bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying a novel cuproptosis-related necroptosis gene subtype-related signature for predicting the prognosis, tumor microenvironment, and immunotherapy of hepatocellular carcinoma
Authors: Shi Yuanxin , Qiu Peng , Zhao Kai , Li Xiangyu , Feng Yunxiang , Deng Zhengdong , Wang Jianming 
Published: May 2023

Background: Cuproptosis and necroptosis represent two distinct programmed cell death modalities implicated in neoplastic progression; however, the role of combining cuproptosis and necroptosis in hepatocellular carcinoma (HCC) remains to be elucidated.Methods: A total of 29 cuproptosis-related necroptosis genes (CRNGs) were identified, followed by an extensive analysis of their mutational characteristics, expression patterns, prognostic implications, and associations with the tumor microenvironment (TME). Subsequently, a CRNG subtype-related signature was developed, and its value of prognostic prediction, TME, and therapeutic responses in HCC were thoroughly investigated. Last, quantitative real-time PCR and Western blotting were employed for investigating the signature gene expression in 15 paired clinical tissue samples.Results: Two distinct CRNG subtypes were discerned, demonstrating associations between CRNG expression patterns, clinicopathological attributes, prognosis, and the TME. A CRNG subtype-related prognostic signature, subjected to external validation, was constructed, serving as an independent prognostic factor for HCC patients, indicating poor prognosis for high-risk individuals. Concurrently, the signature’s correlations with an immune-suppressive TME, mutational features, stemness properties, immune checkpoint genes, chemoresistance-associated genes, and drug sensitivity were observed, signifying its utility in predicting treatment responses. Subsequently, highly accurate and clinically convenient nomograms were developed, and the signature genes were validated via quantitative real-time PCR and Western blotting, further substantiating the stability and dependability of the CRNG subtype-related prognostic signature.Conclusion: Overall, this investigation presented an extensive panorama of CRNGs and developed the CRNG subtype-related prognostic signature, which holds potential for implementation in personalized treatment strategies and prognostic forecasting for HCC patients.
Comparative dosimetric study of radiotherapy in high-grade gliomas based on the guidelines of EORTC and NRG-2019 target delineation
Authors: Yan Ouying , Teng Haibo , Jiang Cuihong , He Lili , Xiao Shuai , Li Yanxian , Wu Wenqiong , Zhao Qi , Ye Xu , Liu Wen , Fan Changgen , Wu Xiangwei , Liu Feng 
Published: May 2023

PurposeRadiotherapy is one of the most important treatments for high-grade glioma (HGG), but the best way to delineate the target areas for radiotherapy remains controversial, so our aim was to compare the dosimetric differences in radiation treatment plans generated based on the European Organization for Research and Treatment of Cancer (EORTC) and National Research Group (NRG) consensus to provide evidence for optimal target delineation for HGG.MethodsWe prospectively enrolled 13 patients with a confirmed HGG from our hospital and assessed dosimetric differences in radiotherapy treatment plans generated according to the EORTC and NRG-2019 guidelines. For each patient, two treatment plans were generated. Dosimetric parameters were compared by dose–volume histograms for each plan.ResultsThe median volume for planning target volume (PTV) of EORTC plans, PTV1 of NRG-2019 plans, and PTV2 of NRG-2019 plans were 336.6 cm3 (range, 161.1–511.5 cm3), 365.3 cm3 (range, 123.4–535.0 cm3), and 263.2 cm3 (range, 116.8–497.7 cm3), respectively. Both treatment plans were found to have similar efficiency and evaluated as acceptable for patient treatment. Both treatment plans showed well conformal index and homogeneity index and were not statistically significantly different (P = 0.397 and P = 0.427, respectively). There was no significant difference in the volume percent of brain irradiated to 30, 46, and 60 Gy according to different target delineations (P = 0.397, P = 0.590, and P = 0.739, respectively). These two plans also showed no significant differences in the doses to the brain stem, optic chiasm, left and right optic nerves, left and right lens, left and right eyes, pituitary, and left and right temporal lobes (P = 0.858, P = 0.858, P = 0.701 and P = 0.794, P = 0.701 and P = 0.427, P = 0.489 and P = 0.898, P = 0.626, and P = 0.942 and P = 0.161, respectively).ConclusionThe NRG-2019 project did not increase the dose of organs at risk (OARs) radiation. This is a significant finding that further lays the groundwork for the application of the NRG-2019 consensus in the treatment of patients with HGGs.Clinical trial registrationThe effect of radiotherapy target area and glial fibrillary acidic protein (GFAP) on the prognosis of high-grade glioma and its mechanism, number ChiCTR2100046667. Registered 26 May 2021.
Conventional ultrasound and contrast-enhanced ultrasound radiomics in breast cancer and molecular subtype diagnosis
Authors: Gong Xuantong , Li Qingfeng , Gu Lishuang , Chen Chen , Liu Xuefeng , Zhang Xuan , Wang Bo , Sun Chao , Yang Di , Li Lin , Wang Yong 
Published: May 2023

ObjectivesThis study aimed to explore the value of conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) radiomics to diagnose breast cancer and predict its molecular subtype.MethodA total of 170 lesions (121 malignant, 49 benign) were selected from March 2019 to January 2022. Malignant lesions were further divided into six categories of molecular subtype: (non-)Luminal A, (non-)Luminal B, (non-)human epidermal growth factor receptor 2 (HER2) overexpression, (non-)triple-negative breast cancer (TNBC), hormone receptor (HR) positivity/negativity, and HER2 positivity/negativity. Participants were examined using CUS and CEUS before surgery. Regions of interest images were manually segmented. The pyradiomics toolkit and the maximum relevance minimum redundancy algorithm were utilized to extract and select features, multivariate logistic regression models of CUS, CEUS, and CUS combined with CEUS radiomics were then constructed and evaluated by fivefold cross-validation.ResultsThe accuracy of the CUS combined with CEUS model was superior to CUS model (85.4% vs. 81.3%, p&lt;0.01). The accuracy of the CUS radiomics model in predicting the six categories of breast cancer is 68.2% (82/120), 69.3% (83/120), 83.7% (100/120), 86.7% (104/120), 73.5% (88/120), and 70.8% (85/120), respectively. In predicting breast cancer of Luminal A, HER2 overexpression, HR-positivity, and HER2 positivity, CEUS video improved the predictive performance of CUS radiomics model [accuracy=70.2% (84/120), 84.0% (101/120), 74.5% (89/120), and 72.5% (87/120), p&lt;0.01].ConclusionCUS radiomics has the potential to diagnose breast cancer and predict its molecular subtype. Moreover, CEUS video has auxiliary predictive value for CUS radiomics.
Treatment paradigm and prognostic factor analyses of rectal squamous cell carcinoma
Authors: Liu Rui , Zhang Jiahui , Zhang Yinjie , Yan Jin 
Published: May 2023

BackgroundRectal squamous cell carcinoma (rSCC) is a rare pathological subtype of rectal cancer. There is no consensus on the treatment paradigm for patients with rSCC. This study aimed to provide a paradigm for clinical treatment and develop a prognostic nomogram.MethodsPatients diagnosed with rSCC between 2010 and 2019 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. According to the TNM staging system, Kaplan−Meier (K-M) survival analysis was used to identify the survival benefits of different treatments in patients with rSCC. The Cox regression method was used to identify independent prognostic risk factors. Nomograms were evaluated by Harrell’s concordance index (C-index), calibration curves, decision curve analysis (DCA) and K-M curves.ResultsData for 463 patients with rSCC were extracted from the SEER database. Survival analysis showed that there was no significant difference in median cancer-specific survival (CSS) among patients with TNM stage 1 rSCC treated with radiotherapy (RT), chemoradiotherapy (CRT) or surgery (P = 0.285). In TNM stage 2 patients, there was a significant difference in median CSS among those treated with surgery (49.5 months), RT (24 months), and CRT (63 months) (P = 0.003). In TNM stage 3 patients, there was a significant difference in median CSS among those treated with CRT (58 months), CRT plus surgery (56 months) and no treatment (9.5 months) (P &lt; 0.001). In TNM stage 4 patients, there was no significant difference in median CSS among those treated with CRT, chemotherapy (CT), CRT plus surgery and no treatment (P = 0.122). Cox regression analysis showed that age, marital status, T stage, N stage, M stage, PNI, tumor size, RT, CT, and surgery were independent risk factors for CSS. The 1-, 3-, and 5-year C-indexes were 0.877, 0.781, and 0.767, respectively. The calibration curve showed that the model had excellent calibration. The DCA curve showed that the model had excellent clinical application value.ConclusionRT or surgery is recommended for patients with stage 1 rSCC, and CRT is recommended for patients with stage 2, and stage 3 rSCC. Age, marital status, T stage, N stage, M stage, PNI, tumor size, RT, CT, and surgery are independent risk factors for CSS in patients with rSCC. The model based on the above independent risk factors has excellent prediction efficiency.
A novel benzothiazole derivative induces apoptosis via the mitochondrial intrinsic pathway producing antitumor activity in colorectal cancer
Authors: Zhou Jing , Zhao Rongce , Zhou Haoxuan , Yang Shuping , Tao Feiyan , Xie Yongmei , Wang Hongli , Yun Jingping 
Published: May 2023

Background: Colorectal cancer (CRC) is one of the most common malignancies causing the third highest mortality rate in the world. It is particularly urgent to explore effective therapeutic strategies to overcome this disease. We identified a novel benzothiazole derivative (BTD) that may serve as a potentially effective agent against CRC.Method: MTT assays, cell colony formation assays, EdU staining assays, flow cytometry, RNA-seq, Western blotting, and migration and invasion assays were used to examine the effects of BTD on cell proliferation, apoptosis, metastasis, and the cell cycle. The antitumor activity of BTD in vivo was investigated in a CT26 tumor-bearing mouse model. Immunohistochemistry (IHC) was performed to examine the protein expression in mouse tumors. Hematology, biochemical analysis, and H&amp;E staining were used to assess the biosafety of BTD.Results: We observed that BTD suppressed cell proliferation and metastasis and promoted the apoptosis of tumor cells in vitro. Treatment with BTD at a tolerable dose significantly reduced tumor growth in CT26-tumor-bearing mice and appeared to be safe. Treatment of BTD induced apoptosis by increasing the generation of reactive oxygen species (ROS) and evoking the loss of mitochondrial transmembrane potential. Overall, BTD suppressed cell proliferation and metastasis, and induced apoptosis of colorectal tumor cells through the ROS–mitochondria-mediated apoptotic pathway. The preliminary proof of the antitumor activity and relative safety of BTD were validated in a mouse model.Conclusion: Our findings suggest that BTD could serve as a potentially safe and effective candidate for CRC treatment.
Revision total hip arthroplasty using a fluted, tapered, modular stem follow-up method for a mean of three years: A preliminary study
Authors: Xing Shu-Xing , Huang Qiang , Li Zheng-Jiang , Li Yong-Kui , Ban Zhao-Nan 
Published: May 2023

Objective: This study aimed to evaluate the results and complications related to revision total hip arthroplasty within a short-to-medium follow up period.Methods: From January 2016 to January 2020, we reviewed 31 prosthetic hip arthroplasty stem revisions using a fluted, tapered modular stem with distal fixation. The median age of the patients was 74.55–79 years. The survival rate was 100%, and there were no re-revisions. The Harris hip score improved from an average of 36.5 ± 7.8 before surgery to 81.8 ± 6.2 at the final follow-up.Results: The average final follow-up was 36 (24–60) months. During this time, there was no periprosthetic infection, no prosthesis loosening or breakage, and no sciatic nerve injury. Complications included four (12.9%) intraoperative fractures and eight (25.8%) dislocations that had no stem fractures. The postoperative limb was lengthened by 17.8 ± 9.8 mm. In most cases, bone regeneration was an early and important finding. Three cases underwent extended trochanteric osteotomy, and bone healing was achieved by the final follow-up.Conclusion: The modular tapered stem reviewed in this study was very versatile, could be used in most femoral revision cases, and allowed for rapid bone reconstruction. However, a long-term follow-up study is needed to confirm these results.
Explanatory model of the psychosocial variables related to the social acceptance of a uranium mine project in northwest Spain
Authors: Sánchez-Tabernero Gonzalo , Hidalgo-Muñoz Antonio R. , Galán José Ignacio , Tabernero Carmen 
Published: May 2023

IntroductionThe demographic growth and the development of the welfare system have been accompanied by an important social dilemma between preserving nature or promoting energy development by assuming the benefits and risks of both proposals. This research attempts to address this social dilemma by analyzing the psychosocial factors that influence the acceptance or rejection of a new uranium mining development and exploitation project. The main objective was to test an explanatory theoretical model of uranium mining project acceptance, based on the interrelation of sociodemographic variables (e.g., age, gender, economic and educational situation, and level of knowledge about uranium energy) and cognitive variables (e.g., environmental beliefs, risk, and benefit perceptions), along with the activation of an emotional balance in response to the proposal of constructing a uranium mine.MethodThree hundred seventy-one individuals responded to the questionnaire about the variables included in the model.ResultsThe results showed that older participants showed lower levels of agreement with the mining proposal people, while women and those with greater knowledge of nuclear energy perceived greater risks and had a more negative emotional balance. The proposed explanatory model based on sociodemographic, cognitive, and affective variables showed good fit indices for explaining the assessment of the uranium mine. Thus, age, level of knowledge, risks and benefits, and emotional balance had a direct effect on the acceptance of the mine. Likewise, emotional balance showed a partial mediation effect between the relationships existing between the perception of benefits and risks and the acceptance of the mining proposal.DiscussionThe results are discussed based on the consideration of analyzing sociodemographic, cognitive, and affective variables to understand potential conflicts in communities affected by energy projects.
“Attitudes to voices”: a survey exploring the factors influencing clinicians’ intention to assess distressing voices and attitudes towards working with young people who hear voices
Authors: Rammou Aikaterini , Berry Clio , Fowler David , Hayward Mark 
Published: May 2023

IntroductionDue to the general psychopathological vulnerability of young people who hear distressing voices, research has stressed the importance for clinicians to assess this experience in youth. Nonetheless, the limited literature on the topic comes from studies with clinicians in adult health services and it primarily reports that clinicians do not feel confident in systematically assessing voice-hearing and doubt the appropriateness of doing so. We applied the Theory of Planned Behavior and identified clinicians’ job attitudes, perceived behavioral control, and perceived subjective norms as putative predictors of their intent to assess voice-hearing in youth.MethodNine hundred and ninety-six clinicians from adult mental health services, 467 from Child and Adolescent Mental Health (CAMHS) and Early Intervention in Psychosis (EIP) services and 318 primary care clinicians across the UK completed an online survey. The survey gathered data on attitudes toward working with people who hear voices, stigmatizing beliefs, and self-perceived confidence in voice-related practices (screening for, discussing and providing psychoeducation material about voice-hearing). Responses from youth mental health clinicians were compared with professionals working in adult mental health and primary care settings. This study also aimed to identify what youth mental health clinicians believe about assessing distressing voices in adolescents and how beliefs predict assessment intention.ResultsCompared to other clinicians, EIP clinicians reported the most positive job attitudes toward working with young voice-hearers, the highest self-efficacy in voice-hearing practices, and similar levels of stigma. Job attitudes, perceived behavioral control and subjective norms explained a large part of the influences on clinician’s intention to assess voice-hearing across all service groups. In both CAMHS and EIP services, specific beliefs relating to the usefulness of assessing voice-hearing, and perceived social pressure from specialist mental health professionals regarding assessment practices predicted clinician intention.DiscussionClinicians’ intention to assess distressing voices in young people was moderately high, with attitudes, subjective norms and perceived behavioral control explaining a large part of its variance. Specifically in youth mental health services, promoting a working culture that encourages opening and engaging in discussions about voice-hearing between clinicians, and with young people, and introducing supportive assessment and psychoeducation material about voice-hearing could encourage conversations about voices.
Controlling Legionella pneumophila in Showerheads: Combination of Remedial Intervention and Preventative Flushing
Authors: Grimard-Conea Marianne , Prévost Michèle 
Published: May 2023

Shock chlorination and remedial flushing are suggested to address Legionella pneumophila (Lp) contamination in buildings or during their (re)commissioning. However, data on general microbial measurements (adenosine tri-phosphate [ATP], total cell counts [TCC]), and the abundance of Lp are lacking to support their temporary implementation with variable water demands. In this study, the weekly short-term (3-week) impact of shock chlorination (20–25 mg/L free chlorine, 16 h) or remedial flushing (5-min flush) combined with distinct flushing regimes (daily, weekly, stagnant) was investigated in duplicates of showerheads in two shower systems. Results showed that the combination of stagnation and shock chlorination prompted biomass regrowth, with ATP and TCC in the first draws reaching large regrowth factors of 4.31–7.07-fold and 3.51–5.68-fold, respectively, from baseline values. Contrastingly, remedial flushing followed by stagnation generally resulted in complete or larger regrowth in Lp culturability and gene copies (gc). Irrespective of the intervention, daily flushed showerheads resulted in significantly (p < 0.05) lower ATP and TCC, as well as lower Lp concentrations than weekly flushes, in general. Nonetheless, Lp persisted at concentrations ranging from 11 to 223 as the most probable number per liter (MPN/L) and in the same order of magnitude (103–104 gc/L) than baseline values after remedial flushing, despite daily/weekly flushing, unlike shock chlorination which suppressed Lp culturability (down 3-log) for two weeks and gene copies by 1-log. This study provides insights on the most optimal short-term combination of remedial and preventative strategies that can be considered pending the implementation of suitable engineering controls or building-wide treatment.
The Genome of Varunaivibrio sulfuroxidans Strain TC8T, a Metabolically Versatile Alphaproteobacterium from the Tor Caldara Gas Vents in the Tyrrhenian Sea
Authors: Patwardhan Sushmita , Phan Jonathan , Smedile Francesco , Vetriani Costantino 
Published: May 2023

Varunaivibrio sulfuroxidans type strain TC8T is a mesophilic, facultatively anaerobic, facultatively chemolithoautotrophic alphaproteobacterium isolated from a sulfidic shallow-water marine gas vent located at Tor Caldara, Tyrrhenian Sea, Italy. V. sulfuroxidans belongs to the family Thalassospiraceae within the Alphaproteobacteria, with Magnetovibrio blakemorei as its closest relative. The genome of V. sulfuroxidans encodes the genes involved in sulfur, thiosulfate and sulfide oxidation, as well as nitrate and oxygen respiration. The genome encodes the genes involved in carbon fixation via the Calvin–Benson–Bassham cycle, in addition to genes involved in glycolysis and the TCA cycle, indicating a mixotrophic lifestyle. Genes involved in the detoxification of mercury and arsenate are also present. The genome also encodes a complete flagellar complex, one intact prophage and one CRISPR, as well as a putative DNA uptake mechanism mediated by the type IVc (aka Tad pilus) secretion system. Overall, the genome of Varunaivibrio sulfuroxidans highlights the organism’s metabolic versatility, a characteristic that makes this strain well-adapted to the dynamic environmental conditions of sulfidic gas vents.
Tandem LC-MS Identification of Antitubercular Compounds in Zones of Growth Inhibition Produced by South African Filamentous Actinobacteria
Authors: Watson Daniel J. , Wiesner Lubbe , Matimela Tlhalefo , Beukes Denzil , Meyers Paul R. 
Published: May 2023

Novel antitubercular compounds are urgently needed to combat drug-resistant Mycobacterium tuberculosis (Mtb). Filamentous actinobacteria have historically been an excellent source of antitubercular drugs. Despite this, drug discovery from these microorganisms has fallen out of favour due to the continual rediscovery of known compounds. To increase the chance of discovering novel antibiotics, biodiverse and rare strains should be prioritised. Subsequently, active samples need to be dereplicated as early as possible to focus efforts on truly novel compounds. In this study, 42 South African filamentous actinobacteria were screened for antimycobacterial activity using the agar overlay method against the Mtb indicator Mycolicibacterium aurum under six different nutrient growth conditions. Known compounds were subsequently identified through extraction and high-resolution mass spectrometric analysis of the zones of growth inhibition produced by active strains. This allowed the dereplication of 15 hits from six strains that were found to be producing puromycin, actinomycin D and valinomycin. The remaining active strains were grown in liquid cultures, extracted and submitted for screening against Mtb in vitro. Actinomadura napierensis B60T was the most active sample and was selected for bioassay-guided purification. This resulted in the identification of tetromadurin, a known compound, but which we show for the first time to have potent antitubercular activity, with the MIC90s within the range of 73.7–151.6 nM against M. tuberculosis H37RvT in vitro under different test conditions. This shows that South African actinobacteria are a good source of novel antitubercular compounds and warrant further screening. It is also revealed that active hits can be dereplicated by HPLC-MS/MS analysis of the zones of growth inhibition produced by the agar overlay technique.