bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenetic Regulation of RNF135 by LSD1 Promotes Stemness Maintenance and Brain Metastasis in Lung Adenocarcinoma
Authors: Qu Xiaohan , Ding Tianjian , Zhao Haoqi , Wang Liming 
Published: August 2024

ABSTRACTRING finger protein 135 (RNF135) is identified as a regulator in certain cancer types. However, its role and molecular mechanisms in lung adenocarcinoma (LUAD) are still unclear. Herein, we investigated the level of RNF135 in tumor tissues of LUAD patients using the UALCAN database and confirmed the data by real‐time PCR and western blot analysis. The effects of RNF135 on stemness maintenance and migration/invasion capability of LUAD cells were investigated by sphere formation, flow cytometry, wound healing, and transwell assay. Limiting dilution xenograft assay and intracardiac injection of LUAD cells were applied to assess the implications of RNF135 in tumorigenesis and brain metastasis. Our results revealed that RNF135 was upregulated in tumor tissues of LUAD patients and was positively correlated with poor prognosis. Knockdown of RNF135 suppressed cancer stem cells (CSCs)‐like properties, and migration/invasion capability of A549 and NCI‐H1975 cells. Conversely, overexpression of RNF135 augmented CSCs‐like traits and migration/invasion ability of LUAD cells. Limiting dilution xenograft assay demonstrated that RNF135 was required for the self‐renewal of CSCs to initiate LUAD development. Overexpression of RNF135 in A549 cells increased their ability to metastasize to the brain in vivo. Mechanistically, the transcriptional activation of RNF135 by LSD1 involved H3K9me2 demethylation at the promoter region of RNF135. Reexpression of RNF135 in LSD1‐silenced A549 cells was able to reverse LSD1‐mediated stemness maintenance and migration/invasion capability. Overall, our results implied that targeting of LSD1/RNF135 axis might be a feasible method to suppress tumorigenesis and brain metastasis of LUAD patients.
The Impact of LIDAR‐Assisted Pitch Control on Floating Offshore Wind Operational Expenditure
Authors: Russell Andrew J. , McMorland Jade , Collu Maurizio , McDonald Alasdair S. , Thies Philipp R. , Keane Aidan , Quayle Alexander R. , McMillan David , Carroll James , Coraddu Andrea 
Published: August 2024

ABSTRACTFloating offshore wind (FOW) is a renewable energy source that is set to play an essential role in addressing climate change and the need for sustainable development. However, due to the increasing threat of climate emergency, more wind turbines are required to be deployed in deep water locations, further offshore. This presents heightened challenges for accessing the turbines and performing maintenance, leading to increased costs. Naturally, methods to reduce operational expenditure (OpEx) are highly desirable. One method that shows potential for reducing OpEx of FOW is LIDAR‐assisted pitch control. This approach uses wind velocity measurements from a nacelle‐mounted LIDAR to enable feedforward control of floating offshore wind turbines (FOWTs) and can result in reductions to the variations of structural loads. Results obtained from a previous study of combined feedforward collective and individual pitch control (FFCPC + FFIPC) are translated to OpEx reductions via reduced component failure rates for future FOW developments, namely, in locations awarded in the recent ScotWind leasing round. The results indicate that LIDAR‐assisted pitch control may allow for an up to 5% reduction in OpEx, increasing to up to 11% with workability constraints included. The results varied across the three ScotWind sites considered, with sites furthest from shore reaping the greatest benefit from LIDAR‐assisted control. This work highlights the potential savings and reduction in the overall levelised cost of energy for future offshore wind turbine projects deliverable through the implementation of LIDAR‐assisted pitch control.
On the Potential of Accelerometers for GNSS on Satellite Positioning and Ensuing Reference Frame Determination
Authors: Schreiner Patrick , Glaser Susanne , König Rolf , Neumayer Karl Hans , Raut Shrishail , Schuh Harald 
Published: August 2024

AbstractSolar Radiation Pressure (SRP) is the largest non-conservative force acting on Global Navigation Satellite Systems (GNSS) satellites. Modeling this force is still one of the challenging tasks in precise orbit determination (POD) of GNSS satellites and therefore also for subsequent applications as geodetic reference frame determination. Commonly used methods for SRP modeling are empirical or analytical ones, as well as combinations of the two. These points give rise to the motivation whether and how alternative observation techniques can improve future GNSS and support them in aspects of POD, reference frame determination and other subsequent applications. For this purpose, we analyze the potential of accelerometers onboard of each Galileo satellite by using simulations for different accelerometer specifications and evaluate the effect on position and clock estimates of the satellite vehicle, as well as the effect on derived Terrestrial Reference Frames (TRF). We thereby see, by assuming accelerometer sensitivities which are already available, the possibility to decorrelate the clock estimates from radial orbit position determinations. The advantages for GNSS based positioning are limited, since radial orbit errors and clock errors almost perfectly compensate. Promising potential for improvements for derived TRF and geocenter determination can be seen, which would bring us one step closer to achieving the accuracy requirements of a global TRF, defined by the Global Geodetic Observing System (GGOS).
1 Introduction
Authors: Fauci Anthony S. , Ghebreyesus Tedros Adhanom 
Published: August 2024

Abstract
Emerging and re-emerging infectious diseases will always be with us. It seems that just as we control one disease, a new threat takes its place. For example, soon after the global community eradicated smallpox in the mid-1970s, Ebola was first detected in Central Africa in 1976. The human immunodeficiency virus was recognized a few years later, having spread undetected for decades. Since then, many other emerging and re-emerging pathogens have threatened the world, including the first severe acute respiratory syndrome coronavirus in 2002, major outbreaks of Ebola, Zika virus, and now of course the second severe acute respiratory syndrome coronavirus, SARS-CoV-2, the cause of coronavirus disease 2019 (COVID-19) (◘ Fig. 1).
8 Building Biomedical Research Capacity in Low- and Middle-Income Countries: Why It Matters and Some of the Barriers to Success
Authors: Bhadelia Nahid , Moorthy Vasee , Sorenson Robert A. , Swaminathan Soumya 
Published: August 2024

Abstract
This chapter elaborates on the importance of preexisting research capacity in low- and middle-income countries (LMICs) for strengthening resilience against emerging and re-emerging infectious disease (EID) threats. In a broad sense, resilience is the ability of societies to maintain their core functions while responding to infectious disease outbreaks and other threats to the well-being of the population in order to minimize their health impact and other socioeconomic consequences. As the COVID-19 pandemic has demonstrated, broadly available research capacity can contribute to resilience by helping the global research community refine the research questions that should be asked, elucidate essential scientific information about emerging pathogens more quickly and effectively, and develop and assess medical countermeasures (MCMs) such as vaccines and treatments for the disease. Strong research capacity in LMICs would help identify, characterize, and then slow or contain the spread of a new or unfamiliar pathogen, especially when it first appears in a geographically confined outbreak in one or a few contiguous LMICs. This may give research scientists more time to understand and counteract it. LMIC research capacity also contributes to more equitable governance of research during outbreaks, with at least the potential for broader distribution of MCMs than was seen during the COVID-19 pandemic. Building biomedical research capacity is not a simple matter as it requires educational and healthcare systems that can support it by producing the necessary personnel, and, through health system functions like biosurveillance, access to patient data and the capacity to conduct clinical trials to assess MCMs. Such capacity building will require sustained investment by countries and international partners, but that investment would be more than justified even on solely economic terms by one averted pandemic. Additionally, the value of progress toward universal healthcare that comes with comprehensive capacity building is incalculable.
17 Integrating Clinical Research into Ebola Response: Liberia Case Study
Authors: Fallah Mosoka P. 
Published: August 2024

Abstract
Once considered unrealistic, conducting clinical research during response to infectious disease emergencies has become the norm among scientists, industry, and government officials, thanks in part to ground-breaking research during the 2014–2016 West Africa Ebola outbreak. The swift development of safe and effective vaccines and therapeutics against coronavirus disease 2019 (COVID-19) made clear that research response is imperative. In confronting the 2014–2016 Ebola outbreak, U.S. and Liberian officials and other stakeholders worked out a partnership to manage and coordinate research efforts, including choosing research targets and supporting capacity-building investments that might bear fruit most quickly. The results in Liberia, and later in other low- to middle-income countries facing outbreaks of new or re-emerging infectious diseases, demonstrate that research response, in the right circumstances, can accelerate the end of an outbreak. Alongside improvements in preparedness for such research, the requirements for success include close professional cooperation and joint research management, along with winning the trust of stakeholder communities.
21.1 In Focus: The Impact and Mechanisms of Superspreading
Authors: Nielsen Bjarke Frost , Sneppen Kim , Simonsen Lone 
Published: August 2024

Abstract
One of the characteristic features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is its tendency toward superspreading, where most onward transmission is linked to relatively few of those infected. Indeed, it has been shown that just around 10% of positive individuals account for 80% of new infections. The data necessary to quantify this superspreading tendency were available quite early, even before the outbreak was declared a pandemic. At the time, the epidemiological consequences of superspreading were not well understood, and mathematical models used for forecasting the pandemic trajectory were not equipped to incorporate this factor. More recently developed models have shown that such heterogeneity in transmission profoundly impacts the effects of mitigation measures, enhancing some strategies while rendering others less effective. This suggests that the overdispersion parameter k, roughly speaking “the estimated proportion of infected individuals responsible for 80% of the total secondary transmissions” (Endo et al. 2020), is a key statistical property of SARS-CoV-2 transmission, and that k should be rapidly quantified for any emerging pathogen, along with the basic reproductive number R
0. While this research is still nascent, the overall picture is that the superspreading potential could be quantified in the early phase of a future pandemic and that this knowledge is a critical factor to inform the outbreak response.
32 Launching a Clinical Research Operation
Authors: Larson Gregg , McNay Laura A. 
Published: August 2024

Abstract
Launching a research operation to support a clinical trial in the midst of an infectious disease emergency is a daunting task. We know that disease outbreaks and epidemics will occur, but not the time, place, or nature of the disease. There may be many unknowns when the disease first appears. Urgently implemented clinical research can make it possible to mitigate morbidity and mortality, help control or end disease transmission, and improve response to subsequent outbreaks. If, as is likely, an outbreak with pandemic potential occurs in a country with little research capacity and meager healthcare infrastructure, the research response will be more difficult but no less urgent. Such countries, especially outside major cities, often lack dependable communications, electrical power, clean water, and transportation. This chapter and other chapters in the section of the book describe some of the obstacles involved and how to overcome them, based on the personal experience as well as the professional expertise of the authors. This chapter lays out a number of organizational requirements for setting up a research program, including the various specialized teams needed. Authors who have worked in such specialized teams provide their perspectives on the requirements in each of these specialized areas in the following chapters.
32.1 Case Study: Clinical Research Communications during an Outbreak: Media Outreach Supporting Liberia–U.S. Research Partnership
Authors: Kiawu Hassan , Doepel Laurie K. 
Published: August 2024

Abstract
The 2014 bilateral agreement signed by the Liberia Minister of Health and Social Welfare and his counterpart at the U.S. Department of Health and Human Services established the Partnership for Research on Ebola Virus in Liberia (PREVAIL). The urgent purpose was to begin a research partnership to assess the safety and efficacy of candidate vaccines and therapies to prevent and treat Ebola virus disease (EVD) during the outbreak that had been affecting Liberia, Guinea, and Sierra Leone since early 2014. As of 2024, PREVAIL continues to conduct research related to a variety of infectious diseases of concern in West Africa. During the Ebola outbreak, PREVAIL’s Communications Pillar within the Social Mobilization and Communications Working Group sought to optimize media messaging, support robust social mobilization and patient recruitment into clinical trials, foster relationships with partner organizations, develop standard operating procedures for communications, conduct media training sessions, and facilitate media interviews and press conferences. It emphasized transparent, honest, and clear communication to support the PREVAIL clinical research infrastructure, the conduct of clinical trials, and community acceptance of research with the potential to mitigate the Ebola virus outbreak in a country with scarce resources and limited clinical research experience.
35 Data Management in Emergency Response Research
Authors: van Loen Harry , Badio Moses , Van Herrewege Yven 
Published: August 2024

Abstract
Proper data management is essential for ensuring the validity and quality of clinical research, a key aspect of good clinical practice (GCP) guidelines and a requirement of research ethics committees and regulatory authorities. Thoughtful planning, validated data management tools, and standardized operating procedures are fundamental to ensure quality research data and essential to rigorous analysis, sound results, and reporting and sharing study conclusions. This chapter focuses on clinical research as the most data-intensive type of research, but the principles and practices outlined also apply to other types of research. We introduce key concepts using examples from emergency research studies, rather than attempting to provide an exhaustive technical overview.
Data management is more than the development of a study database or the mere collection and maintenance of study data; nor should it simply be considered as information technology (IT) or data analysis. It refers to a series of processes and activities during the study but also before and after the collection of data. Essential elements include precautions to protect the rights, privacy, and safety of research participants and their communities. Data management is thus a key task in emergency clinical research, and there must be sufficient resources to ensure adherence to GCP guidelines, governmental regulations, and data management standards and to support timely reporting of high-quality research results. Unfortunately, good data management is often not given the priority needed to ensure regulatory-level, interpretable results.
36 Safety and Pharmacovigilance in Emergency Research Response
Authors: Teitelbaum Marc , Atri Negin , Cahill Kelly 
Published: August 2024

Abstract
Pharmacovigilance is an essential element of clinical trials. Even though a trial is based on the hypothesis that the intervention being tested will provide benefits that outweigh the risks, that hypothesis often turns out to be wrong. The impact of the COVID-19 pandemic and coverage in traditional and social media have raised public awareness of the clinical research enterprise, and in particular the pharmacovigilance (PV) and safety aspects of emerging and re-emerging infectious disease (EID) research response. Fundamental concepts of PV and clinical research, safety goals, and methods are introduced and explained, and the key players, factors, constraints, and stakeholders comprising the system are covered, with examples drawn from the response to both the COVID-19 pandemic and the 2018 Democratic Republic of the Congo (DRC) Ebola outbreak. Finally, key operational concepts, preparedness activities, and global response considerations are presented to help practitioners assess their personal, programmatic, and jurisdictional readiness to successfully develop and adapt research pharmacovigilance and safety programs in the context of EID response.
40.1 In Practice: Improving Patient Care in the Field: The CUBE Isolation Unit
Authors: Kojan Richard 
Published: August 2024

Abstract
The CUBE (
C

hambre d’

U

rgence

B

iosécurisée pour

E

pidémies, or emergency biosecurity chamber for epidemics) is an innovative, field-deployable shelter and isolation system for treating patients with dangerous infectious diseases. After the experience of working in cumbersome personal protective equipment (PPE) in tropical heat in the old Ebola treatment unit design, allowing caregivers to interact with patients for only 20 minutes at a stretch, the Alliance for International Medical Action (ALIMA) convened a working group to devise a better way to care for patients with Ebola and other highly transmissible, dangerous diseases. The result was the CUBE, a smaller containment structure for each patient, with transparent plastic walls, built-in ports resembling full-body gloves and airlock door and window portals. The CUBE allows for face-to-face contact between patients and their relatives as well as caregivers, without the need for PPE except when the caregiver needs direct contact with the patient.
42 Locally Hired Staff for Clinical Research Sites in Low-Resource Settings
Authors: Baseler Beth , Smolskis Mary , Doe-Anderson Jestina , Johnson Melvin , Njoh Wissedi , Albert Sara , Worthington Chris 
Published: August 2024

Abstract
This chapter provides insight on identifying, hiring, and training staff to conduct clinical research during an emergency response to infectious disease outbreaks in resource-limited settings. The authors illustrate human resourcing strategies employed and describe their experiences establishing local human resource capacity to support and conduct clinical trials during the Ebola outbreaks in West Africa (2014–2016) and the Democratic Republic of the Congo (2018–2020).
It is very likely that future emergency research responders will face similar challenges, even in quite distinct situations. The lessons presented here should help to establish an adaptable framework for future emergency responses that emphasizes team communication, collaboration, partnership, and mutual respect. In particular, this chapter offers insights into the following:

Contracting and legal requirements

Timing of activities

Key positions that should be filled to ensure study success

Strategies for legally and ethically hiring local staff while also incorporating international staff and volunteers

Training methods to ensure staff are adequately prepared for study implementation and participant safety

Requirements for respectful and mutually beneficial collaboration with local stakeholders while contributing to the outbreak response through clinical research
Video Reconstruction and Content Analysis of the Maidan Massacre on February 20, 2014
Authors: Katchanovski Ivan 
Published: August 2024

AbstractThis chapter presents video reconstruction and the content analysis of the Maidan massacre in Ukraine using over 2,000 videos and recordings of live Internet and TV broadcasts of the massacre in nearly 50 countries, news reports and social media posts by some 120 journalists covering the massacre from Kyiv, over 6,000 photos, and nearly 30 gigabytes of publicly available radio intercepts of snipers and commanders of the Security Service of Ukraine and Internal Troops. Synchronized videos show that specific times and directions of shooting by the Berkut policemen did not coincide with specific times and directions of killings of specific protesters.
The Maidan Massacre Trial Verdict, and Cover-up, Stonewalling, and Evidence Tampering
Authors: Katchanovski Ivan 
Published: August 2024

AbstractThe Maidan massacre trial verdict in Ukraine in October 2023 confirmed that many Maidan activists were killed and woundedand BBCand ARDTV journalists were shot at on February 20, 2014, not by Berkut or other law enforcement but by snipers in Hotel Ukraina and other Maidan-controlled locations, that this hotel was controlled by Maidan activists, including a far-right-linked Maidan company of snipers, that Russian agents were not involved in the massacre, that there were no massacre orders by President Yanukovych and his police and security chiefs, and that EuroMaidan then was an armed rebellion, which involved the massacre of the Berkut and Internal Troops.
The Social Paradigm of Automation
Authors: Betancourt Michael 
Published: August 2024

AbstractThe lineage of industrialisation that began in the eighteenth century continues with the development of artificial intelligence (AI). It reveals a heuristic apparent in/as the social paradigm that defines labour as interchangeable with the machinery it operates. Placing AI into a socio-cultural context with the industrial revolution reveals the on-going impacts of the social disparities created by capitalist production in the nineteenth century that were justified by reifying Immanuel Kant’s Enlightenment philosophy concerning judgement (human agency) continue to shape contemporary developments. Examining this philosophical justification and its influence illuminates a social paradigm focused on the replacement of labour with automation. This interdisciplinary approach links moral and aesthetic claims to the questions of labour to reveal a heuristic in which workers were cast as the “intellectual organs” of the machine, anticipating “machine learning” and other forms of digital automation that replace intelligent labour. This cultural foundation developes from the continuity of technological changes that defined each stage of industrialisation through disparate social, cultural and aesthetic claims about machinery and the social significance of the industrial factory. The regimentation of labour by industrialization concerned nineteenth century artists and critics whose ideas established an archetype whose structural effects shape and constrain the contemporary implementation of automation and AI.