bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosomal radiosensitivity in oncological and non-oncological patients with rheumatoid arthritis and connective tissue diseases
Authors: Rzepka Dinah , Schenker Hannah , Geinitz Hans , Silberberger Elisabeth , Kaudewitz Dorothee , Schuster Barbara , Kuhlmann Lukas , Schonath Miriam , Ayala Gaona Horacio , Aschacher Bernhard , Fietkau Rainer , Schett Georg , Distel Luitpold 
Published: June 2023

Abstract
Background
The risk of developing late radiotoxicity after radiotherapy in patients with high chromosomal radiosensitivity after radiotherapy could potentially be higher compared to the risk in patients with average radiosensitivity. In case of extremely high radiosensitivity, dose reduction may be appropriate. Some rheumatic diseases (RhD), including connective tissue diseases (CTDs) appear to be associated with higher radiosensitivity. The question arises as to whether patients with rheumatoid arthritis (RA) also generally have a higher radiosensitivity and whether certain parameters could indicate clues to high radiosensitivity in RA patients which would then need to be further assessed before radiotherapy.

Methods
Radiosensitivity was determined in 136 oncological patients with RhD, 44 of whom were RA patients, and additionally in 34 non-oncological RA patients by three-colour fluorescence in situ hybridization (FiSH), in which lymphocyte chromosomes isolated from peripheral blood are analysed for their chromosomal aberrations of an unirradiated and an with 2 Gy irradiated blood sample. The chromosomal radiosensitivity was determined by the average number of breaks per metaphase. In addition, correlations between certain RA- or RhD-relevant disease parameters or clinical features such as the disease activity score 28 and radiosensitivity were assessed.

Results
Some oncological patients with RhD, especially those with connective tissue diseases have significantly higher radiosensitivity compared with oncology patients without RhD. In contrast, the mean radiosensitivity of the oncological patients with RA and other RhD and the non-oncological RA did not differ. 14 of the 44 examined oncological RA-patients (31.8%) had a high radiosensitivity which is defined as ≥ 0.5 breaks per metaphase. No correlation of laboratory parameters with radiosensitivity could be established.

Conclusions
It would be recommended to perform radiosensitivity testing in patients with connective tissue diseases in general. We did not find a higher radiosensitivity in RA patients. In the group of RA patients with an oncological disease, a higher percentage of patients showed higher radiosensitivity, although the average radiosensitivity was not high.
Establishment and validation of a prognostic pomogram in unresectable hepatocellular carcinoma treated with intensity modulated radiotherapy: a real world study
Authors: Long Meiying , Li Jianxu , He Meiling , Qiu Jialin , Zhang Ruijun , Liu Yingchun , Liang Chunfeng , Lu Haiyan , Pang Yadan , Zhou Hongmei , Yu Hongping , Qiu Moqin 
Published: June 2023

Abstract
Background
To establish a prognostic model to predict the overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC) treated with intensity modulated radiotherapy (IMRT).

Methods
The unresectable HCC patients treated with IMRT were retrospectively analyzed and randomized into development cohort (n = 237) and validation cohort (n = 103) in a 7:3 ratio. We developed a prognosis model with the multivariate Cox regression analysis in the development cohort to derive the predictive nomogram, which was then validated in the validation cohort. Model performance was evaluated by the c-index, the area under curve(AUC) and the calibration plot.

Results
A total of 340 patients were enrolled. Tumor numbers > 3 (HR = 1.69, 95% CI = 1.21–2.37), AFP ≥ 400 ng/ml (HR = 1.52, 95% CI = 1.10–2.10), PLT < 100 × 10^9(HR = 1.7495% CI = 1.11–2.73), ALP > 150U/L (HR = 1.65, 95% CI = 1.15–2.37) and prior surgery (HR = 0.63, 95% CI = 0.43–0.93) were independent prognostic factors. The nomogram based on independent factors was constructed. The c-index for OS prediction was 0.658 (95% CI, 0.647–0.804) and 0.683 (95% CI, 0.580–0.785) in the development and validation cohort, respectively. The nomogram demonstrated good discriminative ability with AUC rates of 0.726, 0.739 and 0.753 at 1-year, 2-year and 3-year models in the development cohort, and 0.715, 0.756 and 0.780 in the validation cohort, respectively. Additionally, good prognostic discrimination of the nomogram is also reflected in stratifying patients into two subgroups with distinct prognosis.

Conclusions
We constructed a prognostic nomogram for predicting the survival of patients with unresectable HCC treated with IMRT.
Identification of Fangjihuangqi Decoction as a late-stage autophagy inhibitor with an adjuvant anti-tumor effect against non-small cell lung cancer
Authors: Chen Qiugu , Liao Yuan , Liu Yujiao , Song Yue , Jiang Junbo , zhang Zhen , Li Anqi , zheng Mengyi , Chen Xiaoyi , Zhao Tingxiu , Gu Jiangyong , Tan Yuhui , Liu Xiaoyi , Jiang Yanjun , Wang Kun , Yi Hua , Xiao Jianyong , Hu Shan 
Published: June 2023

Abstract
Background
Clinically, although chemotherapy is one of the most commonly used methods of treating tumors, chemotherapeutic drugs can induce autophagic flux and increase tumor cell resistance, leading to drug tolerance. Therefore, theoretically, inhibiting autophagy may improve the efficacy of chemotherapy. The discovery of autophagy regulators and their potential application as adjuvant anti-cancer drugs is of substantial importance. In this study, we clarified that Fangjihuangqi Decoction (FJHQ, traditional Chinese medicine) is an autophagy inhibitor, which can synergistically enhance the effect of cisplatin and paclitaxel on non-small cell lung cancer (NSCLC) cells.

Methods
We observed the changes of autophagy level in NSCLC cells under the effect of FJHQ, and verified the level of the autophagy marker protein and cathepsin. Apoptosis was detected after the combination of FJHQ with cisplatin or paclitaxel, and NAC (ROS scavenger) was further used to verify the activation of ROS-MAPK pathway by FJHQ.

Results
We observed that FJHQ induced autophagosomes in NSCLC cells and increased the levels of P62 and LC3-II protein expression in a concentration- and time-gradient-dependent manner, indicating that autophagic flux was inhibited. Co-localization experiments further showed that while FJHQ did not inhibit autophagosome and lysosome fusion, it affected the maturation of cathepsin and thus inhibited the autophagic pathway. Finally, we found that the combination of FJHQ with cisplatin or paclitaxel increased the apoptosis rate of NSCLC cells, due to increased ROS accumulation and further activation of the ROS-MAPK pathway. This synergistic effect could be reversed by NAC.

Conclusion
Collectively, these results demonstrate that FJHQ is a novel late-stage autophagy inhibitor that can amplify the anti-tumor effect of cisplatin and paclitaxel against NSCLC cells.
Infiltrating myeloid cell diversity determines oncological characteristics and clinical outcomes in breast cancer
Authors: Yang Chenxuan , Liu Jiaxiang , Zhao Shuangtao , Shang Qingyao , Ren Fei , Feng Kexin , Zhang Ruixuan , Kang Xiyu , Wang Xin , Wang Xiang 
Published: June 2023

Abstract
Background
Breast cancer presents as one of the top health threats to women around the world. Myeloid cells are the most abundant cells and the major immune coordinator in breast cancer tumor microenvironment (TME), target therapies that harness the anti-tumor potential of myeloid cells are currently being evaluated in clinical trials. However, the landscape and dynamic transition of myeloid cells in breast cancer TME are still largely unknown.

Methods
Myeloid cells were characterized in the single-cell data and extracted with a deconvolution algorithm to be assessed in bulk-sequencing data. We used the Shannon index to describe the diversity of infiltrating myeloid cells. A 5-gene surrogate scoring system was then constructed and evaluated to infer the myeloid cell diversity in a clinically feasible manner.

Results
We dissected the breast cancer infiltrating myeloid cells into 15 subgroups including macrophages, dendritic cells (DCs), and monocytes. Mac_CCL4 had the highest angiogenic activity, Mac_APOE and Mac_CXCL10 were highly active in cytokine secretion, and the DCs had upregulated antigen presentation pathways. The infiltrating myeloid diversity was calculated in the deconvoluted bulk-sequencing data, and we found that higher myeloid diversity was robustly associated with more favorable clinical outcomes, higher neoadjuvant therapy responses, and a higher rate of somatic mutations. We then used machine learning methods to perform feature selection and reduction, which generated a clinical-friendly scoring system consisting of 5 genes (C3, CD27, GFPT2, GMFG, and HLA-DPB1) that could be used to predict clinical outcomes in breast cancer patients.

Conclusions
Our study explored the heterogeneity and plasticity of breast cancer infiltrating myeloid cells. By using a novel combination of bioinformatic approaches, we proposed the myeloid diversity index as a new prognostic metric and constructed a clinically practical scoring system to guide future patient evaluation and risk stratification.

Graphical Abstract
Global posture reeducation compared with segmental muscle stretching exercises in the treatment of fibromyalgia: a randomized controlled trial
Authors: Matsutani Luciana Akemi , Sousa do Espírito Santo Adriana de , Ciscato Marina , Yuan Susan Lee King , Marques Amelia Pasqual 
Published: June 2023

Abstract
Background
Muscle stretching exercises preserve corporal flexibility and decrease the retraction and shortening of myofascial and articular structures. These exercises are recommended for the treatment of fibromyalgia (FM). The purpose of the study was to verify and compare the effect of muscle stretching exercises on FM patients based on the global posture reeducation method against segmental muscle stretching exercises, both used in concert with an educational approach rooted in cognitive behavioral therapy.

Methods
Forty adults with FM were randomly allocated into two groups: global and segmental. The two kinds of therapies were performed in 10 individual sessions once a week. Two assessments were made: one at baseline and one at the end of therapy. The primary outcome variable was pain intensity (Visual Analog Scale). The secondary outcome variables were multidimensional pain (McGill Pain Questionnaire), the pain threshold at tender points (dolorimetry), attitudes toward chronic pain (Survey of Pain Attitudes-Brief Version), body posture (Postural Assessment Software Protocol), postural control (Modified Clinical Test of Sensory Interaction on Balance), flexibility (sit-and-reach test), the impact of FM on quality of life (Fibromyalgia Impact Questionnaire, FIQ), and self-reported perceptions and body self-care.

Results
At the end of treatment, there were no statistically significant differences between the groups in the outcome variables. Furthermore, the groups presented lower pain intensity (baseline vs. final; global group: 6 ± 1.8 vs. 2.2 ± 1.6 cm, p<0.01; segmental group: 6.3 ± 2.1 vs. 2.5 ± 1.7 cm, p<0.01), higher pain threshold (p ≤ 0.01), lower total FIQ score (p < 0.01), and greater postural control (p < 0.01) after treatment.

Conclusions
Muscle stretching exercises based on global posture reeducation and segmental muscle stretching exercises, both used in concert with an educational approach rooted in cognitive behavioral therapy, reduced the pain intensity and impact of FM on quality of life. These exercises also improved FM patients’ pain threshold at tender points, attitudes toward chronic pain, and postural control. There were no differences between global posture reeducation and segmental muscle stretching exercises.

Trial registration
ClinicalTrials.gov NCT02384603. Registered on 10 March 2015.
The genetic structure of populations of Isthmiophora melis (Schrank, 1788) (Digenea: Echinostomatidae). Does the host’s diet matter?
Authors: Zaleśny Grzegorz , Kanarek Gerard , Pyrka Ewa , Kołodziej-Sobocińska Marta , Zalewski Andrzej , Hildebrand Joanna 
Published: June 2023

Abstract
Background
Here we provide a comparative analysis of the genetic structure of populations (based on nad1 mtDNA) of Isthmiophora melis isolated from the American mink (Neogale vison), an introduced invasive species, commonly occurring in the territory of Poland, and from the striped field mouse (Apodemus agrarius).

Methods
A total of 133 specimens of I. melis were obtained from naturally infected N. vison collected from six localities in Poland (108 samples) and 25 individuals of I. melis from A. agrarius. All sequences of the nad1 gene obtained during the present study were assembled and aligned. The standard statistics for haplotype composition, i.e., the number of haplotypes, haplotype diversity, nucleotide diversity, and average number of nucleotide differences, were calculated. Haplotype analysis and visualization of haplotype frequency among populations were performed using a median-joining network.

Results
Based on the samples collected from different localities in Poland, our study revealed that the overall genetic diversity of I. melis isolated from the American mink and of the striped field mouse do not differ significantly. The median-joining network showed that the three main haplotypes are in the centre of a star-like structure, with the remaining haplotypes as the satellites, reflecting the recent expansion of the populations.

Conclusions
The overall genetic diversity of I. melis isolated from the American mink and striped field mouse reveals a high level of homogeneity. Moreover, regional differences in the food composition of the definitive hosts play an important role in shaping the genetic structure of the trematode populations.

Graphical Abstract
Silencing LncRNA SNHG16 suppresses the diabetic inflammatory response by targeting the miR-212-3p/NF-κB signaling pathway
Authors: Huang Linjuan , Xiong Shengxi , Liu Hanshuang , Zhang Ranran , Wu Ying , Hu Xiaolei 
Published: June 2023

Abstract
Background
Long noncoding RNAs (LncRNAs) have been identified to play an important role in diabetes. The aim of the present study was to determine the expression and function of small nucleolar RNA host gene 16 (SNHG16) in diabetic inflammation.

Methods
For the in vitro experiments, quantitative real-time PCR (qRT-PCR), Western blotting and immunofluorescence were used to detect LncRNA SNHG16 expression in the high-glucose state. The potential microRNA sponge target of LncRNA SNHG16, miR-212-3p, was detected by dual-luciferase reporter analysis and qRT-PCR. For the in vivo experiments, glucose changes in mice were detected after si-SNHG16 treatment, and SNHG16 and inflammatory factor expression in kidney tissues were detected by qRT-PCR and immunohistochemistry.

Results
LncRNA SNHG16 was upregulated in diabetic patients, HG-induced THP-1 cells, and diabetic mice. Silencing SNHG16 inhibited the diabetic inflammatory response and the development of diabetic nephropathy. miR-212-3p was found to be directly dependent on LncRNA SNHG16. miR-212-3p could inhibitor P65 phosphorylation in THP-1 cells. The miR-212-3p inhibitor reversed the action of si-SNHG16 in THP-1 cells and induced an inflammatory response in THP-1 cells. LncRNA SNHG16 was also found to be higher in the peripheral blood of diabetic patients than in the normal person. The area under the ROC curve is 0.813.

Conclusion
These data suggested that silencing LncRNA SNHG16 suppresses diabetic inflammatory responses by competitively binding miR-212-3p to regulate NF-κB. LncRNA SNHG16 can be used as a novel biomarker for patients with type 2 diabetes.
Lifestyle factors, metabolic factors and socioeconomic status for pelvic organ prolapse: a Mendelian randomization study
Authors: Liu Hailang , Wu Wei , Xiang Wei , Yuan Jingdong 
Published: June 2023

Abstract
Background
Previous observational studies have reported that lifestyle factors, metabolic factors and socioeconomic status are associated with the development of female pelvic organ prolapse (POP); however, whether these associations are causal remains unclear. The current study aimed to assess the causal effect of lifestyle factors, metabolic factors and socioeconomic status on POP risk.

Methods
We conducted a two-sample Mendelian randomization (MR) study based on summary-level data from the largest available genome-wide association studies (GWAS) to evaluate whether lifestyle factors, metabolic factors and socioeconomic status are causally related to POP. We used single nucleotide polymorphisms that are strongly associated with exposure at the genome-wide significance level (P < 5 × 10–8) as instrumental variables from genome-wide association studies. The method of random-effect inverse-variance weighting (IVW) was used as the primary analysis method, supplemented with the weighted median, MR-Egger and the MR pleiotropy residual sum and outlier applied to verify the MR assumptions. Two-step MR was conducted to investigate potential intermediate factors that are on the causal pathway from exposure to POP.

Results
There were associations with POP for genetically predicted waist-to-hip ratio (WHR) (odds ratio (OR) 1.02, 95% confidence interval (CI) 1.01–1.03 per SD-increase, P < 0.001), WHR adjusted for body mass index (WHRadjBMI) (OR 1.017, 95% CI 1.01–1.025 per SD-increase, P < 0.001) and education attainment (OR 0.986, 95% CI 0.98–0.991 per SD-increase) in the meta-analysis. Additionally, genetically predicted coffee consumption (OR per 50% increase 0.67, 95% CI 0.47–0.96, P = 0.03), vigorous physical activity (OR 0.83, 95% CI 0.69–0.98, P = 0.043) and high-density lipoprotein cholesterol (HDL-C) (OR 0.91, 95% CI 0.84–0.98 per SD-increase, P = 0.049) were inversely associated with POP in the FinnGen Consortium. The mediation analysis showed that the indirect effects of education attainment on POP were partly mediated by WHR and WHRadjBMI, with a mediated proportion of 27% and 13% in the UK Biobank study, respectively.

Conclusions
Our study provides MR evidence of a robust causal association of WHR, WHRadjBMI and education attainment with POP.
CLOCK inhibits the proliferation of porcine ovarian granulosa cells by targeting ASB9
Authors: Huang Liang , Yuan Huan , Shi Shengjie , Song Xiangrong , Zhang Lutong , Zhou Xiaoge , Gao Lei , Pang Weijun , Yang Gongshe , Chu Guiyan 
Published: June 2023

Abstract
Background
Clock circadian regulator (CLOCK) is a core factor of the mammalian biological clock system in regulating female fertility and ovarian physiology. However, CLOCK's specific function and molecular mechanism in porcine granulosa cells (GCs) remain unclear. In this study, we focused on CLOCK’s effects on GC proliferation.

Results
CLOCK significantly inhibited cell proliferation in porcine GCs. CLOCK decreased the expression of cell cycle-related genes, including CCNB1, CCNE1, and CDK4 at the mRNA and protein levels. CDKN1A levels were upregulated by CLOCK. ASB9 is a newly-identified target of CLOCK that inhibits GC proliferation; CLOCK binds to the E-box element in the ASB9 promoter.

Conclusions
These findings suggest that CLOCK inhibits the proliferation of porcine ovarian GCs by increasing ASB9 level.
Circumstances, policing, and attrition of multiple compared to single perpetrator rape cases within the South African criminal justice system
Authors: Machisa Mercilene Tanyaradzwa , Jina Ruxana , Labuschagne Gerard , Vetten Lisa , Loots Lizle , Jewkes Rachel 
Published: June 2023

Abstract
Background
Research into the circumstances of rape, and criminal justice system responses, is pivotal to informing prevention and improving the likelihood of justice for victims. In this paper, we explore the differences in the circumstances of multiple-perpetrator rapes (MPRs) and single-perpetrator rapes (SPRs), their case management, and attrition, and describe areas for improvemensuplt around rape response within the South African criminal justice system.

Methods
The sample comprised 3952 rape cases reported to the South African Police Services (SAPS) in 2012, selected through a multi-stage random sampling of 172 police stations from a total of 1164 police stations in the nine provinces, followed by the random selection of cases from each station’s case list. Data were abstracted from police dockets, medico-legal examination forms, charge sheets, and trial transcripts. MPRs were defined as cases in which more than one perpetrator had sexual contact with the victim during a single incident, i.e., sexually assaulted or raped. Descriptive statistics and Chi-square tests for associations were used to compare MPRs and SPRs in circumstances of the rape, case management, and attrition.

Results
Seventeen percent of cases were MPRs. MPRs were comparably more violent crimes with a higher frequency of aggressive tactics employed by perpetrators, for example, abductions, firearms use, and threats to kill. Overall, cases were often poorly handled by police, and there were deviations from standard policing and investigation procedures; we found more evidence of this with MPRs compared to SPRs. MPR cases were most likely to have been closed by police due to undetected perpetrators in combination with other victim reasons. The weaker investigations of MPRs were associated with higher attrition rates compared to SPRs, firstly at the police investigation and subsequent stages.

Conclusions
The findings confirm differences in case management, patterns of attrition and trajectories of MPRs compared to SPRs. In an overall context of high rape case attrition and impunity for perpetrators, MPR victims are even less likely to see justice served than SPR victims. There needs to be much more effective supervision of rape case investigations by SAPS, particularly in MPR cases. Continual investigator training strengthened supervision and better resourcing are necessary to improve MPRs detection and convictions in adherence to the Directives for rape policing.