bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-derived xenograft models capture genomic heterogeneity in endometrial cancer
Authors: Bonazzi Vanessa F. , Kondrashova Olga , Smith Deborah , Nones Katia , Sengal Asmerom T. , Ju Robert , Packer Leisl M. , Koufariotis Lambros T. , Kazakoff Stephen H. , Davidson Aimee L. , Ramarao-Milne Priya , Lakis Vanessa , Newell Felicity , Rogers Rebecca , Davies Claire , Nicklin James , Garrett Andrea , Chetty Naven , Perrin Lewis , Pearson John V. , Patch Ann-Marie , Waddell Nicola , Pollock Pamela M. 
Published: January 2022

Abstract
Background
Endometrial cancer (EC) is a major gynecological cancer with increasing incidence. It comprises four molecular subtypes with differing etiology, prognoses, and responses to chemotherapy. In the future, clinical trials testing new single agents or combination therapies will be targeted to the molecular subtype most likely to respond. As pre-clinical models that faithfully represent the molecular subtypes of EC are urgently needed, we sought to develop and characterize a panel of novel EC patient-derived xenograft (PDX) models.

Methods
Here, we report whole exome or whole genome sequencing of 11 PDX models and their matched primary tumor. Analysis of multiple PDX lineages and passages was performed to study tumor heterogeneity across lineages and/or passages. Based on recent reports of frequent defects in the homologous recombination (HR) pathway in EC, we assessed mutational signatures and HR deficiency scores and correlated these with in vivo responses to the PARP inhibitor (PARPi) talazoparib in six PDXs representing the copy number high/p53-mutant and mismatch-repair deficient molecular subtypes of EC.

Results
PDX models were successfully generated from grade 2/3 tumors, including three uterine carcinosarcomas. The models showed similar histomorphology to the primary tumors and represented all four molecular subtypes of EC, including five mismatch-repair deficient models. The different PDX lineages showed a wide range of inter-tumor and intra-tumor heterogeneity. However, for most PDX models, one arm recapitulated the molecular landscape of the primary tumor without major genomic drift. An in vivo response to talazoparib was detected in four copy number high models. Two models (carcinosarcomas) showed a response consistent with stable disease and two models (one copy number high serous EC and another carcinosarcoma) showed significant tumor growth inhibition, albeit one consistent with progressive disease; however, all lacked the HR deficiency genomic signature.

Conclusions
EC PDX models represent the four molecular subtypes of disease and can capture intra-tumor heterogeneity of the original primary tumor. PDXs of the copy number high molecular subtype showed sensitivity to PARPi; however, deeper and more durable responses will likely require combination of PARPi with other agents.
Impact of lung function decline on time to hospitalisation events in systemic sclerosis-associated interstitial lung disease (SSc-ILD): a joint model analysis
Authors: Kreuter Michael , Del Galdo Francesco , Miede Corinna , Khanna Dinesh , Wuyts Wim A. , Hummers Laura K. , Alves Margarida , Schoof Nils , Stock Christian , Allanore Yannick 
Published: January 2022

Abstract
Background
Interstitial lung disease (ILD) is a common organ manifestation in systemic sclerosis (SSc) and is the leading cause of death in patients with SSc. A decline in forced vital capacity (FVC) is an indicator of ILD progression and is associated with mortality in patients with SSc-associated ILD (SSc-ILD). However, the relationship between FVC decline and hospitalisation events in patients with SSc-ILD is largely unknown. The objective of this post hoc analysis was to investigate the relationship between FVC decline and clinically important hospitalisation endpoints.

Methods
We used data from SENSCIS®, a phase III trial investigating the efficacy and safety of nintedanib in patients with SSc-ILD. Joint models for longitudinal and time-to-event data were used to assess the association between rate of decline in FVC% predicted and hospitalisation-related endpoints (including time to first all-cause hospitalisation or death; time to first SSc-related hospitalisation or death; and time to first admission to an emergency room [ER] or admission to hospital followed by admission to intensive care unit [ICU] or death) during the treatment period, over 52 weeks in patients with SSc-ILD.

Results
There was a statistically significant association between FVC decline and the risk of all-cause (n = 78) and SSc-related (n = 42) hospitalisations or death (both P < 0.0001). A decrease of 3% in FVC corresponded to a 1.43-fold increase in risk of all-cause hospitalisation or death (95% confidence interval [CI] 1.24, 1.65) and a 1.48-fold increase in risk of SSc-related hospitalisation or death (95% CI 1.23, 1.77). No statistically significant association was observed between FVC decline and admission to ER or to hospital followed by admission to ICU or death (n = 75; P = 0.15). The estimated slope difference for nintedanib versus placebo in the longitudinal sub-model was consistent with the primary analysis in SENSCIS®.

Conclusions
The association of lung function decline with an increased risk of hospitalisation suggests that slowing FVC decline in patients with SSc-ILD may prevent hospitalisations. Our findings also provide evidence that FVC decline may serve as a surrogate endpoint for clinically relevant hospitalisation-associated endpoints.

Trial registration
ClinicalTrials.govNCT02597933. Registered on 8 October 2015.
Inter-rater reliability of optic nerve sheath diameter measurement using real-time ultrasonography
Authors: Jennings Jason B. , Oliva Cynthia , Joyce Michael , Vitto Michael J. , Tozer Jordan , Taylor Lindsay A. , Evans David P. 
Published: January 2022

Abstract
Objectives
Ultrasound measurement of the optic nerve sheath diameter (ONSD) is a rapid, non-invasive means to indirectly assess intracranial pressure. Previous research has demonstrated the ability of emergency physicians to measure ONSD accurately with bedside ultrasound when compared to CT scan or MRI, however the reliability of this measurement between two or more operators has been called into question (Hassen et al. in J Emerg Med 48:450–457, 2015; Shirodkar et al. in Ind J Crit Care Med 19:466–470, 2015). Given the need for accurate and precise measurement to use this as a screening exam, we sought to determine the inter-rater reliability between ONSD measurements obtained in real time by fellowship-trained emergency ultrasound physicians.

Methods
Three ultrasound fellowship-trained emergency physicians measured bilateral ONSD of 10 healthy volunteers using a high-frequency linear transducer. The physicians were blinded to the other scanners’ measurements, and no instructions were given other than to obtain the ONSD. Each sonographer measured the ONSD in real time and it was recorded by a research coordinator. All measurements were recorded in millimeters. Intraclass correlation coefficients (ICCs) were calculated to estimate the inter-rater reliability.

Results
A total of 60 measurements of ONSD were obtained. The average measurement was 4.3 mm (3.83–4.77). Very little variation was found between the three physicians, with a calculated ICC of 0.82 (95% confidence interval 0.63–0.92).

Conclusions
ONSD measurement obtained by ultrasound fellowship-trained emergency medicine physicians is a reliable measurement with a high degree of correlation between scanners.
Contemporary (2019) prevalence of cardiovascular disease in adults with type 2 diabetes in Brazil: the cross-sectional CAPTURE study
Authors: Vencio Sérgio , Vianna André Gustavo Daher , da Silva Mariana Arruda Camara Ferreira , Precoma Dalton Bertolim 
Published: January 2022

Abstract
Background
Type 2 diabetes (T2D) is a known risk factor for cardiovascular disease (CVD), and CVD is a major cause of mortality in patients with T2D. The CAPTURE study investigated the contemporary (2019) prevalence of established CVD in adults with T2D around the world. We report the findings from Brazil.

Methods
The multinational, non-interventional, cross-sectional CAPTURE study was conducted across 13 countries from five continents. The current manuscript explores data for the CAPTURE study sample in Brazil. Standardized demographic and clinical data were collected from adults with T2D aged ≥ 18 years attending a single routine healthcare visit in primary or specialized care between December 2018 and September 2019. Data were analyzed descriptively.

Results
Data from 912 adults with T2D were collected in the CAPTURE study in Brazil, with 822 patients from primary care and 90 patients from specialized care. Median (interquartile range [IQR]) patient characteristics were as follows: age 64 years (57; 71), diabetes duration 11 years (6; 19), glycated hemoglobin 7.7% (6.7; 9.1), and body mass index 29.5 kg/m2 (26.4; 33.5); 59% were female. The CVD prevalence and atherosclerotic CVD prevalence in the Brazil sample were 43.9% (95% confidence interval [CI] 40.9; 46.8) and 37.6% (95% CI 34.7; 40.5), respectively. The majority of patients with CVD had atherosclerotic CVD (85.8%). For the specific CVD subtypes, coronary heart disease prevalence was 27.9% (95% CI 25.2; 30.5), heart failure was 12.4% (95% CI 10.4; 14.4), cerebrovascular disease was 8.7% (95% CI 6.8; 10.5), and carotid artery disease was 3.4% (95% CI 2.3; 4.5). Glucagon-like peptide-1 receptor agonists and/or sodium-glucose co-transporter-2 inhibitors with proven cardiovascular benefit were prescribed to 15.5% of patients with CVD, compared with 18.4% of patients without CVD.

Conclusions
CAPTURE was the first multinational, standardized study to provide contemporary data on CVD prevalence in adults with T2D in Brazil, and it demonstrated that almost one in two adults with T2D had established CVD. Except for carotid artery disease, the prevalence of all CVD subtypes in adults with T2D in Brazil appeared higher than the global CAPTURE prevalence.
Trial registration NCT03786406, NCT03811288
Development and characterization of microsatellite markers for the French endemic Angelica heterocarpa (Apiaceae) and congeneric sympatric species
Authors: Revardel Emmanuelle , Lepais Olivier 
Published: January 2022

Abstract
Objective
Angelica heterocarpa (Apiaceae) is a wild endemic French species with special conservation interest in the European Union. It belongs to Angelica complex genus which is widespread throughout the north temperate zone, and is sympatric with other congeneric species. The objective of this work is to develop and characterize microsatellite markers as a new tool for understanding the ecology and evolution of Angelica species complex.

Results
We identified simple sequence repeat (SSR) regions in a microsatellite‐enriched library from A. heterocarpa and A. sylvestris. All 16 selected SSR regions were found to amplify in these species and were highly polymorphic. Marker transferability was validated in A. razulii and A. archangelica. These markers will help us to better understand the evolutionary dynamic between rare endemics and widespread sister species, and be useful for conservation of the endemic species. Moreover, they can provide new tools for studying the numerous traditional medicinal herbs of the Angelica genus.
UM171A-induced ROS promote antigen cross-presentation of immunogenic peptides by bone marrow-derived mesenchymal stromal cells
Authors: Salame Natasha , Bikorimana Jean-Pierre , El-Hachem Nehme , Saad Wael , Kurdi Mazen , Zhao Jing , Eliopoulos Nicoletta , Shammaa Riam , Rafei Moutih 
Published: January 2022

Abstract
Background
Mesenchymal stromal cells (MSCs) have been extensively used in the clinic due to their exquisite tissue repair capacity. However, they also hold promise in the field of cellular vaccination as they can behave as conditional antigen presenting cells in response to interferon (IFN)-gamma treatment under a specific treatment regimen. This suggests that the immune function of MSCs can be pharmacologically modulated. Given the capacity of the agonist pyrimido-indole derivative UM171a to trigger the expression of various antigen presentation-related genes in human hematopoietic progenitor cells, we explored the potential use of UM171a as a means to pharmacologically instill and/or promote antigen presentation by MSCs.

Methods
Besides completing a series of flow-cytometry-based phenotypic analyses, several functional antigen presentation assays were conducted using the SIINFEKL-specific T-cell clone B3Z. Anti-oxidants and electron transport chain inhibitors were also used to decipher UM171a’s mode of action in MSCs. Finally, the potency of UM171a-treated MSCs was evaluated in the context of therapeutic vaccination using immunocompetent C57BL/6 mice with pre-established syngeneic EG.7T-cell lymphoma.

Results
Treatment of MSCs with UM171a triggered potent increase in H2-Kb cell surface levels along with the acquisition of antigen cross-presentation abilities. Mechanistically, such effects occurred in response to UM171a-mediated production of mitochondrial-derived reactive oxygen species as their neutralization using anti-oxidants or Antimycin-A mitigated MSCs’ ability to cross-present antigens. Processing and presentation of the immunogenic ovalbumin-derived SIINFEKL peptide was caused by de novo expression of the Psmb8 gene in response to UM171a-triggered oxidative stress. When evaluated for their anti-tumoral properties in the context of therapeutic vaccination, UM171a-treated MSC administration to immunocompetent mice with pre-established T-cell lymphoma controlled tumor growth resulting in 40% survival without the need of additional supportive therapy and/or standard-of-care.

Conclusions
Altogether, our findings reveal a new immune-related function for UM171a and clearly allude to a direct link between UM171a-mediated ROS induction and antigen cross-presentation by MSCs. The fact that UM171a treatment modulates MSCs to become antigen-presenting cells without the use of IFN-gamma opens-up a new line of investigation to search for additional agents capable of converting immune-suppressive MSCs to a cellular tool easily adaptable to vaccination.

Graphical abstract
Reappraisal of gap analysis for effusive crises at Piton de la Fournaise
Authors: Peltier Aline , Chevrel Magdalena Oryaëlle , Harris Andrew J. L. , Villeneuve Nicolas 
Published: January 2022

AbstractEffective and rapid effusive crisis response is necessary to mitigate the risks associated with lava flows that could threaten or inundate inhabited or visited areas. At Piton de la Fournaise (La Réunion, France), well-established protocols between Observatoire Volcanologique du Piton de la Fournaise – Institut de Physique du Globe de Paris (OVPF-IPGP) and civil protection, and between scientists of a multinational array of institutes, allow effective tracking of eruptive crises and hazard management embracing all stakeholders. To assess the outstanding needs for such responses Tsang and Lindsay (J Appl Volcanol 9:9, 2020) applied a gap analysis to assess research gaps in terms of preparedness, response and recovery at 11 effusive centers, including Piton de la Fournaise. For Piton de la Fournaise, their gap analysis implied widespread gaps in the state of knowledge. However, their work relied on incomplete and erroneous data and methods, resulting in a gap analysis that significantly underrepresented this state of knowledge. We thus here re-build a correct database for Piton de la Fournaise, properly define the scope of an appropriate gap analysis, and provide a robust gap analysis, finding that there are, actually, very few gaps for Piton de la Fournaise. This is a result of the existence of a great quantity of published work in the peer-reviewed literature, as well as frequent reports documenting event impact in the local press and observatory reports. At Piton de la Fournaise, this latter (observatory-based) resource is largely due to the efforts of OVPF-IPGP who have a wealth of experience having responded to 81 eruptions since its creation in 1979 through the end of September 2021.Although welcome and necessary, especially if it is made by a group of scientists outside the local management of the volcanic risk (i.e., a neutral group), such gap analysis need to be sure to fully consider all available peer-reviewed literature, as well as newspaper reports, observatory releases and non-peer-reviewed eruption reports, so as to be complete and correct. Fundamentally, such an analysis needs to consider the information collected and produced by the volcano observatory charged with handling surveillance operations and reporting duties to civil protection for the volcano under analysis. As a very minimum, to ensure that a necessarily comprehensive and complete treatment of the scientific literature has been completed, we recommend that a third party expert, who is a recognized specialist in terms of research at the site considered, reviews and checks the material used for the gap analysis before final release of recommendations.
Mapping European research networks providing health data: results from the InfAct Joint Action on health information
Authors: Unim Brigid , Haverinen Elsi , Mattei Eugenio , Carle Flavia , Faragalli Andrea , Gesuita Rosaria , Thissen Martin , Abboud Linda , Grisetti Tiziana , Bogaert Petronille , Palmieri Luigi 
Published: January 2022

Abstract
Background
Research networks offer multidisciplinary expertise and promote information exchange between researchers across Europe. They are essential for the European Union’s (EU) health information system as providers of health information and data. The aim of this mapping exercise was to identify and analyze EU research networks in terms of health data collection methods, quality assessment, availability and accessibility procedures.

Methods
A web-based search was performed to identify EU research networks that are not part of international organizations (e.g., WHO-Europe, OECD) and are involved in collection of data for health monitoring or health system performance assessment. General characteristics of the research networks (e.g., data sources, representativeness), quality assessment procedures, availability and accessibility of health data were collected through an ad hoc extraction form.

Results
Fifty-seven research networks, representative at national, international or regional level, were identified. In these networks, data are mainly collected through administrative sources, health surveys and cohort studies. Over 70% of networks provide information on quality assessment of their data collection procedures. Most networks share macrodata through articles and reports, while microdata are available from ten networks. A request for data access is required by 14 networks, of which three apply a financial charge. Few networks share data with other research networks (8/49) or specify the metadata-reporting standards used for data description (9/49).

Conclusions
Improving health information and availability of high quality data is a priority in Europe. Research networks could play a major role in tackling health data and information inequalities by enhancing quality, availability, and accessibility of health data and data sharing across European networks.
Small businesses and their challenges during COVID-19 pandemic in developing countries: in the case of Ethiopia
Authors: Engidaw Abriham Ebabu 
Published: January 2022

AbstractMainly this study was aimed at demonstrating the challenges of small businesses during the corona virus pandemic in developing countries, specifically in Ethiopia. Methodologically, the study deployed secondary data analysis following a descriptive research design. Furthermore, this study was conducted through both qualitative and quantitative research approaches. The secondary data analysis result shows that many small and large businesses are suffering challenges and this unprecedented coronavirus crisis has caused destruction for many businesses in the globe and it is challenging to survive with reduced revenue, jobs lost and life slowing down and weak marketing performance even difficult to keep a calm head and their business alive. To support these businesses, the government should use different mechanisms by cooperating with wealthy peoples and other non-governmental organizations. Besides, small business owners should manage expectations and communicate with staff, suppliers, banks, and customers throughout this coronavirus frightening. Reduce expenses be open to their employees about their finances and keep marketing, use different alternatives to deliver their product, and recover from the crisis.
Silica nanoparticles with encapsulated DNA (SPED) to trace the spread of pathogens in healthcare
Authors: Ullrich Cinzia , Luescher Anne M. , Koch Julian , Grass Robert N. , Sax Hugo 
Published: January 2022

Abstract
Background
To establish effective infection control protocols, understanding pathogen transmission pathways is essential. Non-infectious surrogate tracers may safely explore these pathways and challenge pre-existing assumptions. We used silica nanoparticles with encapsulated DNA (SPED) for the first time in a real-life hospital setting to investigate potential transmission routes of vancomycin-resistant enterococci in the context of a prolonged outbreak.

Methods
The two study experiments took place in the 900-bed University Hospital Zurich, Switzerland. A three-run ‘Patient experiment’ investigated pathogen transmission via toilet seats in a two-patient room with shared bathroom. First, various predetermined body and fomite sites in a two-bed patient room were probed at baseline. Then, after the first patient was contaminated with SPED at the subgluteal region, both patients sequentially performed a toilet routine. All sites were consequently swabbed again for SPED contamination. Eight hours later, further spread was tested at predefined sites in the patient room and throughout the ward. A two-run ‘Mobile device experiment’ explored the potential transmission by mobile phones and stethoscopes in a quasi-realistic setting. All SPED contamination statuses and levels were determined by real-time qPCR.

Results
Over all three runs, the ‘Patient experiment’ yielded SPED in 59 of 73 (80.8%) predefined body and environmental sites. Specifically, positivity rates were 100% on subgluteal skin, toilet seats, tap handles, and entertainment devices, the initially contaminated patients’ hands; 83.3% on patient phones and bed controls; 80% on intravenous pumps; 75% on toilet flush plates and door handles, and 0% on the initially not contaminated patients’ hands. SPED spread as far as doctor’s keyboards (66.6%), staff mobile phones (33.3%) and nurses’ keyboards (33.3%) after eight hours. The ‘Mobile device experiment’ resulted in 16 of 22 (72.7%) positive follow-up samples, and transmission to the second patient occurred in one of the two runs.

Conclusions
For the first time SPED were used to investigate potential transmission pathways in a real hospital setting. The results suggest that, in the absence of targeted cleaning, toilet seats and mobile devices may result in widespread transmission of pathogens departing from one contaminated patient skin region.