bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the Strength of Binding Affinity via Delta–Delta‐G for Hit Screening After a Deming Regression Calibration
Authors: Tatikola Kanaka , Cabrera Javier 
Published: February 2025

ABSTRACTIn compound hit screening, an important chemical property is target binding affinity, represented by a parameter ΔΔG. You can measure ΔΔG experimentally (ΔΔGexp) or by calculations via simulations (ΔΔGcalc). Because it is expensive to measure ΔΔG experimentally, only a few experimental runs are performed. The relationship between the experimental data and the calculated results is a straight line with a slope that is not necessarily one. The goal is to estimate the linear relationship between ΔΔGexp and ΔΔGcalc by fitting a Deming regression model that will be used to predict future values of ΔΔGtrue based on the obtained ΔΔGcalc.
New Methods for Two‐Stage Treatment Switching Estimation
Authors: Jackson Dan , Ran Di , Zhang Fanni , Ouwens Mario , Druker Vitaly , Sweeting Michael , Hettle Robert , White Ian R. 
Published: February 2025

ABSTRACTTreatment switching is common in randomized trials of oncology treatments. For example, control group patients may receive the experimental treatment as a subsequent therapy. One possible estimand is the effect of trial treatment if this type of switching had instead not occurred. Two‐stage estimation is an established approach for estimating this estimand. We argue that other estimands of interest instead describe the effect of trial treatments if the proportion of patients who switched was different. We give precise definitions of such estimands. By motivating estimands using real‐world data, decision‐making in universal health care systems is facilitated. Focusing on estimation, we show that an alternative choice of secondary baseline, the time of first subsequent treatment, is easily defined, and widely applicable, and makes alternative estimands amenable to two‐stage estimation. We develop methodology using propensity scores, to adjust for confounding at a secondary baseline, and a new quantile matching technique that can be used to implement any parametric form of the post‐secondary baseline survival model. Our methodology was motivated by a recent immuno‐oncology trial where a substantial proportion of control group patients subsequently received a form of immunotherapy.
Sample Size Estimation for Correlated Count Data With Changes in Dispersion
Authors: Hou Jintong , McClure Leslie A. , Jaeger Savina , Robinson Lucy F. 
Published: February 2025

ABSTRACTClinical endpoints based on repeated measurements arise in many clinical research studies, and require specialized methods for sample size and power calculations. In clinical trials that measure counts over time, such as bleeding events in hemophilia, the dispersion of their distributions might change upon treatment and the measurements might be correlated. The generalized estimating equations (GEE) approach has been widely used for modeling correlated data and comparing rates. In this paper, we investigate the properties of GEE when applied to count outcomes with changes in dispersion. We derive general closed‐form formulas to estimate sample size when the dispersion parameters and distributions of count data vary across two correlated measurements based on the GEE approach. These formulas allow for power and sample size estimation for intra‐participant comparison of rates before and after an intervention, randomized controlled trials with equal allocation, or matched pairs designs. These formulas are derived for the following distributions: Poisson, negative binomial, zero‐inflated Poisson, and zero‐inflated negative binomial distributions, and do not assume that measurements before and after an intervention come from the same distribution. Furthermore, we propose modified methods for estimating sample size and confidence intervals for the negative binomial distributions to overcome Type I error inflation, which is especially useful for large changes in the negative binomial dispersion parameter. We perform simulations, and evaluate the performance of the empirical power and Type I error over a range of parameters. Applications and R functions implementing the methods are also provided.
Investigation on Diabetes and Mechanism of Thiadiazole–Schiff Base as Therapeutic Hybrid: Enzyme Activity and Molecular Docking Studies
Authors: Iqbal Tayyiaba , Khan Shoaib , Hussain Rafaqat , Hawsawi Mohammed B. , Mehmood Tariq , Tahir Yameena , Alluhaibi Mustafa S. , Alharbi Majed 
Published: February 2025

AbstractIn an approach to combat diabetes mellitus, a widely spread noncommunicable disease (NCDs), a novel series of compounds (1–18) containing substituted thiadiazole bearing Schiff base derivative was synthesized and evaluated against enzymes causing diabetes mellitus. The results confirm that most of the compounds were found active and exhibit excellent biological activity as compared to the standard drug acarbose. Their minimal inhibitory concentrations for both enzymes lie in a range between 18.10 ± 0.30 and 2.10 ± 0.30 µM for α‐amylase and 19.20 ± 0.30 µM and 2.70 ± 0.80 µM for α‐glucosidase in contrast with the reference drug having IC50 of 4.30 ± 0.40 and 5.10 ± 0.70 µM. The most active analogs were found to be 2, 4, 7, 9, and 15, which displayed few‐fold higher potency than the control drug. Structural evaluation was conducted using various spectroscopic techniques such as 1H NMR, 13C NMR and HREIMS for all the synthesized derivatives, and in silico molecular docking studies of all the active analogs confirms the interactions between ligand and binding proteins.
Enhanced Wire‐Shaped Micro‐Supercapacitor Treated with a Continuous Surface Atmospheric Pressure Plasma Jet Approach
Authors: Kim Minju , Kim Woo Jong , Kim Min Kyeong , Seo Jeongwoo , Song Saegyoung , Kim Dong Il , Sim Byeongchan , Lee Huigu , Lee Minjeong , Ryu Gyeong Hee , Hong John , Hong Jin Pyo 
Published: February 2025

AbstractMicroscale, wire‐shaped flexible supercapacitors are gaining significant attention due to the growing demand for wearable electronics and microrobotic technologies. Among various materials, copper sulfide stands out as an ideal candidate because of its superior electrochemical properties, which can be attributed to its nanostructured composition. This structure enhances the surface area, reduces ion transport distances, and improves charge–discharge kinetics. However, conventional electrode synthesis methods—such as annealing and hydrothermal processes—are limited by long production times and scalability issues, making them unsuitable for wire‐shaped supercapacitor development. In this study, an innovative fabrication technique using an atmospheric pressure plasma jet (APPJ) for both surface treatment and material synthesis is proposed. By integrating the APPJ with a winding mechanism, roll‐to‐roll processing for continuous production is enabled, significantly enhancing the scalability of the manufacturing process. The fabricated wire‐shaped microscale electrodes demonstrate high specific capacitance (153.39 mF cm−2), specific energy density (15.48 µWh cm−2), and excellent capacitance retention (91.32%) after 30 000 charge–discharge cycles. Furthermore, a wire‐shaped solid‐state flexible asymmetric supercapacitor is assembled using the fabricated electrodes in a coaxial configuration. The supercapacitor exhibits exceptional flexibility and energy storage performance, underscoring the practical applicability of the proposed method for advanced electronics.
Anticholinergic drugs and dementia risk: Using stem cell–based studies to complement pharmacoepidemiology
Authors: Schwarze‐Taufiq Tiara A. , Pranoto Inez K. A. , Hui Katherine , Kinoshita Chizuru , Yu Onchee , Crane Paul K. , Gray Shelly L. , Young Jessica E. 
Published: February 2025

AbstractBACKGROUNDAnticholinergic (AC) use remains common in older adults despite evidence of safety risks, including increased risk in dementia. Pharmacoepidemiology studies from various populations report associations between specific anticholinergic classes – antidepressants and bladder antimuscarinics – and increased dementia incidence. However, it is difficult to determine whether these associations are directly caused by the neurotoxic effects of anticholinergic drugs or by the underlying health conditions which the medications are taken for, known as confounding by indication. Here, we leverage human induced pluripotent stem cells‐derived‐neurons (hiPSC‐Ns) to complement the pharmacoepidemiology studies by directly examining the effects of various anticholinergic classes on dementia‐related cellular phenotypes.METHODSWe treated human induced pluripotent stem cell (hiPSC)–derived neurons with eight drugs representing different AC medication classes, including antidepressants, bladder antimuscarinics, antihistamines, and antispasmodics. We analyzed these neurons for cytotoxicity, amyloid beta (Aβ) peptide levels in the conditioned medium, and the level of intracellular phosphorylated tau from these cultures.RESULTSWe observed that antidepressants and bladder antimuscarinics were consistently cytotoxic, whereas antihistamines and antispasmodics did not show overt cytotoxicity at the times and concentrations that we tested. Some of the cytotoxic medications altered the amounts of Aβ1‐42 peptides, but there were no significant differences in the intracellular ratio of phosphorylated tau/total tau between AC drug treatments.CONCLUSIONSThese results corroborate population‐based studies and suggest a molecular basis for the differences in dementia risk observed according to AC class. This warrants future work examining the effect of AC medications on hiPSC‐derived cells from multiple subjects and examining other molecular outcomes including synaptic function and neuroinflammation in hiPSC‐based models.Highlights
Certain classes of anticholinergic (AC) medications are linked to dementia.
Human‐induced pluripotent stem cell (hiPSC) models are used to directly test the cytotoxicity of AC medications.
AC classes that are associated with dementia are more neurotoxic.
Problematizing and Reappraising Critiques of “Ethno‐Nationalism”: Collective Self‐Determination, Liberal Democracy, and Human Rights in Dynamic Synergy
Authors: Schimmel Noam 
Published: February 2025

ABSTRACTThis commentary argues that the typically left‐wing critique of ethnic‐national self‐determination is often inadvertently neo‐imperial and forces a largely Anglo‐American theory and practice of democracy on other states and peoples who have different identities, values, cultures, and conceptions and practices of democracy that are well within the normative boundaries of the framework of international law and international human rights law. In so doing, it discriminates against many peoples and ethnic groups who organize themselves politically in ways that give expression to both liberal democracy and ethnic‐national collective identity—in dynamic relationship, sometimes in tension, but not in fundamentally mutually exclusive and contradictory ways as they are often depicted and inaccurately and unfairly accused.
The Problem of Words and Language in Interdisciplinary Collaborations
Authors: Lenz Taguchi Hillevi , Bodén Linnea 
Published: February 2025

Abstract
This chapter presents a discussion on the problem of language, concepts, and metaphors in interdisciplinary collaborations. The chapter relates back to Chap. 2 and the discussions on development to consider some of the problems and possibilities in language practices that involve researchers with different ontological and epistemological backgrounds. Outlining the discussions around words, metaphors, and language use in the Enhancing Children’s Attention project, the chapter shows how all researchers in interdisciplinary collaborations need to learn more about what their collaborators take for granted in terms of ontological, epistemological, and political notions in their respective disciplines and, thus, learn more about the ontological, epistemological, and political blockages inherent in their own disciplinary research practices.
Troubling Ethics in Developmental and Postdevelopmental Inquiry Involving Children
Authors: Lenz Taguchi Hillevi , Bodén Linnea 
Published: February 2025

Abstract
This chapter provides an analysis of how ethics is discussed in the literature within the field of child and childhood studies and early childhood education. Inquiry that involves children is often discussed in terms of whether the research is conducted on, to, with, for, or by children. In this chapter, we problematize a value scale that positions research on children at the bad end of the scale and research by children at the good end. We look at how research departs from certain philosophical assumptions about ethics: ethics as social justice and fairness; ethics as inclusion, participation, and empowerment; and ethics as producing potential new worlds. We argue for multiethical perspectives, where different ethical underpinnings are laid side by side to strengthen research practices.
Introduction: Service Design in East and Southeast Asia as a Phenomenon
Authors: Lee Jung-Joo , Baek Joon Sang , Yu Eun 
Published: February 2025

Abstract
This book explores the adoption and practices of service design within the socio-cultural contexts of East and Southeast Asia, where its applications are shaped by local economic, political, and cultural influences. Through case studies and narratives from academia and practice, the book highlights the plurality of service design in this region, examining how it is understood, institutionalized, and enacted in diverse localities. By focusing on cultural specificity, this work seeks to broaden the conceptualization and practice of service design, emphasizing the importance of local knowledge, values, and contexts in its global development. Key themes include pragmatic adoption, cultural manifestations of value co-creation, and the interplay between traditional and modern approaches in service design.
Stop the bleed “ – Prehospital bleeding control in patients with multiple and/or severe injuries – A systematic review and clinical practice guideline – A systematic review and clinical practice guideline
Authors: Trentzsch H. , Goossen K. , Prediger B. , Schweigkofler U. , Hilbert-Carius P. , Hanken H. , Gümbel D. , Hossfeld B. , Lier H. , Hinck D. , Suda A. J. , Achatz G. , Bieler D. 
Published: February 2025

Abstract

Purpose
Our aim was to develop new evidence-based and consensus-based recommendations for bleeding control in patients with multiple and/or severe injuries in the prehospital setting. This guideline topic is part of the 2022 update of the German Guideline on the Treatment of Patients with Multiple and/or Severe Injuries.

Methods
MEDLINE and Embase were systematically searched until June 2021. Further literature reports were obtained from clinical experts. Randomised controlled trials, prospective cohort studies, and comparative registry studies were included if they compared interventions for bleeding control in the prehospital setting using manual pressure, haemostatic agents, tourniquets, pelvic stabilisation, or traction splints in patients with multiple and/or severe injuries. We considered patient-relevant clinical outcomes such as mortality and bleeding control. Transfusion requirements and haemodynamic stability were surrogate outcomes. Risk of bias was assessed using NICE 2012 checklists. The evidence was synthesised narratively, and expert consensus was used to develop recommendations and determine their strength.

Results
Fifteen studies were identified. Interventions covered were pelvic binders (n = 4 studies), pressure dressings (n = 1), tourniquets (n = 6), traction splints (n = 1), haemostatic agents (n = 3), and nasal balloon catheters (n = 1). Fourteen new recommendations were developed. All achieved strong consensus.

Conclusion
Bleeding control is the basic objective of treatment. This can be easily justified based on empirical evidence. There is, however, a lack of reliable and high-quality studies that assess and compare methods for bleeding control in patients with multiple and/or severe injuries. The guideline provides reasonable and practical recommendations (although mostly with a low grade of recommendation) and also reveals several open research questions that can hopefully be answered when the guideline is revised again.
Balancing storage cost and customization time in product platform design: a bi-objective optimization model
Authors: Naldi Ludovica Diletta , Galizia Francesco Gabriele , Bortolini Marco 
Published: February 2025

Abstract
In the modern market scenario governed by the Mass Customization paradigm, the so-called delayed product differentiation (DPD) rose as a production strategy best balancing traditional Make-to-Stock (MTS) and Make-to-Order (MTO), potentially reducing storage cost and customization time. In industry, DPD uses product platforms, defined as a set of components forming a common structure, from which a stream of derivative variants is produced. Early-stage platforms, made of few components, limit their storage cost, increasing the time to customize and turn them into final variants. The literature widely discusses the product platform design problem, asking to explore quantitatively the trade-off between platform storage cost and customization time. This paper contributes to applied research in mass customization, proposing and applying a bi-objective optimization model able to assign the most suitable production strategy to each product variant among MTS, MTO, and DPD. In the case of DPD selection, the model designs the product platforms best balancing storage cost and customization time as the target metrics to optimize, subject to industrial constraints to produce and store them, matching each variant to the most suitable platform. A case study adapted from the electronic components sector exemplifies the use of the bi-objective model, supporting companies in managing high-variety mixes.
Inhibition of protein phosphatases attenuates A1-adenosine receptor-stimulation induced negative inotropic effects of cAMP-increasing agents in the isolated human atrium
Authors: Schwarz Rebecca , Hofmann Britt , Gergs Ulrich , Neumann Joachim 
Published: February 2025

Abstract
N6-(R)-Phenylisopropyladenosine (R-PIA), an agonist at A1-adenosine receptors, alone exerts negative inotropic effects (NIE) in the human atrium. This NIE is augmented in the presence of cAMP-increasing agonists like phosphodiesterase inhibitors (cilostamide, rolipram) or a direct activator of adenylyl cyclase (forskolin). Cantharidin inhibits protein phosphatases 1 and 2A (PP1, PP2A). We hypothesized that cantharidin would attenuate this NIE of R-PIA in the presence of cilostamide or forskolin. During open heart surgery (patients were suffering from severe coronary heart disease), isolated human atrial preparations (HAP) were obtained. These HAP were mounted in organ baths and electrically stimulated (1 Hz). For comparison, we studied isolated electrically stimulated (1 Hz) left atrial preparations (LA) from wild type mice. We noted that R-PIA exerted negative inotropic effects in LA and HAP in the presence of cilostamide or rolipram and forskolin that were attenuated by cantharidin. We hypothesize that R-PIA in the presence of phosphodiesterase inhibitors or forskolin stimulates PP in the human atrium. Hence, R-PIA acts, at least in part, by stimulating PP in HAP.
Development and evaluation of [11C]DPA-813 and [18F]DPA-814: novel TSPO PET tracers insensitive to human single nucleotide polymorphism rs6971
Authors: Beaino Wissam , JM Kooijman Esther , Werry Eryn L. , Vellinga Rens J. , Van den Hoek Johan , Sohler Greta , Cumbers Grace A. , Genetzakis Elijah , Harvey-Latham Edward D. , Schuit Robert C. , Kassiou Michael , Windhorst Albert D. , Danon Jonathan J. 
Published: February 2025

Abstract

Purpose
The translocator protein 18 kDa (TSPO) is a widely used marker for imaging neuroinflammation via Positron Emission Tomography (PET). However, the vast majority of reported TSPO PET tracers display low binding affinity to a common isoform of human TSPO (rs6971; A147T), making them unsuitable for universal use in the general population. In this study, we have developed and preclinically validated two novel tracers designed to image TSPO in patients of all genotypes.

Methods
Novel analogues of known TSPO ligands were synthesised, evaluated for TSPO binding affinity in vitro (membranes prepared from transfected HEK-293T cells expressing wild-type (WT) or A147T TSPO) and radiolabelled with carbon-11 or fluorine-18. They were evaluated in situ (autoradiography on genotyped human brain tissue) and in vivo (rat, both WT and clinically relevant experimental autoimmune encephalomyelitis (EAE) neuroinflammation model) as potential polymorphism-insensitive TSPO PET tracers.

Results
Two new TSPO ligands, DPA-813 and DPA-814, displayed equivalent single-digit nanomolar binding affinities in vitro towards both human TSPO isoforms. [11C]DPA-813 and [18F]DPA-814 were synthesised in moderate radiochemical yields, high radiochemical purity, and high molar activity. Autoradiography on human MS tissues showed high specific binding for both tracers, irrespective of the TSPO isoform. The tracers demonstrated high plasma stability after 45 min and no brain metabolism with > 99% intact tracer. Biodistribution in WT animals indicated good brain uptake for both tracers (0.28 and 0.41%ID/g for [18F]DPA-814 and [11C]DPA-813, respectively). PET imaging in the clinically relevant EAE neuroinflammation model in rats showed significantly higher uptake of [11C]DPA-813 and [18F]DPA-814 in the spinal cord of the EAE rats compared to the controls.

Conclusion
We have developed two novel PET tracers that display indiscriminately high binding affinity to both common isoforms of human TSPO, show favourable metabolic stability and brain penetration in rats, and significantly higher uptake in the spinal cord of a neuroinflammatory rat model of multiple sclerosis. Going forward, first-in-human clinical validation will mark a critical juncture in the development of these tracers, which could offer substantial improvements over existing imaging tools for detecting neuroinflammation, irrespective of genetic variations.
Combining immunosuppressive therapy with low dosage eltrombopag in Chinese patients with severe aplastic anemia: mild aggravation of hepatic injury
Authors: Chen Xiaoyu , Yu Qingling , Qin ChengTao , Zhang Yawen , Sun Jingnan , Jia Jinsong , Ye Baodong , Gong Yuemin , He Guangsheng , Fan Lei 
Published: February 2025

Abstract
Eltrombopag (EPAG) is an oral thrombopoietin receptor agonist analog with the potential risk to induce liver injury. This prospective registry study evaluated the prevalence and severity of hepatic injury in Chinese patients with severe aplastic anemia undergoing low-dose EPAG treatment (75 mg/day) in the context of standard immunosuppressive therapy (IST). The incidence of acute drug-induced liver injury was slightly higher in the IST + EPAG group than in the IST group at the 1st and 2nd month, but no statistically significant difference was observed: 10% vs 5% (p = 0.400), 9% vs 8% (p = 1.000). At the 1st month, the incidences of alanine aminotransferase, aspartate aminotransferase, and total bilirubin increased of grade 3 or higher in the IST + EPAG and the IST groups, were 5% vs 3% (p = 0.228), 2% vs 1% (p = 1.000), 2% vs 1% (p = 1.000), respectively. The logistic analysis indicated that serum ferritin level was associated with severe liver injury events. There was a slight increase in the incidence of severe hepatic injury events in the patients with SAA treated by EPAG, but it was insignificant.