bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of pathological contrast enhancement with synthetic brain imaging from quantitative multiparametric MRI
Authors: Donatelli Graziella , Migaleddu Gianmichele , Cencini Matteo , Cecchi Paolo , D'Amelio Claudio , Peretti Luca , Buonincontri Guido , Tosetti Michela , Costagli Mauro , Cosottini Mirco 
Published: April 2024

AbstractBackground and PurposeWe aimed to test whether synthetic T1‐weighted imaging derived from a post‐contrast Quantitative Transient‐state Imaging (QTI) acquisition enabled revealing pathological contrast enhancement in intracranial lesions.MethodsThe analysis included 141 patients who underwent a 3 Tesla‐MRI brain exam with intravenous contrast media administration, with the post‐contrast acquisition protocol comprising a three‐dimensional fast spoiled gradient echo (FSPGR) sequence and a QTI acquisition. Synthetic T1‐weighted images were generated from QTI‐derived quantitative maps of relaxation times and proton density. Two neuroradiologists assessed synthetic and conventional post‐contrast T1‐weighted images for the presence and pattern of pathological contrast enhancement in intracranial lesions. Enhancement volumes were quantitatively compared.ResultsUsing conventional imaging as a reference, synthetic T1‐weighted imaging was 93% sensitive in revealing the presence of contrast enhancing lesions. The agreement for the presence/absence of contrast enhancement was almost perfect both between readers (k = 1 for both conventional and synthetic imaging) and between sequences (k = 0.98 for both readers). In 91% of lesions, synthetic T1‐weighted imaging showed the same pattern of contrast enhancement visible in conventional imaging. Differences in enhancement pattern in the remaining lesions can be due to the lower spatial resolution and the longer acquisition delay from contrast media administration of QTI compared to FSPGR. Overall, enhancement volumes appeared larger in synthetic imaging.ConclusionsQTI‐derived post‐contrast synthetic T1‐weighted imaging captures pathological contrast enhancement in most intracranial enhancing lesions. Further comparative studies employing quantitative imaging with higher spatial resolution is needed to support our data and explore possible future applications in clinical trials.
The first primer for the QuantCrit‐curious critical race theorist or psychologist: On intersectionality theory, interaction effects, and AN(C)OVA/regression models
Authors: Vargas Jose H. , Peet J. Zak 
Published: April 2024

AbstractModerated general linear modeling (MGLM) is a highly popular statistical approach in the social sciences, as it allows analysts to examine the separate and interactive effects of 2+ variables on a numerically‐measured outcome. Despite correspondences between MGLM and intersectionality theory, interdisciplinary cross‐communication is rare. Quantitative research can be strengthened when vetted through a critical race theory (CRT) framework. Also, qualitative intersectionality work can be complemented with statistics. To promote greater appreciation and usage of MGLM in CRT‐informed psychological research, it is argued that readers, reviewers, and editors should familiarize themselves with the basics of QuantCrit. Have all variables been accurately measured? Has the dataset been properly structured? Have all statistical assumptions been met? What data tables and figures are reported? How are the results interpreted? This primer addresses these questions while minimizing MGLM technicalities. After covering the historical context of QuantCrit, data from a houselessness dataset are examined to demonstrate the QuantCrit protocols. Limitations of MGLM, as well as QuantCrit‐based guidelines for reporting MGLM results, are discussed.
Neutrophil response to Porphyromonas gingivalis is modulated by low‐level laser application
Authors: Özkan Karasu Yerda , Öner Fatma , Kantarci Alpdogan 
Published: April 2024

AbstractObjectivesNeutrophil response is critical in inflammatory regulation and immune response to bacterial infections. During periodontal disease, pathogenic bacteria lead to exaggerated neutrophil responses. We hypothesized that low‐level laser application (LLLT), therapeutic strategy for dampening inflammatory processes, will regulate neutrophil activity in response to periodontopathogens.Materials and MethodsThe impact of LLLT on neutrophil responses was measured by light delivered at wavelength of 850 nm. The direct effect of LLLT on P. gingivalis A7436 was determined by flow cytometry using LIVE/DEADTM Cell Vitality kit. The phagocytosis of P. gingivalis A7436 by human neutrophils was measured using flow cytometry. Superoxide generation was measured by cytochrome‐C‐reduction in the presence of N‐formyl‐L‐methionyl‐L‐leucyl‐L‐phenylalanine (fMLP; 1 mM). Cytokine release by neutrophils was measured by multiplex immunoassay.ResultsThe phagocytosis of P. gingivalis by primary human neutrophils was significantly reduced in response to LLLT (p < 0.05). While LLLT led to increased superoxide production in neutrophils that were not challenged by P. gingivalis, it dampened the increased superoxide and IL‐6 release by the neutrophils in response to P. gingivalis. LLLT did not directly affect the viability of P. gingivalis.ConclusionThese results suggested that LLLT can provide therapeutic strategy in periodontal disease, regulating the neutrophil response to P. gingivalis.
Kierkegaard on the Relationship Between Practical and Epistemic Reasons for Belief
Authors: Quanbeck Z 
Published: April 2024

AbstractOn the dominant contemporary accounts of how practical considerations affect what we ought to believe, practical considerations either encroach on epistemic rationality by affecting whether a belief is epistemically justified, or constitute distinctively practical reasons for belief which can only affect what we ought to believe by conflicting with epistemic rationality. This paper argues that Søren Kierkegaard offers a promising alternative view on which practical considerations can affect what we ought to believe without either encroaching on or (necessarily) conflicting with epistemic rationality by determining which among the epistemically permitted outright doxastic attitudes one should all‐things‐considered adopt.
Smallholder farms in the sustainable food transition: A critical examination of the new Common Agricultural Policy
Authors: Alessandrini Mirta , Alblas Edwin , Batten Lin , Bothé Sumira 
Published: April 2024

AbstractAlmost two thirds of working farms in the European Union are considered smallholder farms. These farms play a crucial role in local food production, rural development, maintaining agrobiodiversity, and promoting cultural heritage. Despite this, agricultural policies have consistently supported on‐farm intensification, specialisation, enlargement, and mechanisation of agricultural production. These policies have been in turn commonly justified through food security and agricultural efficiency arguments. Considering the European Union's Farm to Fork Strategy and the Green Deal's aims of transitioning towards sustainable food systems, this article presents a novel empirical analysis of the legal position of small farmers in the new Common Agricultural Policy (CAP) of 2023. This analysis outlines the critical but complex position of smallholder farmers in the National Strategic Plans of 10 Member States. The reformed CAP increasingly acknowledges the important role of smallholder farmers in moving towards sustainable food systems. However, in this article, we question the CAP's sufficiency for improving the legal position of smallholders, promoting (economic) viability and harnessing the sustainability potential of smallholder farms.
Behavioural instruments in environmental law and policy: Potential and challenges
Authors: Shen Yayun , Faure Michael 
Published: April 2024

AbstractThe behavioural revolution in law and economics led to the insight that command‐and‐control and market‐based instruments have limitations in bringing about behavioural change. Environmental behavioural instruments use persuasive strategies or techniques rather than direct incentives to encourage environmentally responsible decision‐making. This article investigates the potential and challenges of behavioural instruments in environmental policy based on a survey of theories and examples concerning environmental behavioural instruments. Behavioural instruments can reduce the information costs of environmental regulation while increasing self‐efficacy for environmental compliance. More importantly, behavioural instruments can be cheap and effective by activating various norms in specific contexts. However, the behavioural approach, because of its focus on individual compliance, may not be well suited to address (transboundary) externalities. Behavioural instruments are especially important in generating positive externalities by appealing to social norms. Such mechanisms are, however, less suited to internalising negative externalities. The effects of behavioural instruments may not be easily guaranteed (in the long run), especially when the environmental goal of the behavioural approach clashes with private interests or fails to consider individual differences and contextual factors. We therefore argue that behavioural instruments should be included alongside standard regulatory tools, thus reaching an optimal mix between both.
A hypothesis-based hop microbiology laboratory module testing the plausibility of the mythical origin of the India Pale Ale
Authors: Molina Pineda Julio , Scholes Amanda N. , Lewis Jeffrey A. 
Published: April 2024

ABSTRACT

As one of the most famous fermented drinks in the world, beer is an especially relatable topic for microbiology courses. Here, we describe a short and easily adaptable module based on the antibacterial properties of hops used in brewing. By the 15th century, beer recipes included hops (the flower of the
Humulus lupulus
plant) as a bittering agent and antimicrobial. By the 19th century, the highly hopped Indian Pale Ale (IPA) became popular, and a modern myth has emerged that IPAs were invented to survive long ocean voyages such as from Britain to India. With that myth in mind, we designed a hypothesis-driven microbiology lab module that tests the plausibility of this brewing myth—namely that highly hopped beers possess enough antibacterial activity to prevent spoilage, while lowly hopped beers do not. The overall design of the module is to test the antimicrobial properties of hops using petri plates containing varying concentrations of hop extract. The module includes hypothesis generation and testing related to bacterial physiology and cell envelope morphology (hops are not equally effective against Gram-positive and Gram-negative bacteria) and to mechanisms of antimicrobial resistance (as beer spoilage bacteria have repeatedly evolved hop resistance). Pre- and post-assessment showed that students made significant gains in the learning objectives for the module, which encourages critical thinking and hypothesis testing by linking microbial physiology and antimicrobial resistance to an important and topical real-world application.
Space-like electromagnetic form factors of lambda- and sigma-baryons from quark-diquark Faddeev equations
Authors: Liu Langtian , Fischer Christian S. 
Published: April 2024

AbstractAn important goal of ongoing and future experiments is to explore spectra and transition form factors of baryons with non-zero strangeness. Of particular interest is the transition form factor$$\gamma ^{(*)} \Sigma ^0 \rightarrow \Lambda $$

γ

(

∗
)

Σ
0

→
Λ

in the time-like momentum region that can be extracted from Dalitz decays. On the road towards a theoretical description of these form factors we extend a covariant dynamical quark-diquark model for the baryon Faddeev equation to the strange-quark sector. Based on an excellent description of the mass spectrum of selected baryon octet and decuplet states and reasonable results for the nucleon form factors we determine the elastic electromagnetic form factors of $$\Lambda $$
Λ
and $$\Sigma ^+, \Sigma ^0, \Sigma ^-$$

Σ
+

,

Σ
0

,

Σ
-

hyperons in the space-like region as well as the ones for the octet transition $$\gamma ^{(*)} \Sigma ^0 \rightarrow \Lambda $$

γ

(

∗
)

Σ
0

→
Λ

. We discuss qualitative and quantitative features of the diquark-quark picture and compare systematically with previous results from a three-body Faddeev approach and lattice data where available.
Nicotinamide in Combination with EGFR-TKIs for the Treatment of Stage IV Lung Adenocarcinoma with EGFR Mutations: A Randomized Double-Blind (Phase IIb) Trial
Authors: Oh Hyung-Joo , Bae Suk-Chul , Oh In-Jae , Park Cheol-Kyu , Jung Kyoung-Mi , Kim Da-Mi , Lee Jung-Won , Kang Chang Kyun , Park Il Yeong , Kim Young-Chul 
Published: April 2024

Abstract

Purpose:
RUNX3 is a tumor suppressor gene, which is inactivated in approximately 70% of lung adenocarcinomas. Nicotinamide, a sirtuin inhibitor, has demonstrated potential in re-activating epigenetically silenced RUNX3 in cancer cells. This study assessed the therapeutic benefits of combining nicotinamide with first-generation EGFR–tyrosine kinase inhibitors (TKI) for patients with stage IV lung cancer carrying EGFR mutations.

Patients and Methods:
We assessed the impact of nicotinamide on carcinogen-induced lung adenocarcinomas in mice and observed that nicotinamide increased RUNX3 levels and inhibited lung cancer growth. Subsequently, 110 consecutive patients with stage IV lung cancer who had EGFR mutations were recruited: 70 females (63.6%) and 84 never-smokers (76.4%). The patients were randomly assigned to receive either nicotinamide (1 g/day, n = 55) or placebo (n = 55). The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively.

Results:
After a median follow-up of 54.3 months, the nicotinamide group exhibited a median PFS of 12.7 months [95% confidence interval (CI), 10.4–18.3], while the placebo group had a PFS of 10.9 months (9.0–13.2; P = 0.2). The median OS was similar in the two groups (31.0 months with nicotinamide vs. 29.4 months with placebo; P = 0.2). Notably, subgroup analyses revealed a significant reduction in mortality risk for females (P = 0.01) and never-smokers (P = 0.03) treated with nicotinamide.

Conclusions:
The addition of nicotinamide with EGFR-TKIs demonstrated potential improvements in PFS and OS, with notable survival benefits for female patients and those who had never smoked (ClinicalTrials.gov Identifier: NCT02416739).
Preclinical Development of CAR T Cells with Antigen-Inducible IL18 Enforcement to Treat GD2-Positive Solid Cancers
Authors: Fischer-Riepe Lena , Kailayangiri Sareetha , Zimmermann Katharina , Pfeifer Rita , Aigner Michael , Altvater Bianca , Kretschmann Sascha , Völkl Simon , Hartley Jordan , Dreger Celine , Petry Katja , Bosio Andreas , von Döllen Angelika , Hartmann Wolfgang , Lode Holger , Görlich Dennis , Mackensen Andreas , Jungblut Melanie , Schambach Axel , Abken Hinrich , Rossig Claudia 
Published: April 2024

Abstract

Purpose:
Cytokine-engineering of chimeric antigen receptor-redirected T cells (CAR T cells) is a promising principle to overcome the limited activity of canonical CAR T cells against solid cancers.

Experimental Design:
We developed an investigational medicinal product, GD2IL18CART, consisting of CAR T cells directed against ganglioside GD2 with CAR-inducible IL18 to enhance their activation response and cytolytic effector functions in the tumor microenvironment. To allow stratification of patients according to tumor GD2 expression, we established and validated immunofluorescence detection of GD2 on paraffin-embedded tumor tissues.

Results:
Lentiviral all-in-one vector engineering of human T cells with the GD2-specific CAR with and without inducible IL18 resulted in cell products with comparable proportions of CAR-expressing central memory T cells. Production of IL18 strictly depends on GD2 antigen engagement. GD2IL18CART respond to interaction with GD2-positive tumor cells with higher IFNγ and TNFα cytokine release and more effective target cytolysis compared with CAR T cells without inducible IL18. GD2IL18CART further have superior in vivo antitumor activity, with eradication of GD2-positive tumor xenografts. Finally, we established GMP-compliant manufacturing of GD2IL18CART and found it to be feasible and efficient at clinical scale.

Conclusions:
These results pave the way for clinical investigation of GD2IL18CART in pediatric and adult patients with neuroblastoma and other GD2-positive cancers (EU CT 2022– 501725–21–00).
See related commentary by Locatelli and Quintarelli, p. 3361
Proton FLASH Radiotherapy Ameliorates Radiation-induced Salivary Gland Dysfunction and Oral Mucositis and Increases Survival in a Mouse Model of Head and Neck Cancer
Authors: Chowdhury Priyanka , Velalopoulou Anastasia , Verginadis Ioannis I. , Morcos George , Loo Phoebe E. , Kim Michele M. , Motlagh Seyyedeh Azar Oliaei , Shoniyozov Khayrullo , Diffenderfer Eric S. , Ocampo Emilio A. , Putt Mary , Assenmacher Charles-Antoine , Radaelli Enrico , Lu Jiawei , Qin Ling , Liu Hengxi , Leli Nektaria Maria , Girdhani Swati , Denef Nicolas , Vander Stappen Francois , Cengel Keith A. , Busch Theresa M. , Metz James M. , Dong Lei , Lin Alexander , Koumenis Constantinos 
Published: April 2024

Abstract
Head and neck cancer radiotherapy often damages salivary glands and oral mucosa, severely negatively impacting patients’ quality of life. The ability of FLASH proton radiotherapy (F-PRT) to decrease normal tissue toxicity while maintaining tumor control compared with standard proton radiotherapy (S-PRT) has been previously demonstrated for several tissues. However, its potential in ameliorating radiation-induced salivary gland dysfunction and oral mucositis and controlling orthotopic head and neck tumor growth has not been reported.
The head and neck area of C57BL/6 mice was irradiated with a single dose of radiotherapy (ranging from 14–18 Gy) or a fractionated dose of 8 Gy × 3 of F-PRT (128 Gy/second) or S-PRT (0.95 Gy/second). Following irradiation, the mice were studied for radiation-induced xerostomia by measuring their salivary flow. Oral mucositis was analyzed by histopathologic examination. To determine the ability of F-PRT to control orthotopic head and neck tumors, tongue tumors were generated in the mice and then irradiated with either F-PRT or S-PRT.
Mice treated with either a single dose or fractionated dose of F-PRT showed significantly improved survival than those irradiated with S-PRT. F-PRT–treated mice showed improvement in their salivary flow. S-PRT–irradiated mice demonstrated increased fibrosis in their tongue epithelium. F-PRT significantly increased the overall survival of the mice with orthotopic tumors compared with the S-PRT–treated mice.
The demonstration that F-PRT decreases radiation-induced normal tissue toxicity without compromising tumor control, suggests that this modality could be useful for the clinical management of patients with head and neck cancer.
A new species of the extant genus Bulasconotus from mid-Cretaceous Kachin amber (Coleoptera: Zopheridae: Colydiinae)
Authors: Li Yan-Da , Jin Zhen-Yu , Ślipiński Adam , Huang Di-Ying , Cai Chen-Yang 
Published: April 2024

A fossil species of the extant colydiine genus Bulasconotus Ślipiński & Lawrence, B. carinisternus Li, Ślipiński & Cai sp. nov., is reported from mid-Cretaceous Kachin amber of northern Myanmar. The new species shares with extant Bulasconotus the 3-segmented antennal club, externally open procoxal cavities, and similar sculpture on the pronotum and elytra, but could be recognized by the medially carinated prosternal process. The present discovery provides a valuable example of morphological stasis in the cylindrical bark beetles.
Global, Regional, and National Burdens of Stroke in Children and Adolescents From 1990 to 2019: A Population-Based Study
Authors: Sun Hao , Ma Bing , Jin Chenye , Li Zhenning , Song Xinying , Bu Yifan , Liu Tingting , Han Xu , Yang Xue , Yang Kaijie , Xu Dongchu , Zhang Jing , Li Yongze 
Published: April 2024

BACKGROUND:
Stroke is one of the leading causes of death among children, yet evidence on stroke incidence and prognosis in this population is largely neglected worldwide. The aim of this study was to estimate the latest burden of childhood stroke, as well as trends, risk factors, and inequalities from 1990 to 2019, at the global, regional, and national levels.

METHODS:
The Global Burden of Disease 2019 study was utilized to evaluate the prevalence, incidence, years lived with disability, years of life lost (YLLs), and average annual percentage changes in stroke among populations aged 0 to 19 years from 1990 to 2019.

RESULTS:
The global age–standardized incidence of stroke increased (average annual percentage change, 0.15% [95% uncertainty interval, 0.09%–0.21%]), while YLLs decreased substantially (average annual percentage change, −3.33% [95% uncertainty interval, −3.38% to −3.28%]) among children and adolescents between 1990 and 2019. Ischemic stroke accounted for 70% of incident cases, and intracerebral hemorrhage accounted for 63% of YLLs. Children under 5 years of age had the highest incidence of ischemic stroke, while adolescents aged 15 to 19 years had the highest incidence of hemorrhagic stroke. In 2019, low-income and middle-income countries were responsible for 84% of incident cases and 93% of YLLs due to childhood stroke. High-sociodemographic index countries had a reduction in YLLs due to stroke that was more than twice as fast as that of low-income and middle-income.

CONCLUSIONS:
Globally, the burden of childhood stroke continues to increase, especially among females, children aged <5 years, and low-sociodemographic index countries, such as sub-Saharan Africa. The burden of childhood stroke is likely undergoing a significant transition from being fatal to causing disability. Global public health policies and the deployment of health resources need to respond rapidly and actively to this shift.
Energy and economic performance optimization of a window with variable transparency shape-stabilized PCM in hot summer and cold winter climate zone
Authors: Zhang Hangming , Zhang Ling , Zheng Yue , Liu Zhongbing 
Published: April 2024

Improving the thermal performance of windows is important for building energy efficiency. Filling windows with variable transparency shape-stabilized phase change materials (VTSS-PCM) improves the thermal inertia of windows while avoiding the leakage of PCM. In this paper, a new type of VTSS-PCM window was proposed, tested, simulated and optimized in hot summer and cold winter climate zone. A numerical model of the VTSS-PCM window was built, and the model was validated using experimental tests. On this basis, three key parameters of VTSS-PCM were investigated and optimized. Finally, the energy and economic performance of the optimized VTSS-PCM window were compared with a typical hollow glass window. The results showed that the total annual unfavourable heat transfer (TAHT) and the annual investment cost (AIC) of the VTSS-PCM window obtained from the optimization were 118.16 kWh/m2 and 8.53 CNY/m2, respectively. Compared with the hollow glass window, the VTSS-PCM window reduced the TAHT by 30.14% and the total annual cost by 28.39%. The VTSS-PCM window produced a better development potential in terms of energy performance and economic performance. This study provided a reference for the application of the VTSS-PCM window in hot summer and cold winter regions of China.