bluuebunny/crossref_metadata_2025 huggingface dataset:
Key Factors Influencing Urban Regenerative Strategies in Public Open Spaces: A Case-Study in Lhasa
Authors: Luo Zhengzheng , Marchi Lia , Zhang Yingzi , Chen Fangyu
Published: October 2024

In the last decades, significant efforts have been made in urban construction to achieve rapid economic development. However, with climate change on the agenda, there is a growing recognition of the importance of urban sustainable development and of its potential impacts on residents. Reflection reveals that many policies, measures, and tools are inadequate; therefore, public open spaces are regarded as a potential target of urban regeneration strategies. This study explores users’ perceptions of public open spaces through participatory methods. The developed methodology is applied to specific areas of Lhasa, the major city of the Tibet region, which was selected as a test-bed site. The survey involved a selected pool of participants and emphasized the coverage of different types of public open spaces. Investigate factors including personal background, overall satisfaction, user evaluation, usage preference, and willingness to change, analyze key factors based on quantitative survey results. Subsequently, identify the key regenerative design elements that require highlighting. The findings indicate that comfort and safety are emphasized by users of all types of public open spaces. Additionally, their initial impression upon entering a space significantly influences their overall satisfaction with it. Besides, although individual background differences play a role, they are not sufficient to significantly influence the user’s evaluation of the space. However, variations in the purpose of space use result in differences in user evaluations and needs, impacting their attitudes based on the type of space. Finally, urban regeneration design strategies are proposed for various types of public open spaces and users.
Enhancing climate adaptation design in urban areas: a workflow for climate integrated impact assessment
Authors: Verde Sara
Published: October 2024

Nowadays, urban settlements face the simultaneous occurrence of environmental, natural, and anthropogenic risks. In this scenario, the contribution proposes the definition of an operational workflow for climate-integrated impact assessment, to support climate adaptation design at the urban and building scale. The methodological approach focuses on the evaluation of heatwave and pluvial flooding integrated impacts to identify urban hotspots. A testing case in Naples is proposed. The workflow represents an innovative tool, employing a multi-hazard analysis at the local scale to assess climate impacts considering both vulnerability and exposure components of the built environment. Grounded in an evidence-based approach, the proposed workflow acts as an effective support tool for decision-makers in the preliminary stages of projects, considering the interaction between impact analysis and climate adaptation design at the local scale. The contribution is developed within the research Partenariato Esteso PE3, RETURN project (multi-Risk SciEnce for resilient commUnities undeR a changiNg climate) - Spoke TS1 “Urban and metropolitan settlements” activities.
Going beyond Climate Neutral Cities: Evidence from a Positive Energy District in the Stuttgart Region
Authors: Beatrice Andreucci Maria , Delli Paoli Marco , Kádár József
Published: October 2024

To successfully develops Positive Energy Districts (PEDs), it is essential to increase citizen awareness and encourage their engagement. Without acceptance and active participation from the citizens, they might not benefit from the technologies and inclusive business models that PEDs offer to foster energy efficiency, productivity, and flexibility. This contribution provides new evidence about the importance of prioritising citizens’ needs when developing PEDs, describing key findings from a case study recently conducted by the authors, in Nürtingen, in the Stuttgart Metropolitan Region, Germany. The research used urban building energy modeling tools, analyzed on-going projects of the city administration, and directly engaged with citizens by different research methods such as d go-along interviewing, SWOT analysis, and the promotion of best practices. The analysis and conclusions on working on the municipality project “Bahnstadt” were checked against the understanding of a “human-centred” PED. Five action areas were considered: energy efficiency, production and flexibility, carbon footprint, water management, and capital expenditures. This action research, part of the EU-funded project TELOS (2020-2024), aimed to provide recommendations to improve the quality of life of the community and enhancing citizen participation in planning and implementation processes, and towards the ambitious European climate neutrality goals.
Urban Digital Twins as socio-technical infrastructures for city regeneration and decarbonization
Authors: Roversi Rossella
Published: October 2024

The awareness of the huge carbon footprint and the related targets aimed at reducing it, require cities to be supported in their climate neutral transition. Urban Digital Twins (UDTs) have emerged as cutting-edge technologies to address urban complexity and to exploit the massive amount of machine-readable data produced by the city physical and non-physical systems. At the centre of the recent debate and scientific research, UDTs are addressed in a rapidly growing literature, pilot projects, proof-of-concepts and applications to several contexts. Studies and prototypes are leading the maturity development of UDT to gradually improve, contributing to gaining consensus among key stakeholders and urban decision makers, but the state of the art has not proved how exactly its potential benefits will be pursued and sustained. In this evolving scenario, the paper objective is the analysis of a literature review and a case studies selection, to identify the current use of the UDT as enabling tool in the comprehensive and joint framework of urban regeneration and decarbonization, addressing, in particular, the under-researched and poorly conceptualized integration of socio-economic-cultural systems.
Introduction
Authors: Kivivuori Janne
Published: October 2024

This chapter introduces the research questions of the book, the operative definition of criminology, and the historical context of its emergence. Criminology is defined as the study of crime and its control is based on large-scale and systematically collected data designed for research. Thus defined, the rise of criminology took place during the post-Napoleonic restoration age, between 1815 and the mid-1830s. The process culminated in and after the publication of the first modern crime report based on administrative statistics, the Compte général de l’administration de la justice criminelle en France (1827). The chapter describes the larger setting of the periodization by dividing the history of criminology into three eras defined by changes in data and instruments: the first criminology based on crime statistics, the second criminology based on measurement of individuals, and the third criminology based on crime surveys. Prior research, the sources, and key interpretive frames are discussed.
From piecemeal reform to incremental research
Authors: Kivivuori Janne
Published: October 2024

This chapter examines how the English scholarly circles responded to the continental rise of the first field of criminology. The continental model of statistical crime research triggered similar activities from the mid-1830s under the auspices of the London Statistical Society. Before that, the English development of crime returns, and their policy use by criminal law reformers, had already impacted the first generation of European crime researchers. The chapter discusses whether the English prehistory of crime returns can be seen as a ‘prequel’ to what happened on the continent from 1827. The decentred nature of crime statistical developments in England is contrasted with the central–bureaucratical path taken on the continent.
Benefits of an automated postoperative delirium risk prediction tool combined with non-pharmacological delirium prevention on delirium incidence and length of stay: a before–after analysis based on a quality improvement project
Authors: Dodsworth Benjamin T , Reeve Kelly A , Zozman Martin , Meier Philipp , Buddeberg Felix , Möller Marius , Wildhaber Simone Pascale , Kedda Mary-Anne , Böttger Sönke , Stocker Reto , Gelsomino Nayeli Schmutz
Published: October 2024

Background

Postoperative delirium (POD) significantly impacts older surgical patients, necessitating effective prevention strategies.

Objective

To assess the effectiveness of the Pre-Interventional Preventive Risk Assessment (PIPRA) automated delirium risk prediction tool alongside non-pharmacological prevention strategies on POD incidence, hospital length of stay (LOS) and nursing time.

Methods

This quality improvement project, set in a 335-bed Swiss private hospital, employed a before–after design to evaluate the impact of PIPRA and preventive measures on POD, LOS and nursing time in non-cardiac and non-intracranial surgery inpatients aged 60 or older. The control phase focused on enhancing POD screening, whilst the intervention phase incorporated PIPRA for risk assessment and staff training to enable targeted non-pharmacological prevention in patients at risk.

Results

A total of 866 patients were included; 299 control and 567 intervention. The odds ratio of POD, comparing the intervention group to the control, was 0.71 [95% confidence interval (CI) 0.44–1.16] when adjusting for baseline patient characteristics. The intervention was associated with an LOS 0.94 (95% CI 0.85–1.05) and nursing time 0.96 (95% CI 0.86–1.07) times that of the control, adjusted for baseline patient characteristics. Medium risk patients (21.6% of patients) had an LOS 0.74 (95% CI 0.59–0.92) and required nursing time 0.79 (95% CI from 0.62–1.00) times the control, adjusted for baseline patient characteristics, equivalent to an LOS reduction of 1.36 days and nursing time saving of 19.3 hours per patient.

Conclusions

Medium risk patients in the intervention group had shorter LOS and nursing time compared to the control group, underscoring the importance of targeted prevention.
Blood Pressure on Ambulatory Monitoring and Risk for Cardiovascular Disease and All-Cause Mortality: Ecological Validity or Measurement Reliability?
Authors: Tanner Rikki M , Jaeger Byron C , Bradley Corey K , Thomas S Justin , Min Yuan-I , Hardy Shakia T , Irvin Marguerite Ryan , Shimbo Daichi , Schwartz Joseph E , Muntner Paul
Published: October 2024

BACKGROUND

The association with cardiovascular disease (CVD) is stronger for mean systolic blood pressure (SBP) estimated using ambulatory blood pressure monitoring (ABPM) vs. office measurements. Determining whether this is due to ABPM providing more measurement reliability or greater ecological validity can inform its use.

METHODS

We estimated the association of mean SBP based on 2 office measurements and 2, 5, 10, and 20 measurements on ABPM with incident CVD in the Jackson Heart Study (n = 773). Hazard ratios (HRs) for CVD were estimated per standard deviation higher mean SBP. CVD events were defined by incident fatal or non-fatal stroke, non-fatal myocardial infarction, or fatal coronary heart disease.

RESULTS

There were 80 CVD events over a median of 15 years. The adjusted HRs for incident CVD were 1.03 (95% CI: 0.90–1.19) for mean office SBP and 1.30 (95% CI: 1.12–1.50), 1.34 (95% CI: 1.15–1.56), 1.36 (95% CI: 1.17–1.59), and 1.38 (95% CI: 1.17–1.63) for mean SBP using the first 2, 5, 10, and 20 ABPM readings. The difference in the HRs for incident CVD ranged from 0.26 (95% CI: 0.07–0.46) to 0.35 (95% CI: 0.15–0.54) when comparing mean office SBP vs. 2, 5, 10, or 20 sequential ABPM readings. The association with incident CVD was also stronger for mean SBP based on 2, 5, 10, and 20 randomly selected ABPM readings vs. 2 office readings.

CONCLUSIONS

Mean SBP based on 2 ABPM readings vs. 2 office measurements had a stronger association with CVD events. The increase in the strength of the association with more ABPM readings was small.
Pioneering bioinformatics with agent-based modelling: an innovative protocol to accurately forecast skin or respiratory allergic reactions to chemical sensitizers
Authors: Russo Giulia , Crispino Elena , Casati Silvia , Corsini Emanuela , Worth Andrew , Pappalardo Francesco
Published: October 2024

The assessment of the allergenic potential of chemicals, crucial for ensuring public health safety, faces challenges in accuracy and raises ethical concerns due to reliance on animal testing. This paper presents a novel bioinformatic protocol designed to address the critical challenge of predicting immune responses to chemical sensitizers without the use of animal testing. The core innovation lies in the integration of advanced bioinformatics tools, including the Universal Immune System Simulator (UISS), which models detailed immune system dynamics. By leveraging data from structural predictions and docking simulations, our approach provides a more accurate and ethical method for chemical safety evaluations, especially in distinguishing between skin and respiratory sensitizers. Our approach integrates a comprehensive eight-step process, beginning with the meticulous collection of chemical and protein data from databases like PubChem and the Protein Data Bank. Following data acquisition, structural predictions are performed using cutting-edge tools such as AlphaFold to model proteins whose structures have not been previously elucidated. This structural information is then utilized in subsequent docking simulations, leveraging both ligand–protein and protein–protein interactions to predict how chemical compounds may trigger immune responses. The core novelty of our method lies in the application of UISS—an advanced agent-based modelling system that simulates detailed immune system dynamics. By inputting the results from earlier stages, including docking scores and potential epitope identifications, UISS meticulously forecasts the type and severity of immune responses, distinguishing between Th1-mediated skin and Th2-mediated respiratory allergic reactions. This ability to predict distinct immune pathways is a crucial advance over current methods, which often cannot differentiate between the sensitization mechanisms. To validate the accuracy and robustness of our approach, we applied the protocol to well-known sensitizers: 2,4-dinitrochlorobenzene for skin allergies and trimellitic anhydride for respiratory allergies. The results clearly demonstrate the protocol’s ability to differentiate between these distinct immune responses, underscoring its potential for replacing traditional animal-based testing methods. The results not only support the potential of our method to replace animal testing in chemical safety assessments but also highlight its role in enhancing the understanding of chemical-induced immune reactions. Through this innovative integration of computational biology and immunological modelling, our protocol offers a transformative approach to toxicological evaluations, increasing the reliability of safety assessments.
Semiparametric sensitivity analysis: unmeasured confounding in observational studies
Authors: Nabi Razieh , Bonvini Matteo , Kennedy Edward H , Huang Ming-Yueh , Smid Marcela , Scharfstein Daniel O
Published: October 2024

Establishing cause–effect relationships from observational data often relies on untestable assumptions. It is crucial to know whether, and to what extent, the conclusions drawn from non-experimental studies are robust to potential unmeasured confounding. In this paper, we focus on the average causal effect (ACE) as our target of inference. We generalize the sensitivity analysis approach developed by Robins et al., Franks et al., and Zhou and Yao. We use semiparametric theory to derive the non-parametric efficient influence function of the ACE, for fixed sensitivity parameters. We use this influence function to construct a one-step, split sample, truncated estimator of the ACE. Our estimator depends on semiparametric models for the distribution of the observed data; importantly, these models do not impose any restrictions on the values of sensitivity analysis parameters. We establish sufficient conditions ensuring that our estimator has $\sqrt{n}$ asymptotics. We use our methodology to evaluate the causal effect of smoking during pregnancy on birth weight. We also evaluate the performance of estimation procedure in a simulation study.
Framing challenges and polarized issues in invasion science: toward an interdisciplinary agenda
Authors: Guareschi Simone , Mathers Kate L , South Josie , Navarro Laetitia M , Renals Trevor , Hiley Alice , Antonsich Marco , Bolpagni Rossano , Bortolus Alejandro , Genovesi Piero , Jere Arthertone , Madzivanzira Takudzwa C , Phaka Fortunate M , Novoa Ana , Olden Julian D , Saccó Mattia , Shackleton Ross T , Vilà Montserrat , Wood Paul J
Published: October 2024

In a hyperconnected world, framing and managing biological invasions poses complex and contentious challenges, affecting socioeconomic and environmental sectors. This complexity distinguishes the field and fuels polarized debates. In the present article, we synthesize four contentious issues in invasion science that are rarely addressed together: vocabulary usage, the potential benefits of nonnative species, perceptions shifting because of global change, and rewilding practices and biological invasions. Researchers have predominantly focused on single issues; few have addressed multiple components of the debate within or across disciplinary boundaries. Ignoring the interconnected nature of these issues risks overlooking crucial cross-links. We advocate for interdisciplinary approaches that better integrate social and natural sciences. Although they are challenging, interdisciplinary collaborations offer hope to overcome polarization issues in invasion science. These may bridge disagreements, facilitate knowledge exchange, and reshape invasion science narratives. Finally, we present a contemporary agenda to advance future research, management, and constructive dialogue.
Iliac vein obstruction: accuracy of direct multidetector computed tomographic venography and duplex ultrasound
Authors: Abdalla Ahmed Shimaa , Elbadawy Ahmed , Khalaf Lamiaa M R , Samy Marwa
Published: October 2024

Objectives

To evaluate the accuracy of direct computed tomographic venography (DCTV) and duplex ultrasound (DUS) in the identification of iliac vein obstruction in highly symptomatic patients with severe chronic venous disease (CVD) compared with intravascular ultrasound (IVUS).

Methods

This study involved patients who had advanced CVD (CEAP C3-6). All patients underwent DCTV, venous duplex scanning, and IVUS. The presence of iliac vein obstruction was detected, and degree of obstruction was classified into three grades (grade I, 0%-49%; grade II, 50%-79%; and grade III, 80% or greater). The sensitivity, specificity, PPV, NPV, and accuracy were calculated for each modality compared with IVUS. Inter-observer agreement was assessed using the κ coefficient

Results

Of the 94 patients with CVD, IVUS identified iliac vein obstruction in 55 (58.5%) patients (25.5% was grade 1, 27.3% was grade 2, 47.3% was grade 3). The sensitivity, specificity of DCTV in diagnosing obstruction were 96%, 95% in grade 1; 100%, 100% grade 2; 100%, 100% in grade 3, respectively. The sensitivity, specificity of DUS were 63.9%, 65% in grade 1; 68%, 82% in grade 2, and 70%, 85% in grade 3, respectively. The overall agreement of DUS was 0.73 (95% CI, 0.70-0.79), and DCTV was 0.96 (95% CI, 0.91-0.97).

Conclusions

DUS is a reasonable initial imaging modality for the identification of significant iliac vein obstruction. DCTV provides an accurate reproducible imaging for accurate estimation needed for treatment planning.

Advances in knowledge

DCTV provides accurate reproducible radiological information required for treatment planning of patients with iliac vein obstruction including accurate assessment of site of obstruction, its morphology, and degree of obstruction and it can replace the use of indirect CT venography using smaller amount of contrast media with accurate diagnosis.
Chemotherapy switch for localized pancreatic cancer: a systematic review and meta-analysis
Authors: Dekker Esther N , Narayan Raja R , Ahmami Mohamed A , Meddouch Anis , Verkolf Eva M M , Gehrels Anne M , Besselink Marc G H , van Eijck Casper H J , Homs Marjolein Y V , Mostert Bianca , O’Kane Grainne M , de Wilde Roeland F , Wilmink Johanna W , O’Reilly Eileen M , Qadan Motaz , Groot Koerkamp Bas
Published: October 2024

Background

Patients with localized (that is non-metastatic) pancreatic ductal adenocarcinoma with an inadequate response or toxicity to first-line chemotherapy may benefit from chemotherapy switch. The aim was to explore the available data on the use and effect of chemotherapy switch, as reported in the literature.

Methods

A systematic search was conducted in Embase, MEDLINE (Ovid), the Web of Science, Cochrane, and Google Scholar on 1 December 2023. The main outcomes were the proportion of patients who underwent chemotherapy switch and the carbohydrate antigen 19-9 response and resection, R0 resection, and ypN0 resection rates after chemotherapy switch. Data were pooled using a random-effects model.

Results

A total of five retrospective studies, representing 863 patients with localized pancreatic ductal adenocarcinoma, were included and 226 of the 863 patients underwent chemotherapy switch. In four studies, first-line chemotherapy consisted of 5-fluorouracil/leucovorin/irinotecan with oxaliplatin (‘FOLFIRINOX’) and patients were switched to gemcitabine with nab-paclitaxel. Reasons for chemotherapy switch included an inadequate biochemical, clinical, or radiological response, or toxicity. Three studies compared patients who underwent chemotherapy switch with patients who only received first-line chemotherapy and found that the proportion of patients who underwent chemotherapy switch was 20.5% (95% c.i. 10.5% to 36.3%). The pooled resection rate after chemotherapy switch was 42.0% (95% c.i. 16.6% to 72.5%). Two studies compared the chance of resection after chemotherapy switch versus first-line chemotherapy alone and found a risk ratio of 0.88 (95% c.i. 0.65 to 1.18). Two studies, with a combined total of 576 patients, found similar postoperative survival for patients who underwent chemotherapy switch and patients who only received first-line chemotherapy.

Conclusion

One in five patients with localized pancreatic ductal adenocarcinoma underwent chemotherapy switch after an inadequate response or toxicity to first-line chemotherapy. The pooled resection rate after chemotherapy switch was 42% and similar in overall survival compared with first-line chemotherapy only. Three ongoing trials are investigating chemotherapy switch in patients with an inadequate radiological or carbohydrate antigen 19-9 response.
Schizophrenia-associated changes in neuronal subpopulations in the human midbrain
Authors: Alsema Astrid M , Puvogel Sophie , Kracht Laura , Webster Marree J , Shannon Weickert Cynthia , Eggen Bart J L , Sommer Iris E C
Published: October 2024

Dysfunctional GABAergic and dopaminergic neurons are thought to exist in the ventral midbrain of patients with schizophrenia, yet transcriptional changes underpinning these abnormalities have not yet been localized to specific neuronal subsets. In the ventral midbrain, control over dopaminergic activity is maintained by both excitatory (glutamate) and inhibitory (GABA) input neurons. To further elucidate neuron pathology at the single-cell level, we characterized the transcriptional diversity of distinct NEUN+ populations in the human ventral midbrain and then tested for schizophrenia-associated changes in neuronal subset proportions and gene activity changes within neuronal subsets.

Combining single nucleus RNA-sequencing with fluorescence-activated sorting of NEUN+ nuclei, we analysed 31,669 nuclei. Initially, we detected 18 transcriptionally distinct neuronal populations in the human ventral midbrain, including 2 “mixed” populations. The presence of neuronal populations in the midbrain was orthogonally validated with immunohistochemical stainings. “Mixed” populations contained nuclei expressing transcripts for vesicular glutamate transporter 2 (SLC17A6) and Glutamate Decarboxylase 2 (GAD2), but these transcripts were not typically co-expressed by the same nucleus. Upon more fine-grained subclustering of the 2 “mixed” populations, 16 additional subpopulations were identified that were transcriptionally classified as excitatory or inhibitory. In the midbrains of individuals with schizophrenia, we observed potential differences in the proportions of two (sub)populations of excitatory neurons, two subpopulations of inhibitory neurons, one “mixed” subpopulation, and one subpopulation of TH-expressing neurons.

This may suggest that transcriptional changes associated with schizophrenia broadly affect excitatory, inhibitory, and dopamine neurons. We detected 99 genes differentially expressed in schizophrenia compared to controls within neuronal subpopulations identified from the 2 “mixed” populations, with the majority (67) of changes within small GABAergic neuronal subpopulations. Overall, single-nucleus transcriptomic analyses profiled a high diversity of GABAergic neurons in the human ventral midbrain, identified putative shifts in the proportion of neuronal subpopulations, and suggested dysfunction of specific GABAergic subpopulations in schizophrenia, providing directions for future research.
Effects of Respiratory Isolation for Tuberculosis to Reduce Community-based Transmission: A Systematic Review
Authors: Nathavitharana Ruvandhi R , Pearl Abarna , Biewer Amanda , Young Laura , Mukasa Leonard , Delrooz Naveed , Subramanian Advaith , Miller Sarah , Mase Sundari , Munsiff Sonal S , Nardell Edward
Published: October 2024

Background

Respiratory isolation of people with pulmonary tuberculosis (TB), including after treatment initiation, is used to prevent community-based transmission; yet guidelines on duration are limited and implementation is heterogeneous. This systematic review synthesized evidence on respiratory isolation for TB to inform National TB Coalition of America guidelines.

Methods

After searching 6 databases, 8 reviewers screened and extracted data in duplicate on effects of respiratory isolation compared to no isolation or masking. Studies were stratified by outcomes: TB infection or disease in contacts, mortality, hospitalization duration, patient and health system costs, and impact on mental health or stigma. We used a convergent integrated approach to synthesize quantitative and qualitative findings and assess limitations.

Results

Seventeen studies were included. There were limited data directly comparing isolation to non-isolation interventions, including effects after treatment initiation. One randomized controlled trial suggested treatment in a sanatorium versus at home did not affect TB incidence in contacts. Modeling studies suggest isolation may reduce transmission but relied on various assumptions, and isolation was implemented alongside other interventions. Descriptive, mixed-methods, and qualitative studies described adverse impacts of isolation on employment, education, food/housing security, and mental health due to transmission fears, stigma, and social isolation. Impacts were compounded in marginalized groups including Indigenous and incarcerated persons.

Conclusions

Data to support current isolation practices, particularly after effective treatment initiation, to reduce TB transmission in communities are limited. Public health guidance should weigh the negative impacts on people with TB against decreased community transmission to make evidence-based decisions about respiratory isolation.
Trust, Contextual Impartiality, and Open-Mindedness in Investor-State Dispute Settlement
Authors: Brekoulakis Stavros , Howard Anna
Published: October 2024

This article analyses impartiality in Investor-State Dispute Settlement (ISDS) by identifying the way that the parties’ trust in arbitrators is constructed. Drawing on the findings of a large-scale empirical project, it questions the applicability of an orthodox judicial doctrine of impartiality to ISDS on the grounds that trust in arbitrators is constructed on a fundamentally different basis from that of trust in judges. The primary feature of a judicial doctrine of impartiality is that trust is founded on an absolutist approach to impartiality which is intended to ensure that judges have no predispositions to parties. In contrast, trust in ISDS is founded on the method of party appointment which is based on a very different assumption—that arbitrators’ predispositions can be valuable and appropriate in the decision-making process. Drawing on empirical findings, moral philosophy, and psychology, this article proposes the idea of contextual impartiality. Under this approach, the question is not whether an arbitrator can meet universal standards of impartiality irrespective of the context within which the arbitrator operates. Rather, the critical distinction is between permissible and impermissible partiality which depends on whether the individual is reasonably expected to act partially because of their circumstances. In this respect, the article identifies open-mindedness as a fundamental feature of a contextual approach to impartiality and a bright line between permissible and impermissible partiality.
StopKB: a comprehensive knowledgebase for nonsense suppression therapies
Authors: Haas Nicolas , Thompson Julie Dawn , Renaud Jean-Paul , Chennen Kirsley , Poch Olivier
Published: October 2024

Nonsense variations, characterized by premature termination codons, play a major role in human genetic diseases as well as in cancer susceptibility. Despite their high prevalence, effective therapeutic strategies targeting premature termination codons remain a challenge. To understand and explore the intricate mechanisms involved, we developed StopKB, a comprehensive knowledgebase aggregating data from multiple sources on nonsense variations, associated genes, diseases, and phenotypes. StopKB identifies 637 317 unique nonsense variations, distributed across 18 022 human genes and linked to 3206 diseases and 7765 phenotypes. Notably, ∼32% of these variations are classified as nonsense-mediated mRNA decay-insensitive, potentially representing suitable targets for nonsense suppression therapies. We also provide an interactive web interface to facilitate efficient and intuitive data exploration, enabling researchers and clinicians to navigate the complex landscape of nonsense variations. StopKB represents a valuable resource for advancing research in precision medicine and more specifically, the development of targeted therapeutic interventions for genetic diseases associated with nonsense variations.

Database URL: https://lbgi.fr/stopkb/
Optimal polyandry in fruit flies
Authors: Yan Janice L , Rosenbaum Jack R , Yang Dan , Dukas Reuven
Published: October 2024

The study of polyandry has received increasing scientific attention with an emphasis on the fitness benefits and costs that females derive from mating with multiple males. There are still gaps in our understanding of how polyandry affects female fitness, however, as many previous studies compared the fitness outcomes of a single mating vs. 2 or 3 matings and did not separate the consequences of multiple mating from the costs of sexual harassment. We, therefore, conducted controlled mating trials with female fruit flies (Drosophila melanogaster) that could mate at either low (every 8 days), medium (every 4 days), or high (every other day) rates while controlling for exposure to harassment from males. We found that female lifetime fitness was highest under the high mating-rate followed by the medium mating-rate conditions. Moreover, we did not detect reductions in lifespan as a consequence of higher rates of polyandry. Our results demonstrate that even at realistically high rates, polyandry can lead to net fitness benefits for females, which can have major implications for sexual selection. Specifically, we discuss the significance of our findings as they relate to competition and the evolution of secondary sex characteristics in females, and sperm competition among males.
A predictive model and rapid multi-dynamic algorithm developed based on tumor-stroma percentage in gastric cancer: a retrospective, observational study
Authors: Xu Yitian , Yang Yan , Cheng Feichi , Luo Zai , Zhang Yuan , Zhang Pengshan , Qiu Jiahui , Qiu Zhengjun , Huang Chen
Published: October 2024

Background

Tumor-stroma percentage (TSP) is a prognostic risk factor in numerous solid tumors. Despite this, the prognostic significance of TSP in gastric cancer (GC) remains underexplored. Through the development of a personalized predictive model and a semi-automatic identification system, our study aimed to fully unlock the predictive potential of TSP in GC.

Methods

We screened GC patients from Shanghai General Hospital (SGH) between 2012 and 2019 to develop and validate a nomogram. Univariate and multivariate Cox proportional hazards regression analyses were employed to identify independent prognostic factors influencing the prognosis for GC patients. The nomogram was further validated externally by using a cohort from Bengbu Medical College (BMC). All patients underwent radical gastrectomy, with those diagnosed with locally advanced GC receiving adjuvant chemotherapy. The primary outcome measured was overall survival (OS). The semi-automatic identification of the TSP was achieved through a computer-aided detection (CAD) system, denoted as TSP-cad, while TSP identified by pathologists was labeled as TSP-visual.

Results

A total of 813 GC patients from SGH and 59 from BMC were enrolled in our study. TSP-visual was identified as an adverse prognostic factor for OS in GC and was found to be associated with pathological Tumor Node Metastasis staging system (pTNM) stage, T stage, N stage, perineural invasion (PNI), lymphovascular invasion (LVI), TSP-visual, tumor size, and other factors. Multivariate Cox regression using the training cohort revealed that TSP-visual (hazard ratio [HR], 2.042; 95% confidential interval [CI], 1.485–2.806; P < 0.001), N stage (HR, 2.136; 95% CI, 1.343–3.397; P = 0.010), PNI (HR , 1.791; 95% CI, 1.270–2.526; P = 0.001), and LVI (HR, 1.482; 95% CI, 1.021–2.152; P = 0.039) were independent predictors. These factors were incorporated into a novel nomogram, which exhibited strong predictive accuracy for 5-year OS in the training, internal validation, and external validation cohorts (area under the curve = 0.744, 0.759, and 0.854, respectively). The decision curve analysis of the nomogram and concordance indexes across the three cohorts outperformed the traditional pTNM (P < 0.05). Additionally, TSP-cad assessment using a rapid multi-dynamic algorithm demonstrated good agreement with TSP-visual.

Conclusions

The novel nomogram based on TSP could effectively identify individuals at risk of a poor prognosis among patients with GC. TSP-cad is anticipated to enhance the evaluation process of TSP.
Mutation potentiates migration swamping in polygenic local adaptation
Authors: Sakamoto Takahiro , Whiting James R , Yeaman Sam
Published: October 2024

Locally adapted traits can exhibit a wide range of genetic architectures, from pronounced divergence at a few loci to small frequency divergence at many loci. The type of architecture that evolves depends strongly on the migration rate, as weakly selected loci experience swamping and do not make lasting contributions to divergence. Simulations from previous studies showed that even when mutations are strongly selected and should resist migration swamping, the architecture of adaptation can collapse and become transient at high mutation rates. Here, we use an analytical two-population model to study how this transition in genetic architecture depends upon population size, strength of selection, and parameters describing the mutation process. To do this, we develop a mathematical theory based on the diffusion approximation to predict the threshold mutation rate above which the transition occurs. We find that this performs well across a wide range of parameter space, based on comparisons with individual-based simulations. The threshold mutation rate depends most strongly on the average effect size of mutations, weakly on the strength of selection, and marginally on the population size. Across a wide range of the parameter space, we observe that the transition to a transient architecture occurs when the trait-wide mutation rate is 10−3–10−2, suggesting that this phenomenon is potentially relevant to complex traits with a large mutational target. On the other hand, based on the apparent stability of genetic architecture in many classic examples of local adaptation, our theory suggests that per-trait mutation rates are often relatively low.
Mental health literacy of adolescents in Bermuda, according to age, gender and race
Authors: Cavanagh Daniel , Jorm Anthony , Reavley Nicola , Basden Shawnee , Hart Laura M
Published: October 2024

Mental health literacy (MHL) is an important part of the help-seeking process, yet there is a lack of knowledge about the MHL of adolescents in the Caribbean. This region is important to study as it is underrepresented in mental health research globally. The aim of this study is to explore the ability of adolescents in Bermuda to recognize depression and social phobia (social anxiety) and their beliefs about the sources of help for a peer with these mental health problems. This cross-sectional study surveyed middle and high school students aged 10–19 years in Bermuda. Online surveys conducted between November 2022 and June 2023 gathered demographic data including age, gender and race, and assessed the ability to recognize depression and social anxiety from descriptions provided in randomly assigned vignettes, and beliefs about sources of help. Across 15 middle and high schools, 2423 adolescents (out of 3593 eligible participants) completed all demographic and MHL survey questions (1139 males, 1272 females). Recognition rates for depression and social anxiety were 60% and 53%, respectively. Compared to females, males endorsed a greater variety of help sources. Reporting symptoms of depression or anxiety reduced the likelihood of endorsing multiple sources of help. MHL of adolescents in Bermuda is sub-optimal, particularly for social anxiety. Mental health promotion programs may be useful in improving recognition rates.
Maintaining breed integrity: Successful introgression of the SLICK1 allele into the Holstein breed
Authors: Zayas Gabriel A , Dikmen Serdal , Mateescu Raluca G , Hansen Peter J
Published: October 2024

This study evaluated the effectiveness of genetic introgression of the SLICK1 allele derived from Senepol cattle into the Holstein breed to enhance thermotolerance. The SLICK1 allele, located in the PRLR gene, confers a short and sleek coat that is inherited as a simple dominant phenotype. Approximately 40 years ago, the University of Florida initiated efforts to introgress this allele into the Holstein population. Here we tracked the introgression of the SLICK1 allele using a medium-density genotyping array and a reference population of both breeds (50 Holstein, 46 Senepol). Among the 31 SLICK1+ Holsteins, there was 15.25% ± 11.11% (mean ± SD) Senepol ancestry on BTA20. Holsteins at the University of Florida descended from slick matings that did not inherit the SLICK1 allele (n = 9) exhibited no Senepol ancestry. A secondary introgression of Senepol genetics in SLICK1+ animals was found on BTA4, spanning 54 markers and 15 genes, with 26.67% Senepol ancestry. This region, previously linked to heat stress adaptation, suggests that the introgression extends beyond the SLICK1 allele to incorporate additional beneficial genetics for thermal stress adaptation. These findings indicate that deliberate introgression of the SLICK1 allele enhances specific traits and potentially introduces other adaptive genetic variations. The study demonstrates the successful use of genetic interventions to improve livestock resilience against environmental challenges without significantly disrupting the recipient breed’s genetic structure. The introgression of the SLICK1 allele serves as a model for breeding programs aimed at optimizing animal welfare and productivity in the face of global climate change while maintaining breed integrity.
Incumbent or Challenger?—Assessing Ecosystem Competition in the DMA
Authors: van den Boom Jasper
Published: October 2024

This article examines the role of ecosystem competition and ecosystem power in designating gatekeepers under the Digital Markets Act (DMA). The study is prompted by ByteDance’s objections to its designation, where it describes itself as a challenger instead of a gatekeeper. The article highlights the differing perspectives of ByteDance, TikTok’s parent company, and the European Commission. ByteDance’s ‘challenger defence’ rests on the idea that they lack ecosystem power. Despite its success within the core platform service, the size of their ecosystem of products is small in comparison to other gatekeepers. This would indicate that they are not entrenched. The Commission focuses on gatekeeper power, and views ByteDance as another incumbent gatekeeper. The Commission currently conducts a very limited assessment of ecosystem power when designating gatekeepers, making it difficult to determine the validity of the ‘challenger defence’. Incorporating a more extensive assessment of ecosystem power and competition between ecosystem operators could enhance fairness and market contestability. Ignoring this aspect could lead to negative consequences and produce negative effects for users and competition in the long-term. The article proposes that there are benefits to contestability if the Commission expands its assessment to include ecosystem competition and offers suggestions on procedural implementation and effectuation of this broader analysis.
Bildung and the significance of place: an overview
Authors: Korsgaard Morten Timmermann , Hilt Line , Wiberg Merete , Solberg Mariann
Published: October 2024

This introduction attempts to map out the educational and philosophical landscape in which the individual papers move. The movement from the familiar to the unknown, from alienation to homeliness, has been central to theories of Bildung since their emergence, while the role of the specific materiality of places in which Bildung takes place has remained somewhat unexplored. This special issue engages the perennial tensions and questions emerging with the notion of Bildung as these appear in literature and philosophy from the vantage point of place.
The Impact of Anterior Pelvic Tilt on Return to Duty/Return to Run in Active Duty Personnel After Hip Arthroscopy for Femoroacetabular Impingement
Authors: Rogers Jill , Garcia E’Stephan , Lopez Preston , Bader Julia
Published: October 2024

Introduction

Annually, 300,000 soldiers are rendered medically nondeployable because of musculoskeletal injuries (MSKIs). Of this population, nearly 10,000 (3.3%) involve injuries to the hip. Factors related to these injuries impose significant healthcare, financial, and readiness burdens on the Army system, degrading overall mission readiness. The purpose of this retrospective study was to assess for correlation between increased anterior pelvic tilt and a lower likelihood for return to duty/return to run (RTD/RTR) in active duty personnel who underwent hip arthroscopy for femoroacetabular impingement (FAI), thus identifying increased anterior pelvic tilt as a potential prognostic indicator for RTD/RTR.

Materials and Methods

Ninety-two active duty U.S. Army service members aged 18 years or older who underwent hip arthroscopy for FAI at the William Beaumont Army Medical Center from September 1, 2014, to September 1, 2019, were included. Utilizing a retrospective review of existing data, the amount of anterior pelvic tilt, as estimated on a presurgical weight-bearing anterior–posterior pelvis radiograph using the distance from the pubic symphysis to the transischial line, was measured and compared to postoperative RTD/RTR statuses, assessing for correlation.

Results

The overall RTD rate was 39.1% with a 22.8% RTR rate. Only 6.5% (6/92) of subjects returned to full, unrestricted duty and running. Logistic regression analyses showed that individuals with increased anterior pelvic tilt (≥7°) were 2.6 times less likely to RTD and 2.9 times less likely to RTR compared to those with minimal or no anterior pelvic tilt (<7°) (respectively, odds ratio (OR) 2.619; 95% CI, 1.107-6.195; P = .029 and OR 2.897; 95% CI, 1.041-8.059; P = .042). Results support the study teams’ hypothesis that increased anterior pelvic tilt is associated with a lower odds of RTD/RTR.

Conclusions

Statistical analysis confirmed the correlation between an increased amount of anterior pelvic tilt and a lower odds of RTD and RTR after hip arthroscopy for FAI in active duty U.S. Army personnel. This information can be used in patient counseling to better inform shared decision-making, provide more thorough informed consent, and help determine the optimal timing for surgical intervention, thus contributing to better stewardship of medical resources and decreasing the ever-growing financial healthcare burden. These findings will spur future research to consider the causes and optimal treatment of anterior pelvic tilt, positively impacting the culture of Army medicine by focusing on preventive and targeted treatments in order to preserve and grow the force.
MeerKAT observations of Herschel protocluster candidates
Authors: Ding Y , Clements D L , Leeuw L L , Heywood I , Dannerbauer H , Parmar A , Legodi P , Ivison R J , Blake R , Gutiérrez C M , Carnero A , Sutherland W
Published: October 2024

High-redshift protoclusters consisting of dusty starbursts are thought to play an important role in galaxy evolution. Their dusty nature makes them bright in the far-infrared (FIR)/submm but difficult to find in optical/near-infrared (NIR) surveys. Radio observations are an excellent way to study these dusty starbursts, as dust is transparent in the radio and there is a tight correlation between the FIR and radio emission of a galaxy. Here, we present MeerKAT 1.28 GHz radio imaging of three Herschel candidate protoclusters, with a synthesized beam size of $\sim 7.5\, \mathrm{ arcsec}\times 6.6$ arcsec and a central thermal noise down to $4.35~\mu$Jy beam−1. Our source counts are consistent with other radio counts with no evidence of overdensities. Around 95 per cent of the Herschel sources have 1.28 GHz IDs. Using the Herschel$250~\mu$m primary beam size as the searching radius, we find 54.2 per cent Herschel sources have multiple 1.28 GHz IDs. Our average FIR-radio correlation coefficient $q_{250\mu \text{m}}$ is $2.33\pm 0.26$. Adding $q_{250\mu \text{m}}$ as a new constraint, the probability of finding chance-aligned sources is reduced by a factor of $\sim 6$, but with the risk of discarding true identifications of radio-loud/quiet sources. With accurate MeerKAT positions, we cross-match our Herschel sources to optical/NIR data followed by photometric redshift estimations. By removing $z< 1$ sources, the density contrasts of two of the candidate protoclusters increase, suggestive of them being real protoclusters at $z> 1$. There is also potentially a $0.9< z< 1.2$ overdensity associated with one candidate protocluster. In summary, photometric redshifts from radio-optical cross-identifications have provided some tentative evidence of overdensities aligning with two of the candidate protoclusters.