bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Mitophagy-Related Gene Signature Associated With Prognosis and Immune Microenvironment in Colorectal Cancer
Authors: Zhang Cong , Zeng Cailing , Xiong Shaoquan , Zhao Zewei , Wu Guoyu 
Published: January 2022

Abstract
Background: Colorectal cancer (CRC) is a heterogeneous disease and one of the most common malignancies in the world. Previous studies have found that mitophagy plays an important role in the progression of colorectal cancer. This study is aimed to investigate the relationship between mitophagy-related genes and the prognosis of patients with CRC.Methods: Gene expression profiles and clinical information of CRC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) regression analysis were used to establish the prognostic signature composed of mitophagy related genes. Kaplan-Meier curve and receiver operating characteristic (ROC) curve were used to analyze patient survival and verify the predictive accuracy of the signature, respectively. Construction of a nomogram prognostic prediction model was based on risk scores and clinicopathological parameters. Using the Genomics of Drug Sensitivity in Cancer (GDSC) database and Tumor Immune Dysfunction and Exclusion (TIDE) algorithm to estimate the sensitivity of chemotherapy, targeted therapy and immunotherapy. Results: A total of 44 mitophagy-driven genes connected with CRC survival were identified, and prognostic signature was established based on the expression of 10 of them (AMBRA1, ATG14, MAP1LC3A, MAP1LC3B, OPTN, VDAC1, ATG5, CSNK2A2, MFN1, TOMM22). Patients were divided into high-risk and low-risk groups based on the median risk score, and the survival of patients in the high-risk group was significantly shorter than that of the low-risk group among the TCGA cohort (median OS 67.3 months vs not reached, p=0.00059) and two independent cohorts from GEO (median OS in GSE17536: 54.0 months vs not reached, p=0.0082; in GSE245: 7.7 months vs not reached, p=0.025). ROC curve showed that the area under the curves (AUC) of 1-, 3- and 5-year survival were 0.66, 0.66 and 0.64, respectively. Multivariate Cox regression analysis confirmed the independent prognostic value of the signature. Then we constructed a nomogram combining the risk score, age and M stage, which had a concordance index of survival prediction of 0.77 (95% CI=0.71-0.83) and more robust predictive sensitivity and specificity. Results showed that CD8+ T cells, regulatory T cells and activated NK cells were significantly more abundant in the high-risk group. Furthermore, patients in the high-risk group were more sensitive to potential targeted therapies, including Motesanib, ATRA, Olaparib, Selumetinib, AZD8055 and immunotherapy. Conclusion: In conclusion, we constructed and validated a novel mitophagy related gene signature that can be used as an independent prognostic biomarker for CRC, and may lead to better stratification and selection of precise treatment for CRC patients.
Scaling of cellular proteome with ploidy
Authors: Yahya Galal , Menges Paul , Ngandiri Devi , Schulz Daniel , Wallek Andreas , Kulak Nils , Mann Matthias , Cramer Patrick , Savage Van , Raeschle Markus , Storchova Zuzana 
Published: January 2022

Abstract
Ploidy changes are frequent in nature and contribute to evolution, functional specialization and tumorigenesis. Analysis of model organisms of different ploidies revealed that increased ploidy leads to an increase in cell and nuclear volume, reduced proliferation, metabolic changes, lower fitness, and increased genomic instability, but the underlying mechanisms remain poorly understood. To investigate how the gene expression changes with cellular ploidy, we analyzed isogenic series of budding yeasts from 1N to 4N. We show that mRNA and protein abundance scales allometrically with ploidy, with tetraploid cells showing only threefold increase in proteins compared to haploids. This ploidy-specific scaling occurs via decreased rRNA and ribosomal protein abundance and reduced translation. We demonstrate that the Tor1 activity is reduced with increasing ploidy, which leads to rRNA gene repression via a novel Tor1-Sch9-Tup1 signaling pathway. mTORC1 and S6K activity are also reduced in human tetraploid cells and the concomitant increase of the Tup1 homolog Tle1 downregulates the rDNA transcription. Our results revealed a novel conserved mTORC1-S6K-Tup1/Tle1 pathway that ensures proteome remodeling in response to increased ploidy.
Fourth Year Intellectual Disability Student Nurses’ Journey and Future Work Intention: A Qualitative Study.
Authors: Doody Owen , Meskell Pauline , Noonan Maria , Murphy-Tighe Sylvia , Kingston Liz 
Published: January 2022

Abstract
BackgroundThe aim of this qualitative study is to explore the views and experiences of final year BSc intellectual disability nursing students’ journey, future work plans and examine factors influencing their migration intentions following graduation.MethodsA qualitative component of a mixed methods study where focus group interviews were conducted with final year BSc intellectual disability nursing students (n-=10). A topic guide was utilised, and participants were interviewed about their programme, future work plans and migration intentions. An inductive approach was utilised, and data were analysed using a pre-existing framework for initial coding and thematic development. Duffy’s conceptual model of identity transformation provided a structure to analyse the data and map themes onto the conceptual framework.ResultsThe findings were mapped onto the five stages of Duffy’s (2013) conceptual model of identity transformation: Pre-Entry; Reaffirming; Surmounting; Stabilising and Actualising. Findings indicate that further work is required to promote intellectual disability nursing and address professional esteem issues, support for education and professional development, such as providing career guidance opportunities prior to course completion, development of clinical skills within their education programme and support for the professional development of new graduates. Participants identified uncertainty about career opportunities and saw scope for future professional developments opportunities particularly in community-based work.ConclusionThis study has identified that final year intellectual disability nursing students are uncertain about career options and opportunities for intellectual disability nurses in other countries. There is an urgent need for the intellectual disability nursing profession to articulate their practice and advocate for their role and contribution to the care of people with intellectual disability. This study identified a clear need for direction and information regarding intellectual disability nursing roles and career opportunities.
Penicillium Arizonense as a Novel Producer Strain for Mycophenolic Acid and Expression Analysis of Biosynthesizing Gene Clusters
Authors: Ammar Hala , Ezzat Saeid , Elshourbagi Ebrahim , Elshahat Hind 
Published: January 2022

Abstract
A novel potent mycophenolic acid (MPA) producer strain of the genus Penicillium was isolated from refrigerated Mozzarella cheese and identified as P. arizonenseHEWt1. The molecular mechanism of MPA production by this new isolate was our main target. To achieve this objective, we first isolated three MPA overproducer mutants by exposing the wild type to different doses of gamma-rays, and the fermentation conditions for the highest production of MPA by both the wild type and mutants were optimized. Then, orthologs of MPA gene clusters in P. brevicompactum were cloned and predicted from the genome of P. arizonense. Sequencing and bioinformatic analysis proved the presence of a cluster containing five putative genes in the P. arizonense HEWt1 genome ortholog to the MPA cluster, mpaA, mpaC, mpaF, mpaG, and mpaH. All predicted genes displayed 96-97% similarity with the related hypothetical protein of P. arizonense. The genes, mpaG, mpaC, and mpaF. represented 69%, 82%, 84%, respectively, similarity with their orthologous genes in P. brevicompactum, whereas mpaG and mpaA represented 75% and 79%, respectively, similarity to their orthologous genes in P. roqueforti. Gene expression analysis through quantitative rPCR indicated an increase in the transcription value of all annotated genes in the three mutants over the wild type. A highly significant increase in the gene expression of mpaC, mpaF, and mpaH was observed, with 8.4561±1.02, 5.6569±0.87, and 4.6268±0.18-fold increases, respectively, in P. arizonense-MT1 compared with wild-type. These results confirmed the potential participation of these genes in MPA biosynthesis and are the first report regarding the molecular mechanism of MPA production by P. arizonense.
Plinabulin and Pegfilgrastim in Combination for the Prevention of Chemotherapy-Induced Neutropenia in Patients with Breast Cancer (PROTECTIVE-2): A Randomized Trial
Authors: Blayney Douglas , Zhang Qingyuan , Mohanlal Ramon , Du Lihua , Ette Ene , Ogenstad Stephan , Adamchuk Hryhoriy , Sun Tao , Li Hongsheng , Feng Jifen , Huang Lan , Shi Yuan-kai 
Published: January 2022

Abstract
PurposePlinabulin is a non-granulocyte colony-stimulating factor (G-CSF) novel small molecule with both anticancer and myeloprotective effects. Single-agent plinabulin is myeloprotective in the first week of the chemotherapy cycle, and pegfilgrastim in the second week. We assessed the efficacy and safety of the combination of plinabulin and pegfilgrastim for the prevention of chemotherapy-induced neutropenia (CIN) following chemotherapy.MethodsThis randomized, open-label, Phase 2 trial enrolled patients with breast cancer. All received docetaxel 75 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide 500 mg/m2 on Day 1. In the combined therapy cohort, patients received plinabulin 20 mg/m2 on Day 1 and 1.5, 3, or 6 mg pegfilgrastim on Day 2. The primary objective was to establish the recommended Phase 3 dose (RP3D). Secondary endpoints included absolute neutrophil count (ANC) nadir, relative dose intensity (RDI), and incidence of adverse events including neutropenia and bone pain.ResultsIn total, 115 patients were randomized and evaluated. The combination therapy at the RP3D (plinabulin 20 mg/m2 and pegfilgrastim 6 mg) was well-tolerated and had superior CIN prevention in terms of Grade 4 and Grade 3/4 neutropenia frequency, absolute neutrophil count (ANC) nadir, higher relative dose intensity (RDI), less bone pain, and less toxicity burden when compared with pegfilgrastim 6 mg alone.ConclusionPlinabulin combined with pegfilgrastim at the RP3D (plinabulin 20 mg/m2 Day 1 and pegfilgrastim 6 mg Day 2) had more favorable efficacy, safety, and tolerability profiles and lower bone pain incidence than did pegfilgrastim alone.Trial information Clinical Trial Registration: ClinicalTrials.gov NCT04227990Date registered: January 14, 2020 Retrospectively registered
Köppen–Geiger Climate Clasification in the Pannonian basin According to SSP5-8.5 Scenario
Authors: Ruman Albert , Ruman Anna 
Published: January 2022

Abstract
The Köppen–Geiger climate classification is used to determine climate types in region of Pannonian Basin with data from the sixth phase of the Coupled Model Intercomparison Project. The study covers a period from years 2021 until 2100, and it shows how certain climate types are changing in percentage in thirty-year averages for six periods. In the period 1960-1990 years of the last century, the dominant climate type was warm summer humid continental climate (Dfb) with 98% presences in the region. The results show that the change of this climate type to the humid subtropical climate type (Cfa) began in the first half of the 21st century. The complete dominance of humid subtropical climate type in the most areas of the Pannonian Basin characterized the second half of the 21st century. Also, results show creation of a warm summer Mediterranean climate type (Csa), which according to certain simulations, is present from 10% to 30% on average in the region. In the central part of the region, a cold desert climate type (Bsk) was formed with approximately 6% presences in the region. This creation of climate types in some parts of the region shows that in the second half of 21st century drier and a warmer climate is expected compared to the last century.
Normal product form of two-mode Wigner operator
Authors: He Rui , Liu Xiangyuan , Wei Xiangfei , Wu Congbing 
Published: January 2022

Abstract
In the context of normal product, we use the method of the integration within an ordered product (IWOP) of operators to derive three representations of the two-mode Wigner operator: SU (2) symmetric description, SU (1, 1) symmetric description and polar coordinate form. We find that two-mode Wigner operator has multiple potential degrees of freedom. As the physical meaning of the selected integral variable changes, Wigner operator shows different symmetries. In particular, in the case of polar coordinates, we reveal the natural connection between the two-mode Wigner operator and the entangled state representation.
Designing an Optimal Model of Blood Logistics Management with the Possibility of Return in the Three-Level Blood Transfusion Network
Authors: Ahmadimanesh monireh , Pooya Alireza , Safabakhsh Hamidreza , Sadeghi Sedigheh 
Published: January 2022

Abstract
Inventory managers in the blood supply chain always seek timely and proper response to their customers, which is essential because of the perishability and uncertainty of blood demand and the direct relationship of its presence or non-presence with human life. On the other hand, timely and regular delivery of blood to consumers is vital, as the weakness in delivery and transportation policies results in increased shortages, returns, blood loss and significant decrease in the quality of blood required by patients. Given the significance of this for the blood transfusion network, the paper tried to design a comprehensive and integrated optimal model of blood transfusion network logistics management by blood group to reduce the cost of losses, returns and blood shortages. This model is divided into two parts: Inventory management and routing. A combination of simulation techniques and neural network with several recurrent layers was used to evaluate the optimal inventory management and a multi-objective planning model was designed to determine the delivery and distribution of blood to consumers. The model designed was implemented in Khorasan Razavi Blood Transfusion Network with a main base, six central bases and 54 hospitals. Solving the model led to estimating the f consumer demand, the optimal value of target inventory and re-ordering point of central bases and hospitals, and blood distribution from the supplier to its consumers that decreased the units of blood returned to bases, increased inventory availability, and reduced costs significantly.
Measurement and Mapping of Maternal Health Service Coverage Through a Novel Composite Index: A Sub-National Level Analysis in India
Authors: Kiran Tanvi , Junaid KP , Rajagopal Vineeth , Gupta Madhu , Sharma Divya 
Published: January 2022

Abstract
Background: Expansion of maternal health service coverage is crucial for the survival and wellbeing of both mother and child. To date, limited literature exists on the measurement of maternal health service coverage at the sub-national level in India. The prime objectives of the study were to comprehensively measure the maternal health service coverage by generating a composite index; map India by categorizing it into low, medium and high zones and examine its incremental changes over time. Methods: Utilising a nationally representative time series data of 15 key indicators spread across three domains of antenatal care, intranatal care and postnatal care, we constructed a novel ‘Maternal Health Service Coverage Index’ (MHSI) for 29 states and 5 union territories of India for the base (2017-18) and reference (2019-20) years. Following a rigorous procedure, MHSI scores were generated using both arithmetic mean and geometric mean approach. We categorized India into low, medium and high maternal health coverage zones and further generated geospatial maps to examine the extent and transition of maternal health service coverage from base to reference year.Results: India registered the highest mean percentage coverage (93.66%) for ‘institutional delivery’ and lowest for ‘treatment for obstetric complications’ (9.25%) among all the indicators. Depending on the usage of arithmetic mean and geometric mean approach, the maternal health service coverage index score for India exhibited marginal incremental change (between 0.015- 0.02 index points) in the reference year. West zone exhibited an upward transition in the coverage of maternal health service indicators, while none of the zones recorded a downward movement. States of Mizoram (east zone), Puducherry (south zone) showed a downward transition. Union territories of Dadra & Nagar Haveli (west zone) and Chandigarh (north zone) along with the states of Maharashtra (west zone), Assam, as well as Jharkhand (both from the east & north east zone), showed upward transition.Conclusion: Overall, maternal health service coverage is increasing across India. Our study offers a novel summary measure to comprehensively quantify the coverage of maternal health service, which can momentously help India to identify lagged indicators and low performing regions, thereby warranting the targeted interventions and concentrated programmatic efforts to bolster the maternal health service coverage at the sub-national level.
Evaluation of Psychopathological Conditions, Corona Anxiety, Death Anxiety and Suicide Risk in Hemodialysis Patients During the COVID-19 Pandemic
Authors: Korkut Süleyman 
Published: January 2022

Abstract
Background

Hemodialysis (HD) patients have serious psychopathological symptoms due to COVID-19 pandemic. Therefore, this study aimed to identify the psychopathological conditions among HD patients during the current pandemic and also to provide a theoretical basis for the implementation of effective preventions and psychological interventions.
Methods

This cross-sectional study was conducted with 114 HD patients who were undergoing treatment in the Dialysis Centers of two state hospitals between July and October 2021. Brief symptom inventory, Death anxiety scale, Suicide probability scale and Corona anxiety scale were applied to the participants for the assessment.
Results

In the study, it was determined that HD patients had high levels of psychopathological symptoms. The mean total score was found to be 26.47 ± 20.2 in TDAS, 0.71 ± 0.51 in GSI, 3.31 ± 2.86 in CAS and 65.86 ± 9.72 in SPS. Of the participants 18.4% had high death anxiety levels and 30.7% had corona anxiety. Suicide risk was higher in HD patients. In correlation analysis; psychological distress positively correlated with suicide probability, corona anxiety and death anxiety. On the other hand, there was a positive correlation between corona anxiety and death anxiety.
Conclusions

As a result, it was concluded that HD patients experienced various mental health problems during the COVID-19 pandemic. Psychosocial support and interventions need to be planned by the healthcare system and healthcare providers to help HD patients in managing their disease and related mental health conditions.
A comparative and diachronic analysis of film title translations and appellative effect transfer into Croatian and German
Authors: Gabrić Petar , Brajković Iva , Licchetta Letizia , Ključarić Dorotea Kelčec , Bezuh Juraj 
Published: January 2022

Abstract
Studies of film title translations remain scant to this day. The existing studies mainly focus on investigating the sources of difficulties during the translation process. Although the studies employ different analytical approaches, the conclusion in almost all investigations is that the decisive objective during the translation process is the transfer or production of the appellative effect. This study investigates which strategies are employed during translation into Croatian and German and why, as well as possible diachronic changes in the choice of translation strategies. We created a corpus of 935 film titles from 1923 to 2017 and their translations into Croatian and German, which we first classified as either direct translations, free translations, transcreations or transcriptions, and finally we quantitatively and qualitatively analysed the data. Our results show significant differences between the two subcorpora in the choice of translation strategies and motivation, as well as in the patterns of diachronic change. Furthermore, correlations with specific cultural-historical processes are observed.
Loss of HAS2 Confers Acquired Antiestrogen Resistance By Upregulating Ezrin Expression In ER-Positive Breast Cancer
Authors: Sun Xiaodan , Tang Fen , Liu Yiwen , He Yiqing , Du Yan , Zhang Guoliang , Gao Feng , Yang Cuixia 
Published: January 2022

Abstract
Background: Resistance to endocrine therapy is a major challenge for estrogen receptor-positive (ER+) breast cancer patients, but the underlying mechanisms remain unclear. Methods: Loss of hyaluronan synthase 2 (Has2) in adaptive resistant cells to tamoxifen and fulvestrant was observed by immunblotting assay. CRISPR/Cas9 technology was used to knock out Has2 in MCF7 cells to verify the effect of Has2 on the expression of ER and Ezrin and Akt and MAPK/ERK signaling routes. We utilized an Ezrin small-interfering RNA and Ezrin inhibitor to inhibit Ezrin expression for evaluating Has2 and ERα expression and the Akt/MAPK signaling cascade upon tamoxifen or fulvestrant treatment.Results: In this work, we showed that a Has2-loss state was acquired from adaptive resistance to tamoxifen and fulvestrant in luminal BrCas. Notably, the adapted loss of Has2 induced acquired resistance to antiestrogens in estrogen receptor (ER)-positive breast cancer cells through up-regulating the expression of Ezrin. Furthermore, we found that the loss of Has2 promoted while the consequent increase of Ezrin inhibited ERα expression/activity through the Akt and MAPK/ERK signaling routes, indicating an opposite effect on ERα expression during the development of antiestrogens-resistance. Inhibition of Ezrin reversed Has2 and ERα expression and the Akt/MAPK signaling cascade upon tamoxifen or fulvestrant, suggesting a Has2-Ezrin-ER negative-feedback loop in governing cellular sensitivity to tamoxifen or fulvestrant in luminal-like breast cancer cells. Finally, Knockdown or inhibition of Ezrin restored sensitivity to antiestrogens, implying that Ezrin could be a potential therapeutic target to tackle endocrine resistance. Conclusions: Taken together, our findings provide a direct relationship between ERα and Has2 implicated in resistance to endocrine therapy and a new insight into how ERα-signaling is regulated upon antiestrogens treatment, suggesting a novel therapeutic target for ER-positive breast cancer.