bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional signature of islet neogenesis-associated protein peptide-treated rat pancreatic islets reveals induction of novel long non-coding RNAs
Authors: Romero Agustín , Heidenreich Ana C. , Román Carolina L. , Algañarás Macarena , Nazer Ezequiel , Gagliardino Juan J. , Maiztegui Bárbara , Flores Luis E. , Rodríguez-Seguí Santiago A. 
Published: September 2023

BackgroundDiabetes mellitus is characterized by chronic hyperglycemia with loss of β-cell function and mass. An attractive therapeutic approach to treat patients with diabetes in a non-invasive way is to harness the innate regenerative potential of the pancreas. The Islet Neogenesis-Associated Protein pentadecapeptide (INGAP-PP) has been shown to induce β-cell regeneration and improve their function in rodents. To investigate its possible mechanism of action, we report here the global transcriptional effects induced by the short-term INGAP-PP in vitro treatment of adult rat pancreatic islets.Methods and findingsRat pancreatic islets were cultured in vitro in the presence of INGAP-PP for 4 days, and RNA-seq was generated from triplicate treated and control islet samples. We performed a de novo rat gene annotation based on the alignment of RNA-seq reads. The list of INGAP-PP-regulated genes was integrated with epigenomic data. Using the new gene annotation generated in this work, we quantified RNA-seq data profiled in INS-1 cells treated with IL1β, IL1β+Calcipotriol (a vitamin D agonist) or vehicle, and single-cell RNA-seq data profiled in rat pancreatic islets. We found 1,669 differentially expressed genes by INGAP-PP treatment, including dozens of previously unannotated rat transcripts. Genes differentially expressed by the INGAP-PP treatment included a subset of upregulated transcripts that are associated with vitamin D receptor activation. Supported by epigenomic and single-cell RNA-seq data, we identified 9 previously unannotated long noncoding RNAs (lncRNAs) upregulated by INGAP-PP, some of which are also differentially regulated by IL1β and vitamin D in β-cells. These include Ri-lnc1, which is enriched in mature β-cells.ConclusionsOur results reveal the transcriptional program that could explain the enhancement of INGAP-PP-mediated physiological effects on β-cell mass and function. We identified novel lncRNAs that are induced by INGAP-PP in rat islets, some of which are selectively expressed in pancreatic β-cells and downregulated by IL1β treatment of INS-1 cells. Our results suggest a relevant function for Ri-lnc1 in β-cells. These findings are expected to provide the basis for a deeper understanding of islet translational results from rodents to humans, with the ultimate goal of designing new therapies for people with diabetes.
Unraveling TIMP1: a multifaceted biomarker in colorectal cancer
Authors: Qiu Xiaode , Quan Guangqian , Ou Wenquan , Wang Pengfei , Huang Xing , Li Xinhua , Shen Yufan , Yang Weifeng , Wang Jian , Wu Xiaohua 
Published: September 2023

Background: The pathogenic genes of colorectal cancer (CRC) have not yet been fully elucidated, and there is currently a lack of effective therapeutic targets. This study used bioinformatics methods to explore and experimentally validate the most valuable biomarkers for colorectal cancer and further investigate their potential as targets.Methods: We analyzed differentially expressed genes (DEGs) based on the Gene Expression Omnibus (GEO) dataset and screened out hub genes. ROC curve and univariate Cox analysis of The Cancer Genome Atlas (TCGA) dataset revealed the most diagnostically and prognostically valuable genes. Immunohistochemistry (IHC) experiments were then conducted to validate the expression level of these selected genes in colorectal cancer. Gene set enrichment analysis (GSEA) was performed to evaluate the enriched signaling pathways associated with the gene. Using the CIBERSORT algorithm in R software, we analyzed the immune infiltrating cell abundance in both high and low gene expression groups and examined the gene’s correlation with immune cells and immune checkpoints. Additionally, we performed drug sensitivity analysis utilizing the DepMap database, and explored the correlation between gene expression levels and ferroptosis based on the The Cancer Genome Atlas dataset.Results: The study identified a total of 159 DEGs, including 7 hub genes: SPP1, MMP1, CXCL8, CXCL1, TIMP1, MMP3, and CXCL10. Further analysis revealed TIMP1 as the most valuable diagnostic and prognostic biomarker for colorectal cancer, with IHC experiments verifying its high expression. Additionally, GSEA results showed that the high TIMP1 expression group was involved in many cancer signaling pathways. Analysis of the TCGA database revealed a positive correlation between TIMP1 expression and infiltration of macrophages (M0, M1, M2) and neutrophils, as well as the expression of immune checkpoint genes, including CTLA-4 and HAVCR2. Drug sensitivity analysis, conducted using the DepMap database, revealed that colorectal cancer cell lines exhibiting elevated levels of TIMP1 expression were more responsive to certain drugs, such as CC-90003, Pitavastatin, Atuveciclib, and CT7001, compared to those with low levels of TIMP1. Furthermore, TIMP1 expression was positively correlated with that of ferroptosis-related genes, such as GPX4 and HSPA5.Conclusion: TIMP1 can be used as a biomarker for colorectal cancer and is associated with the immunological microenvironment, drug sensitivity, and ferroptosis inhibition in this disease.
Identification of specific prognostic markers for lung squamous cell carcinoma based on tumor progression, immune infiltration, and stem index
Authors: Wu Rihan , Ma Ru , Duan Xiaojun , Zhang Jiandong , Li Kexin , Yu Lei , Zhang Mingyang , Liu Pengxia , Wang Changshan 
Published: September 2023

IntroductionLung squamous cell carcinoma (LUSC) is a unique subform of nonsmall cell lung cancer (NSCLC). The lack of specific driver genes as therapeutic targets leads to worse prognoses in patients with LUSC, even with chemotherapy, radiotherapy, or immune checkpoint inhibitors. Furthermore, research on the LUSC-specific prognosis genes is lacking. This study aimed to develop a comprehensive LUSC-specific differentially expressed genes (DEGs) signature for prognosis correlated with tumor progression, immune infiltration,and stem index.MethodsRNA sequencing data for LUSC and lung adenocarcinoma (LUAD) were extracted from The Cancer Genome Atlas (TCGA) data portal, and DEGs analyses were conducted in TCGA-LUSC and TCGA-LUAD cohorts to identify specific DEGs associated with LUSC. Functional analysis and protein–protein interaction network were performed to annotate the roles of LUSC-specific DEGs and select the top 100 LUSC-specific DEGs. Univariate Cox regression and least absolute shrinkage and selection operator regression analyses were performed to select prognosis-related DEGs.ResultsOverall, 1,604 LUSC-specific DEGs were obtained, and a validated seven-gene signature was constructed comprising FGG, C3, FGA, JUN, CST3, CPSF4, and HIST1H2BH. FGG, C3, FGA, JUN, and CST3 were correlated with poor LUSC prognosis, whereas CPSF4 and HIST1H2BH were potential positive prognosis markers in patients with LUSC. Receiver operating characteristic analysis further confirmed that the genetic profile could accurately estimate the overall survival of LUSC patients. Analysis of immune infiltration demonstrated that the high risk (HR) LUSC patients exhibited accelerated tumor infiltration, relative to low risk (LR) LUSC patients. Molecular expressions of immune checkpoint genes differed significantly between the HR and LR cohorts. A ceRNA network containing 19 lncRNAs, 50 miRNAs, and 7 prognostic DEGs was constructed to demonstrate the prognostic value of novel biomarkers of LUSC-specific DEGs based on tumor progression, stemindex, and immune infiltration. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index. In vitro experimental models confirmed that LUSC-specific DEG FGG expression was significantly higher in tumor cells and correlated with immune tumor progression, immune infiltration, and stem index.ConclusionOur study demonstrated the potential clinical implication of the 7- DEGs signature for prognosis prediction of LUSC patients based on tumor progression, immune infiltration, and stem index. And the FGG could be an independent prognostic biomarker of LUSC promoting cell proliferation, migration, invasion, THP-1 cell infiltration, and stem cell maintenance.
Cell-permeable peptide nucleic acid antisense oligonucleotide platform targeting human betacoronaviruses
Authors: Park Soree , Kim Seong Ho , Dezhbord Mehrangiz , Lee Eun-Hwi , Jeon Yeasel , Jung Daram , Gu Se Hun , Yu Chiho , Lee Seung Ho , Kim Sung Chun , Kim Kyun-Hwan 
Published: September 2023

IntroductionAntisense oligonucleotides (ASOs) with therapeutic potential have recently been reported to target the SARS-CoV-2 genome. Peptide nucleic acids (PNAs)-based ASOs have been regarded as promising drug candidates, but intracellular delivery has been a significant obstacle. Here, we present novel modified PNAs, termed OPNAs, with excellent cell permeability that disrupt the RNA genome of SARS-CoV-2 and HCoV-OC43 by introducing cationic lipid moiety onto the nucleobase of PNA oligomer backbone.MethodsHCT-8 cells and Caco-2 cells were treated with 1 μM antisense OPNAs at the time of viral challenge and the Viral RNA levels were measured by RT-qPCR three days post infection.ResultsNSP 14 targeting OPNA 5 and 11, reduced the viral titer to a half and OPNA 530, 531 and 533 lowered viral gene expression levels to less than 50% of control by targeting the 5’ UTR region. Several modifications (oligo size and position, etc.) were introduced to enhance the efficacy of selected OPNAs. Improved OPNAs exhibited a dose-dependent reduction in viral replication and nucleoprotein (NP) protein. When a mixture of oligomers was applied to infected cells, viral titer and NP levels decreased by more than eightfold.DiscussionIn this study, we have developed a modified PNA ASO platform with exceptional chemical stability, high binding affinity, and cellular permeability. These findings indicate that OPNAs are a promising platform for the development of antivirals to combat future pandemic viral infections that do not require a carrier.
Computer-assisted cognitive rehabilitation in neurological patients: state-of-art and future perspectives
Authors: Maggio Maria Grazia , De Bartolo Daniela , Calabrò Rocco Salvatore , Ciancarelli Irene , Cerasa Antonio , Tonin Paolo , Di Iulio Fulvia , Paolucci Stefano , Antonucci Gabriella , Morone Giovanni , Iosa Marco 
Published: September 2023

Background and aimAdvances in computing technology enabled researchers and clinicians to exploit technological devices for cognitive training and rehabilitation interventions. This expert review aims to describe the available software and device used for cognitive training or rehabilitation interventions of patients with neurological disorders.MethodsA scoping review was carried out to analyze commercial devices/software for computerized cognitive training (CCT) in terms of feasibility and efficacy in both clinical and home settings. Several cognitive domains responding to the different patients’ needs are covered.ResultsThis review showed that cognitive training for patients with neurological diseases is largely covered by several devices that are widely used and validated in the hospital setting but with few translations to remote/home applications. It has been demonstrated that technology and software-based devices are potential and valuable tools to administer remotely cognitive rehabilitation with accessible costs.ConclusionAccording to our results, CCT entails the possibility to continue cognitive training also in different settings, such as home, which is a significant breakthrough for the improvement of community care. Other possible areas of use should be the increase in the amount of cognitive therapy in the free time during the hospital stay.
Determinants of acute malnutrition among 6–59 months old children in public hospitals in Gambella town, Southwest Ethiopia: unmatched case-control study
Authors: Gesese Abreha Addis , Khot Luel Duoth 
Published: September 2023

BackgroundAcute malnutrition is a severe public health issue caused by poor nutrition over a short period of time. It is a powerful predictor of mortality. The Gambella region’s risk factors for acute malnutrition, however, are not well understood. Thus, the risk factors for acute malnutrition were identified in this study.MethodsA facility-based unmatched-case control study design was conducted in public hospitals in Gambella town from February 15 to March 30, 2019. A total of 85 cases and 170 controls were included in the study. According to the average monthly caseload, children between the ages of 6 and 59 months were distributed among the public hospitals. Then, cases and controls were chosen using a systematic random sampling technique. A standardized, previously tested questionnaire was used to collect the data. EPI-data version 3.1 was used to enter the data, which was subsequently exported to SPSS version 20 for analysis. Statistical significance was set at p 0.05 for the bivariate and multivariable logistic regressions that were employed.ResultsHousehold income of &lt;=1,500 birr [AOR = 2.46 at 95% CI (1.37–4.39)], being unemployed [AOR = 2.37 at 95% CI (1.34–4.20)], rural residence [AOR = 1.96 at 95% CI (1.10–3.51)], having diarrhea [AOR = 2.47, 95% CI (1.36–4.51)], fever [AOR = 2.05, 95% CI (1.03–4.10)], and pneumonia (AOR = 2.41), and exclusive breast feeding (AOR = 1.96, and exclusive breast feeding [AOR = 1.96, 95% CI (1.18–4.91)], and exclusive breast feeding (AOR = 1.96) minimum dietary diversity [AOR = 2.86, 95% CI (1.06–3.64)], minimum dietary diversity [AOR = 2.86, 95% CI (1.37–5.95)], weight measurement at birth [AOR = 0.86, 95% CI (0.08–0.93)], unplanned birth of the child [AOR = 1.97, 95% CI (1.02–3.78)], and non-immunized [AOR = 4.12, 95% CI (1.05–16.13)] were associated with acute malnutrition.ConclusionThis research identified multiple risk factors for acute malnutrition in children aged 6–59 months, suggesting health interventions, and programs at all levels of the system executed in an organized manner with substantial program ramifications.
Radiomics nomogram for prediction of glypican-3 positive hepatocellular carcinoma based on hepatobiliary phase imaging
Authors: Zhang Ning , Wu Minghui , Zhou Yiran , Yu Changjiang , Shi Dandan , Wang Cong , Gao Miaohui , Lv Yuanyuan , Zhu Shaocheng 
Published: September 2023

IntroductionThe hepatobiliary-specific phase can help in early detection of changes in lesion tissue density, internal structure, and microcirculatory perfusion at the microscopic level and has important clinical value in hepatocellular carcinoma (HCC). Therefore, this study aimed to construct a preoperative nomogram for predicting the positive expression of glypican-3 (GPC3) based on gadoxetic acid-enhanced (Gd-EOB-DTPA) MRI hepatobiliary phase (HBP) radiomics, imaging and clinical feature.MethodsWe retrospectively included 137 patients with HCC who underwent Gd-EOB-DTPA-enhanced MRI and subsequent liver resection or puncture biopsy at our hospital from January 2017 to December 2021 as training cohort. Subsequently collected from January 2022 to June 2023 as a validation cohort of 49 patients, Radiomic features were extracted from the entire tumor region during the HBP using 3D Slicer software and screened using a t-test and least absolute shrinkage selection operator algorithm (LASSO). Then, these features were used to construct a radiomics score (Radscore) for each patient, which was combined with clinical factors and imaging features of the HBP to construct a logistic regression model and subsequent nomogram model. The clinicoradiologic, radiomics and nomogram models performance was assessed by the area under the curve (AUC), calibration, and decision curve analysis (DCA). In the validation cohort,the nomogram performance was assessed by the area under the curve (AUC).ResultsIn the training cohort, a total of 1688 radiomics features were extracted from each patient. Next, radiomics with ICCs&lt;0.75 were excluded, 1587 features were judged as stable using intra- and inter-class correlation coefficients (ICCs), 26 features were subsequently screened using the t-test, and 11 radiomics features were finally screened using LASSO. The nomogram combining Radscore, age, serum alpha-fetoprotein (AFP) &gt;400ng/mL, and non-smooth tumor margin (AUC=0.888, sensitivity 77.7%, specificity 91.2%) was superior to the radiomics (AUC=0.822, sensitivity 81.6%, specificity 70.6%) and clinicoradiologic (AUC=0.746, sensitivity 76.7%, specificity 64.7%) models, with good consistency in calibration curves. DCA also showed that the nomogram had the highest net clinical benefit for predicting GPC3 expression.In the validation cohort, the ROC curve results showed predicted GPC3-positive expression nomogram model AUC, sensitivity, and specificity of 0.800, 58.5%, and 100.0%, respectively.ConclusionHBP radiomics features are closely associated with GPC3-positive expression, and combined clinicoradiologic factors and radiomics features nomogram may provide an effective way to non-invasively and individually screen patients with GPC3-positive HCC.
Isolation and characterization of ZK002, a novel dual function snake venom protein from Deinagkistrodon acutus with anti-angiogenic and anti-inflammatory properties
Authors: Chan Brandon Dow , Wong Wing-Yan , Lee Magnolia Muk-Lan , Yue Patrick Ying-Kit , Dai Xiangrong , Tsim Karl Wah-Keung , Hsiao Wen-Luan Wendy , Li Mandy , Li Xiao-Yi , Tai William Chi-Shing 
Published: September 2023

Introduction: Pathological angiogenesis, the abnormal or excessive generation of blood vessels, plays an important role in many diseases including cancer, diabetic retinopathy, psoriasis, and arthritis. Additionally, increasing evidence supports the close linkage between angiogenesis and inflammation. Snake venoms are a rich natural source of biologically active molecules and carry rich potential for the discovery of anti-angiogenic and anti-inflammatory modulators.Methods: Here, we isolated and purified a novel protein, ZK002, from the venom of the snake Deinagkistrodon acutus, and investigated its anti-angiogenic and anti-inflammatory activities and mechanisms.Results: ZK002 was identified as a 30 kDa heterodimeric protein of α and β chains, which exhibited anti-angiogenic activity in various in vitro assays. Mechanistically, ZK002 inhibited activation of VEGF signaling and related mediators including eNOS, p38, LIMK, and HSP27. ZK002 also upregulated the metalloproteinase inhibitor TIMP3 and inhibited components of the VEGF-induced signaling cascade, PPP3R2 and SH2D2A. The anti-angiogenic activity of ZK002 was confirmed in multiple in vivo models. ZK002 could also inhibit the in vitro expression of pro-inflammatory cytokines, as well as in vivo inflammation in the carrageenin-induced edema rat model.Conclusion: Our findings highlight the potential for further development of ZK002 as a dual function therapeutic against diseases with involvement of pathogenic angiogenesis and chronic inflammation.
Heat hardening enhances metabolite-driven thermoprotection in the Mediterranean mussel Mytilus galloprovincialis
Authors: Georgoulis Ioannis , Bock Christian , Lannig Gisela , Pörtner Hans O. , Sokolova Inna M. , Feidantsis Konstantinos , Giantsis Ioannis A. , Michaelidis Basile 
Published: September 2023

Introduction: Temperature affects organisms’ metabolism and ecological performance. Owing to climate change, sea warming constituting a severe source of environmental stress for marine organisms, since it increases at alarming rates. Rapid warming can exceed resilience of marine organisms leading to fitness loss and mortality. However, organisms can improve their thermal tolerance when briefly exposed to sublethal thermal stress (heat hardening), thus generating heat tolerant phenotypes.Methods: We investigated the “stress memory” effect caused by heat hardening on M. galloprovincialis metabolite profile of in order to identify the underlying biochemical mechanisms, which enhance mussels’ thermal tolerance.Results: The heat hardening led to accumulation of amino acids (e.g., leucine, isoleucine and valine), including osmolytes and cytoprotective agents with antioxidant and anti-inflammatory properties that can contribute to thermal protection of the mussels. Moreover, proteolysis was inhibited and protein turnover regulated by the heat hardening. Heat stress alters the metabolic profile of heat stressed mussels, benefiting the heat-hardened individuals in increasing their heat tolerance compared to the non-heat-hardened ones.Discussion: These findings provide new insights in the metabolic mechanisms that may reinforce mussels’ tolerance against thermal stress providing both natural protection and potential manipulative tools (e.g., in aquaculture) against the devastating climate change effects on marine organisms.
The mediating roles of workplace support and ethical work environment in associations between leadership and moral distress: a longitudinal study of Canadian health care workers during the COVID-19 pandemic
Authors: Plouffe Rachel A. , Nazarov Anthony , Heesters Ann M. , Dickey Chandlee C. , Foxcroft Laura , Hosseiny Fardous , Le Tri , Lum P. Andrea , Nouri Maede S. , Smith Patrick , Richardson J. Don 
Published: September 2023

IntroductionThe COVID-19 pandemic has resulted in heightened moral distress among health care workers (HCWs) worldwide. Past research has shown that effective leadership may mitigate potential for the development of moral distress. However, no research to date has considered the mechanisms by which leadership might have an influence on moral distress. We sought to evaluate longitudinally whether Canadian HCWs’ perceptions of workplace support and ethical work environment would mediate associations between leadership and moral distress.MethodsA total of 239 French- and English-speaking Canadian HCWs employed during the COVID-19 pandemic were recruited to participate in a longitudinal online survey. Participants completed measures of organizational and supervisory leadership at baseline and follow-up assessments of workplace support, perceptions of an ethical work environment, and moral distress.ResultsAssociations between both organizational and supervisory leadership and moral distress were fully mediated by workplace supports and perceptions of an ethical work environment.DiscussionTo ensure HCW well-being and quality of care, it is important to ensure that HCWs are provided with adequate workplace supports, including manageable work hours, social support, and recognition for efforts, as well as an ethical workplace environment.