bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of X-ray and carbon-ion beam irradiation with chemotherapy for the treatment of cervical adenocarcinoma cells in 2D and 3D cultures
Authors: Sekihara Kazumasa , Himuro Hidetomo , Saito Nao , Ota Yukihide , Kouro Taku , Kusano Yohsuke , Minohara Shinichi , Hirayama Ryoichi , Katoh Hiroyuki , Sasada Tetsuro , Hoshino Daisuke 
Published: December 2022

Abstract
Background
Cervical cancer is the second most common cancer in women and causes more than 250,000 deaths worldwide. Among these, the incidence of cervical adenocarcinomas is increasing. Cervical adenocarcinoma is not only difficult to detect and prevent in the early stages with screening, but it is also resistant to chemotherapy and radiotherapy, and its prognosis worsens significantly as the disease progresses. Furthermore, when recurrence or metastasis is observed, treatment options are limited and there is no curative treatment. Recently, heavy-particle radiotherapy has attracted attention owing to its high tumor control and minimal damage to normal tissues. In addition, heavy particle irradiation is effective for cancer stem cells and hypoxic regions, which are difficult to treat.

Methods
In this study, we cultured cervical adenocarcinoma cell lines (HeLa and HCA-1) in two-dimensional (2D) or three-dimensional (3D) spheroid cultures and evaluated the effects of X-ray and carbon-ion (C-ion) beams.

Results
X-ray irradiation decreased the cell viability in a dose-dependent manner in 2D cultures, whereas this effect was attenuated in 3D spheroid cultures. In contrast, C-ion irradiation demonstrated the same antitumor effect in 3D spheroid cultures as in 2D cultures. In 3D spheroid cultures, X-rays and anticancer drugs are attenuated because of hypoxia inside the spheroids. However, the impact of the C-ion beam was almost the same as that of the 2D culture, because heavy-particle irradiation was not affected by hypoxia.

Conclusion
These results suggest that heavy-particle radiotherapy may be a new therapeutic strategy for overcoming the resistance of cervical adenocarcinoma to treatment.
LncRNA HOTAIR impairs the prognosis of papillary thyroid cancer via regulating cellular malignancy and epigenetically suppressing DLX1
Authors: Kuo Feng-Chih , Wang Yu-Ting , Liu Chia-Hsin , Li Yao-Feng , Lu Chieh-Hua , Su Sheng-Chiang , Liu Jhih-Syuan , Li Peng-Fei , Huang Chia-Luen , Ho Li-Ju , Lin Chien-Ming , Lee Chien-Hsing 
Published: December 2022

Abstract
Purpose
Papillary thyroid cancer (PTC) is the most common endocrine malignancy with a fast-growing incidence in recent decades. HOTAIR as a long non-coding RNA has been shown to be highly expressed in papillary thyroid cancer tissues with only a limited understanding of its functional roles and downstream regulatory mechanisms in papillary thyroid cancer cells.

Methods
We applied three thyroid cancer cell lines (MDA-T32, MDA-T41 and K1) to investigate the phenotypic influence after gain or loss of HOTAIR. The Cancer Genome Atlas (TCGA) database were utilised to select candidate genes possibly regulated by HOTAIR with validation in the cellular system and immunohistochemical (IHC) staining of PTC tissues.

Results
We observed HOTAIR was highly expressed in MDA-T32 cells but presents significantly decreased levels in MDA-T41 and K1 cells. HOTAIR knockdown in MDA-T32 cells significantly suppressed proliferation, colony formation, migration with cell cycle retardation at G1 phase. On the contrary, HOTAIR overexpression in MDA-T41 cells dramatically enhanced proliferation, colony formation, migration with cell cycle driven toward S and G2/M phases. Similar phenotypic effects were also observed as overexpressing HOTAIR in K1 cells. To explore novel HOTAIR downstream mechanisms, we analyzed TCGA transcriptome in PTC tissues and found DLX1 negatively correlated to HOTAIR, and its lower expression associated with reduced progression free survival. We further validated DLX1 gene was epigenetically suppressed by HOTAIR via performing chromatin immunoprecipitation. Moreover, IHC staining shows a significantly stepwise decrease of DLX1 protein from normal thyroid tissues to stage III PTC tissues.

Conclusions
Our study pointed out that HOTAIR is a key regulator of cellular malignancy and its epigenetic suppression on DLX1 serves as a novel biomarker to evaluate the PTC disease progression.
Potential of Z-100, extracted from Mycobacterium tuberculosis strain Aoyama B, as a hot tumor inducer
Authors: Horii Takayuki , Orikawa Yuki , Ohira Yuta , Eta Runa , Kobayashi Nobuyoshi , Sato Takanori , Watanabe Takeshi , Tanaka Takao 
Published: December 2022

AbstractThe tumor microenvironment is one of the most important factors determining the efficacy of cancer immunotherapy. In particular, variability in efficacy has been linked to whether tumors are hot or cold, with hot tumors exhibiting greater T cell infiltration and responding better to immunotherapy. Z-100 extracted from Mycobacterium tuberculosis Aoyama B strain has been reported to increase cytokine production from immune cells. In this study, we examined its effect on the tumor microenvironment and its potential as a hot tumor inducer. The antitumor effect of Z-100 was confirmed in a mouse oral squamous cell carcinoma (Sq-1979) tumor model by starting administration before tumor injection. Treated tumors were collected to identify infiltrating CD8+ T cells. The antitumor effects of Z-100 were additionally examined in mice treated with anti-CD8 antibody and in IL-12p40 knockout (KO) mice. We found that Z-100 had strong antitumor effects and increased the proportion of CD8+ T cells in tumors. Moreover, the CD8+ T cells infiltrating tumors were identified as effector memory CD8+ T cells. Furthermore, the antitumor effects of Z-100 were abolished in mice treated with an anti-CD8 antibody and in IL-12p40 KO mice. Thus, Z-100 induces its antitumor effects by increasing tumor-infiltrating CD8+ T cells, suggesting that Z-100 may be a useful cancer therapy by acting as a hot tumor inducer.
Disseminated Mycobacterium chimaera infection favoring the development of Kaposi’s sarcoma: a case report
Authors: Clemente Tommaso , Spagnuolo Vincenzo , Bottanelli Martina , Ripa Marco , Del Forno Benedetto , Busnardo Elena , Di Lucca Giuseppe , Castagna Antonella , Danise Anna 
Published: December 2022

Abstract
Background
Disseminated Mycobacterium chimaera infection is an emerging disease in people undergone to cardiothoracic surgery, which need to be suspected also with atypical presentations.

Case presentation
We report the case of a 74-year-old man with fever of unknown origin, purple nodules on both feet and a history of open-heart surgery. Imaging investigations showed an abscess near aortic bioprosthesis but screening for endocarditis resulted negative and pyrexia did not respond to antibiotic therapy. A biopsy of cutaneous lesions showed HHV8-related Kaposi’s sarcoma, so bone marrow biopsy was executed with evidence of HHV8 localization. Bone marrow and urine mycobacterial cultures resulted positive for M. chimaera and a specific antimicrobial therapy was started, with apyrexia after 7 weeks.

Conclusions
M. chimaera infection should be always investigated as a possible etiology of fever of unknow origin in people with a history of open-heart surgical intervention, even with negative mycobacterial blood cultures. The possible role of disseminated infection in inducing immunodepression with the occurrence of other opportunistic diseases (such as Kaposi’s sarcoma) cannot be excluded.
TSPAN4-positive migrasome derived from retinal pigmented epithelium cells contributes to the development of proliferative vitreoretinopathy
Authors: Wu Liangjing , Yang Shuai , Li Hui , Zhang Yao , Feng Le , Zhang Conghui , Wei Jiayi , Gu Xunyi , Xu Guotong , Wang Zhaoyang , Wang Fang 
Published: December 2022

Abstract
Background
Proliferative vitreoretinopathy (PVR) is a blind-causing disease initiated by the activation of retinal pigmented epithelium (RPE) primarily induced by TGF-β families. Migrasome is a recently discovered type of extracellular vesicle related to cell migration.

Results
Here, we used ex vivo, in vitro, and in vivo models, to investigate the characteristics and functions of migrasomes in RPE activation and PVR development. Results indicated that the migrasome marker tetraspanin-4 (TSPAN4) was abundantly expressed in human PVR-associated clinical samples. The ex vivo model PVR microenvironment is simulated by incubating brown Norway rat RPE eyecups with TGF-β1. Electron microscope images showed the formation of migrasome-like vesicles during the activation of RPE. Further studies indicated TGF-β1 increased the expression of TSPAN4 which results in migrasome production. Migrasomes can be internalized by RPE and increase the migration and proliferation ability of RPE. Moreover, TSPAN4-inhibited RPE cells are with reduced ability of initiating experimental PVR. Mechanically, TSPAN4 expression and migrasome production are induced through TGF-β1/Smad2/3 signaling pathway.

Conclusion
In conclusion, migrasomes can be produced by RPE under PVR microenvironment. Migrasomes play a pivotal role in RPE activation and PVR progression. Thus, targeting TSPAN4 or blocking migrasome formation might be a new therapeutic method against PVR.
Cystic angiomatosis in children: clinical experience and review of literature
Authors: Li Wen Chao , Liu Li , Wang Zhen Dong , Chen Hui , Liu Guang , Feng Zhi Chun 
Published: December 2022

Abstract
Background
Cystic angiomatosis is a rare benign disease manifesting as multiple lytic and sclerotic bone lesions, described as the proliferation of vascular and lymphatic channels lined by a single layer of endothelial cells. However, the potential pathogenetic mechanism of the disease still remains unknown. Here, we reported a case of cystic angiomatosis with multifocal bone lesion evaluated by whole exome sequencing.

Case description
In this presentation, we reported a case of an 11-year-old boy with pain in his chest. Computed tomography (CT) revealed the multiple lytic of the bone in the ribs, clavicle, vertebra thoracalis, skull, mandibula, shoulder blade, etc. The blood test showed ALP to be 393U/L and VEGF to be 287.26 pg/ml. The patient was performed with an open biopsy in the ribs and was diagnosed with cystic angiomatosis. Besides, the whole exome sequencing reported the single-nucleotide substitutions in the coding region of BRIP1, CHEK2, GRM4, and MUC16. Then, the upregulated genes involved CASC15, CENPF, ABCA13, ALK, BLM, and FGFR3.

Conclusions
In this article, we report a rare case of cystic angiomatosis in a child with abnormal VEGF and ALP reported by peripheral blood examination. The whole exome sequencing could provide the reference for the potential molecular mechanism in the diagnosis and treatment of cystic angiomatosis.
Observed and personally experienced discrimination: findings of a cross-sectional survey of physicians and nursing staff
Authors: Yolci Arda , Schenk Liane , Sonntag Pia-Theresa , Peppler Lisa , Schouler-Ocak Meryam , Schneider Anna 
Published: December 2022

Abstract
Background
Discrimination against hospital staff based on ascribed features is prevalent in healthcare systems worldwide. Detrimental effects on health and quality of patient care have been shown. Our study aims to describe and analyse the discrimination experiences of both physicians and nurses, specifically for the German hospital context.

Methods
A cross-sectional online survey on observed and personally experienced discrimination at work addressed staff from 22 hospitals of two organizations in Germany. Sociodemographic and occupational as well as institutional characteristics served as independent variables. In multivariable analyses, block- and stepwise logistic regressions were calculated for the two dependent variables (witness and victim of discrimination). Sensitivity analyses with imputed data for missings were performed.

Results
N = 800 healthcare professionals (n = 243 physicians, n = 557 nurses; response rate: 5.9%) participated in the survey. 305 respondents (38.1%) were witnesses of discrimination, while 108 respondents (13.5%) were victims of discrimination in their wards. Reasons for observed discriminatory acts were predominantly attributed to the ethnicity of the person concerned, their appearance and language, whereas personally affected staff most frequently cited gender as a reason, followed by ethnicity, and physical appearance. In multivariable models, cultural competence significantly increased the likelihood of witnessing discrimination (β = .575; p = .037). In terms of the likelihood of being a victim of discrimination, in addition to cultural competence (β = 2.838; p =  < .001), the interaction of the effects of gender and professional group was statistically significant (β = .280; p = .010).

Conclusions
Given the extent of experienced and observed discrimination, appropriate institutional responses are needed. Further research on discriminatory structures in the German-speaking health care system should focus on discrimination at the intersection of ethnicity, gender and occupation.
Cook like a Boss Online: an adapted intervention during the COVID-19 pandemic that effectively improved children’s perceived cooking competence, movement competence and wellbeing
Authors: Hollywood Lynsey , Issartel Johann , Gaul David , McCloat Amanda , Mooney Elaine , Collins Clare Elizabeth , Lavelle Fiona 
Published: December 2022

AbstractBackgroundThe COVID-19 pandemic has further exacerbated physical inactivity, poor dietary intake and reduced mental wellbeing, contributing factors to non-communicable diseases in children. Cooking interventions are proposed as having a positive influence on children’s diet quality. Motor skills have been highlighted as essential for performance of cooking skills, and this movement may contribute to wellbeing. Additionally, perceived competence is a motivator for behaviour performance and thus important for understanding intervention effectiveness. Therefore, this research aimed to assess the effectiveness of an adapted virtual theory-based cooking intervention on perceived cooking competence, perceived movement competence and wellbeing.MethodsThe effective theory-driven and co-created ‘Cook Like A Boss’ was adapted to a virtual five day camp-styled intervention, with 248 children across the island of Ireland participating during the pandemic. Pre- and post-intervention assessments of perceived cooking competence, perceived movement competence and wellbeing using validated measurements were completed through online surveys. Bivariate Correlations, paired samples t-tests and Hierarchical multiple regression modelling was conducted using SPSS to understand the relationships between the variables and the effect of the intervention.Results210 participants had matched survey data and were included in analysis. Significant positive correlations were shown between perceived cooking competence, perceived movement competence and wellbeing (P < 0.05). Children’s perceived cooking competence (P < 0.001, medium to large effect size), perceived movement competence (P < 0.001, small to medium effect size) and wellbeing (P = 0.013, small effect size) all significantly increased from pre to post intervention. For the Hierarchical regression, the final model explained 57% of the total variance in participants’ post-intervention perceived cooking competence. Each model explained a significant amount of variance (P < 0.05). Pre-intervention perceived cooking competence, wellbeing, age and perceived movement competence were significant predictors for post-intervention perceived cooking competence in the final model.ConclusionThe ‘Cook Like A Boss’ Online intervention was an adapted virtual outreach intervention. It provides initial evidence for the associations between perceived cooking competence, perceived movement and wellbeing as well as being effective in their improvement. This research shows the potential for cooking to be used as a mechanism for targeting improvements in not only diet quality but also movement and wellbeing.Trial RegistrationNCT05395234. Retrospectively registered on 26th May 2022.
A bispecific, crosslinking lectibody activates cytotoxic T cells and induces cancer cell death
Authors: Rosato Francesca , Pasupuleti Rajeev , Tomisch Jana , Meléndez Ana Valeria , Kolanovic Dajana , Makshakova Olga N. , Wiltschi Birgit , Römer Winfried 
Published: December 2022

AbstractBackgroundAberrant glycosylation patterns play a crucial role in the development of cancer cells as they promote tumor growth and aggressiveness. Lectins recognize carbohydrate antigens attached to proteins and lipids on cell surfaces and represent potential tools for application in cancer diagnostics and therapy. Among the emerging cancer therapies, immunotherapy has become a promising treatment modality for various hematological and solid malignancies. Here we present an approach to redirect the immune system into fighting cancer by targeting altered glycans at the surface of malignant cells. We developed a so-called “lectibody”, a bispecific construct composed of a lectin linked to an antibody fragment. This lectibody is inspired by bispecific T cell engager (BiTEs) antibodies that recruit cytotoxic T lymphocytes (CTLs) while simultaneously binding to tumor-associated antigens (TAAs) on cancer cells. The tumor-related glycosphingolipid globotriaosylceramide (Gb3) represents the target of this proof-of-concept study. It is recognized with high selectivity by the B-subunit of the pathogen-derived Shiga toxin, presenting opportunities for clinical development.MethodsThe lectibody was realized by conjugating an anti-CD3 single-chain antibody fragment to the B-subunit of Shiga toxin to target Gb3+cancer cells. The reactive non-canonical amino acid azidolysine (AzK) was inserted at predefined single positions in both proteins. The azido groups were functionalized by bioorthogonal conjugation with individual linkers that facilitated selective coupling via an alternative bioorthogonal click chemistry reaction. In vitro cell-based assays were conducted to evaluate the antitumoral activity of the lectibody. CTLs, Burkitt´s lymphoma-derived cells and colorectal adenocarcinoma cell lines were screened in flow cytometry and cytotoxicity assays for activation and lysis, respectively.ResultsThis proof-of-concept study demonstrates that the lectibody activates T cells for their cytotoxic signaling, redirecting CTLs´ cytotoxicity in a highly selective manner and resulting in nearly complete tumor cell lysis—up to 93%—of Gb3+tumor cells in vitro.ConclusionsThis research highlights the potential of lectins in targeting certain tumors, with an opportunity for new cancer treatments. When considering a combinatorial strategy, lectin-based platforms of this type offer the possibility to target glycan epitopes on tumor cells and boost the efficacy of current therapies, providing an additional strategy for tumor eradication and improving patient outcomes.
Associated factors and global adherence of cervical cancer screening in 2019: a systematic analysis and modelling study
Authors: Zhang Wanting , Gao Kai , Fowkes Freya J. I. , Adeloye Davies , Rudan Igor , Song Peige , Jin Mingjuan , Chen Kun 
Published: December 2022

Abstract
Background
Cervical cancer screening is vital for its prevention. Adherence is a crucial indicator that implies the individual willingness to take cervical cancer screening. We aimed to estimate the global and regional adherence rates of cervical cancer screening in 2019 and identify its associated factors among general women.

Method
We searched studies in PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Database, ProQuest theses database and Google Web, without a lower time limit and until 23 June, 2021. Survey studies were considered eligible if they investigated cervical cancer screening adherence among general women, with data on sample size, the number of adherent subjects, and/or adherence rate. Random-effects were used to pool the odds ratios (ORs) of associated factors of adherence. Using modelling analysis, we estimated 2019 overall and age-specific adherence rates at the global and regional levels in women aged 20–69 years.

Results
Eight thousand two hundred ninety records were identified, and 153 articles were included. Being married (vs not married: OR, 1.34; 95% confidence interval [CI]: 1.23–1.46), higher educational attainment (higher than high school vs less than high school: OR, 1.44; 95% CI: 1.35–1.53), having healthcare (OR, 1.64; 95% CI: 1.43–1.88), former smoking (OR, 1.20; 95% CI: 1.07–1.34), physical activity (OR, 1.19; 95% CI: 1.05–1.36), parity (OR, 1.07; 95% CI: 1.01–1.12), and chronic disease (OR, 1.17; 95% CI: 1.04–1.32) were associated with better adherence, whereas obesity (vs normal: OR, 0.85; 95% CI: 0.74–0.97) and current smoking (vs former/never: OR, 0.64; 95% CI: 0.54–0.76) were associated with worse adherence. In 2019, the adherence was at 33.66% (95% CI: 23.34–39.30%) worldwide, and was higher in high-income countries (HICs) (75.66, 95% CI: 66.74–82.81%) than in low and middle-income countries (LMICs) (24.91, 95% CI: 14.30–30.24%). It varied across regions, the highest in the European region (65.36, 95% CI: 55.40–74.19%), but the lowest in the African region (5.28, 95% CI: 3.43–8.03%).

Conclusions
Cervical cancer screening adherence remained low globally, exhibiting geographical discrepancy with HICs higher than LMICs. Further implementations of screening programs should comprehensively consider the local economy, social benefits, and demographic structure to adapt delivery for vulnerable or underserved women to boost screening adherence.