteria. At the time of review, 6 patients (29%) were up to date with high-risk surveillance recommendations. The mean duration of adherence was 17 months. Female sex was found to be associated with longer duration of adherence (mean 21 mo vs. 3.5 mo for males, p = 0.02). A personal history or active diagnosis of cancer was also associated with increased adherence (p = 0.02). However, neither age (p = 0.89), geography (p = 0.84), or known family history of LFS (p = 0.08) were associated with duration of adherence.

Conclusion
Female sex as well as a personal history of cancer were associated with longer duration of adherence to recommended high-risk surveillance among patients with LFS. Identification of barriers to surveillance will be essential moving forward to increase adherence and promote early detection of cancer, thereby reducing the morbidity and mortality of LFS.