bluuebunny/crossref_metadata_2025_split huggingface dataset:
A diagnostic support system based on pain drawings: binary and k-disease classification of EDS, GBS, FSHD, PROMM, and a control group with Pain2D
Authors: Emmert D. , Szczypien N. , Bender Tim T. A. , Grigull L. , Gass A. , Link C. , Klawonn F. , Conrad R. , Mücke M. , Sellin J. 
Published: March 2023

Abstract
Background and objective
The diagnosis of rare diseases (RDs) is often challenging due to their rarity, variability and the high number of individual RDs, resulting in a delay in diagnosis with adverse effects for patients and healthcare systems. The development of computer assisted diagnostic decision support systems could help to improve these problems by supporting differential diagnosis and by prompting physicians to initiate the right diagnostic tests. Towards this end, we developed, trained and tested a machine learning model implemented as part of the software called Pain2D to classify four rare diseases (EDS, GBS, FSHD and PROMM), as well as a control group of unspecific chronic pain, from pen-and-paper pain drawings filled in by patients.

Methods
Pain drawings (PDs) were collected from patients suffering from one of the four RDs, or from unspecific chronic pain. The latter PDs were used as an outgroup in order to test how Pain2D handles more common pain causes. A total of 262 (59 EDS, 29 GBS, 35 FSHD, 89 PROMM, 50 unspecific chronic pain) PDs were collected and used to generate disease specific pain profiles. PDs were then classified by Pain2D in a leave-one-out-cross-validation approach.

Results
Pain2D was able to classify the four rare diseases with an accuracy of 61–77% with its binary classifier. EDS, GBS and FSHD were classified correctly by the Pain2D k-disease classifier with sensitivities between 63 and 86% and specificities between 81 and 89%. For PROMM, the k-disease classifier achieved a sensitivity of 51% and specificity of 90%.

Conclusions
Pain2D is a scalable, open-source tool that could potentially be trained for all diseases presenting with pain.
APOBEC3-mediated mutagenesis in cancer: causes, clinical significance and therapeutic potential
Authors: Butler Kelly , Banday A. Rouf 
Published: March 2023

AbstractApolipoprotein B mRNA-editing enzyme, catalytic polypeptides (APOBECs) are cytosine deaminases involved in innate and adaptive immunity. However, some APOBEC family members can also deaminate host genomes to generate oncogenic mutations. The resulting mutations, primarily signatures 2 and 13, occur in many tumor types and are among the most common mutational signatures in cancer. This review summarizes the current evidence implicating APOBEC3s as major mutators and outlines the exogenous and endogenous triggers of APOBEC3 expression and mutational activity. The review also discusses how APOBEC3-mediated mutagenesis impacts tumor evolution through both mutagenic and non-mutagenic pathways, including by inducing driver mutations and modulating the tumor immune microenvironment. Moving from molecular biology to clinical outcomes, the review concludes by summarizing the divergent prognostic significance of APOBEC3s across cancer types and their therapeutic potential in the current and future clinical landscapes.
Targeting IGF1R signaling enhances the sensitivity of cisplatin by inhibiting proline and arginine metabolism in oesophageal squamous cell carcinoma under hypoxia
Authors: Fang Kang , Sun Mingchuang , Leng Zhuyun , Chu Yuan , Zhao Ziying , Li Zhaoxing , Zhang Yunwei , Xu Aiping , Zhang Zehua , Zhang Li , Chen Tao , Xu Meidong 
Published: March 2023

Abstract
Background
Cisplatin (DDP)-based chemotherapy is commonly adopted as the first-line treatment for patients with oesophageal squamous cell carcinoma (OSCC), but the high rate of drug resistance limits its clinical application and the underlying mechanisms at play remain unclear. The aims of this study were to elucidate the role of abnormal signal transmission and metabolism in the chemoresistance of OSCC under hypoxia and to identify targeted drugs that enhance the sensitivity of DDP chemotherapy.

Methods
Upregulated genes in OSCC were determined by RNA sequencing (RNA-seq), the Cancer Genome Atlas (TCGA) database, immunohistochemistry (IHC), real-time quantitative PCR (RT-qPCR), and western blotting (WB). The clinicopathological significance of insulin-like growth factor-I receptor (IGF1R), argininosuccinate synthetase 1 (ASS1), and pyrroline-5-carboxylate reductase 1 (PYCR1) in OSCC was analysed using tissue micriarray (TMA). Metabolic abnormalities were determined by untargeted metabolomics analysis. The DDP-resistance role of IGF1R, ASS1, and PYCR1 in OSCC was investigated in vitro and in vivo.

Results
Generally, tumour cells exist in a hypoxic microenvironment. By genomic profiling, we determined that IGF1R, as a receptor tyrosine kinase (RTK), was upregulated in OSCC under low-oxygen conditions. Clinically, enhanced IGF1R expression was associated with higher tumour stages and a poorer prognosis in OSCC patients, and its inhibitor, linsitinib, showed synergistic effects with DDP therapy in vivo and in vitro. Since oxygen-deprivation frequently lead to metabolic reprogramming, we further learned via metabolomics analysis that abnormal IGF1R pathways promoted the expression of metabolic enzymes ASS1 and PYCR1 by the transcriptional activity of c-MYC. In detail, enhanced expression of ASS1 promotes arginine metabolism for biological anabolism, whereas PYCR1 activates proline metabolism for redox balance, which maintains the proliferation ability of OSCC cells during DDP treatment under hypoxic conditions.

Conclusion
Enhanced expression of ASS1 and PYCR1 via IGF1R pathways rewired arginine and proline metabolism, promoting DDP resistance in OSCC under hypoxia. Linsitinib targeting IGF1R signaling may lead to promising combination therapy options for OSCC patients with DDP resistance.
HES1-mediated down-regulation of miR-138 sustains NOTCH1 activation and promotes proliferation and invasion in renal cell carcinoma
Authors: Liu Shuangjie , Dou Lei , Miao Miao , Man Xiaojun , Wei Baojun , Jiang Zhaowei , Ouyang Yongze , Ozaki Toshinori , Yu Meng , Zhu Yuyan 
Published: March 2023

Abstract
Background
Although the aberrant activation of NOTCH1 pathway causes a malignant progression of renal cell carcinoma (RCC), the precise molecular mechanisms behind the potential action of pro-oncogenic NOTCH1/HES1 axis remain elusive. Here, we examined the role of tumor suppressive miR-138–2 in the regulation of NOTCH1-HES1-mediated promotion of RCC.

Methods
This study employed bioinformatics, xenotransplant mouse models, ChIP assay, luciferase reporter assay, functional experiments, real-time PCR and Western blot analysis to explore the mechanisms of miR-138–2 in the regulation of NOTCH1-HES1-mediated promotion of RCC, and further explored miR-138–2-containing combination treatment strategies.

Results
There existed a positive correlation between down-regulation of miR-138 and the aberrant augmentation of NOTCH1/HES1 regulatory axis. Mechanistically, HES1 directly bound to miR-138–2 promoter region and thereby attenuated the transcription of miR-138-5p as well as miR-138–2-3p. Further analysis revealed that miR-138-5p as well as miR-138–2-3p synergistically impairs pro-oncogenic NOTCH1 pathway through the direct targeting of APH1A, MAML1 and NOTCH1.

Conclusions
Collectively, our current study strongly suggests that miR-138–2 acts as a novel epigenetic regulator of pro-oncogenic NOTCH1 pathway, and that the potential feedback regulatory loop composed of HES1, miR-138–2 and NOTCH1 contributes to the malignant development of RCC. From the clinical point of view, this feedback regulatory loop might be a promising therapeutic target to treat the patients with RCC.
Exercise in adults admitted to hospital with diabetes‐related foot ulcers: a pilot study of feasibility and safety
Authors: Aitken Emily , Hiew Jonathan , Hamilton Emma J , Manning Laurens , Ritter Jens Carsten , Raby Edward , Gittings Paul M 
Published: March 2023

AbstractBackgroundDiabetes‐related foot ulcers result in significant mortality, morbidity and economic costs. Pressure offloading is important for ulcer healing, but patients with diabetes‐related foot ulcers are presented with a dilemma, because whilst they are often advised to minimise standing and walking, there are also clear guidelines which encourage regular, sustained exercise for patients with diabetes. To overcome these apparently conflicting recommendations, we explored the feasibility, acceptability and safety of a tailored exercise program for adults admitted to hospital with diabetes‐related foot ulcers.MethodsPatients with diabetes‐related foot ulcers were recruited from an inpatient hospital setting. Baseline demographics and ulcer characteristics were collected, and participants undertook a supervised exercise training session comprising aerobic and resistance exercises followed by prescription of a home exercise programme. Exercises were tailored to ulcer location, which complied with podiatric recommendations for pressure offloading. Feasibility and safety were assessed via recruitment rate, retention rate, adherence to inpatient and outpatient follow up, adherence to home exercise completion, and recording of adverse events.ResultsTwenty participants were recruited to the study. The retention rate (95%), adherence to inpatient and outpatient follow up (75%) and adherence to home exercise (50.0%) were all acceptable. No adverse events occurred.ConclusionsTargeted exercise appears safe to be undertaken by patients with diabetes‐related foot ulcers during and after an acute hospital admission. Recruitment in this cohort may prove challenging, but adherence, retention and satisfaction with participation in exercise were high.Trial registrationThe trial is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12622001370796).
Host-mediated RNA editing in viruses
Authors: Zhu Tongtong , Niu Guangyi , Zhang Yuansheng , Chen Ming , Li Chuan-Yun , Hao Lili , Zhang Zhang 
Published: March 2023

AbstractViruses rely on hosts for life and reproduction, cause a variety of symptoms from common cold to AIDS to COVID-19 and provoke public health threats claiming millions of lives around the globe. RNA editing, as a crucial co-/post-transcriptional modification inducing nucleotide alterations on both endogenous and exogenous RNA sequences, exerts significant influences on virus replication, protein synthesis, infectivity and toxicity. Hitherto, a number of host-mediated RNA editing sites have been identified in diverse viruses, yet lacking a full picture of RNA editing-associated mechanisms and effects in different classes of viruses. Here we synthesize the current knowledge of host-mediated RNA editing in a variety of viruses by considering two enzyme families, viz., ADARs and APOBECs, thereby presenting a landscape of diverse editing mechanisms and effects between viruses and hosts. In the ongoing pandemic, our study promises to provide potentially valuable insights for better understanding host-mediated RNA editing on ever-reported and newly-emerging viruses.
Metabolic syndrome among people living with HIV in Ethiopia: a systematic review and meta-analysis
Authors: Girma Derara , Dejene Hiwot , Geleta Leta Adugna , Malka Erean Shigign , Tesema Mengistu , Awol Mukemil , Oyato Befekadu Tesfaye 
Published: March 2023

Abstract
Background
Human Immuno-deficiency Virus (HIV) infection and antiretroviral therapy (ART) can cause metabolic disorders such as lipodystrophy, dyslipidemia, and insulin resistance, all of which are symptoms of metabolic syndrome (MetS). In Ethiopia, despite the existence of the primary studies, there was no pooled study conducted to summarize the country-level MetS among people living with HIV (PLHIV). Therefore, this study aims to estimate the pooled prevalence of MetS among PLHIV in Ethiopia.

Methods
A systematic search was conducted to retrieve studies on the prevalence of MetS among PLHIV in Ethiopia from PubMed, Google Scholar, Science Direct, Web of Sciences, HINARI, and other relevant sources. A random-effects model was used to estimate the MetS in this study. The overall variation between studies was checked by the heterogeneity test (I2). The Joanna Briggs Institute (JBI) quality appraisal criteria were used to assess the quality of the studies. The summary estimates were presented with forest plots and tables. Publication bias was checked with the funnel plot and Egger’s regression test.

Results
Overall, 366 articles were identified and evaluated using the PRISMA guidelines, with 10 studies meeting the inclusion criteria included in the final analysis. The pooled prevalence of MetS among PLHIV in Ethiopia was 21.7% (95% CI:19.36–24.04) using National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III) and 29.91% (95% CI: 21.54–38.28) using International Diabetes Federation (IDF) criteria. The lowest and highest prevalence of MetS were 19.14% (95%CI: 15.63–22.64) and 25.6% (95%CI: 20.18–31.08) at Southern Nation and Nationality People Region (SNNPR) and Addis Ababa, respectively. There was no statistical evidence of publication bias in both NCEP-ATP III and IDF pooled estimates.

Conclusion
MetS was common among PLHIV in Ethiopia. Therefore, optimizing regular screening for MetS components and promoting a healthy lifestyle is suggested for PLHIV. Furthermore, more study is contributory to identify the barriers to implementing planned interventions and meeting recommended treatment goals. Trial registration: The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO): CRD42023403786.
Impact of informal institutions on youth agribusiness participation in Southern Benin
Authors: Magbondé Kadoukpè Gildas , Mignouna Djana , Manyong Victor , Adéoti Razack , Sossou Ayélé Odile 
Published: March 2023

AbstractThe agribusiness sector development is often portrayed as an essential component of economic development. Though Benin is a country with inestimable agricultural potential, the agribusiness sector appears unappealing to the local youths. Prior investigations diagnosed the impeding factors as a paucity of financial resource and a dearth of land and technical knowledge. This article departs from past studies by considering the importance of informal institutions for youth participation in the agribusiness sector. Exploring a rich data set of 478 youths aged 15 to 35, collected in Southern Benin based on the stratified random sampling technique, the article uses propensity score matching to address selection bias and logistic regression on the matched sample to link informal institutions to youth participation in agribusiness. Results highlight that agribusiness-unfriendly informal institutions discourage youth participation in the agribusiness sector. Though easing access to finance is crucial for the youths to initiate agribusiness activities, findings make a case for long-term policies that aim to increase the societal levels of trust and desirability for the agribusiness sector.
Soil conditions and the plant microbiome boost the accumulation of monoterpenes in the fruit of Citrus reticulata ‘Chachi’
Authors: Su Jianmu , Wang Yayu , Bai Mei , Peng Tianhua , Li Huisi , Xu Hui-Juan , Guo Guifang , Bai Haiyi , Rong Ning , Sahu Sunil Kumar , He Hanjun , Liang Xiangxiu , Jin Canzhi , Liu Wei , Strube Mikael Lenz , Gram Lone , Li Yongtao , Wang Ertao , Liu Huan , Wu Hong 
Published: March 2023

AbstractBackgroundThe medicinal material quality ofCitrus reticulata‘Chachi’ differs depending on the bioactive components influenced by the planting area. Environmental factors, such as soil nutrients, the plant-associated microbiome and climatic conditions, play important roles in the accumulation of bioactive components in citrus. However, how these environmental factors mediate the production of bioactive components of medicinal plants remains understudied.ResultsHere, a multi-omics approach was used to clarify the role of environmental factors such as soil nutrients and the root-associated microbiome on the accumulation of monoterpenes in the peel ofC. reticulata‘Chachi’ procured from core (geo-authentic product region) and non-core (non-geo-authentic product region) geographical regions. The soil environment (high salinity, Mg, Mn and K) enhanced the monoterpene content by promoting the expression of salt stress-responsive genes and terpene backbone synthase in the host plants from the core region. The microbial effects on the monoterpene accumulation of citrus from the core region were further verified by synthetic community (SynCom) experiments. Rhizosphere microorganisms activated terpene synthesis and promoted monoterpene accumulation through interactions with the host immune system. Endophyte microorganisms derived from soil with the potential for terpene synthesis might enhance monoterpene accumulation in citrus by providing precursors of monoterpenes.ConclusionsOverall, this study demonstrated that both soil properties and the soil microbiome impacted monoterpene production in citrus peel, thus providing an essential basis for increasing fruit quality via reasonable fertilization and precision microbiota management.
Mediating role of resilience in the relationship between COVID-19 related stigma and mental health among COVID-19 survivors: a cross-sectional study
Authors: Xiao Weijun , Liu Xiaoyang , Wang Hao , Huang Yiman , Dai Zhenwei , Si Mingyu , Fu Jiaqi , Chen Xu , Jia Mengmeng , Leng Zhiwei , Cui Dan , Mak Winnie W. S. , Dong Liming , Su Xiaoyou 
Published: March 2023

AbstractBackgroundThe global coronavirus disease 2019 (COVID-19) has caused many negative effects on physical and mental health of patients who have survived COVID-19. Apart from some long-lasting physical sequelae, those COVID-19 survivors are also suffering stigma and discrimination at different levels around the world. The current study aims to assess the role resilience played in stigma and mental disorders among COVID-19 survivors.MethodsThe cross-sectional study was carried out among former COVID-19 patients in Jianghan District (Wuhan, China) from June 10 to July 25, 2021. The demographic questions, the Impact of Events Scale-Revised, the Generalized Anxiety Disorder Questionnaire, the Patient Health Questionnaire, the Resilience Style Questionnaire and the Short Version of COVID-19 Stigma Scale of 12 items were used to collect relevant information of the participants. Descriptive analyses, Pearson correlation analysis and Structural Equation Modeling were used to make data description and analysis.ResultsA total of 1541 out of 1601 COVID-19 survivors (887 females and 654 males) were included in the analysis. Perceived stigma of those COVID-19 survivors correlates significantly with anxiety (r = 0.335,P < 0.001), depression (r = 0.325,P < 0.001) and post-traumatic stress disorder (PTSD) (r = 0.384,P < 0.001). It has a direct effect on COVID-19 survivors’ anxiety (β = 0.326,P < 0.001), depression (β = 0.314,P < 0.001), PTSD (β = 0.385,P < 0.001) and their resilience (β = − 0.114,P < 0.01). Resilience partially mediated the association between perceived stigma and anxiety (β = 0.020,P < 0.01), depression (β = 0.020,P < 0.01), and PTSD (β = 0.014,P < 0.01) among COVID-19 survivors.ConclusionStigma has a significant negative impact on mental health, while resilience plays a mediator role in the relationship between stigma and mental health among COVID-19 survivors. Based on our study, we suggested that when designing psychological interventions for COVID-19 survivors, consideration should be taken into account to reduce stigma and improve resilience.
Thiram, an inhibitor of 11ß-hydroxysteroid dehydrogenase type 2, enhances the inhibitory effects of hydrocortisone in the treatment of osteosarcoma through Wnt/β-catenin pathway
Authors: Zhang You , Li Nanjing , Li He , Chen Maojia , Jiang Wei , Guo Wenhao 
Published: March 2023

Abstract
Background
The anti-osteosarcoma effects of hydrocortisone and thiram, an inhibitor of type 2 11ß-hydroxysteroid dehydrogenase (11HSD2), have not been reported. The purpose of this study was to investigate the effects of hydrocortisone alone or the combination of hydrocortisone with thiram on osteosarcoma and the molecular mechanism, and determine whether they can be as new therapeutic agents for osteosarcoma.

Methods
Normal bone cells and osteosarcoma cells were treated with hydrocortisone or thiram alone or in combination. The cell proliferation, migration, cell cycle and apoptosis were detected by using CCK8 assay, wound healing assay, and flow cytometry, respectively. An osteosarcoma mouse model was established. The effect of drugs on osteosarcoma in vivo was assessed by measuring tumor volume. Transcriptome sequencing, bioinformatics analysis, RT–qPCR, Western blotting (WB), enzymelinked immunosorbent assay (ELISA) and siRNA transfection were performed to determine the molecular mechanisms.

Results
Hydrocortisone inhibited the proliferation and migration, and induced apoptosis and cell cycle arrest of osteosarcoma cells in vitro. Hydrocortisone also reduced the volume of osteosarcoma in mice in vivo. Mechanistically, hydrocortisone decreased the levels of Wnt/β-catenin pathway-associated proteins, and induced the expression of glucocorticoid receptor α (GCR), CCAAT enhancer-binding protein β (C/EBP-beta) and 11HSD2, resulting in a hydrocortisone resistance loop. Thiram inhibited the activity of the 11HSD2 enzyme, the combination of thiram and hydrocortisone further enhanced the inhibition of osteosarcoma through Wnt/β-catenin pathway.

Conclusions
Hydrocortisone inhibits osteosarcoma through the Wnt/β-catenin pathway. Thiram inhibits 11HSD2 enzyme activity, reducing hydrocortisone inactivation and promoting the effect of hydrocortisone through the same pathway.
Effects of selected solvents on PMMA after prolonged exposure: unilateral NMR and ATR-FTIR investigations
Authors: Kavda Stefani , Golfomitsou Stavroula , Richardson Emma 
Published: March 2023

Abstract
Exposure of heritage plastics to solvents can cause several changes to their surface layers and bulk. The amorphous nature of certain plastics, particularly polymethyl methacrylate (PMMA), allows penetration and diffusion of low-molecular liquids, which can lead to swelling, cracking, plasticisation or stiffening, extraction and dissolution of polymer and additive components. Such phenomena compromise the visual characteristics, chemical and physical structure of heritage collections and remain, for the most part, unexplored. Research studies present contradicting evidence concerning the use of solvents and their safe application on PMMA. The main discrepancy is about PMMA being permeable to water or not. Alcohols have also triggered debates about whether they cause leaching and/or depolymerisation. This paper investigates the potential effects that selected free polar and non-polar solvents—employed in different media as cleaning systems—can have on PMMA after prolonged contact. The Hildebrand solubility theory was used to select solvents based on PMMA’s miscibility. The effects of deionised water, ethanol, isopropanol and petroleum ether are examined through a 30-day immersion study of PMMA via microscopic examination, weight change measurements, ATR-FTIR, peak height ratios, and NMR MOUSE. All four solvents extracted soluble components, i.e. unreacted residual monomer, and increased PMMA’s surface sensitivity to abrasions. Water and petroleum ether did not cause any measurable chemical or physical changes. Alcohols caused surface crystallisation and crazing, with isopropanol leading to stiffening and ethanol to plasticisation of the material. These effects, although extreme and absent in most routine cleaning timeframes, demonstrate the cumulative damage these solvents can potentially induce to PMMA.