bluuebunny/crossref_metadata_2025_split huggingface dataset:
Who to escalate during a pandemic? A retrospective observational study about decision-making during the COVID-19 pandemic in the UK
Authors: Beresford Stephanie , Tandon Aditi , Farina Sofia , Johnston Brian , Crews Maryam , Welters Ingeborg Dorothea 
Published: June 2023

BackgroundOptimal decision-making regarding who to admit to critical care in pandemic situations remains unclear. We compared age, Clinical Frailty Score (CFS), 4C Mortality Score and hospital mortality in two separate COVID-19 surges based on the escalation decision made by the treating physician.MethodsA retrospective analysis of all referrals to critical care during the first COVID-19 surge (cohort 1, March/April 2020) and a late surge (cohort 2, October/November 2021) was undertaken. Patients with confirmed or high clinical suspicion of COVID-19 infection were included. A senior critical care physician assessed all patients regarding their suitability for potential intensive care unit admission. Demographics, CFS, 4C Mortality Score and hospital mortality were compared depending on the escalation decision made by the attending physician.Results203 patients were included in the study, 139 in cohort 1 and 64 in cohort 2. There were no significant differences in age, CFS and 4C scores between the two cohorts. Patients deemed suitable for escalation by clinicians were significantly younger with significantly lower CFS and 4C scores compared with patients who were not deemed to benefit from escalation. This pattern was observed in both cohorts. Mortality in patients not deemed suitable for escalation was 61.8% in cohort 1 and 47.4% in cohort 2 (p<0.001).ConclusionsDecisions who to escalate to critical care in settings with limited resources pose moral distress on clinicians. 4C score, age and CFS did not change significantly between the two surges but differed significantly between patients deemed suitable for escalation and those deemed unsuitable by clinicians. Risk prediction tools may be useful in a pandemic to supplement clinical decision-making, even though escalation thresholds require adjustments to reflect changes in risk profile and outcomes between different pandemic surges.
Prevalence and risk factors for silicosis among a large cohort of stone benchtop industry workers
Authors: Hoy Ryan F , Dimitriadis Christina , Abramson Michael , Glass Deborah C , Gwini StellaMay , Hore-Lacy Fiona , Jimenez-Martin Javier , Walker-Bone Karen , Sim Malcolm R 
Published: June 2023

ObjectivesHigh silica content artificial stone has been found to be associated with silicosis among stone benchtop industry (SBI) workers. The objectives of this study were to determine the prevalence of and risk factors for silicosis among a large cohort of screened SBI workers, and determine the reliability of respiratory function testing (RFT) and chest x-ray (CXR) as screening tests in this industry.MethodsSubjects were recruited from a health screening programme available to all SBI workers in Victoria, Australia. Workers undertook primary screening, including an International Labour Office (ILO) classified CXR, and subject to prespecified criteria, also underwent secondary screening including high-resolution CT (HRCT) chest and respiratory physician assessment.ResultsAmong 544 SBI workers screened, 95% worked with artificial stone and 86.2% were exposed to dry processing of stone. Seventy-six per cent (414) required secondary screening, among whom 117 (28.2%) were diagnosed with silicosis (median age at diagnosis 42.1 years (IQR 34.8–49.7)), and all were male. In secondary screening, silicosis was associated with longer SBI career duration (12 vs 8 years), older age, lower body mass index and smoking. In those with silicosis, forced vital capacity was below the lower limit of normal in only 14% and diffusion capacity for carbon monoxide in 13%. Thirty-six (39.6%) of those with simple silicosis on chest HRCT had an ILO category 0 CXR.ConclusionScreening this large cohort of SBI workers identified exposure to dry processing of stone was common and the prevalence of silicosis was high. Compared with HRCT chest, CXR and RFTs had limited value in screening this high-risk population.
The Volterra cliff in the mind of philosophers, savants and geologists (1282–1830)
Authors: Dominici Stefano 
Published: June 2023

Abstract
The Pliocene fossiliferous succession of the Volterra hill, a prominent place in Tuscany, Italy and, since the Renaissance, the site of important archaeological finds of the ancient Etruscan civilization, has formed the object of enquiry over six centuries of research on the inner nature of the Earth system. The works of Restoro d'Arezzo, Leonardo da Vinci, Nicolaus Steno, Giovanni Targioni, Nicolas Desmarest, Giambattista Brocchi, Alexandre Brongniart and Charles Lyell testify to the early recognition through fieldwork that those strata with seashells had formed at the bottom of the sea. This interpretation served different approaches to knowledge. Restoro, Leonardo and Steno, spanning nearly four centuries in the history of science (1282–1669), including the ‘Copernican Revolution’ and the start of the Modern Age, relied also on textual sources and trusted a speculative model of the Earth's interior, so that at Volterra they focused on vertical movements of the earth–water system. The authors of the eighteenth and nineteenth centuries abandoned pre-built young-Earth models and emphasized the geography of ancient Tuscany. Brocchi, Brongniart and Lyell promoted the taxonomic use of seashells to correlate rocks across Europe. This place deserves higher standards of valorization to promote understanding of the history and sociology of ideas.
Hypoxia-Responsive lncRNA AC115619 Encodes a Micropeptide That Suppresses m6A Modifications and Hepatocellular Carcinoma Progression
Authors: Zhang Qiangnu , Wei Teng , Yan Lesen , Zhu Siqi , Jin Wen , Bai Yu , Zeng Yuandi , Zhang XiaoFei , Yin Zexin , Yang Jilin , Zhang Wenjian , Wu Meilong , Zhang Yusen , Liu Liping 
Published: June 2023

Abstract

Long noncoding RNAs (lncRNA) regulate a number of aspects of cancer biology. Recent research has shown that lncRNAs can encode micropeptides that mediate their functions in tumors. Here, we revealed that the liver-specific putative lncRNA, AC115619, is expressed at low levels in hepatocellular carcinoma (HCC) and encodes a micropeptide, designated as AC115619–22aa. AC115619 played a crucial role in the regulation of tumor progression and was a prognostic indicator in HCC. The encoded micropeptide AC115619–22aa inhibited the progression of HCC by binding to WTAP and impeding the assembly of the N6-methyladenosine (m6A) methyltransferase complex, which regulates the expression of tumor-associated genes, such as SOCS2 and ATG14. AC115619 was cotranscribed with the adjacent upstream coding gene APOB, and hypoxia induced transcriptional repression of both APOB and AC115619 by controlling HIF1A/HDAC3 and HNF4A signaling. In animal and patient-derived models, AC115619–22aa reduced global m6A levels and suppressed tumor growth. In conclusion, this study establishes AC115619 and its encoded micropeptide as potential prognostic markers and therapeutic targets for patients with HCC.

Significance:
A micropeptide encoded by lncRNA AC115619 impedes formation of the m6A methylation complex to lower m6A levels and reduce the growth of hepatocellular carcinoma.
Bavituximab Decreases Immunosuppressive Myeloid-Derived Suppressor Cells in Newly Diagnosed Glioblastoma Patients
Authors: Ly K. Ina , Richardson Leland G. , Liu Mofei , Muzikansky Alona , Cardona Jonathan , Lou Kevin , Beers Andrew L. , Chang Ken , Brown James M. , Ma Xiaoyue , Reardon David A. , Arrillaga-Romany Isabel C. , Forst Deborah A. , Jordan Justin T. , Lee Eudocia Q. , Dietrich Jorg , Nayak Lakshmi , Wen Patrick Y. , Chukwueke Ugonma , Giobbie-Hurder Anita , Choi Bryan D. , Batchelor Tracy T. , Kalpathy-Cramer Jayashree , Curry William T. , Gerstner Elizabeth R. 
Published: June 2023

Abstract

Purpose:
We evaluated the efficacy of bavituximab—a mAb with anti-angiogenic and immunomodulatory properties—in newly diagnosed patients with glioblastoma (GBM) who also received radiotherapy and temozolomide. Perfusion MRI and myeloid-related gene transcription and inflammatory infiltrates in pre-and post-treatment tumor specimens were studied to evaluate on-target effects (NCT03139916).

Patients and Methods:
Thirty-three adults with IDH--wild-type GBM received 6 weeks of concurrent chemoradiotherapy, followed by 6 cycles of temozolomide (C1-C6). Bavituximab was given weekly, starting week 1 of chemoradiotherapy, for at least 18 weeks. The primary endpoint was proportion of patients alive at 12 months (OS-12). The null hypothesis would be rejected if OS-12 was ≥72%. Relative cerebral blood flow (rCBF) and vascular permeability (Ktrans) were calculated from perfusion MRIs. Peripheral blood mononuclear cells and tumor tissue were analyzed pre-treatment and at disease progression using RNA transcriptomics and multispectral immunofluorescence for myeloid-derived suppressor cells (MDSC) and macrophages.

Results:
The study met its primary endpoint with an OS-12 of 73% (95% confidence interval, 59%–90%). Decreased pre-C1 rCBF (HR, 4.63; P = 0.029) and increased pre-C1 Ktrans were associated with improved overall survival (HR, 0.09; P = 0.005). Pre-treatment overexpression of myeloid-related genes in tumor tissue was associated with longer survival. Post-treatment tumor specimens contained fewer immunosuppressive MDSCs (P = 0.01).

Conclusions:
Bavituximab has activity in newly diagnosed GBM and resulted in on-target depletion of intratumoral immunosuppressive MDSCs. Elevated pre-treatment expression of myeloid-related transcripts in GBM may predict response to bavituximab.
Activin A–Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer
Authors: Pich-Bavastro Christine , Yerly Laura , Di Domizio Jeremy , Tissot-Renaud Stéphanie , Gilliet Michel , Kuonen François 
Published: June 2023

Abstract

Purpose:
Cemiplimab is approved for the treatment of locally advanced basal cell carcinomas (BCC), although with mitigated results. We sought to interrogate the cellular and molecular transcriptional reprogramming underlying BCC resistance to immunotherapy.

Experimental Design:
Here, we combined spatial and single-cell transcriptomics to deconvolute the spatial heterogeneity of the tumor microenvironment in regard with response to immunotherapy, in a cohort of both naïve and resistant BCCs.

Results:
We identified subsets of intermingled cancer-associated fibroblasts (CAF) and macrophages contributing the most to CD8 T-cell exclusion and immunosuppression. Within this spatially resolved peritumoral immunosuppressive niche, CAFs and adjacent macrophages were found to display Activin A–mediated transcriptional reprogramming towards extracellular matrix remodeling, suggesting active participation to CD8 T-cell exclusion. In independent datasets of human skin cancers, Activin A–conditioned CAFs and macrophages were associated with resistance to immune checkpoint inhibitors (ICI).

Conclusions:
Altogether, our data identify the cellular and molecular plasticity of tumor microenvironment (TME) and the pivotal role of Activin A in polarizing the TME towards immune suppression and ICI resistance.
Continuous Administration of Anti-VEGFA Antibody Upregulates PAI-1 Secretion from Ovarian Cancer Cells via miR-143-3p Downregulation
Authors: Yagi Taro , Sawada Kenjiro , Miyamoto Mayuko , Shimizu Aasa , Oi Yukako , Toda Aska , Nakamura Koji , Kinose Yasuto , Kodama Michiko , Hashimoto Kae , Kimura Tadashi 
Published: June 2023

Abstract

Although bevacizumab (BEV) plays a key role in ovarian cancer treatment, BEV resistance is often observed in clinical settings. This study aimed to identify the genes responsible for BEV resistance. C57BL/6 mice inoculated with ID-8 murine ovarian cancer cells were treated with anti-VEGFA antibody or IgG (control) twice weekly for 4 weeks. The mice were sacrificed, then, RNA was extracted from the disseminated tumors. qRT-PCR assays were performed to identify angiogenesis-related genes and miRNAs that were altered by anti-VEGFA treatment. SERPINE1/PAI-1 was found to be upregulated during BEV treatment. Therefore, we focused on miRNAs to elucidate the mechanism underlying the upregulation of PAI-1 during BEV treatment. Kaplan–Meier plotter analysis revealed that higher expression levels of SERPINE1/PAI-1 were associated with poor prognoses among BEV-treated patients, suggesting that SERPINE1/PAI may be involved in the acquisition of BEV resistance. miRNA microarray analysis followed by in silico and functional assays revealed that miR-143-3p targeted SERPINE1 and negatively regulated PAI-1 expression. The transfection of miR-143-3p suppressed PAI-1 secretion from ovarian cancer cells and inhibited in vitro angiogenesis in HUVECs. Next, miR-143-3p-overexpressing ES2 cells were intraperitoneally injected into BALB/c nude mice. ES2-miR-143-3p cells downregulated PAI-1 production, attenuated angiogenesis, and significantly inhibited intraperitoneal tumor growth following treatment with anti-VEGFA antibody. Continuous anti-VEGFA treatment downregulated miR-143-3p expression, which upregulated PAI-1 and activated an alternative angiogenic pathway in ovarian cancer. In conclusion, the substitution of this miRNA during BEV treatment may help overcome BEV resistance, and this may be used as a novel treatment strategy in clinical settings.

Implications:
Continuous administration of VEGFA antibody upregulates SERPINE1/PAI-1 expression via the downregulation of miR-143-3p, which contributes to acquiring bevacizumab resistance in ovarian cancer.
Picturing the Snakes
Authors: Bhaumik Rahul 
Published: June 2023

Abstract
This paper explores the ways in which Indian snakes were represented through natural history paintings along with textual taxonomic descriptions—a principal means of modern “exploratory experimentation” in early British India. It specifically examines Patrick Russell’s scientific engagement with the subcontinental snakes (a “new” branch of natural history of snakes fashioned by him) and the nature of “local” involvements in his undertaking. While considering the crucial role of colonial natural history in knowing and making visible the “terror” of Indian snakes to manage the snakebite-laden landscape, this paper elucidates how both the Western inferiorisation of non-Western perspective and the non-European indifference towards the European planetary vision disrupted the heterogeneous network of “knowledge making” in late eighteenth-century British India. Thus, this paper questions the recent historiography that projected a seamless “collaboration” or “hybridisation” in the formation of scientific knowledge across the globalised space of empire.
A study of optical properties of copper sulphate pentahydrate doped IOTA-carrageenan polymer electrolytes
Authors: Saranya P. , Vanitha D. , Sundaramahalingam K. , Nandhinilakshmi M. 
Published: June 2023

Biodegradable polymer films composed of Iota-Carrageenan and Copper Sulphate Pentahydrate (CuSO4.5H2O) were prepared by using the Solution Casting process. To investigate the optical property, different wt.% of CuSO4.5H2O were added to I-carrageenan polymer films. X-Ray diffraction analysis was used to study the structural properties of prepared electrolytes. FTIR study revealed the complexation between the polymer and the salt. The increase in the amorphous nature of the film by the addition of the salt was confirmed using an X-Ray Diffraction (XRD) pattern. The functional group and interaction between the different components present in the polymer film are observed from Fourier Transform Infrared (FTIR) analysis, implying that the addition of (CuSO4.5H2O) salt causes microstructural differences in the polymer film. The UV-Visible Spectrometer was used to record the optical properties like the absorption coefficient, extinction coefficient, and optical bandgap energy of the polymer blend electrolytes. From this, it was observed that the absorption value was increased with the addition of salt. The optical band gap was also recorded and it was observed that 20 wt.% of CuSO4.5H2O added film was found to have a higher energy gap (4.3 eV) compared with the other.
Clinical Application of Thromboelastography in Patients With Severe Fever With Thrombocytopenia Syndrome
Authors: Li Yingbo , An Changjuan , Xue Peng , Ni Lina , Yu Xia , Qu Jiangli , Yao Yingjie , Yu Chengyong 
Published: June 2023

Aim To investigate the clinical application of thromboelastography (TEG) in severe fever with thrombocytopenia syndrome (SFTS). Methods One hundred and fifty-seven patients with SFTS were included in the study. The participants were distributed into 3 groups; A, B, and C. And 103 patients in group A met the clinical criteria as they exhibited slight liver and kidney dysfunction. Group B consisted of 54 patients with SFTS who were critically ill while group C was a healthy control group with 58 participants. Results Patients with SFTS exhibited lower coagulation than the healthy participants. Group B patients exhibited significantly lower coagulation compared to group A. There was no significant difference in platelet count and fibrinogen content between patients in group A and group B, but platelet aggregation function and fibrinogen activity were significantly lower in group B patients. Conclusion Our results suggest that it is risky to solely rely on platelet count and the fibrinogen in SFTS. Monitoring of TEG and other coagulation indexes should be emphasized.
Multi-omics Pathways Workflow (MOPAW): An Automated Multi-omics Workflow on the Cancer Genomics Cloud
Authors: Nguyen Trinh , Bian Xiaopeng , Roberson David , Khanna Rakesh , Chen Qingrong , Yan Chunhua , Beck Rowan , Worman Zelia , Meerzaman Daoud 
Published: June 2023

Introduction: In the era of big data, gene-set pathway analyses derived from multi-omics are exceptionally powerful. When preparing and analyzing high-dimensional multi-omics data, the installation process and programing skills required to use existing tools can be challenging. This is especially the case for those who are not familiar with coding. In addition, implementation with high performance computing solutions is required to run these tools efficiently. Methods: We introduce an automatic multi-omics pathway workflow, a point and click graphical user interface to Multivariate Single Sample Gene Set Analysis (MOGSA), hosted on the Cancer Genomics Cloud by Seven Bridges Genomics. This workflow leverages the combination of different tools to perform data preparation for each given data types, dimensionality reduction, and MOGSA pathway analysis. The Omics data includes copy number alteration, transcriptomics data, proteomics and phosphoproteomics data. We have also provided an additional workflow to help with downloading data from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium and preprocessing these data to be used for this multi-omics pathway workflow. Results: The main outputs of this workflow are the distinct pathways for subgroups of interest provided by users, which are displayed in heatmaps if identified. In addition to this, graphs and tables are provided to users for reviewing. Conclusion: Multi-omics Pathway Workflow requires no coding experience. Users can bring their own data or download and preprocess public datasets from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium using our additional workflow based on the samples of interest. Distinct overactivated or deactivated pathways for groups of interest can be found. This useful information is important in effective therapeutic targeting.
Digitalization, stress, and social worker–client relationships during the COVID-19 pandemic
Authors: Nordesjö Kettil , Scaramuzzino Gabriella 
Published: June 2023

Summary The COVID-19 pandemic has dramatically changed the possibilities for people to interact and communicate. This article examines Swedish social workers’ experiences of the extent to which the COVID-19 pandemic has affected the use of digital tools in their work, and whether this use has affected the social worker–client relationship and their stress levels. The article draws on a web survey (N  =  541) via a quantitative analysis of responses and a qualitative analysis of answers to an open-ended question. Findings Most respondents agreed on experiencing increased use of digital tools in the relationship with the clients, increased skills in using digital tools, and a more positive view of digital tools in the social worker–client relationship. However, experiences on whether stress levels had increased and the relationship with the clients worsened, were divided. Age correlates positively with increased stress levels, and social workers working with social assistance, as well as women, are more likely to agree on that the relationship with the clients has worsened. Responses from open-ended questions highlight a rapid shift where social workers have gained a more positive view of digital tools, that video meetings can increase efficiency and flexibility, but also work environment problems. Applications This article contributes with useful insights into how the use of digital tools during the COVID-19 pandemic has changed and affected stress and the social worker–client relationship. It can support discussions on the future implementation of digital tools in social work after the pandemic.