bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early, precise, and safe clinical evaluation of the pharmacodynamic effects of novel agents in the intact human tumor microenvironment
Authors: Gundle Kenneth R. , Rajasekaran Karthik , Houlton Jeffrey , Deutsch Gary B. , Ow Thomas J. , Maki Robert G. , Pang John , Nathan Cherie-Ann O. , Clayburgh Daniel , Newman Jason G. , Brinkmann Elyse , Wagner Michael J. , Pollack Seth M. , Thompson Matthew J. , Li Ryan J. , Mehta Vikas , Schiff Bradley A. , Wenig Barry I. , Swiecicki Paul L. , Tang Alice L. , Davis Jessica L. , van Zante Annemieke , Bertout Jessica A. , Jenkins Wendy , Turner Atticus , Grenley Marc , Burns Connor , Frazier Jason P. , Merrell Angela , Sottero Kimberly H. W. , Derry Jonathan M. J. , Gillespie Kate C. , Mills Bre , Klinghoffer Richard A. 
Published: April 2024

Introduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit).Methods: The clinical in vivo oncology (CIVO®) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4–96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure.Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment.Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development.
Spontaneously hypertensive rats exhibit increased liver flavin monooxygenase expression and elevated plasma TMAO levels compared to normotensive and Ang II-dependent hypertensive rats
Authors: Gawryś-Kopczyńska Marta , Szudzik Mateusz , Samborowska Emilia , Konop Marek , Chabowski Dawid , Onyszkiewicz Maksymilian , Ufnal Marcin 
Published: April 2024

Background: Flavin monooxygenases (FMOs) are enzymes responsible for the oxidation of a broad spectrum of exogenous and endogenous amines. There is increasing evidence that trimethylamine (TMA), a compound produced by gut bacteria and also recognized as an industrial pollutant, contributes to cardiovascular diseases. FMOs convert TMA into trimethylamine oxide (TMAO), which is an emerging marker of cardiovascular risk. This study hypothesized that blood pressure phenotypes in rats might be associated with variations in the expression of FMOs.Methods: The expression of FMO1, FMO3, and FMO5 was evaluated in the kidneys, liver, lungs, small intestine, and large intestine of normotensive male Wistar-Kyoto rats (WKY) and two distinct hypertensive rat models: spontaneously hypertensive rats (SHRs) and WKY rats with angiotensin II-induced hypertension (WKY-ANG). Plasma concentrations of TMA and TMAO were measured at baseline and after intravenous administration of TMA using liquid chromatography-mass spectrometry (LC-MS).Results: We found that the expression of FMOs in WKY, SHR, and WKY-ANG rats was in the descending order of FMO3 &gt; FMO1 &gt;&gt; FMO5. The highest expression of FMOs was observed in the liver. Notably, SHRs exhibited a significantly elevated expression of FMO3 in the liver compared to WKY and WKY-ANG rats. Additionally, the plasma TMAO/TMA ratio was significantly higher in SHRs than in WKY rats.Conclusion: SHRs demonstrate enhanced expression of FMO3 and a higher plasma TMAO/TMA ratio. The variability in the expression of FMOs and the metabolism of amines might contribute to the hypertensive phenotype observed in SHRs.
Synergistic variation of rhizosphere soil phosphorus availability and microbial diversity with stand age in plantations of the endangered tree species Parashorea chinensis
Authors: Li Wannian , Ullah Saif , Liu Fang , Deng Fuchun , Han Xiaomei , Huang Songdian , Xu Yuanyuan , Yang Mei 
Published: April 2024

IntroductionSoil physicochemical properties and nutrient composition play a significant role in shaping microbial communities, and facilitating soil phosphorus (P) transformation. However, studies on the mechanisms of interactions between P transformation characteristics and rhizosphere microbial diversity in P-deficient soils on longer time scales are still limited.MethodsIn this study, rhizosphere soils were collected from a pure plantation of Parashorea chinensis (P. chinensis) at six stand ages in the subtropical China, and the dynamic transformation characteristics of microbial diversity and P fractions were analyzed to reveal the variation of their interactions with age.ResultsOur findings revealed that the rhizosphere soils across stand ages were in a strongly acidic and P-deficient state, with pH values ranging from 3.4 to 4.6, and available P contents ranging from 2.6 to 7.9 mg·kg-1. The adsorption of P by Fe3+ and presence of high levels of steady-state organic P highly restricted the availability of P in soil. On long time scales, acid phosphatase activity and microbial biomass P were the main drivers of P activation. Moreover, pH, available P, and ammonium nitrogen were identified as key factors driving microbial community diversity. As stand age increased, most of the nutrient content indicators firstly increased and then decreased, the conversion of other forms of P to bio-available P became difficult, P availability and soil fertility began to decline. However, bacteria were still able to maintain stable species abundance and diversity. In contrast, stand age had a greater effect on the diversity of the fungal community than on the bacteria. The Shannon and Simpson indices varied by 4.81 and 0.70 for the fungi, respectively, compared to only 1.91 and 0.06 for the bacteria. Microorganisms play a dominant role in the development of their relationship with soil P.DiscussionIn conclusion, rhizosphere microorganisms in P. chinensis plantations gradually adapt to the acidic, low P environment over time. This adaptation is conducive to maintaining P bioeffectiveness and alleviating P limitation.
Psychometric properties and item response theory analysis of the Persian version of the social pain questionnaire
Authors: Sepehrinia Mahya , Farahani Hojjatollah , Watson Peter , Amini Nasim 
Published: April 2024

IntroductionSocial pain is an emotional reaction which is triggered by social exclusion and has been extensively investigated in the literature. The Social Pain Questionnaire (SPQ) is a self-report instrument which is the only scale for measuring social pain as a dispositional factor. The current study aimed at examining the psychometric properties of the SPQ in an Iranian sample.Materials and methodsA sample of participants (N = 400) was recruited in a cross-sectional validation study. Exploratory Factor Analysis (EFA) as well as Confirmatory Factor Analysis (CFA) were conducted. The Item Response Theory (IRT) model parameters were evaluated and item response category curves were presented. Convergent and divergent validities as well as the reliability (by using Cronbach’s alpha coefficient) were also assessed.ResultsThe SPQ’s unidimensionality was affirmed (RMSEA = 0.078; CFI = 0.915; TLI = 0.99) and its internal consistency was robust (Cronbach’s α = 0.94). The correlation between the SPQ and the following measures endorsed its divergent and convergent validity: Self-esteem (r = −0.424), Perceived Social Support (r = −0.161), and Interpersonal Sensitivity (r = 0.636). Finally, Item Response Theory Analysis emphasized the effectiveness of the SPQ items in discerning various levels of social pain. The theta level ranged between −1 and + 1.2 and the IRT-based marginal reliability was 0.92 for the total score.DiscussionThe Persian SPQ stands as a reliable and valid measure for evaluating social pain. This scale has the potential to stimulate further research in the field for both clinical and non-clinical settings.ConclusionBy employing Item Response Theory (IRT) analysis, we have transcended the theoretical psychometric evaluation of the SPQ scale and demonstrated that SPQ is a unidimensional, valid and reliable measurement tool.
Determinants of default from completion of child immunization among children aged 15–23 months in Kacha Bira district, Kembata Tembaro zone, South Ethiopia: a case–control study
Authors: Masebo Sitota Tesema , Wolka Eskinder , Kussa Sintayehu , Uloro Muluken Markos , Handiso Selamu Abera , Libabo Dilugeta Mathewos , Anjajo Eyosiyas Abreham , Bogino Efa Ambaw 
Published: April 2024

BackgroundChild immunization is crucial to protect children from vaccine-preventable diseases. However, if a child defaults from completing immunization, they are at a greater risk of contracting such diseases. Previous studies have evaluated various factors that contribute to defaulting from immunization, but they did not consider the fear of COVID-19 as a variable. Additionally, there is inconsistency in the factors identified across different areas. This study aimed to examine the determinants of defaulting from child immunization among children aged 15–23 months in Kacha Bira district, Kembata Tembaro zone, South Ethiopia.MethodsA study was conducted using a community-based unmatched case–control design to identify the determinants of child immunization completion. The study included 255 children aged 15–23 months in the Kacha Bira district from 3 May 2022 to 1 June 2022, using a multi-stage sampling technique. Face-to-face interviews of mothers or immediate caretakers of the child were conducted using a mobile device, and the questionnaire was developed using the Kobo Toolbox. The data collected were analyzed using SPSS version 25. Multivariable logistic regression was used to identify the determinants, and the adjusted odds ratio with 95% CI and a p &lt; 0.05 were considered statistical significant.ResultsThe multivariable logistic regression analysis identified four independent predictors of immunization defaulting. Antenatal care (ANC) follow-up [AOR = 5.40, 95% CI (2.24–13.52)], postponing vaccination schedule [AOR = 2.28, 95% CI: (1.05–4.93)], parity of the mother [AOR = 3.25, 95% CI: (1.45–7.27)], and knowledge of the mother about vaccination [AOR = 6.77, 95% CI: (2.33–19.64)] were determinants of immunization defaulting.ConclusionIn this study, lack of ANC follow-up, postponement of the vaccination schedule, mothers with parity of greater than four, and poor knowledge of the mothers about immunization were identified as determinants of immunization defaulting.
Experimental study to characterize water contaminated by lunar dust
Authors: Freer Rieke , Pesch Victoria , Zabel Paul 
Published: April 2024

The establishment of a permanent lunar base is the goal of several space missions, such as NASA’s Artemis program. The feasibility of a lunar base is highly dependent on the supply of clean water, which can be recycled within the life support system or extracted in-situ on the Moon. Contamination of the water by lunar dust is an unavoidable problem due to the fact that lunar dust covers the entire surface and has adhesive properties as well as a very fine particle size. It is therefore important to study and characterise water contaminated by lunar dust in order to develop a safe water supply system. We combined existing studies on the dissolution behaviour of lunar regolith in aqueous solutions and performed dissolution experiments ourselves. We conducted dissolution experiments using the Lunar Highland Dust simulant from Exolith Lab (Orlando, United States), which resembles the Apollo 16 regolith and thus the terrain of the suspected Artemis landing sites. Our dissolution experiments investigate the effects of the dust to solution ratio, the aqueous solution used (ultrapure water and 5.5 buffer), the short exposure time (2 min up to 72 h), the dissolved oxygen in the solutions and the particle size of the simulant. As a result, this study provides a characterisation of lunar dust contaminated water and compares the results with the World Health Organization (WHO) and NASA requirements for drinking water. For all test batches, the lunar dust contaminated water exceeds the requirements for pH, turbidity and Al concentration.
Body Size of Female Strepsipteran Parasites (Strepsiptera, Xenidae, Xenos) Depends on Several Key Factors in a Vespine Wasp (Hymenoptera, Vespidae, Vespa)
Authors: Kudô Kazuyuki , Oyaizu Wataru , Kusama Rikako , Yamaguchi Yuki , Koji Shinsaku 
Published: April 2024

Parasite growth in hosts depends on their hosts’ nutritional status. This study examined whether the body size of the strepsipteran parasite Xenos oxyodontes, which parasitizes the eusocial wasp Vespa analis, is affected by several key factors, including host body size. We collected V. analis using bait traps for three years in Niigata, Japan, and evaluated the number of male and female X. oxyodontes parasites throughout the seasons. A total of 185 female parasites were collected, and their cephalothorax widths were measured. The widths of female parasites did not statistically vary among seasons and were positively correlated with the head widths of female host wasps but negatively correlated with the number of parasites per host wasp. In addition, we examined whether the reproductive conditions of post-hibernation solitary queens affected the cephalothorax width of female parasites. The widths of the female parasites were greater when the queens had less-developed ovaries. These results suggested that nutrient availability by female parasites depends on the host wasp and competition with conspecific individuals.
Intérêts, orientation et réussite scolaire
Authors: Larcebeau Solange 
Published: April 2024

L'objet de notre recherche était de préciser l'importance des intérêts d'élèves de 3e, estimés au moyen d'un questionnaire comportant des séries d'activités de loisirs variées, à l'égard de deux critères : réussite en français ou en mathématiques en classe de 3e et choix d’une orientation des études de second cycle conduisant à un certain baccalauréat.
Nous avons vérifié que l'influence du niveau des intérêts correspondants, sur la réussite dans une discipline donnée, était très faible. L'intelligence, mesurée par un test composite et les aptitudes, mesurées au moyen de tests de matériel homogène (verbal, numérique ou figuré), déterminent en grande partie la réussite scolaire pour la majorité des élèves. Cependant, lorsque les résultats dans une discipline ne sont pas ceux qu'on pouvait attendre d'après le niveau général d'aptitude des élèves, qu'ils soient inférieurs pour des élèves bien doués ou supérieurs pour des élèves peu doués, les intérêts paraissent être plus souvent à l'origine de ces décalages que les aptitudes spécifiques, pourtant relativement indépendantes de l'aptitude générale.
Mais le rôle essentiel des intérêts consiste à orienter l’activité de l’individu dans certaines directions. Nous avons pu mettre en évidence l'influence très nette de l'organisation particulière des intérêts d'un élève de 3e, sur le choix des études qu'il entreprendra et poursuivra dans le second cycle, et en conséquence sur sa carrière future. On comprend aisément qu’on puisse être attiré par un certain domaine d'étude ou d'activité sans posséder pour autant les aptitudes qui permettraient d'accéder dans ce domaine à un haut niveau de savoir ou de qualification, ce qui explique la faiblesse des liaisons entre intérêts et réussite scolaire ou professionnelle (exprimée en terme de classement ou de hiérarchie). Un même intérêt peut trouver satisfaction à des niveaux différents de la hiérarchie scolaire ou professionnelle — un exemple en est fourni par le parallélisme des profils d'intérêts des futurs techniciens et des futurs ingénieurs d'une même spécialité — . On peut en conclure que les critères à l'égard desquels les intérêts ont des chances d'être valides doivent être plutôt la satisfaction éprouvée dans le travail et la stabilité dans un même emploi ou la continuité dans une même carrière que le niveau hiérarchique auquel on parviendra.
Il est surtout intéressant de constater, d’après cette recherche, la valeur prédictive des intérêts inventoriés, puisqu’on effet l'organisation intra-individuelle des intérêts d'élèves examinés en classe de 3e est un indice des plus sûrs du type d'études qu’ils poursuivront et mèneront à bien trois ou quatre ans plus tard, et peut-être ultérieurement.
L’affectation réelle d’une population scolaire à l’issue du premier cycle. La distorsion entre les décisions d’orientation et la situation des élèves après la classe de 3e
Authors: Desmoulins Jacques 
Published: April 2024

Cette étude portant sur 4 094 élèves qui fréquentaient une classe de 3e en 1974 dans l’Enseignement Public des Côtes-du-Nord a été réalisée par l’Inspecteur de l’Information et d’Orientation (1). Elle poursuit trois objectifs essentiels :
— cerner le flux scolaire de l’ensemble de la population des classes de 3e du département (enseignement public), c’est-à-dire localiser le plus exactement possible cette population après la fin des phases d’orientation et d’affectation ; — mettre en évidence de façon relativement précise la distorsion enregistrée entre les décisions d’orientation d’une part, la position réelle des élèves à la rentrée d’autre part ;
— révéler ce qui s’est passé au niveau de chaque type d’enseignement.
Pour une approche opérationnelle des relations entre formations techniques et emplois
Authors: Ricaud Yves de 
Published: April 2024

Se démarquant des analyses traditionnelles en termes d’adéquation, l’auteur propose une nouvelle approche des relations entre formations initiales et emplois, fondée sur les interdépendances observées entre le système éducatif et le système productif, et la variété de ces interdépendances selon les spécialités de formation, les établissements d’accueil et l’environnement économique et social.
Une grille systématique, «nourrie» par des observations monographiques, est présentée qui permet de classer et de comparer, pour l’ensemble des formations, les données relatives au système éducatif, au processus d’insertion professionnelle et au système d’emplois.
Tout en s’efforçant de montrer que le recueil de ces informations ne poserait pas de problèmes insurmontables, l’auteur s’attache à mettre en lumière leur utilité en particulier pour les décisions«courantes» prises par les responsables éducatifs locaux (ouverture de sections par exemple).
Un test adapté aux enfants de migrants : Mathématique Sans Paroles (M.S.P.)
Authors: Léonardi Daniel , Pelnard-Considère Jacqueline 
Published: April 2024

Le but de ce travail était de construire une épreuve de mathématique applicable à des élèves de CM2, sixième et cinquième non francophones.
L'article présente tout d'abord le contenu de l’épreuve MSP, ainsi que l’esprit dans lequel il a été conçu.
Le test a été appliqué à un groupe d'élèves étrangers récemment arrivés en France. Plusieurs groupes linguistiques ont été examinés : des jeunes Asiatiques, des Italo-Ibériques ainsi que des enfants d’origine maghrébine. L’analyse des résultats met en évidence de larges différences entre les groupes.
Ce sont les jeunes Asiatiques qui s’adaptent le mieux aux exigences en mathématiques du système scolaire français, les Maghrébins figurent quant à eux parmi ceux qui présentent le plus de difficultés. Plusieurs facteurs peuvent expliquer ces différences : la motivation des familles pour une intégration complète dans le milieu d’accueil, les problèmes de distance culturelle, ainsi que la qualité inégale des structures scolaires du pays d'origine.
L'orientation dans les formations des jeunes sans qualification
Authors: Kokosowski Alain 
Published: April 2024

The surveys and works which have been conducted for three years within the context of social and vocational action of insertion for young people in difficulties have given prominence to a certain number of conclusions which are able to directly question the professionna/s of guidance.
in fact, four essential reports can be drawn up :
-the change in the social request for guidance :
-the spreading and setting up of guidance practices by non professional : -specific characteristics of young and without any qualification public with flimsy vocational intention ;
-the efficiency of some training practices which modify the attitudes, the abilities and their own image for young people.
The whole of these conclusions leads to the opening of a different discussion on the place and part of the guidance office, and this just well for the adults as for the young people.
Thus it seemed that for young people the understanding of the functioning of the organization which produce the training situations, as well as the intervention of these organizations -and not directly on the young users -could constitute a priority.
On the other hand, the development of the dual practices find their complete justification in the adults ' guidance.
This reversal of problematic seems to differently set out the objectives, the strategies, and therefore, the status and the training of the career advisers which intervene in these plans of action.
Déterminants de la performance scolaire. Étude de la validité prédictive d’un modèle multidimensionnel
Authors: Kneip Nico 
Published: April 2024

A l'aide de l'analyse en éléments, l'auteur étudie dans cette première publication concernant la détermination de la performance scolaire, la validité prédictive d'un modèle multidimensionnel. Ce modèle qui comprend des déterminants concernant l'individu (intelligence, personnalité, histoire scolaire) et le milieu (social et scolaire), est appliqué dans le cadre d’une étude longitudinale. Cette recherche est effectuée sur un échantillon de 395 élèves des écoles du Grand-Duché de Luxem¬ bourg, au moment du passage de l'enseignement primaire à l'enseignement post-primaire (6e à 8e année d'études).
Les résultats indiquent que le modèle permet de faire, à partir de la 6e, une bonne prédiction du niveau hiérarchique de la classe fréquentée en 8e par l'élève : près de 70 % des différences existant entre les élèves peuvent être expliquées. Il paraît également possible, d'établir un ordre hiérarchique des déterminants : les facteurs scolaires devancent largement les facteurs intellectuels, sociaux et de personnalité. Cette hiérarchie doit cependant être relativisée par suite des nombreux effets communs. Mais l'emploi du modèle multidimensionnel s'en trouve justifié. La prédominance des facteurs scolaires subsiste également au niveau des effets indépendants. A retenir surtout que même le milieu de la classe a une influence indépendante.
L'auteur discute les résultats en relevant certaines particularités méthodologiques, mais en soulignant surtout l'apparente unidimensionnalité de l'appréciation des élèves. Il relève l'importance d'une remise en question des critères d'évaluation.