bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk assessment for the surface water quality evaluation of a hydrological basin
Authors: Brito Irene , Gonçalves A. Manuela , Pedra Ana
Published: October 2024

This paper proposes a risk assessment methodology for evaluating the surface water quality of hydrological basins based on physico-chemical parameter concentrations. Considering the Douro River basin in Portugal and monthly recorded dissolved oxygen and conductivity parameter measurements in 18 water sampling stations from January 2002 to December 2013, the work intends to answer the research question of identifying the riskiest periods for water pollution in the year and classifying the water sampling stations in terms of risk for water pollution. The methodology consists first in determining the pollution risk implied by the physico-chemical parameters, based on the monthly water station measurements, using six different risk measures, namely mean, variance, loss probability, entropy, mean excess loss and value at risk. The risk values are ordered according to each risk measure and a final ranking is established through a ranking aggregation method. The final ranking permitted identifying the high risk period as ranging from May to October and the low risk period from November to April. Furthermore, July was classified as riskiest month concerning the dissolved oxygen concentration, and August as riskiest month regarding the conductivity levels. On the other hand, the ranking allowed classifying the water sampling stations, previously grouped in clusters, in terms of similar risk for water pollution: six sampling stations in the west of the basin formed the riskiest cluster in the dry period considering the dissolved oxygen concentrations, and four of those stations formed also the riskiest cluster concerning the conductivity levels.
AI robots pioneer the Smarter Inclusive Society
Authors: Hirata Yasuhisa
Published: October 2024

This paper outlines a project aimed at realizing a “Smarter Inclusive Society” by 2050 through the integration of AI robots into various public facilities. Led by the Cabinet Office’s “Moonshot Research and Development Program,” the project focuses on developing Adaptable AI-enabled Robots that enhance self-efficacy by supporting users’ abilities while maintaining their sense of independence. Key to the project is the Robotic Nimbus, a soft and flexible robot designed to provide tailored assistance while preserving user agency. The concept of “Adaptable AI-enabled Robots” is introduced to ensure versatility in accommodating user needs and preferences. In addition to physical assistance, the project emphasizes creating engaging experiences through activities like dance and sports, fostering excitement and inclusivity. Collaborations, such as the “Yes We Dance!” performance, demonstrate the potential of AI technology in enhancing rehabilitation opportunities and promoting social participation. By 2050, the project aims to establish a society where AI robots contribute to mental, physical, and social wellbeing, empowering individuals to engage in independent activities and fostering a vibrant, inclusive community. This paper is a compilation of articles/papers/presentations previously presented on the Moonshot Hirata project.
Groundwater monitoring in challenging environments: an argument for the construction of observation wells based on data from Niamey, Niger
Authors: Groeschke Maike , Bosch Kolja , Aboubacar Samira Daba , Kroemer Laura , Koeniger Paul , Vassolo Sara
Published: October 2024

Groundwater sampling in challenging environments often leads to compromises in following best practices to obtain representative samples from aquifers. This includes collecting samples from existing production or domestic wells instead of using properly constructed monitoring wells or using a bailer instead of a submersible pump for sampling. To address unusual patterns and trends in groundwater chemistry data collected in Niamey, Niger from 2012–2021, a state-of-the-art monthly sampling routine was established for eight wells tapping the basement aquifer. This was based on the hypothesis that the observed changes in groundwater composition were mainly due to differences in sampling technique, and the aim of the study was to gain insights into possible seasonal variations in water composition, to examine if the previously observed trends could be validated and to provide baseline data for future studies. The results indicate that in most cases the long well response zones in the stratified aquifer system led to the collection of water from different strata/aquifers or of strongly mixed samples. Therefore, any sample from those wells is only of limited value for the interpretation of hydrogeological processes. To obtain sound data for the development of groundwater management strategies, the monitoring has to be shifted from existing production wells to properly constructed monitoring wells. In the complex hydrogeological setting of Niamey, with hydraulically interacting aquifers and occurrences of density layering, it is fundamental to ensure that a monitoring well taps one specific depth of one target aquifer and that well-volume purging is applied properly.
Pedal to the metal: accelerating intracerebral hemorrhage treatment with robotic-assisted surgery. A systematic review & meta-analysis of clinical effectiveness
Authors: Łajczak Paweł , Łajczak Anna
Published: October 2024

Intracerebral hemorrhage (ICH) is a severe condition in vascular neurological surgery, often leading to high mortality and severe disability. Recent advancements in robotic-assisted (RA) systems, including ROSA, Remebot, and CAS-R-2, have shown promise in enhancing surgical precision and outcomes. This study aims to evaluate the effectiveness of RA systems in ICH surgery compared to conventional methods. This systematic review followed PRISMA 2020 guidelines. The inclusion criteria were peer-reviewed English language articles reporting on the use of RA systems for ICH surgery in humans. Data extraction focused on surgical time, mortality rates, neurological outcomes, complication rates, and economic effectiveness. Meta-analyses were performed using R software, employing a random effects model to account for variations between studies. Seventeen studies were included in the systematic review, with thirteen qualifying for the meta-analysis. The results demonstrated that RA systems significantly reduced surgery time (MD -86.2447 [-128.5111; -43.9782], p < 0.0001) and mortality at last follow-up (OR 0.3652 [0.1457; 0.9158], p = 0.0317). RA systems also improved neurological outcomes, with lower mean modified Rankin Scale (mRS) scores (MD -0.8063 [-1.0786; -0.5341], p < 0.0001) and higher Glasgow Outcome Scale (GOS) scores (MD 0.6792 [0.1599; 1.1985], p = 0.0104). Complications such as rebleeding, pulmonary infections, and intracranial infections were significantly reduced. Robot-assisted surgery may provide benefits in ICH surgery, by reducing surgery time, lowering rates of mortality, better neurological outcomes, and reduced complications. Currently, the published studies are highly prone to bias and many outcomes are very heterogenous. Additional research done on larger, more standardized studies is needed for the full ascertainment of such techniques in being integrated into normal clinical practice.
Validity of test score interpretations and cross-cultural comparisons in the First and Second International Science Studies
Authors: Sosa Paredes Yuriko K. , Andersson Björn
Published: October 2024

In international large-scale assessments, student performance comparisons across educational systems are frequently done to assess the state and development in different domains. These results often have a large impact on educational policy and on the perceptions of an educational system’s performance. Early assessments, such as the First and Second International Science Studies (FISS and SISS), have been used alongside recent studies to create unique scales for investigating changes in constructs. The implicit assumptions in system comparisons are that the measures are valid, reliable, and comparable. However, these assumptions have not always been investigated thoroughly. This study aims to investigate the validity and cross-system comparability of scores from the FISS and SISS, conducted by the International Association for the Evaluation of Educational Achievement in 1970–1971 and 1983–1984. Findings based on item response theory (IRT) modeling indicate that scores in most educational systems can be viewed as reliable measures of a single science construct, supporting the validity of test score interpretations in these educational systems individually. In a robust assessment of measurement invariance using standard IRT methods, an alignment-based method, and the root mean square difference (RMSD) fit statistic, we demonstrate that measurement invariance is violated across systems. The alignment-based method identified a well-fitting model with complex restrictions but no items exhibited invariance across all systems, a result supported by the RMSD statistics. These results question the appropriateness of score comparisons across systems in FISS and SISS. We discuss the implications of these results and outline consequences for score comparisons across time.
Emission Factors, Chemical Composition and Ecotoxicity of PM10 from Road Dust Resuspension in a Small Inland City
Authors: Cipoli Yago Alonso , Rienda Ismael Casotti , de la Campa Ana M. Sánchez , Kováts Nora , Nunes Teresa , Feliciano Manuel , Hoffer András , Jancsek-Turóczi Beatrix , Alves Célia
Published: October 2024

Road dust resuspension in urban environments can contribute to high human exposure to metal(loid)s, polycyclic aromatic hydrocarbons, and other potentially toxic organic compounds. However, for many regions, information on loadings, emission factors and chemical profiles is lacking to accurately apply emission inventories and source apportionment models. In the present study, PM10 samples were collected with an in situ road dust sampler from eleven representative streets of Bragança, an inland city of the Iberian Peninsula, and were analysed for organic and elemental carbon by a thermal-optical technique, elemental composition by ICP-MS and ICP-OES, and ecotoxicity by a luminescence inhibition bioassay with Allivibrio fischeri. A global emission factor of 5.36 ± 2.35 mg veh−1 km−1 was obtained but in suburban areas the values reached twice the average. Total carbon accounted for 14.9 ± 6.8% of the PM10 mass, while element oxides represented the largest share (28.6 ± 18.7%). Very high enrichments were found for typical traffic-related elements such as Cu, Zn, S, Pb and Ni. The geochemical index Igeo further confirmed that road dust of the study region is extremely contaminated by elements mainly originated from tyre and brake wear. Although the total non-carcinogenic and carcinogenic risks associated with metal exposure were found to be low for both children and adults, the bioluminescence inhibition assay showed (eco)toxic responses for all samples, indicating that road dust resuspension may pose a significant human health and ecological threat.
Multi-scale mechanical and acoustic characterization of low noise pavements
Authors: Poulikakos Lily. D. , Schlatter Felix , Huber Liliane , Mikhailenko Peter , Arraigada Martin , Griffa Michele , Angst Christian , Bühlmann Erik
Published: October 2024

Using data on in situ performance of low noise pavements, three well performing mixtures were selected: SDA 4, SDA 6, and SDA 8. These mixtures and the corresponding mastic (filler + bitumen + additive) were tested for their mechanical and acoustic performance in non-aged and aged states using a multi-scale approach (mm to km). Thereafter, an optimization protocol was applied to these mastics (mm-scale) and promising combinations were implemented at the mixture scale (cm-scale). As a result, the best performing mixture parameters were implemented in the m-scale slabs where the mechanical and acoustic performance were determined. The proposed work could uniquely combine knowledge from in situ long term and laboratory performance of low noise pavements. Using a traffic simulator and measurements before and after trafficking, the acoustic modeling showed that the modified mixtures’ noise levels were maintained after loading. This indicates that the modification assured acoustical integrity of the mixture after loading.
Mentale Repräsentationen von Inklusion und Exklusion
Authors: Krauskopf Karsten
Published: October 2024

Dieser Beitrag in der Zeitschrift für Psychodrama und Soziometrie widmet sich der Analyse von Exklusions- und Inklusionsdynamiken in Bildungssettings aus psychodramatischer Perspektive. Der Autor schlägt vor, das sozio-kulturelle Atom als ein Modell für die mentalen Repräsentationen von Beziehungen zu verstehen und es als Ausgangspunkt für inklusive Prozesse zu verwenden. Dabei wird Inklusion als Förderung sozialer Teilhabe definiert und die dafür notwendigen Prozesse als Reparatur(en) sozio-kultureller Atome beschrieben. Ausgehend von Forschungsergebnissen zu sozialen Beziehungen im Klassenzimmer beschreibt der Autor vier Aspekte von Behinderung sozialer Teilhabe als mentale Manipulationen sozio-kultureller Atome durch Abwesenheit, Verleugnen, Ignorieren oder Ablehnen. Es werden mögliche Ansätze für psychodramatische Interventionen zur Gestaltung inklusiver Bildungsprozesse angedeutet.
Delayed Withdrawal of Life-Sustaining Treatment in Disorders of Consciousness: Practical and Theoretical Considerations
Authors: Williams Aaron , Bass Geoffrey D. , Hampton Stephen , Klinedinst Rachel , Giacino Joseph T. , Fischer David
Published: October 2024

Disorders of consciousness (DoC) resulting from severe acute brain injuries may prompt clinicians and surrogate decision makers to consider withdrawal of life-sustaining treatment (WLST) if the neurologic prognosis is poor. Recent guidelines suggest, however, that clinicians should avoid definitively concluding a poor prognosis prior to 28 days post injury, as patients may demonstrate neurologic recovery outside the acute time period. This practice may increase the frequency with which clinicians consider the option of delayed WLST (D-WLST), namely, WLST that would occur after hospital discharge, if the patient’s recovery trajectory ultimately proves inconsistent with an acceptable quality of life. However acute care clinicians are often uncertain about what D-WLST entails and therefore find it difficult to properly counsel surrogates about this option. Here, we describe practical and theoretical considerations relevant to D-WLST. We first identify post-acute-care facilities to which patients with DoC are likely to be discharged and where D-WLST may be considered. Second, we describe how clinicians and surrogates may determine the appropriate timing of D-WLST. Third, we outline how D-WLST is practically implemented. And finally, we discuss psychosocial barriers to D-WLST, including the regret paradox, in which surrogates of patients who do not recover to meet preestablished goals frequently choose not to ultimately pursue D-WLST. Together, these practical, logistic, and psychosocial factors must be considered when potentially deferring WLST to the post-acute-care setting to optimize neurologic recovery for patients, avoid prolonged undue suffering, and promote informed and shared decision-making between clinicians and surrogates.
Primary Mast Cell Sarcoma of the Maxillary Sinus and Gingiva Mimicking Malignant Neuroendocrine Tumor: A Case Report
Authors: Cheng Tzu-Chien , Chen Jim-Ray , Wang Ren-Ching , Chang Kung-Chao , Hang Jen-Fan
Published: October 2024

Mast cell sarcoma (MCS) is an extremely rare and aggressive malignancy primarily affecting bones, with limited literature associating it with neuroendocrine marker expression. This report presents a rare case of MCS arising in the maxillary sinus and gingiva. A 74-year-old man presented with a progressively enlarging ulcer on the right-sided upper gingiva. Magnetic resonance imaging revealed a 3.4 cm tumor on the floor of the right maxillary sinus. The patient underwent an inferior maxillectomy and right-sided neck dissection. Microscopically, the tumor consisted of monotonous round cells with oval nuclei, vesicular chromatin, inconspicuous nucleoli, and brisk mitoses. A panel of immunohistochemical stains was initially applied to exclude common sinonasal undifferentiated neoplasms, such as sinonasal undifferentiated carcinoma, melanoma, rhabdomyosarcoma, Ewing sarcoma, and lymphoma. The tumor cells showed patchy staining for INSM1 and synaptophysin, but were negative for AE1/AE3, CAM5.2, p40, chromogranin, S100, HMB45, NKX2.2, desmin, CD45 (LCA), CD3, and CD20, with intact INI1 and BRG1 expression. No specific diagnosis could be rendered based on the staining results, leading to consideration of other rare malignancies. Additional staining revealed positivity for CD117, mast cell tryptase, CD13, CD33, CD43, and CD68, confirming the MCS diagnosis. Molecular testing for KIT mutation was negative. Subsequent bone marrow biopsy demonstrated infiltration of atypical mast cells, which led to a diagnosis of mast cell leukemia. Despite high-dose chemotherapy, the patient died three months after the initial diagnosis. The undifferentiated epithelioid morphology and unusual aberrant neuroendocrine marker expression posed significant diagnostic challenges. The major differential diagnoses were discussed in this report.
Clarifying some confusion: indecisiveness and procrastination are distinct constructs
Authors: Lauderdale Sean A. , Lahman Kelli R. , Desai Hela
Published: October 2024

Aversive indecisiveness is a trait-like, threat-based cognitive style associated with decision-making that is correlated with risks for and symptoms of anxiety and depression. By contrast, procrastination is the intentional delay of making a decision or pursuing a course of action despite expecting negative outcomes. In past research, the terms indecisiveness and procrastination have been used interchangeably contrary to the operationalization and nomological networks of these constructs. In this investigation, the distinction between aversive indecisiveness and procrastination was assessed and it was expected that items marking these constructs would load on distinct latent factors. It was also expected that aversive indecisiveness and procrastination would be more strongly associated with variables from their respective nomological networks. In an online survey, 500 (n = 355 women) undergraduate participants completed measures assessing aversive indecisiveness, procrastination, and other variables from their respective nomological networks. Exploratory and confirmatory factor analyses indicated that aversive indecisiveness, decisional procrastination, and implemental procrastination loaded on separate latent factors, with no significant cross-loadings, and sharing only a modest amount of variance. Aversive indecisiveness was more strongly predictive of neuroticism, Intolerance of Uncertainty, general distress, worry, and avoidance than procrastination. In contrast, procrastination was more strongly predictive of conscientiousness and self-discipline than aversive indecisiveness. Both aversive indecisiveness and procrastination were equally correlated with anxious arousal, anhedonic depression, and emotionally driven impulsivity. Implications for future research of the measurement and explication of indecisiveness are discussed.
Opportunities and challenges for identifying undiagnosed Rare Disease patients through analysis of primary care records: long QT syndrome as a test case
Authors: Evans William , Akyea Ralph K. , Simms Alex , Kai Joe , Qureshi Nadeem
Published: October 2024

Background

Patients with rare genetic diseases frequently experience significant diagnostic delays. Routinely collected data in the electronic health record (EHR) may be used to help identify patients at risk of undiagnosed conditions. Long QT syndrome (LQTS) is a rare inherited cardiac condition associated with significant morbidity and premature mortality. In this study, we examine LQTS as an exemplar disease to assess if clinical features recorded in the primary care EHR can be used to develop and validate a predictive model to aid earlier detection.

Methods

1495 patients with an LQTS diagnostic code and 7475 propensity-score matched controls were identified from 10.5 million patients’ electronic primary care records in the UK’s Clinical Practice Research Datalink (CPRD). Associated clinical features recorded before diagnosis (with p < 0.05) were incorporated into a multivariable logistic regression model, the final model was determined by backwards regression and validated by bootstrapping to determine model optimism.

Results

The mean age at LQTS diagnosis was 58.4 (SD 19.41). 18 features were included in the final model. Discriminative accuracy, assessed by area under the curve (AUC), was 0.74, (95% CI 0.73, 0.75) (optimism 6%). Features occurring at significantly greater frequency before diagnosis included: epilepsy, palpitations, syncope, collapse, mitral valve disease and irritable bowel syndrome.

Conclusion

This study demonstrates the potential to develop primary care prediction models for rare conditions, like LQTS, in routine primary care records and highlights key considerations including disease suitability, finding an appropriate linked dataset, the need for accurate case ascertainment and utilising an approach to modelling suitable for rare events.
“Which Proof for Which Class?” Factors Influencing the Selection of Mathematical Proofs for Teaching
Authors: Sommerhoff Daniel , Brunner Esther , Ufer Stefan
Published: October 2024

Selecting a proof for teaching is a frequent task for teachers. However, it is so far unclear, which factors are considered by teachers when selecting proofs. Is the selection based on task and proof characteristics such as the didactical type of proof? Or based on class characteristics such as students’ algebraic skills? Or do teachers’ characteristics such as their proof skills govern their decision? Or is the selection too non-generic for these characteristics to show a meaningful impact?

To address these questions, a quasi-experimental study with N = 183 pre-service teachers was conducted to evaluate the influence of each of these factors on their selection of proofs for teaching. Results highlight several significant effects of the abovementioned characteristics and underline that—even at the pre-service level—the selection of proofs is more nuanced than often assumed in prior research and that teachers deliberately and adaptively select proofs for their teaching based on these factors.
Just Simulating? Linguistic Support for Continuism About Remembering and Imagining
Authors: Liefke Kristina
Published: October 2024

Much recent work in philosophy of memory discusses the question whether episodic remembering is continuous with imagining. This paper contributes to the debate between continuists and discontinuists by considering a previously neglected source of evidence for continuism: the linguistic properties of overt memory and imagination reports (e.g. sentences of the form ‘x remembers/imagines p’). I argue that the distribution and truth-conditional contribution of episodic uses of the English verb remember is surprisingly similar to that of the verb imagine – even when compared to the distribution of other experiential attitude verbs like see, hallucinate, or dream. This holds despite the presence of some remarkable truth-conditional differences between remember and imagine. I show how these differences can be explained by a continuist account of remembering, on which remembering is past-directed, referential, and accurate experiential imagining.
Intraspecific crop diversity for enhanced crop pollination success. A review
Authors: Chabert Stan , Eeraerts Maxime , DeVetter Lisa W. , Borghi Monica , Mallinger Rachel E.
Published: October 2024

Interspecific crop diversity (e.g., intercropping) has been documented to promote sustainability in agroecological systems with benefits for pollination services and insect pollinators. These benefits may also be extended to intraspecific crop diversity (e.g., cultivation of multiple genotypes or cultivars in a production space), but no review to date has examined the benefits of intraspecific crop diversity for pollination and pollinator communities. While mixing cultivars is necessary and a widespread practice for pollination of self-incompatible or male-sterile crops, it is not as widespread for other crop species. However, many other crops have shown reduced yield quantity or quality with self-fertilization due to partial self-sterility, early acting inbreeding depression, and xenia. These crops could thus experience increased production in diverse cultivar mixtures. Cultivar mixtures could also benefit pollinator communities through providing complementary and temporally consistent floral resources, with cascading effects on pollination services. However, successfully implementing cultivar mixtures requires an understanding of how cultivar identity and arrangement affect successful cross-pollination. In this review, we describe the potential benefits of increased intraspecific crop diversity for optimal pollination and pollinator populations across insect-pollinated crops. Additionally, we explore how research advances in cultivar characteristics and insect pollinator behavior and movement, as well as crop pollen flow, can inform cultivar mixtures and spatial arrangements. We find evidence that mixing cultivars, even in self-compatible crops, improves pollination outcomes and yields. Additionally, given insect pollinator behavior and pollen flow, such mixing must occur at relatively small spatial scales. Furthermore, cultivar diversity could ensure successful pollination and resource production for pollinators under extreme weather events. We also discuss costs and benefits of diverse cultivar mixtures from a grower’s perspective and offer suggestions for future research including translating findings within the context of farming systems so that recommendations are practical and achievable.
Management of cytotoxic chemotherapy in patients undergoing dialysis: a still unresolved issue of onconephrology
Authors: Pirovano Marta , Ganini Carlo , Gallieni Maurizio , Porta Camillo , Cosmai Laura
Published: October 2024

The incidence of tumors increases significantly in individuals with chronic kidney disease (CKD), particularly among those undergoing dialysis. This dialysis-associated condition not only impacts therapy but also influences the prognosis of oncological patients, contributing to heightened mortality rates related to both cancer and non-cancer causes. Importantly, it stands as a primary factor leading to suboptimal utilization of therapies. Dosage adjustment for many types of chemotherapy is a necessity in patients with kidney impairment. However, due to a lack of comprehensive knowledge about the pharmacokinetic and pharmacodynamic properties of these drugs in dialysis, adjustments are often made empirically, and in many cases, chemotherapy is avoided altogether. In this review, we highlight the current challenges and gaps in knowledge, and emphasize the imperative need for dedicated research to establish evidence-based guidelines for chemotherapy management in this vulnerable patient population.

Graphical abstract
Odontogenic myxoma of the maxilla: a case report
Authors: Saha Ashmita , Tummidi Santosh , Ghosh Debangshu , Bhattacharya Souvik
Published: October 2024

Background

Odontogenic myxomas are rare tumours of the mesenchymal portion of developing tooth and account for 3–6% of all odontogenic tumours. Microscopically, odontogenic myxomas have a characteristic histologic appearance, which distinguishes it from other odontogenic tumours. However, it can mimic normal dental follicles of a developing tooth, from which it can be differentiated histologically by the nature of connective tissue and also by clinical and radiological appearances.

Case presentation

We present a case of a 30-year-old female with a large mass involving the left maxillary sinus. Histopathology showed features of odontogenic myxoma.

Discussion

Early diagnosis of such lesions is critical for avoiding extensive surgical procedures and the subsequent impact on the patient’s quality of life.

Conclusion

Complete surgical excision is the treatment choice, which can be difficult owing to the tumour’s invasive borders. Hence, the patients should benefit from regular follow-ups.
Of other reefs: designing habitats in blasted seascapes
Authors: Weber Rasa
Published: October 2024

Migrating reefs, unprecedented species assemblages, neophytes, toxicities, pollutants, aquatic ruins – The future of coral reefs in the Anthropocene is likely to look different from anything we have experienced so far. While the classic conservation debate on coral reef restoration still treats these ecosystems as “sick patients,” a radically different view of convivial conservation is beginning to challenge exclusive human control over these endangered habitats. Putting aside notions of natural “purity” and adopting a much more humble and highly interconnected perspective on marine habitats, we can begin to see reefs as transformative, sympoïetic and blasted seascapes for a convivial future. The discipline of biodesign has been primarily focussed on researching ecological relationships with regard to new materials and products. The emerging interest in shaping the multi-layered ecological relationships of habitats for other-than-human lives, however, is steering design practice towards terraforming or, in the case of marine environments, “aquaforming.” This paper argues for taking convivial conservation practices in marine environments as a starting point for the development of a new design methodology that focuses on the design of living systems in open environments: a proposed methodology called Sympoïetic Design.
Preparing better: Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) therapeutics trials lessons learned: A call to the future
Authors: Adam Stacey J. , Buchman Timothy G. , Currier Judith S. , Draghia-Akli Ruxandra , Fessel Josh P. , Higgs Elizabeth S. , Hughes Eric A. , LaVange Lisa , Menetski Joseph P. , Read Sarah W. , Rosenberg Yves , Tressler Randall ,   ACTIV Therapeutics-Clinical Working Group
Published: October 2024

The Accelerating COVID-19 Therapeutic Interventions and Vaccines Therapeutic-Clinical Working Group members gathered critical recommendations in follow-up to lessons learned manuscripts released earlier in the COVID-19 pandemic. Lessons around agent prioritization, preclinical therapeutics testing, master protocol design and implementation, drug manufacturing and supply, data sharing, and public–private partnership value are shared to inform responses to future pandemics.
Lessons learned from the conduct of inpatient clinical trials in a pandemic
Authors: O’Halloran Jane A. , Beitler Jeremy R. , Chung Lucy K. , Jain Mamta K. , Khan Akram , Merck Lisa H. , Mourad Ahmad , Oh Minn A. , Sharma Shweta , Yokum Tammy , Nayak Seema U.
Published: October 2024

Background:

The COVID-19 pandemic amplified known challenges associated with the conduct of inpatient clinical trials, while also introducing new ones that needed to be addressed.

Methods:

Stakeholders based in the United States who participated in the conduct of inpatient therapeutic trials for the treatment of COVID-19 as part of the Accelerating COVID-19 Therapeutic Interventions and Vaccines program identified challenges experienced in the conduct of these trials through a series of meeting to discuss and identify common themes. In addition, innovations developed to address these challenges and other potential solutions that may be utilized in future pandemics were highlighted.

Results:

Six thematic challenges including infection control considerations, the interplay between provision of clinical care and research, competing clinical trials, arduous consenting procedures, onerous procedural requirements, and participant recruitment including achieving representation of diverse populations were identified and are discussed here.

Conclusions:

Consideration of the lessons learned and recommendation outlined here may allow for more efficient conduct of inpatient clinical trials in future pandemics.
Practical application of good participatory practices for trials of emerging pathogens: Developing materials for use in ACTIV-3, -3b, and ACTIV-associated COVID-19 trials
Authors: Guerra-de-Blas Paola del Carmen , Marines-Price Rubria , Milman Olga , Deal Danae , Marchand Jonathan , Linton Jessica , Meger Sue , Rule John , Holland Thomas L. , Kitonsa Jonathan , Delph Yvette ,   for the INSIGHT OTAC, ACTIV-3 TICO, ACTIV-3 substudy VATICO, and ACTIV-3b TESICO Study Groups
Published: October 2024

The emergence of the COVID-19 pandemic required an immediate global clinical research response. The ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines)-3 trials and the ACTIV-associated Outpatient Treatment with Anti-Coronavirus Immunoglobulin trial used Good Participatory Practices (GPP) to develop materials for study implementation from a global network perspective. GPP guidelines offer a framework for engaging stakeholders throughout the research process. This paper provides an overview of the materials developed and their applicability in various settings, reports results from a survey of study site personnel on the materials’ usefulness, summarizes important lessons learned, and serves as a reference for networks eager to apply GPP. Survey results showed that flipbooks and overview videos were highly ranked. Stakeholder input was valuable in developing easily understandable participant-facing materials with culturally appropriate images. Materials should be available to submit with the initial protocol submissions to ethics committees, and in formats that accommodate a wide range of institutional resources, policies, and infection-control practices. This article emphasizes the importance of GPP, including stakeholder consultation, in developing materials that support clinical research and address language, cultural, and sociopolitical barriers during a pandemic. The findings will be used to optimize efforts and resource allocation for new and ongoing studies.
ACTIV trials: cross-trial lessons learned for master protocol implementation
Authors: Keshtkar-Jahromi Maryam , Adam Stacey J. , Brar Indira , Chung Lucy K. , Currier Judith S. , Daar Eric S. , Davey Victoria J. , Denning Eileen T. , Gelijns Annetine C. , Higgs Elizabeth S. , Jagannathan Prasanna , Javan Arzhang Cyrus , Jensen Tomas O. , Jilg Nikolaus , Kalomenidis Ioannis , Kim Peter , Nayak Seema U. , Newell Matthew , Taiwo Babafemi O. , Yokum Tammy , Delph Yvette
Published: October 2024

The United States Government (USG) public-private partnership “Accelerating COVID-19 Treatment Interventions and Vaccines” (ACTIV) was launched to identify safe, effective therapeutics to treat patients with Coronavirus Disease 2019 (COVID-19) and prevent hospitalization, progression of disease, and death. Eleven original master protocols were developed by ACTIV, and thirty-seven therapeutic agents entered evaluation for treatment benefit. Challenges encountered during trial implementation led to innovations enabling initiation and enrollment of over 26,000 participants in the trials. While only two ACTIV trials continue to enroll, the recommendations here reflect information from all the trials as of May 2023. We review clinical trial implementation challenges and corresponding lessons learned to inform future therapeutic clinical trials implemented in response to a public health emergency and the conduct of complex clinical trials during “peacetime,” as well.
Case C-80/23: A Quest for Clarity. The Law Enforcement Directive 2016/680, a Bulgarian Court and Case C-205/21
Authors: Nikiforov Liubomir
Published: October 2024

This contribution examines the legal intricacies surrounding law enforcement data collection practices in Bulgaria within the framework of the Law Enforcement Directive 2016/680 (LED) and relevant Court of Justice of the European Union (CJEU) rulings, particularly cases C-205/21 and C-80/23. The analysis underscores challenges in interpreting the concept of “strict necessity” and ensuring compliance with its provisions, in particular, Art. 10. Key findings reveal ambiguities in the LED’s application, particularly concerning judicial review and the scope of data collection. The subsequent Case C-80/23 further seeks clarification on the strict necessity standard and the scope of judicial review in the collection of biometric and genetic data. The outcome of both cases has broader implications for EU member states, highlighting the need for legislative alignment and underscoring the complexities and challenges in balancing effective law enforcement with the protection of fundamental rights.
Impact of coffee-derived chlorogenic acid on cognition: a systematic review and meta-analysis
Authors: Johal Karen , Jones Dan J. W. , Bell Lynne , Lovegrove Julie A. , Lamport Daniel Joseph
Published: October 2024

Coffee drinking has been associated with benefits for various health outcomes, with many attributed to the most prevalent family of polyphenols within coffee, chlorogenic acids (CGA). Whilst reviews of the association between coffee and cognition exist, evidence exploring effects of coffee-specific CGA on cognition has yet to be systematically synthesised. The purpose was to systematically review the current literature investigating the relationship between CGA from coffee and cognitive performance. A further objective was to undertake a meta-analysis of relevant randomised controlled trials (RCT). Observational and intervention studies were included if they considered coffee-based CGA consumption in human participants and applied a standardised measure of cognition. Furthermore, intervention studies were required to define the CGA content and include a control group/placebo. Studies were excluded if they examined CGA alone as an extract or supplement. A search of Scopus, PubMed, Web of Science, ScienceDirect and PsycINFO resulted in including twenty-three papers, six of which were interventions. The evidence from the broader systematic review suggests that CGA from coffee may need to be consumed chronically over a sustained period to produce cognitive benefits. However, the meta-analysis of RCT showed no benefits of coffee CGA intake on cognitive function (d = 0.00, 95% CI −0.05, 0.05). Overall, this review included a limited number of studies, the sample sizes were small, and a wide range of cognitive measures have been utilised. This indicates that further, good-quality interventions and RCT are required to systematically explore the conditions under which coffee CGA may provide benefits for cognitive outcomes.
LASSOing the Governor’s Mansion: A Machine-Learning Approach to Forecasting Gubernatorial Elections
Authors: Love Gregory J. , Carlin Ryan E. , Singer Matthew M.
Published: October 2024

Despite governors’ crucial roles in shaping important policies, including abortion, education, and infrastructure, forecasters have paid little attention to gubernatorial elections. We posit that institutional idiosyncrasies and lack of public opinion data have exacerbated the classic problem facing all election forecasts: there are too many predictors and too few cases, leading to overfitting. To address these problems, we combine new governor and state-level presidential approval data with a machine-learning approach, LASSO, for variable selection. LASSO examines numerous variables but retains only those that substantively improve model performance. Results demonstrate the efficacy of gubernatorial and presidential approval ratings measured two quarters preelection in predicting both incumbent-party vote share and election winners in out-of-sample predictions. For 2022, our approach outperformed the Cook Political Report’s Partisan Voting Index and compared well with 538’s Election Day prediction. For 2024, our LASSO-Popularity model predictions indicate that it will likely be a difficult year for Democrats in gubernatorial contests.
Refugee Protection as a Public Good: What Benefits Do States Derive?
Authors: Lutz Philipp , Caballero-Vélez Diego
Published: October 2024

While a growing number of refugees is in need of humanitarian protection, most states are reluctant to admit them. For more than two decades, scholars have thought to understand this intricate challenge of international governance through the prism of collective action theory and the concept of refugee protection as an international public good. However, the specific benefits that states gain from refugee protection and that are assumed to constitute the public good remain surprisingly vague and under-specified. In this Reflection, we make three contributions to address this issue. First, we take stock of the literature and assess the evolution of the collective action theory in asylum governance. Second, we identify and conceptualize legitimacy, security, reputation, and development as four types of benefits that states derive from refugee protection. Third, we discuss the limitations of the dominant rational-choice approach and contend that the nature of refugee protection in the international realm is the product of international and domestic politics based on the contestation of interests and norms. These insights result in a series of recommendations for future research of refugee protection as a collective action problem.
Source Geometry and Rupture Characteristics of the 20 February 2023 Mw 6.4 Hatay (Türkiye) Earthquake at Southwest Edge of the East Anatolian Fault
Authors: Yolsal‐Çevikbilen Seda , Taymaz Tuncay , Irmak Tahir Serkan , Erman Ceyhun , Kahraman Metin , Özkan Berkan , Eken Tuna , Öcalan Taylan , Doğan Ali Hasan , Altuntaş Cemali
Published: October 2024

Following the catastrophic 6 February 2023 Mw 7.8 and Mw 7.6 Kahramanmaraş earthquakes in the East Anatolian Fault Zone (EAFZ; southeast Türkiye), numerous aftershocks occurred along the major branches of this left‐lateral shear zone. The spatio‐temporal distribution of the earthquakes implied the stress‐triggering effects of co‐seismic ruptures on closely connected fault segments over large distances. On the 20 February 2023 two earthquakes with Mw 6.4 and Mw 5.2 struck Hatay (Türkiye) located near the Samandağ‐Antakya segment of the EAFZ. To understand the rupture evolution of these earthquakes, we first re‐located the aftershock sequence that occurred over a 3‐month period in the Hatay‐Syria region. A normal faulting mechanism with a significant amount of left‐lateral strike‐slip component at a shallow focal depth of 12 km was estimated for the 2023 Mw 6.4 earthquake from the inversion of seismological data. Our slip models describe a relatively simple and unilateral rupture propagation along about 36 km‐long active segments of the EAFZ. The co‐seismic horizontal displacements inferred from the Global Navigation Satellite System data are compatible with the oblique slip kinematics. Furthermore, we suggest that this earthquake did not produce notable tsunami waves on the adjacent coasts since the rupture plane did not extend to the seafloor of the Eastern Mediterranean with substantial amount of vertical displacement. We reckon that a future large earthquake (Mw ≥ 7.0) in the Hatay‐Syria region where increased stress was transferred to the fault segments of the EAFZ and the Dead Sea Fault Zone (DSFZ) after the 2023 earthquakes will be a probable source of tsunami at the coastal plains of the Eastern Mediterranean Sea region.
Designing a Fully‐Tunable and Versatile TKE‐l Turbulence Parameterization for the Simulation of Stable Boundary Layers
Authors: Vignon É. , Arjdal K. , Cheruy F. , Coulon‐Decorzens M. , Dehondt C. , Dubos T. , Fromang S. , Hourdin F. , Lange L. , Raillard L. , Rivière G. , Roehrig R. , Sima A. , Spiga A. , Tiengou P.
Published: October 2024

This study presents the development of a so‐called Turbulent Kinetic Energy (TKE)‐l, or TKE‐l, parameterization of the diffusion coefficients for the representation of turbulent diffusion in neutral and stable conditions in large‐scale atmospheric models. The parameterization has been carefully designed to be completely tunable in the sense that all adjustable parameters have been clearly identified and the number of parameters has been minimized as much as possible to help the calibration and to thoroughly assess the parametric sensitivity. We choose a mixing length formulation that depends on both static stability and wind shear to cover the different regimes of stable boundary layers. We follow a heuristic approach for expressing the stability functions and turbulent Prandlt number in order to guarantee the versatility of the scheme and its applicability for planetary atmospheres composed of an ideal and perfect gas such as that of Earth and Mars. Particular attention has been paid to the numerical stability and convergence of the TKE equation at large time steps, an essential prerequisite for capturing stable boundary layers in General Circulation Models (GCMs). Tests, parametric sensitivity assessments and preliminary tuning are performed on single‐column idealized simulations of the weakly stable boundary layer. The robustness and versatility of the scheme are assessed through its implementation in the Laboratoire de Météorologie Dynamique Zoom GCM and the Mars Planetary Climate Model and by running simulations of the Antarctic and Martian nocturnal boundary layers.
Mucosal sugars delineate pyrazine vs pyrazinone autoinducer signaling in Klebsiella oxytoca
Authors: Hamchand Randy , Wang Kevin , Song Deguang , Palm Noah W. , Crawford Jason M.
Published: October 2024

Virulent Klebsiella oxytoca strains are associated with gut and lung pathologies, yet our understanding of the molecular signals governing pathogenesis remains limited. Here, we characterized a family of K. oxytoca pyrazine and pyrazinone autoinducers and explored their roles in microbial and host signaling. We identified the human mucin capping sugar Neu5Ac as a selective elicitor of leupeptin, a protease inhibitor prevalent in clinical lung isolates of K. oxytoca, and leupeptin-derived pyrazinone biosynthesis. Additionally, we uncovered a separate pyrazine pathway, regulated by general carbohydrate metabolism, derived from a broadly conserved PLP-dependent enzyme. While both pyrazine and pyrazinone signaling induce iron acquisition responses, including enterobactin biosynthesis, pyrazinone signaling enhances yersiniabactin virulence factor production and selectively activates the proinflammatory human histamine receptor H4 (HRH4). Our findings suggest that the availability of specific carbohydrates delineates distinct autoinducer pathways in K. oxytoca that may have differential effects on bacterial virulence and host immune responses.
A genome-first study of sex chromosome aneuploidies provides evidence of Y chromosome dosage effects on autism risk
Authors: Berry Alexander S. F. , Finucane Brenda M. , Myers Scott M. , Walsh Lauren K. , Seibert John M. , Martin Christa Lese , Ledbetter David H. , Oetjens Matthew T.
Published: October 2024

A female protective effect has long been postulated as the primary explanation for the four-fold increase of autism spectrum disorder (ASD) diagnoses in males versus females. However, genetic and epidemiological investigations of this hypothesis have so far failed to explain the large difference in ASD prevalence between the sexes. To address this knowledge gap, we examined sex chromosome aneuploidy in a large ASD case-control cohort to evaluate the relationship between X and Y chromosome dosage and ASD risk. From these data, we modeled three relationships between sex chromosome dosage and ASD risk: the extra Y effect, the extra X effect, and sex chromosome haploinsufficiency. We found that the extra Y effect increased ASD risk significantly more than the extra X effect. Among females, we observed a large association between 45, X and ASD, confirming sex chromosome haploinsufficiency as a strong ASD risk factor. These results provide a framework for understanding the relationship between X and Y chromosome dosage on ASD, which may inform future research investigating genomic contributors to the observed sex difference.