bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine learning-based test smell detection
Authors: Pontillo Valeria , Amoroso d’Aragona Dario , Pecorelli Fabiano , Di Nucci Dario , Ferrucci Filomena , Palomba Fabio
Published: March 2024

Test smells are symptoms of sub-optimal design choices adopted when developing test cases. Previous studies have proved their harmfulness for test code maintainability and effectiveness. Therefore, researchers have been proposing automated, heuristic-based techniques to detect them. However, the performance of these detectors is still limited and dependent on tunable thresholds. We design and experiment with a novel test smell detection approach based on machine learning to detect four test smells. First, we develop the largest dataset of manually-validated test smells to enable experimentation. Afterward, we train six machine learners and assess their capabilities in within- and cross-project scenarios. Finally, we compare the ML-based approach with state-of-the-art heuristic-based techniques. The key findings of the study report a negative result. The performance of the machine learning-based detector is significantly better than heuristic-based techniques, but none of the learners able to overcome an average F-Measure of 51%. We further elaborate and discuss the reasons behind this negative result through a qualitative investigation into the current issues and challenges that prevent the appropriate detection of test smells, which allowed us to catalog the next steps that the research community may pursue to improve test smell detection techniques.
Enhancing dietary diversity and food security through the adoption of climate-smart agricultural practices in Nigeria: a micro level evidence
Authors: Omotoso Abeeb Babatunde , Omotayo Abiodun Olusola
Published: March 2024

The paranoid belief that climate change will gradually reduce the ability of the world to meet the demand for food serves as the rationale for Nigerian smallholder farmers’ advocacy of climate-smart agriculture (CSA) techniques. The study investigates the effects of CSA practice on the food security status of rural farming households in Nigeria. A multi-stage sampling technique was employed in selecting 480 rural farming households across three selected states from Southwest, Nigeria. Data were analyzed using descriptive and inferential statistics. Obtained results showed that 59.79% of the respondents were food insecure while severe and depth of food insecure among the farming households were 0.0711 and 0.1913 respectively. The result of the household dietary diversity score revealed the diverse consumption-ability of the respondents and the contributions of CSA practice in their farming system. This implies that households engaged in climate-smart farming are more likely to achieve higher levels of food consumption score, dietary diversity, and food security. The probit regression revealed that the food security status among rural farming households was significantly influenced by household heads’ gender, farm size, and contact with extension agents as well as adopted CSA practices such as crop diversification, agroforestry, and use of Fadama land for agricultural activities. This research concludes that CSA lowered the probability of food insecurity among rural farming households in Nigeria. Accordingly, the study suggests that the government and the key players should encourage the use of CSA practices in order to ensure agricultural sustainability and food security in agrarian communities by reducing the impact of climate change.
Work, Heat and Internal Energy in Open Quantum Systems: A Comparison of Four Approaches from the Autonomous System Framework
Authors: Seegebrecht Anja , Schilling Tanja
Published: March 2024

We compare definitions of the internal energy of an open quantum system and strategies to split the internal energy into work and heat contributions as given by four different approaches from the autonomous system framework. Our discussion focuses on methods that allow for arbitrary environments (not just heat baths) and driving by a quantum mechanical system. As a simple application we consider an atom as the system of interest and an oscillator field mode as the environment. Three different types of coupling are analyzed. We discuss ambiguities in the definitions and highlight differences that appear if one aims at constructing environments that act as pure heat or work reservoirs. Further, we identify different sources of work (e.g. coherence, correlations, or frequency offset), depending on the underlying framework. Finally, we give arguments to favour the approach based on minimal dissipation.
Transcriptome profiling of longissimus dorsi during different prenatal stages to identify genes involved in intramuscular fat deposition in lean and obese pig breeds
Authors: Chen Jun Feng , Wang Jing , Chai Jin , Jin Wei , Ren Qiao Ling , Ma Qiang , Lu Qing Xia , Sun Jia Jie , Mo De Lin , Zhang Jia Qing , Xing Bao Song
Published: March 2024

Background

There was significant difference in muscle development between fat-type and lean-type pig breeds.

Methods and results

In current study, transcriptome analysis and bioinformatics analysis were used to compare the difference in longissimus dorsi (LD) muscle at three time-points (38 days post coitus (dpc), 58 dpc, and 78 dpc ) between Huainan (HN) and Large white (LW) pig breeds. A total of 24500 transcripts were obtained in 18 samples, and 2319, 2799, and 3713 differently expressed genes (DEGs) were identified between these two breeds at 38 dpc, 58 dpc, and 78 dpc, respectively. And the number and foldchange of DEGs were increased, the alternative splice also increased. The cluster analysis of DEGs indicated the embryonic development progress of LD muscle between these two breeds was different. There were 539 shared DEGs between HN and LW at three stages, and the top-shared DEGs were associated with muscle development and lipid deposition, such as KLF4, NR4A1, HSP70, ZBTB16 and so on.

Conclusions

The results showed DEGs between Huainan (HN) and Large white (LW) pig breeds, and contributed to the understanding the muscle development difference between HN and LW, and provided basic materials for improvement of meat quality.
The assessment of probabilistic seismic risk using ground-motion simulations via a Monte Carlo approach
Authors: Rudman Archie , Douglas John , Tubaldi Enrico
Published: March 2024

Accurately characterizing ground motions is crucial for estimating probabilistic seismic hazard and risk. The growing number of ground-motion models, and increased use of simulations in hazard and risk assessments, warrants a comparison between the different techniques available to predict ground motions. This research aims at investigating how the use of different ground-motion models can affect seismic hazard and risk estimates. For this purpose, a case study is considered with a circular seismic source zone and two line sources. A stochastic ground-motion model is used within a Monte Carlo analysis to create a benchmark hazard output. This approach allows the generation of many records, helping to capture details of the ground-motion median and variability, which a ground motion prediction equation may fail to properly model. A variety of ground-motion models are fitted to the simulated ground motion data, with fixed and magnitude-dependant standard deviations (sigmas) considered. These include classic ground motion prediction equations (with basic and more complex functional forms), and a model using an artificial neural network. Hazard is estimated from these models and then we extend the approach to a risk assessment for an inelastic single-degree-of-freedom-system. Only the artificial neural network produces accurate hazard results below an annual frequency of exceedance of 1 × 10–3 years−1. This has a direct impact on risk estimates—with ground motions from large, close-to-site events having more influence on results than expected. Finally, an alternative to ground-motion modelling is explored through an observational-based hazard assessment which uses recorded strong-motions to directly quantify hazard.
Patient experiences in ulcerative colitis: conceptual model and review of patient-reported outcome measures
Authors: Kim Chong , Brown Fiona L. , Burk Caroline , Anatchkova Milena , Sargalo Nashmel , Kaushik Ankita
Published: March 2024

Purpose

To identify symptoms and their impacts on daily functioning and health-related quality of life (HRQoL) experienced by adult patients with ulcerative colitis (UC) and evaluate patient-reported outcome (PRO) measures for UC clinical studies.

Methods

A conceptual model of symptoms and impacts of UC were developed from a literature review. PRO measures were identified from the literature, clinical trials databases, health technology assessment submissions, and regulatory label claims, and were selected for conceptual analysis based on disease specificity and use across information sources. PRO measures covering the most concepts when mapped against the conceptual model were assessed for gaps in psychometric properties using Food and Drug Administration (FDA) guidance and consensus-based standards for the selection of health measurement instruments (COSMIN) criteria.

Results

The conceptual model grouped the 52 symptom concepts and 72 proximal and distal impacts into eight, two, and five dimensions, respectively. Of 65 PRO measures identified, eight underwent conceptual analysis. Measures covering the most concepts and assessed for psychometric properties were the Inflammatory Bowel Disease Questionnaire, Symptoms and Impacts Questionnaire for UC, UC-PRO symptoms modules, UC-PRO impact modules, and Crohn’s and UC Questionnaire; all had good or excellent support for content validity. The UC-PRO Signs and Symptoms fully met FDA guidance and COSMIN criteria for content validity and most psychometric properties.

Conclusion

Existing PRO measures assess concepts relevant to patients with UC, but all PRO measures reviewed require further psychometric evaluation to demonstrate they are fit for purpose.
What is a mathematical structure of conscious experience?
Authors: Kleiner Johannes , Ludwig Tim
Published: March 2024

Several promising approaches have been developed to represent conscious experience in terms of mathematical spaces and structures. What is missing, however, is an explicit definition of what a ‘mathematical structure of conscious experience’ is. Here, we propose such a definition. This definition provides a link between the abstract formal entities of mathematics and the concreta of conscious experience; it complements recent approaches that study quality spaces, qualia spaces, or phenomenal spaces; and it provides a general method to identify and investigate structures of conscious experience. We hope that ultimately this work provides a basis for developing a common formal language to study consciousness.
Ballistic and Blast-Relevant, High-Rate Material Properties of Physically and Chemically Crosslinked Hydrogels
Authors: Bremer-Sai E. C. , Yang J. , McGhee A. , Franck C.
Published: March 2024

Background

Hydrogels are one of the most ubiquitous polymeric materials. Among them gelatin, agarose and polyacrylamide-based formulations have been effectively utilized in a variety of biomedical and defense-related applications including ultrasound-based therapies and soft tissue injury investigations stemming from ballistic and blast exposures. Interestingly, while in most cases accurate prediction of the mechanical response of these surrogate gels requires knowledge of the underlying finite deformation, high-strain rate material properties, it is these properties that have remained scarce in the literature.

Objective

Building on our prior works using Inertial Microcavitation Rheometry (IMR), here we present a comprehensive list of the high-strain rate (> 10$$^3$$

3

1/s) mechanical properties of these three popular classes of hydrogel materials characterized via laser-based IMR, further showing that the choice in finite-deformation, rate-dependent constitutive model can be informed directly by the type of crosslinking mechanism and resultant network structure of the hydrogel, thus providing a chemophysical basis of the the choice of phenomenological constitutive model.

Methods

We analyze existing experimental gelatin IMR datasets and compare the results with prior data on polyacrylamide.

Results

We show that a Neo-Hookean Kelvin-Voigt (NHKV) model can suitably simulate the high-rate material response of dynamic, physically crosslinked hydrogels like gelatin, while the introduction of a strain-stiffening parameter through the use of the quadratic Kelvin-Voigt (qKV) model was necessary to appropriately model chemically crosslinked hydrogels such as polyacrylamide due to the nature of the static,covalent bonds that comprise their structure.

Conclusions

In this brief we show that knowledge of the type of underlying polymer structure, including its bond mobility, can directly inform the appropriate finite deformation, time-dependent viscoelastic material model for commonly employed tissue surrogate hydrogels undergoing high strain rate loading within the ballistic and blast regimes.
A matter of trust: Public support for country ownership over aid
Authors: Hirose Kentaro , Montinola Gabriella R. , Winters Matthew S. , Kohno Masaru
Published: March 2024

International donors emphasize greater recipient-country ownership in the delivery of foreign assistance because it ostensibly promotes the efficient use of resources and strengthens recipient-country administrative capacity. The preferences of citizens in developing countries, however, are not well understood on this matter. Do they prefer that their own governments control foreign aid resources, or are there conditions under which they instead prefer that donors maintain control over how aid is implemented? We explore these questions through parallel survey experiments in Myanmar, Nepal, and Indonesia. Our experimental vignettes include two informational treatments: one about who implements aid (i.e., the donor or the recipient government) and the other about the trustworthiness of the foreign donor. The trust-in-donor treatment, on average, increases levels of support for aid in all three countries. In contrast, we observe heterogenous average treatment effects regarding aid control: control of aid by the donor rather than the government reduces levels of support in Indonesia and Myanmar, whereas it increases support levels in Nepal. We show how the cross-country variation in ATEs originates in consistent individual-level variation in reactions to aid control that is more shaped by respondents’ trust in their own government than their trust in the donor.
Reflections
Authors: Gur-Arye Miriam
Published: March 2024

Reflections on the various articles which will be published in the criminal law and philosophy dedicated to my retirement.
Motivations in the adoption and conversion of freemium services: insights for digital entrepreneurship
Authors: Martins João , Rodrigues Ricardo
Published: March 2024

Technological advancements have created opportunities for entrepreneurship and innovation and enabled the development of new products, services, platforms, and business models, including the freemium business model. The freemium business model is present in several digital services (e.g., music, social networking, and gaming), but, for businesses to succeed, it is of the utmost importance that users convert their subscriptions from free to premium. Previous research has endeavored to explain what motivations drive consumers to adopt different digital services and platforms and what motivations and user characteristics lead them to convert to the premium service, but little research has been dedicated to the motivations for consumers to distinguish between competing platforms. To enhance comprehension of these matters, this study analyzes a group of motivations and user characteristics as explanatory variables. Data was obtained via an online questionnaire, with a sample of 231 users of music streaming platforms. The main results suggest that satisfaction, perceived value, and ubiquity are statistically significant motivations that positively influence choosing a platform. Regarding subscribing to the premium service, the same motivations, as well as users’ age and occupation, present influential results, which are relevant from theoretical and managerial points of view, especially for entrepreneurs aiming to define the best strategy to successfully deploy their digital businesses.
Evaluation of the impact of coal mining on surface water in the Boesmanspruit, Mpumalanga, South Africa
Authors: Dzhangi Thandi R. , Atangana Ernestine
Published: March 2024

Surface water quality has major environmental and socioeconomic consequences, notably in terms of the country’s long-term fresh water supply. This study aimed at assessing the current state of water quality and status of the Boesmanspruit in a coal mining environment. The study used historical water quality data for a period of five years from 2017 to 2021. Aluminum, calcium, iron, manganese, magnesium, sodium, sulfate, electrical conductivity, pH, and total dissolved solids were the water quality variables selected for the study; the chosen variables were chosen based on the available secondary data. The water quality was evaluated against South African resource quality objectives, the South African water quality guidelines, and the Canadian Council of Ministers of the Environment water quality index (CCME-WQI). The data were analyzed using such as the CCME-WQI, the comprehensive pollution index (CPI), and multivariate statistics. The following parameters were above the prescribed thresholds: pH, total dissolved solids, electrical conductivity, sulfate, manganese, and iron. The CCME-WQI results showed that monitoring locations GR S26 and GR S21 near mining activities had poor water quality (40–44), whereas comprehensive pollution index (CPI) also had similar category results for the monitoring points, indicating that they were heavily polluted (2.4–4.8). The WQI showed that if certain variables, such as aluminum, iron, magnesium, sulfate, electrical conductivity, and total dissolved solids, exceed the permissible range, the water quality would deteriorate in accordance with the CPI classification. Therefore, the CPI was the best way to categorize the water quality. The principal component analysis and cluster analysis identified two primary sources of pollution which are anthropogenic and natural. The utilization of statistical analysis proved to be effective in determining the ideal quantity of significant variables within the study area. The study recommends low-cost options for reducing the effects of acid mine drainage, which includes passive mine water treatment methods using artificial wetlands.
The Role of Utilizing Load in Different Cases While Numerical Modeling of Multi-story Buildings on Alluvial Stratum: A Comparison Study
Authors: Arslan Eylem , Kayaturk Dua , Durmus Mehmet Rıfkı , Bagca Irem , Imamoglu Tuncay , Sert Sedat
Published: March 2024

Industrialization and population growth have made surface areas more valuable, thereby the multi-story buildings have become an absolute necessity. At this point, numeric models became the fastest and simplest way to evaluate the response of soils and structures. The issued factor in the current paper is related to the way of transferring the multi-story building loads to an alluvial stratum and evaluate the accuracy of different cases, in order to save time and economy. For load transfer, the first case (case i) includes uniform distributed load, the second case (case ii) includes the transfer from the basement columns and walls, and the third case (case iii) includes modeling the real state of the building. Mainly, all three cases gave close results in terms of settlement magnitudes of 2.21, 1.96, and 1.81 cm, respectively. It was inspected that case (i) showed 12.8% more deformation than case (ii) and 22.1% more deformation than case (iii). However, the situation is not the same for the settlement pattern, and the under-column and corner effects are neglected in uniform load. Additionally, the bending moments, which is a critical parameter for the design of a reinforced concrete foundation, have developed different results. In case (ii) and (iii) a bending moment of 500 kNm/m is observed in the center column, while in case (i) the moments converge to 0. Therefore, this study highlights the importance of outstanding decision making when assessing the load-transferring mechanism in modeling with numerical methods. The necessity of the determination of the convenient load transfer way depending on the parameter that is crucial in the evaluation of the soil–structure interaction comes to the fore with current paper.
Towards a core outcome set (COS) for intrinsic capacity (IC) intervention studies in adults in midlife and beyond: a scoping review to identify frequently used outcomes and measurement tools
Authors: Sanchez-Rodriguez Dolores , Bruyère Olivier , Surquin Murielle , Reginster Jean-Yves , Beaudart Charlotte
Published: March 2024

This scoping review was conducted to identify the outcomes and measurement tools used in IC intervention studies, as first step towards the development of a core outcome set (COS) for IC trials. PRISMA-ScR and COS-STAD were followed. The review considered randomized controlled trials targeting IC published in Medline, Scopus, Embase, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov, until June 2023. Of 699 references, 534 studies were screened once duplicates were removed, 15 were assessed for eligibility, and 7 (4 articles and 3 protocols) met eligibility criteria. Twenty-eight outcomes were identified (19 related to IC and its domains and 9 unrelated). The most reported primary outcome was the change in IC levels postintervention (5 over 7 studies) and the most reported outcomes (either as primary and/or secondary) were the changes in physical performance and in depressive symptoms (6 over 7 studies). Fifty-five tools used to construct the domains’ z-scores and/or assess the effect of interventions were identified (47 related to IC and its domains and 8 unrelated). The most reported tool was an IC Z-score, calculated by 4 domains’ z-scores: locomotor, vitality, cognitive, and psychological (5 over 7 studies). The tools differed among studies (10 locomotor related, 6 vitality related, 16 cognitive related, 8 psychological related, 6 sensorial related, 8 unrelated tools). The vast heterogeneity (28 outcomes and 55 tools within 7 studies) highlighted the need of a COS. These outcomes and tools will be presented to experts in a future step, to select the ones that should be taken into consideration in IC trials.
The Relationship Between Dual Filial Piety and Mental Disorders and Symptoms Among Adolescents: A Systematic Review of Quantitative and Qualitative Studies
Authors: Han Xu , Cheung Mei-chun
Published: March 2024

Filial piety, a core value in Chinese culture, emphasizes the importance of children showing respect, obedience, and care toward their parents. The dual filial piety model distinguishes between reciprocal filial piety, associated with love and care, and authoritarian filial piety, associated with hierarchy. This study systematically reviewed the associations between dual filial piety and mental disorders and symptoms. The authors reviewed 17 studies among Chinese and Korean adolescents published between 2004 and 2022 on filial piety and mental disorders/symptoms and distinguished reciprocal filial piety and authoritarian filial piety based on the dual filial piety model. Meta-analyses based on quantitative analyses were also conducted to examine the relationship between dual filial piety and depression/anxiety. The results indicate that reciprocal filial piety is negatively associated with mental disorders/symptoms, including depression, anxiety, aggression, deviant behaviors, internet addiction, self-harm and eating disorders. Conversely, authoritarian filial piety is not related to mental disorders/symptoms but is negatively associated with suicide and positively associated with eating disorders. Based on the results, it is evident that filial piety has a significant relationship with various mental disorders and symptoms and that different forms of filial piety may have distinct associations with mental health.
Grounding, Fundamentality and Ultimate Explanations
Authors: Bliss Ricki
Published: March 2024

This Element shows there is a long lineage of philosophers concerned with coming to understand what explains everything broadly construed or within a certain domain. The authors call such explanations ultimate explanations. Contemporarily, philosophers of a certain stripe have devoted much attention to the notion of fundamentality - that there is something that is without explanation. In this Element, the author explores some of the connections between fundamentality and ultimate explanations.
Tracial weights on topological graph algebras
Authors: CHRISTENSEN JOHANNES
Published: March 2024

We describe two kinds of regular invariant measures on the boundary path space
$\partial E$
of a second countable topological graph E, which allows us to describe all extremal tracial weights on
$C^{*}(E)$
which are not gauge-invariant. Using this description, we prove that all tracial weights on the C
$^{*}$
-algebra
$C^{*}(E)$
of a second countable topological graph E are gauge-invariant when E is free. This in particular implies that all tracial weights on
$C^{*}(E)$
are gauge-invariant when
$C^{*}(E)$
is simple and separable.
Nef cones of fiber products and an application to the cone conjecture
Authors: Gachet Cécile , Lin Hsueh-Yung , Wang Long
Published: March 2024

We prove a decomposition theorem for the nef cone of smooth fiber products over curves, subject to the necessary condition that their Néron–Severi space decomposes. We apply it to describe the nef cone of so-called Schoen varieties, which are the higher-dimensional analogues of the Calabi–Yau threefolds constructed by Schoen. Schoen varieties give rise to Calabi–Yau pairs, and in each dimension at least three, there exist Schoen varieties with nonpolyhedral nef cone. We prove the Kawamata–Morrison–Totaro cone conjecture for the nef cones of Schoen varieties, which generalizes the work by Grassi and Morrison.
Impact of universal chlorhexidine bathing with or without COVID-19 intensive training on staff and resident COVID-19 case rates in nursing homes
Authors: Gussin Gabrielle M. , Singh Raveena D. , Gohil Shruti K. , Saavedra Raheeb , Tjoa Thomas T. , Nguyen Kristine P. , Pedroza Robert , Hsi Joshua B. , O’Brien Kevin , Berman Chase , Park Jessica , Hsi Emily A. , Ghasemian Kimia , Osalvo Avy , Chun Stephanie , Fonda Emily , Huang Susan S.
Published: March 2024

We evaluated whether universal chlorhexidine bathing (decolonization) with or without COVID-19 intensive training impacted COVID-19 rates in 63 nursing homes (NHs) during the 2020–2021 Fall/Winter surge. Decolonization was associated with a 43% lesser rise in staff case-rates (P < .001) and a 52% lesser rise in resident case-rates (P < .001) versus control.
Don’t Call It a Failure: Systemic Risk Governance for Complex Financial Systems
Authors: Castellano Giuliano G.
Published: March 2024

The probability that an event will avalanche into an impairment of essential services constitutes a “systemic risk.” Owing to the inherent complexities of modern societies, the outbreak of a novel disease or the failure of a financial institution can rapidly escalate into an impact significantly larger than the initial event. Through the lens of complex system theory, this article draws a parallel between financial crises and disasters to contend that the regulatory framework for financial systemic risk is unequipped to address its fundamental dynamics. Epitomized by the market failure rationale, financial regulation is premised on a reductionist view that purports both systemic risk and law as external to the actions of market participants. Conversely, this article advances a twofold conceptual framework. First, it shows that systemic risk emerges from the same complex dynamics that generate the financial system. Second, it understands law as an agent of complexity, thus contributing to the emergence of finance and its inherent instability. Normatively, this conceptual framework reveals the limits of current regulatory approaches and constructs a holistic risk governance framework that is akin to the one adopted to govern disaster risks.
IDEMPOTENT GENERATORS OF INCIDENCE ALGEBRAS
Authors: KOLEGOV N. A.
Published: March 2024

The minimum number of idempotent generators is calculated for an incidence algebra of a finite poset over a commutative ring. This quantity equals either
$\lceil \log _2 n\rceil $
or
$\lceil \log _2 n\rceil +1$
, where n is the cardinality of the poset. The two cases are separated in terms of the embedding of the Hasse diagram of the poset into the complement of the hypercube graph.
The cost-effectiveness of germline BRCA testing-guided olaparib treatment in metastatic castration resistant prostate cancer
Authors: Teppala Srinivas , Scuffham Paul A. , Tuffaha Haitham
Published: March 2024

Background

Olaparib targets the DNA repair pathways and has revolutionized the management of metastatic castration resistant prostate cancer (mCRPC). Treatment with the drug should be guided by genetic testing; however, published economic evaluations did not consider olaparib and genetic testing as codependent technologies. This study aims to assess the cost-effectiveness of BRCA germline testing to inform olaparib treatment in mCRPC.

Methods

We conducted a cost-utility analysis of germline BRCA testing-guided olaparib treatment compared to standard care without testing from an Australian health payer perspective. The analysis applied a decision tree to indicate the germline testing or no testing strategy. A Markov multi-state transition approach was used for patients within each strategy. The model had a time horizon of 5 years. Costs and outcomes were discounted at an annual rate of 5 percent. Decision uncertainty was characterized using probabilistic and scenario analyses.

Results

Compared to standard care, BRCA testing-guided olaparib treatment was associated with an incremental cost of AU$7,841 and a gain of 0.06 quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was AU$143,613 per QALY. The probability of BRCA testing-guided treatment being cost effective at a willingness-to-pay threshold of AU$100,000 per QALY was around 2 percent; however, the likelihood for cost-effectiveness increased to 66 percent if the price of olaparib was reduced by 30 percent.

Conclusion

This is the first study to evaluate germline genetic testing and olaparib treatment as codependent technologies in mCRPC. Genetic testing-guided olaparib treatment may be cost-effective with significant discounts on olaparib pricing.
Some properties of convex and increasing convex orders under Archimedean copula
Authors: Guan Qingyuan , Wang Bing Xing
Published: March 2024

In this paper, the ordering properties of convex and increasing convex orders of the dependent random variables are studied. Some closure properties of the convex and increasing convex orders under independent random variables are extended to the dependent random variables under the Archimedean copula. Two applications are provided to illustrate our results.
Rock Magnetic‐Based Cyclic Expression in Late Visean Ramp Carbonates and an Astrochronology for the Late Asbian From Northwest England
Authors: Hounslow Mark W. , Cózar Pedro , Somerville Ian D. , Biggin Andrew J.
Published: March 2024

The late Asbian appears to mark the initial, well‐documented, onset of far‐field glacio‐eustatic changes in equatorial Mississippian strata. This work unravels the nature of cyclicity in upper Asbian shallow marine carbonates, using a combination of petrographic study, rock magnetic proxies and astrochronological testing on samples from the Trowbarrow section, NW England. Rock magnetic data express the content of two types of siliciclastic sources; a marine‐delivered magnetite‐dominated source, and an eolian‐delivered, hematite‐dominated source. The eolian‐sourced material generally peaked during regressive and low‐stand parts of the carbonate rhythms. Astrochronologic testing methods based around the average spectral misfit and TimeOpt methodology show the magnetite abundance proxies are principally carrying the astronomically forced signal. Two likely sedimentation rate models are derived from the five better magnetic proxies using evolutive methods. In addition, a set of three likely major hiatus levels are inferred in the sedimentation rate models, based on testing possible major hiatus scenarios with TimeOpt methods, using eccentricity modulation. From these, using the three best proxies, an average astrochronologic duration for the Trowbarrow section suggests a late Asbian duration of 1976 ± 86 kyr (1σ), and a basal late Asbian age of 334.48 ± 0.35 Ma (2σ). Coupled atmosphere‐ocean models for the late Paleozoic, suggest that lows in short eccentricity correspond to glacials, when inferred delivery of siliciclastic sediment to the carbonate ramp is generally at a maximum. The glacial and lower sea‐level intervals also coincide with maximum delivery of eolian siliciclastics, likely linked to increased aridity and less vegetation cover on adjacent and distal parts of Laurentia.
The Best Way to Kill Trees to Create Habitat
Authors: Wilke Carolyn
Published: March 2024

Standing dead trees—or snags—shelter animals, store carbon, and cycle nutrients. A long-term monitoring study found that lopping off a tree’s top branches is a good way to turn it into a snag within about 20 years.
Source or Sink? A Review of Permafrost’s Role in the Carbon Cycle
Authors: Derouin Sarah
Published: March 2024

Understanding the role of permanently frozen soil, which covers a large portion of land in the Northern Hemisphere, is crucial to reaching global climate targets.
SIRT1 ISGylation accelerates tumor progression by unleashing SIRT1 from the inactive state to promote its deacetylase activity
Authors: Kang Ji An , Kim Yoon Jung , Jang Kyu Yun , Moon Hye Won , Lee Haeseung , Lee Seonjeong , Song Hyun Kyu , Cho Sang Woo , Yoo Yoon Sun , Han Hye Gyeong , Kim Min-Ju , Chung Myoung Ja , Choi Cheol Yong , Lee Cheolju , Chung Chaeuk , Hur Gang Min , Kim You-Sun , Jeon Young Joo
Published: March 2024

ISG15 is an interferon-stimulated ubiquitin-like protein (UBL) with multifaceted roles as a posttranslational modifier in ISG15 conjugation (ISGylation). However, the mechanistic consequences of ISGylation in cancer have not been fully elucidated, largely due to a lack of knowledge on the ISG15 target repertoire. Here, we identified SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase, as a new target for ISGylation. SIRT1 ISGylation impairs the association of SIRT1 with its negative regulator, deleted in breast cancer 1 (DBC1), which unleashes SIRT1 from its inactive state and leads to an increase in its deacetylase activity. Importantly, SIRT1 ISGylation promoted lung cancer progression and limited lung cancer cell sensitivity to DNA damage-based therapeutics in vivo and in vitro models. The levels of ISG15 mRNA and protein were significantly higher in lung cancer tissues than in adjacent normal tissues. Accordingly, elevated expression of SIRT1 and ISG15 was associated with poor prognosis in lung cancer patients, a finding that could be translated for lung cancer patient stratification and disease outcome evaluation. Taken together, our findings provide a mechanistic understanding of the regulatory effect of SIRT1 ISGylation on tumor progression and therapeutic efficacy in lung cancer.
Waist-circumference-to-height-ratio had better longitudinal agreement with DEXA-measured fat mass than BMI in 7237 children
Authors: Agbaje Andrew O.
Published: March 2024

Background

The absolute agreement of surrogate measures of adiposity with dual-energy X-ray absorptiometry (DEXA)-measured body composition was examined.

Methods

Over a 15-year follow-up, 7237 (3667 females) nine-year-old children from the Avon Longitudinal Study of Parents and Children (ALSPAC) UK birth cohort were included. Total fat mass (FM) and trunk FM were serially measured with DEXA at ages 9, 11, 15, 17, and 24 years. BMI and waist circumference-to-height ratio (WHtR) were computed. Pearson’s correlations, intraclass correlations (ICC), and area under curve (AUC) analyses were conducted.

Results

Over 15 years, BMI, total FM, and trunk FM, increased but WHtR was relatively stable. WHtR provided a better longitudinal absolute agreement [males ICC 0.84 (95% CI 0.84–0.85); females 0.81 (0.80–0.82)] than BMI [(males (0.65 (0.64–0.66); females 0.72 (0.71–0.73)] with total FM as well as trunk FM from ages 9–24 years. WHtR cut-point for predicting excess total FM (75th–95th percentile) was 0.50–0.53 in males [AUC 0.86–0.94, sensitivity 0.51–0.79 and specificity 0.93–0.95]. WHtR cut-point for predicting excess total FM (75th–95th percentile) was 0.52–0.54 in females [AUC 0.83–0.95, sensitivity 0.38–0.68 and specificity 0.92–0.95]. Results were similar with trunk FM.

Conclusion

WHtR is an inexpensive alternative to BMI for predicting FM in pediatrics.

Impact

Waist circumference-to-height ratio (WHtR) is a better adiposity surrogate measure than body mass index (BMI) in predicting fat mass and discriminating lean mass from childhood through young adulthood.

BMI has been used as an inexpensive surrogate measure of adiposity in children for several decades. However, emerging findings suggest that BMI fails to discriminate between fat mass adiposity and lean mass.

This is the first-ever longitudinal study in over 7000 children followed up for 15 years that identified WHtR as an inexpensive accurate measure that discriminates fat mass from lean mass that could replace BMI measure of obesity in pediatrics.
Distinct correlation network of clinical characteristics in suicide attempters having adolescent major depressive disorder with non-suicidal self-injury
Authors: Peng Bo , Wang Ruoxi , Zuo Wenlong , Liu Haitao , Deng Chunshan , Jing Xiaoyuan , Hu Hongtao , Zhao Weitan , Qin Peiwu , Dai Lei , Chen Zuxin , Zhang Yingli , Liu Xin-an
Published: March 2024

Suicidal behavior and non-suicidal self-injury (NSSI) are common in adolescent patients with major depressive disorder (MDD). Thus, delineating the unique characteristics of suicide attempters having adolescent MDD with NSSI is important for suicide prediction in the clinical setting. Here, we performed psychological and biochemical assessments of 130 youths having MDD with NSSI. Participants were divided into two groups according to the presence/absence of suicide attempts (SAs). Our results demonstrated that the age of suicide attempters is lower than that of non-attempters in participants having adolescent MDD with NSSI; suicide attempters had higher Barratt Impulsiveness Scale (BIS-11) impulsivity scores and lower serum CRP and cortisol levels than those having MDD with NSSI alone, suggesting levels of cortisol and CRP were inversely correlated with SAs in patients with adolescent MDD with NSSI. Furthermore, multivariate regression analysis revealed that NSSI frequency in the last month and CRP levels were suicidal ideation predictors in adolescent MDD with NSSI, which may indicate that the increased frequency of NSSI behavior is a potential risk factor for suicide. Additionally, we explored the correlation between psychological and blood biochemical indicators to distinguish suicide attempters among participants having adolescent MDD with NSSI and identified a unique correlation network that could serve as a marker for suicide attempters. Our research data further suggested a complex correlation between the psychological and behavioral indicators of impulsivity and anger. Therefore, our study findings may provide clues to identify good clinical warning signs for SA in patients with adolescent MDD with NSSI.
Gut microbial CAZymes markers for depression
Authors: Xie Peijun , Zhou Xingyu , Li Yifan , Wu Jing , Zhang Hanping , Huang Yu , Tan Xunmin , Wen Lu , Olasunkanmi Oluwatayo Israel , Zhou Jingjing , Sun Zuoli , Liu Min , Zhang Guofu , Wang Ying , Xie Peng , Yang Jian , Zheng Peng
Published: March 2024

Major depressive disorder (MDD) is a serious mental illness, characterized by disturbances of gut microbiome, it is required to further explore how the carbohydrate-active enzymes (CAZymes) were changed in MDD. Here, using the metagenomic data from patients with MDD (n = 118) and heath controls (HC, n = 118), we found that the whole CAZymes signatures of MDD were significantly discriminated from that in HC. α-diversity indexes of the two groups were also significantly different. The patients with MDD were characterized by enriched Glycoside Hydrolases (GHs) and Polysaccharide Lyases (PLs) relative to HC. A panel of makers composed of 9 CAZymes mainly belonging to GHs enabled to discriminate the patients with MDD and HC with AUC of 0.824. In addition, this marker panel could classify blinded test samples from the two groups with an AUC of 0.736. Moreover, we found that baseline 4 CAZymes levels also could predict the antidepressant efficacy after adjusted confounding factors and times of depressive episode. Our findings showed that MDD was associated with disturbances of gut CAZymes, which may help to develop diagnostic and predictive tools for depression.
The m6A reader IGF2BP2 regulates glycolytic metabolism and mediates histone lactylation to enhance hepatic stellate cell activation and liver fibrosis
Authors: Zhou Yongqiang , Yan Jiexi , Huang He , Liu Lu , Ren Longfei , Hu Jinjing , Jiang Xiaoxu , Zheng Yan , Xu Lingcong , Zhong Fupeng , Li Xun
Published: March 2024

Evidence for the involvement of N6-Methyladenosine (m6A) modification in the etiology and progression of liver fibrosis has emerged and holds promise as a therapeutic target. Insulin-like growth factor 2 (IGF2) mRNA-binding protein 2 (IGF2BP2) is a newly identified m6A-binding protein that functions to enhance mRNA stability and translation. However, its role as an m6A-binding protein in liver fibrosis remains elusive. Here, we observed that IGF2BP2 is highly expressed in liver fibrosis and activated hepatic stellate cells (HSCs), and inhibition of IGF2BP2 protects against HSCs activation and liver fibrogenesis. Mechanistically, as an m6A-binding protein, IGF2BP2 regulates the expression of Aldolase A (ALDOA), a key target in the glycolytic metabolic pathway, which in turn regulates HSCs activation. Furthermore, we observed that active glycolytic metabolism in activated HSCs generates large amounts of lactate as a substrate for histone lactylation. Importantly, histone lactylation transforms the activation phenotype of HSCs. In conclusion, our findings reveal the essential role of IGF2BP2 in liver fibrosis by regulating glycolytic metabolism and highlight the potential of targeting IGF2BP2 as a therapeutic for liver fibrosis.
EMQN best practice guidelines for genetic testing in hereditary breast and ovarian cancer
Authors: McDevitt Trudi , Durkie Miranda , Arnold Norbert , Burghel George J. , Butler Samantha , Claes Kathleen B. M. , Logan Peter , Robinson Rachel , Sheils Katie , Wolstenholme Nicola , Hanson Helen , Turnbull Clare , Hume Stacey
Published: March 2024

Hereditary Breast and Ovarian Cancer (HBOC) is a genetic condition associated with increased risk of cancers. The past decade has brought about significant changes to hereditary breast and ovarian cancer (HBOC) diagnostic testing with new treatments, testing methods and strategies, and evolving information on genetic associations. These best practice guidelines have been produced to assist clinical laboratories in effectively addressing the complexities of HBOC testing, while taking into account advancements since the last guidelines were published in 2007. These guidelines summarise cancer risk data from recent studies for the most commonly tested high and moderate risk HBOC genes for laboratories to refer to as a guide. Furthermore, recommendations are provided for somatic and germline testing services with regards to clinical referral, laboratory analyses, variant interpretation, and reporting. The guidelines present recommendations where ‘must’ is assigned to advocate that the recommendation is essential; and ‘should’ is assigned to advocate that the recommendation is highly advised but may not be universally applicable. Recommendations are presented in the form of shaded italicised statements throughout the document, and in the form of a table in supplementary materials (Table S4). Finally, for the purposes of encouraging standardisation and aiding implementation of recommendations, example report wording covering the essential points to be included is provided for the most common HBOC referral and reporting scenarios. These guidelines are aimed primarily at genomic scientists working in diagnostic testing laboratories.
Bevacizumab, olaparib, and durvalumab in patients with relapsed ovarian cancer: a phase II clinical trial from the GINECO group
Authors: Freyer Gilles , Floquet Anne , Tredan Olivier , Carrot Aurore , Langlois-Jacques Carole , Lopez Jonathan , Selle Frédéric , Abdeddaim Cyril , Leary Alexandra , Dubot-Poitelon Coraline , Fabbro Michel , Gladieff Laurence , Lamuraglia Michele
Published: March 2024

Most patients with advanced ovarian cancer (AOC) ultimately relapse after platinum-based chemotherapy. Combining bevacizumab, olaparib, and durvalumab likely drives synergistic activity. This open-label phase 2 study (NCT04015739) aimed to assess activity and safety of this triple combination in female patients with relapsed high-grade AOC following prior platinum-based therapy. Patients were treated with olaparib (300 mg orally, twice daily), the bevacizumab biosimilar FKB238 (15 mg/kg intravenously, once-every-3-weeks), and durvalumab (1.12 g intravenously, once-every-3-weeks) in nine French centers. The primary endpoint was the non-progression rate at 3 months for platinum-resistant relapse or 6 months for platinum-sensitive relapse per RECIST 1.1 and irRECIST. Secondary endpoints were CA-125 decline with CA-125 ELIMination rate constant K (KELIM-B) per CA-125 longitudinal kinetics over 100 days, progression free survival and overall survival, tumor response, and safety. Non-progression rates were 69.8% (90%CI 55.9%-80.0%) at 3 months for platinum-resistant relapse patients (N = 41), meeting the prespecified endpoint, and 43.8% (90%CI 29.0%-57.4%) at 6 months for platinum-sensitive relapse (N = 33), not meeting the prespecified endpoint. Median progression-free survival was 4.1 months (95%CI 3.5–5.9) and 4.9 months (95%CI 2.9–7.0) respectively. Favorable KELIM-B was associated with better survival. No toxic deaths or major safety signals were observed. Here we show that further investigation of this triple combination may be considered in AOC patients with platinum-resistant relapse.