bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global Harmonization of Biosimilar Development by Overcoming Existing Differences in Regional Regulatory Requirements - Outcomes of a Descriptive Review
Authors: Kirchlechner Thomas M. , Cohen Hillel P. 
Published: January 2025

Abstract
Global harmonization of biosimilar developmental requirements will facilitate development leading to increased patient and societal benefits. However, there are several technical and regulatory hurdles that must be addressed to harmonize the regulatory requirements in different countries and regions. At times, there is a requirement for use of locally sourced reference product, forcing biosimilar developers to repeat analytical or clinical comparability studies against reference product batches sourced from within a given country. While most health authorities no longer require comparative animal toxicology studies of the proposed biosimilar and reference product, these are still required in several countries, forcing biosimilar companies to conduct such studies or risk non-approval of their product. At times, different health authorities request different clinical study designs. In some jurisdictions there is a requirement to generate clinical data in local ethnic populations. Some health authorities require a hybrid label that combines clinical data from the reference biologic and the biosimilar, in the patient leaflet. Recommendations are provided to address each of these hurdles to facilitate global regulatory harmonization of biosimilars. Overcoming these barriers will ultimately increase patient access to these medicines in all regions while providing financial relief to healthcare systems.
Early Intervention in Component and Composite Skills for Arithmetic Decomposition
Authors: Patterson Ally , Moyher Robin , Pasnak Robert , Kaminski Barbara J. 
Published: January 2025

Abstract
As early as first grade, some children are more likely than others to perform arithmetic using inefficient or other overt counting strategies. To partially address this problem, the primary investigator developed a skill hierarchy with procedures based on applied behavior analysis. The novel early-intervention program included a combination of instructional videos and live rehearsal to teach children how to decompose and accurately solve complex addition problems using only “mental math.” Six first graders who did not use decomposition strategies at baseline participated in a single-subject, multiple-probe across participants design. Participants first learned component decomposition skills to identify ones and tens place digits, add tens place values, and retrieve simple addition facts. However, despite mastery of these skills, participants did not use the composite decomposition skill spontaneously when presented with complex addition problems. The primary investigator then provided training on how to apply the component skills to the composite skill. Following training, participants immediately used the composite skill to solve random, complex addition problems with sums up to 198. Results suggest that, through explicit instruction informed by skill hierarchies, children who do not use broadly applicable and efficient methods of solving math problems may come to match their peers in more challenging, mathematics-related activities.
“We Learn How to Stay Out of Trouble”: Children in Conflict with the Law’s Perspectives on Mentorship as a Diversion Programme in Tshwane, South Africa
Authors: Zitha Moitsadi , van Rensburg Shandré Kim Jansen 
Published: January 2025

Abstract
South Africa has seen a surge in child offending. Child offenders commit violent crimes such as armed robbery, housebreaking, rape and murder. Conversely, not all child offenders commit violent crimes. Many child offenders are detained for minor charges such as shoplifting, theft and possession of illegal substances. Most of these children face numerous levels of adversity, including poverty, dysfunctional households and limited parental involvement. Responses to child criminal behaviour accentuate rehabilitation through measures such as diversion. Narrative accounts of children in conflict with the law who underwent mentorship programmes, as a diversion initiative, are scarce and underrepresented. Through a qualitative inquiry, 13 children who completed the National Youth Development Outreach (NYDO) Centre’s Mentoring Diversion Programme were interviewed and data were analysed thematically. Findings provided insight into the participants’ background and context, the mentor–mentee relationship, responsibility, effectiveness of the programme, and aftercare support. This paper contributes to scientific research and is conducive to curtailing child offending.
Accentuation explains the difference between choice and rejection better than compatibility: A commentary on Chandrashekar et al. (2021)
Authors: Ganzach Yoav 
Published: January 2025

Abstract
In this comment, I examine the results of two studies (Shafir, 1993 and Chandrashekar et al., 2021) that relied on the same stimuli to examine the effect of framing selection tasks in terms of choosing versus rejecting, and discuss how, despite the failure of the later study to replicate the results of the earlier one, analyzing the similarities and differences between the two advances our understanding of the processes underlying decisions in general, and decision in such tasks in particular.
Industrial Distraction
Authors: O’Connor Cailin , Freeborn David Peter Wallis 
Published: January 2025

Abstract
There are myriad techniques industry actors use to shape the public understanding of science. While a naive view might assume these techniques typically involve fraud or outright deception, the truth is more nuanced. This paper analyzes industrial distraction, a common technique where industry actors fund and share research that is accurate, often high quality, but nonetheless misleading on important matters of fact. This involves reshaping causal understanding of phenomena with distracting information. Using case studies and causal models, we illustrate how this impacts belief and decision making even for rational learners, informing science policy and debates about misleading content.
The Nun in the Parmenides: Not Another Exaiphnês
Authors: Pavani Anna 
Published: January 2025

Abstract
After some preliminary remarks about Plato’s use of the adverb nun, I explain what the nun is by offering a close textual analysis of the key passage in which it is explicitly addressed (Parm. 151e3–153b7). Its metaxu nature, between duration and limit, requires one to consider another temporal notion of the second part of the Parmenides that is metaxu, namely the exaiphnês. I explain why the nun does not conceptually overlap with the exaiphnês, arguing moreover that there is no model where both notions fit, but rather a model accounting for a switch and another one accounting for continuous change.
Hybrid wellbeing and the value of freedom
Authors: Intropi Pietro 
Published: January 2025

Abstract
Which implications follow for the value of freedom on a hybrid account of wellbeing that appeals to endorsement? On the basis of Olsaretti’s empirical claim that one is unlikely to endorse wellbeing when one is forced to achieve it, I show that standardly on the hybrid account there is a reason to protect people’s freedom to dysfunction, and hence that the freedoms to dysfunction are valuable. I also discuss whether freedom is non-specifically valuable on grounds of endorsement. I advance an epistemic version of freedom’s non-specific value that is especially relevant for a theory of justice that appeals to publicity.
Morbidity and Mortality of Drowning Children in Jerusalem District - Retrospective Analysis
Authors: Chavkin Maor , Ohana Sarna Cahan Lea , Shavit Itai , Brooks Rebecca , Sadeh Michal , Hashavya Saar , Gross Itai , Rekhtman David 
Published: January 2025

AbstractBackground:Drowning persists as a preventable pediatric cause of severe morbidity and mortality. This study aims to investigate the risk factors, circumstances, and medical consequences associated with pediatric drowning incidents in order to identify patterns that can inform targeted interventions.Methods:This was a retrospective analysis of a cohort of pediatric drowning cases. The study encompassed children aged 0-18 years who presented to the pediatric emergency departments (PEDs) of Hadassah Medical Centers in Jerusalem from January 1, 2004 through April 30, 2023. Inclusion criteria were individuals with main registration diagnosis containing the terms “drowning” or “submersion.”Results:Analysis revealed 129 cases of pediatric drowning, males comprising 66% of the cohort. The average age was 4.9 years (SD = 4.5). Predominantly, drownings occurred in private (38%) or public pools (27.1%). Forty-eight percent of children required hospitalization in intensive care. Notably, children from the Arab minority were significantly younger at the time of drowning (3.8 years; P = .04) and were at elevated risk of severe neurologic outcomes necessitating rehabilitation (P = .03). Incidents occurring on weekends were associated with younger victim ages (3.5 years; P = .04) and with increased likelihood of outcomes necessitating rehabilitation (P = .04). Conversely, children from families with four or more siblings were notably older at the time of drowning (5.3 years; P = .01). No other statistically significant differences were observed among demographic groups.Conclusions:Strategies aimed at promoting child health and preventing drowning must surmount feasibility barriers. Intervention efforts should be tailored to populations at heightened risk, including younger children, minority groups, and incidents occurring during weekends.
A four-dimensional dosimeter and quality assurance phantom to quantify respiratory motion effects on the dose delivery for adaptive radiation therapy
Authors: Meyers Taylor , Alsbou Nesreen , Ahmad Salahuddin , Ali Imad 
Published: January 2025

Abstract

Purpose:
A 4D-dosimeter and quality assurance phantom prototype was developed to quantify the effects of respiratory motion.

Methods:
The dose distributions were measured using two-dimensional detectors that were mounted on a mobile platform capable of sinusoidal motion in one direction with different patterns using adjustable motion amplitude and frequency. The dose distributions were obtained from various treatment plans including conformal and intensity-modulated beams for both photon and proton therapy. Dose delivery and measurement were conducted using this 4D-dosimeter with the mobile phantom for different motion amplitudes (0–35 mm) and frequencies (0.25–0.33 Hz).

Results:
The increase in motion amplitude increased the blurring of the dose distributions at the beam edges along the direction of motion and led to large dose discrepancies. This produced larger dose deficits inside the treatment planning volume (PTV) and increasing dose deposition in the surrounding normal tissue with increasing motion amplitudes. For both the IMRT and VMAT-treatment plans, the dose profile for each increased amplitude increment showed a reproducible flattening of the penumbra at the beam edge, all changing around the 40–60% isodose line.

Conclusion:
The 4D-dosimeter developed in this work provides a noble clinical tool to quantify the deviations in the dose distributions induced by respiratory motion.
Timing based clustering of childhood BMI trajectories reveals differential maturational patterns; Study in the Northern Finland Birth Cohorts 1966 and 1986
Authors: Heiskala Anni , Tucker J. Derek , Choudhary Priyanka , Nedelec Rozenn , Ronkainen Justiina , Sarala Olli , Järvelin Marjo-Riitta , Sillanpää Mikko J. , Sebert Sylvain 
Published: January 2025

Abstract

Background/Objectives
Children’s biological age does not always correspond to their chronological age. In the case of BMI trajectories, this can appear as phase variation, which can be seen as shift, stretch, or shrinking between trajectories. With maturation thought of as a process moving towards the final state - adult BMI, we assessed whether children can be divided into latent groups reflecting similar maturational age of BMI. The groups were characterised by early factors and time-related features of the trajectories.

Subjects/Methods
We used data from two general population birth cohort studies, Northern Finland Birth Cohorts 1966 and 1986 (NFBC1966 and NFBC1986). Height (n = 6329) and weight (n = 6568) measurements were interpolated in 34 shared time points using B-splines, and BMI values were calculated between 3 months to 16 years. Pairwise phase distances of 2999 females and 3163 males were used as a similarity measure in k-medoids clustering.

Results
We identified three clusters of trajectories in females and males (Type 1: females, n = 1566, males, n = 1669; Type 2: females, n = 1028, males, n = 973; Type 3: females, n = 405, males, n = 521). Similar distinct timing patterns were identified in males and females. The clusters did not differ by sex, or early growth determinants studied.

Conclusions:
Trajectory cluster Type 1 reflected to the shape of what is typically illustrated as the childhood BMI trajectory in literature. However, the other two have not been identified previously. Type 2 pattern was more common in the NFBC1966 suggesting a generational shift in BMI maturational patterns.
Reduced contribution of sulfur to the mass extinction associated with the Chicxulub impact event
Authors: Rodiouchkina Katerina , Goderis Steven , Senel Cem Berk , Kaskes Pim , Karatekin Özgür , Böttcher Michael Ernst , Rodushkin Ilia , Vellekoop Johan , Claeys Philippe , Vanhaecke Frank 
Published: January 2025

Abstract
The Chicxulub asteroid impact event at the Cretaceous-Paleogene (K-Pg) boundary ~66 Myr ago is widely considered responsible for the mass extinction event leading to the demise of the non-avian dinosaurs. Short-term cooling due to massive release of climate-active agents is hypothesized to have been crucial, with S-bearing gases originating from the target rock vaporization considered an important driving force. Yet, the magnitude of the S release remains poorly constrained. Here we empirically estimate the amount of impact-released S relying on the concentration of S and its isotopic composition within the impact structure and a set of terrestrial K-Pg boundary ejecta sites. The average value of 67 ± 39 Gt obtained is ~5-fold lower than previous numerical estimates. The lower mass of S-released may indicate a less prominent role for S emission leading to a milder impact winter with key implications for species survival during the first years following the impact.
Gypsum heterogenous nucleation pathways regulated by surface functional groups and hydrophobicity
Authors: Guan Yan-Fang , Hong Xiang-Yu , Karanikola Vasiliki , Wang Zhangxin , Pan Weiyi , Wu Heng-An , Wang Feng-Chao , Yu Han-Qing , Elimelech Menachem 
Published: January 2025

Abstract
Gypsum (CaSO4·2H2O) plays a critical role in numerous natural and industrial processes. Nevertheless, the underlying mechanisms governing the formation of gypsum crystals on surfaces with diverse chemical properties remain poorly understood due to a lack of sufficient temporal-spatial resolution. Herein, we use in situ microscopy to investigate the real-time gypsum nucleation on self-assembled monolayers (SAMs) terminated with −CH3, −hybrid (a combination of NH2 and COOH), −COOH, −SO3, −NH3, and −OH functional groups. We report that the rate of gypsum formation is regulated by the surface functional groups and hydrophobicity, in the order of −CH3 > −hybrid > −COOH > −SO3 ≈ − NH3 > − OH. Results based on classical nucleation theory and molecular dynamics simulations reveal that nucleation pathways for hydrophilic surfaces involve surface-induced nucleation, with ion adsorption sites (i.e., functional groups) serving as anchors to facilitate the growth of vertically oriented clusters. Conversely, hydrophobic surfaces involve bulk nucleation with ions near the surface that coalesce into larger horizontal clusters. These findings provide new insights into the spatial and temporal characteristics of gypsum formation on various surfaces and highlight the significance of surface functional groups and hydrophobicity in governing gypsum formation mechanisms, while also acknowledging the possibility of alternative nucleation pathways due to the limitations of experimental techniques.
Integrated analysis of cellulose structure and properties using solid-state low-field H-NMR and photoacoustic spectroscopy
Authors: Csóka Levente , Csoka Worakan , Tirronen Ella , Nikolskaya Ekaterina , Hiltunen Yrjö , Ohtani Bunsho 
Published: January 2025

Abstract
In this study, we explore the structural intricacies of cellulose, a polymer composed of glucose monomers arranged in a linear chain, primarily investigated through solid-state NMR techniques. Specifically, we employ low-field proton nuclear magnetic resonance (H-NMR) to delve into the diverse hydrogen atom types within the cellulose molecule. The low-field H-NMR technique allows us to discern these hydrogen atoms based on their distinct chemical shifts, providing valuable insights into the various functional groups present in cellulose. Our focus extends to the examination of anomeric protons of glucose units and protons linked to carbon atoms engaged in glycosidic linkages within cellulose chains, which exist in diverse crystalline and amorphous forms. Solid-state low-field H-NMR spectroscopy aids in characterizing the crystallinity degrees and amorphous regions within cellulose, revealing time-dependent changes in free induction decay (FID) signals. Complementing this, we investigate the photo-absorption properties of cellulose fibers under both continuous and modulated irradiation using reversed double-beam photoacoustic spectroscopy (RDB-PAS). This photoacoustic approach allows us to observe ultraviolet- and visible light-induced processes, including electron trap filling and reductive changes on the fiber surface. Our findings suggest that RDB-PAS is a feasible method for estimating the electron trap distribution, serving as a potential measure of the density of crystalline cellulose defects. This integrated approach of combining solid-state low-field H-NMR and RDB-PAS techniques offers a comprehensive understanding of cellulose structure and properties, enhancing our ability to characterize its diverse features.
Evaluating energy consumption patterns in novel foamed ternary alkali-activated masonry blocks
Authors: Nandipati Sunil , Degloorkar Nikhil Kumar , Pullagura Gandhi , Barik Debabrata , Paramasivam Prabhu , Althaqafi Essam , Islam Saiful , Al-sareji Osamah J. 
Published: January 2025

Abstract
This study endeavors to tackle the energy requirements of the building sector by employing passive design strategies. However, there exists a dearth of comprehension regarding the energy efficiency performance of foamed alkali-activated materials. To bridge this research gap, the study proposes a solution in the form of a thermally proficient wall material crafted from ceramic tile dust (CTD), class C fly ash (FA), and Ground Granulated Blast-Furnace Slag (GGBS), all of which are industrial by-products. The foamed ternary alkali-activated (FTAA) blocks, developed as a result of this research, exhibited commendable performance in terms of mechanical strength of 18.6 MPa, lower density of 1200 kg/m3, porosity of 15.95%, lower specific heat capacity (SHC) of 831 J/(Kg·K), and thermal conductivity (TC) of 0.38 W/(m·K). The thermal efficiency of FTAA blocks curtails the transfer of heat from the external environment to the interior, thereby engendering a more agreeable indoor milieu for occupants. A simulation study utilizing the eQuest tool was executed to evaluate the thermal attributes of the developed blocks and their consequential impact on energy requirements. The findings revealed that in comparison to clay bricks, employing FTAA blocks could yield potential annual energy savings of approximately 4%. Furthermore, notable cost savings of about 4.94% during peak summer months and 5.51% annually were observed. The significance of utilizing these ternary blocks, derived from industrial waste, resides in their affirmative contribution to environmental preservation, augmented indoor thermal comfort, and diminished energy consumption for end users. Consequently, this research makes a meaningful stride towards diminishing operational energy in buildings, harmonizing with sustainability objectives.
Response of negative ion beamlet width and axis deflection to RF field in beam extraction region
Authors: Nagaoka Kenichi , Nakano Haruhisa , Hamajima Taiga , Nakamoto Ryoya , Tsumori Katsuyoshi , Osakabe Masaki , Kisaki Masashi , Miyamoto Kenji , Takahashi Kazunori , Fantz Ursel 
Published: January 2025

Abstract
Beam-divergence characteristics of single negative ion beamlet have been experimentally investigated with a superimposition of a controlled perturbation of a radio frequency wave (RF) field in a filament-arc discharge negative ion source. Oscillations of a negative-ion beamlet width and axis responding to the RF perturbation were observed, which may be a cause of the larger beam divergence angle of the RF negative ion source for ITER. It is pointed out that the oscillation of the beamlet width depends on the perveance and on an RF frequency such that the oscillation is suppressed at perveance-matched conditions and at low RF frequency.
Contribution of hypoxia-inducible factor 1alpha to pathogenesis of sarcomeric hypertrophic cardiomyopathy
Authors: Raj Murthi Sarala , Petry Andreas , Shashikadze Bachuki , Stöckl Jan B. , Schmid Manuel , Santamaria Gianluca , Klingel Karin , Kračun Damir , Chen Xinpei , Bauer Sabine , Schmitt Joachim P. , Flenkenthaler Florian , Gorham Josh , Toepfer Christopher N. , Potěšil David , Hruška Pavel , Zdráhal Zbyněk , Mayer Zsuzsanna , Klop Mathieu , Lehmann Luisa , Qin Yishi , Papanakli Laura , Spielmann Nadine , Moretti Alessandra , Fröhlich Thomas , Ewert Peter , Holdenrieder Stefan , Seidman Jonathan G. , Seidman Christine E. , Görlach Agnes , Wolf Cordula M. 
Published: January 2025

Abstract
Hypertrophic cardiomyopathy (HCM) caused by autosomal-dominant mutations in genes coding for structural sarcomeric proteins, is the most common inherited heart disease. HCM is associated with myocardial hypertrophy, fibrosis and ventricular dysfunction. Hypoxia-inducible transcription factor-1α (Hif-1α) is the central master regulators of cellular hypoxia response and associated with HCM. Yet its exact role remains to be elucidated. Therefore, the effect of a cardiomyocyte-specific Hif-1a knockout (cHif1aKO) was studied in an established α-MHC719/+ HCM mouse model that exhibits the classical features of human HCM. The results show that Hif-1α protein and HIF targets were upregulated in left ventricular tissue of α-MHC719/+ mice. Cardiomyocyte-specific abolishment of Hif-1a blunted the disease phenotype, as evidenced by decreased left ventricular wall thickness, reduced myocardial fibrosis, disordered SRX/DRX state and ROS production. cHif1aKO induced normalization of pro-hypertrophic and pro-fibrotic left ventricular remodeling signaling evidenced on whole transcriptome and proteomics analysis in α-MHC719/+ mice. Proteomics of serum samples from patients with early onset HCM revealed significant modulation of HIF. These results demonstrate that HIF signaling is involved in mouse and human HCM pathogenesis. Cardiomyocyte-specific knockout of Hif-1a attenuates disease phenotype in the mouse model. Targeting Hif-1α might serve as a therapeutic option to mitigate HCM disease progression.