bluuebunny/crossref_metadata_2025_split huggingface dataset:
Explaining in-vitro to in-vivo efficacy correlations in oncology pre-clinical development via a semi-mechanistic mathematical model
Authors: Huber Heinrich J. , Mistry Hitesh B. 
Published: November 2023

AbstractIn-vitro to in-vivo correlations (IVIVC), relating in-vitro parameters like IC50 to in-vivo drug exposure in plasma and tumour growth, are widely used in oncology for experimental design and dose decisions. However, they lack a deeper understanding of the underlying mechanisms. Our paper therefore focuses on linking empirical IVIVC relations for small-molecule kinase inhibitors with a semi-mechanistic tumour-growth model. We develop an approach incorporating parameters like the compound’s peak-trough ratio (PTR), Hill coefficient of in-vitro dose-response curves, and xenograft-specific properties. This leads to formulas for determining efficacious doses for tumor stasis under linear pharmacokinetics equivalent to traditional empirical IVIVC relations, but enabling more systematic analysis. Our findings reveal that in-vivo xenograft-specific parameters, specifically the growth rate (g) and decay rate (d), along with the average exposure, are generally more significant determinants of tumor stasis and effective dose than the compound’s peak-trough ratio. However, as the Hill coefficient increases, the dependency of tumor stasis on the PTR becomes more pronounced, indicating that the compound is more influenced by its maximum or trough values rather than the average exposure. Furthermore, we discuss the translation of our method to predict population dose ranges in clinical studies and propose a resistance mechanism that solely relies on specific in-vivo xenograft parameters instead of IC50 exposure coverage. In summary, our study aims to provide a more mechanistic understanding of IVIVC relations, emphasizing the importance of xenograft-specific parameters and PTR on tumor stasis.
Geef artsen al vroeg onderwijs over beleid en bestuur
Authors: van den Broek Robert , Dongelmans Edo , van Beeck Ed 
Published: November 2023

SamenvattingHet dagelijks werk van een arts bestaat uit patiëntenzorg (eerste vak) en uit allerlei andere zaken, zoals verandermanagement of beleidsontwikkeling (tweede vak). Op dit moment worden studenten geneeskunde nog onvoldoende op het tweede vak voorbereid. In 2019 zijn wij daarom gestart met nieuw onderwijs binnen de master geneeskunde, waarbij alle studenten vroeg in hun carrière proactief kennismaken met het tweede vak. Uit de huidige evaluatie blijkt dat deelnemers het onderwijs als zeer waardevol ervaren, met hoge waarderingen voor inhoud en docent. Wij overwegen nu verdere uitbreiding van het onderwijs. Daarnaast zou soortgelijk onderwijs ook in andere opleidingsregio’s geïntroduceerd kunnen worden.
Een 67-jarige man met verdenking op forse enkelzijdige hydronefrose; een beeld veroorzaakt door renale lymfangiëctasie
Authors: Feikema Astrid , Dijkstra Siebren , Kemper Frank 
Published: November 2023

SamenvattingEen 67-jarige patiënt werd verwezen in verband met nierfunctiestoornissen en een echografisch beeld verdacht voor hydronefrose links. De CT-blanco liet hydronefrose links zien met een kaliberwisseling mid-ureter. Om een urotheelcelcarcinoom als oorzaak van de hydronefrose uit te sluiten, werd een CT-urografie verricht, die het beeld van renale lymfangiëctasie liet zien, zonder aanwijzingen voor maligniteit. Deze zeer zeldzame aandoening komt vaak als toevalsbevinding aan het licht bij verdenking van hydronefrose op echografie of een CT-blanco. Renale lymfangiëctasie verloopt vaak asymptomatisch en behoeft om die reden geen behandeling. Indien er toch sprake is van symptomen, zoals flankpijn, hematurie of complicaties als gevolg van verhoogde druk op het pyelocalicieel systeem kan behandeling overwogen worden middels drainage of chirurgische interventie.
Sticky nonlinear SDEs and convergence of McKean–Vlasov equations without confinement
Authors: Durmus Alain , Eberle Andreas , Guillin Arnaud , Schuh Katharina 
Published: November 2023

AbstractWe develop a new approach to study the long time behaviour of solutions to nonlinear stochastic differential equations in the sense of McKean, as well as propagation of chaos for the corresponding mean-field particle system approximations. Our approach is based on a sticky coupling between two solutions to the equation. We show that the distance process between the two copies is dominated by a solution to a one-dimensional nonlinear stochastic differential equation with a sticky boundary at zero. This new class of equations is then analyzed carefully. In particular, we show that the dominating equation has a phase transition. In the regime where the Dirac measure at zero is the only invariant probability measure, we prove exponential convergence to equilibrium both for the one-dimensional equation, and for the original nonlinear SDE. Similarly, propagation of chaos is shown by a componentwise sticky coupling and comparison with a system of one dimensional nonlinear SDEs with sticky boundaries at zero. The approach applies to equations without confinement potential and to interaction terms that are not of gradient type.
Atomic Dispersed Hetero-Pairs for Enhanced Electrocatalytic CO2 Reduction
Authors: Jin Zhaoyong , Yang Meiqi , Dong Yilong , Ma Xingcheng , Wang Ying , Wu Jiandong , Fan Jinchang , Wang Dewen , Xi Rongshen , Zhao Xiao , Xu Tianyi , Zhao Jingxiang , Zhang Lei , Singh David J. , Zheng Weitao , Cui Xiaoqiang 
Published: November 2023

AbstractElectrochemical carbon dioxide reduction reaction (CO2RR) involves a variety of intermediates with highly correlated reaction and ad-desorption energies, hindering optimization of the catalytic activity. For example, increasing the binding of the *COOH to the active site will generally increase the *CO desorption energy. Breaking this relationship may be expected to dramatically improve the intrinsic activity of CO2RR, but remains an unsolved challenge. Herein, we addressed this conundrum by constructing a unique atomic dispersed hetero-pair consisting of Mo-Fe di-atoms anchored on N-doped carbon carrier. This system shows an unprecedented CO2RR intrinsic activity with TOF of 3336 h−1, high selectivity toward CO production, Faradaic efficiency of 95.96% at − 0.60 V and excellent stability. Theoretical calculations show that the Mo-Fe diatomic sites increased the *COOH intermediate adsorption energy by bridging adsorption of *COOH intermediates. At the same time, d-d orbital coupling in the Mo-Fe di-atom results in electron delocalization and facilitates desorption of *CO intermediates. Thus, the undesirable correlation between these steps is broken. This work provides a promising approach, specifically the use of di-atoms, for breaking unfavorable relationships based on understanding of the catalytic mechanisms at the atomic scale.
Study on deep learning methods for coal burst risk prediction based on mining-induced seismicity quantification
Authors: Cheng Xianggang , Qiao Wei , He Hu 
Published: November 2023

AbstractThe assessment of Coal burst risk (CBR) is the premise of bump disaster prevention and control. It is the implementation criterion to guide various rock burst prevention and control measures. The existing static prediction and evaluation methods for CBR cannot be effectively combined with the results of underground dynamic monitoring. This study proposed a mining-induced seismicity information quantification method based on the fractal theory. Deep learning methods were used to construct a deep learning framework of coal burst risk (DLFR) based on the fractal dimension of microseismic information. Gray correlation analysis (GRA), information gain ratio (IGR), and Pearson correlation coefficient are used to screen and compare factors. Statistical evaluation indicators such as macro-F1, accuracy rate, and fitness curve were used to evaluate model performance. Taking the Gaojiapu coal mine as a case study, the performance of deep learning models such as BP Neural Network (BP), Support Vector Machine (SVM) and its optimized model based on particle swarm optimization (PSO) algorithm under this framework is discussed. The research results' reliability and validity are verified by comparing the predicted results with the actual results. The research results show that the prediction results of CBR in DLFR are consistent with the actual results, and the model is reliable and effective. The mining-induced seismicity quantification can solve the problem of insufficient training samples for the CBR. With this, different pressure relief measures can be formulated based on the results of the CBR predictions to achieve "graded" precise prevention and control.
A sustainable preparation strategy for the nitrogen-doped hierarchical biochar with high surface area for the enhanced removal of organic dye
Authors: Mao Yiting , Cai Bo , Huang Ming , Liu Xiaohuan , Zhang Wenbiao , Ma Zhongqing 
Published: November 2023

AbstractBiochar is a potential porous carbon to remove the contaminants from aquatic environments. Herein, N-doped hierarchical biochar was produced by the combined approach of ammonia torrefaction pretreatment (ATP) and alkali activation. ATP could not only incorporate N element into poplar wood, but obtain the loose structure of poplar wood. The highest surface area of N-doped hierarchical biochar was 2324.61 m2 g−1 after ammonia wet torrefaction pretreatment, which was higher than that of activation carbon (1401.82 m2 g−1) without torrefaction pretreatment, the hierarchical biochar (2111.03 m2 g−1) without ammonia atmosphere. The N-doped hierarchical biochar presented the highest adsorption capacity (564.7 mg g−1) of methyl orange (MO), which was 14.64-fold of that on biochar without N doping. In addition, the pseudo-second-order and Langmuir model fitted well with the adsorption kinetics and isotherms of the N-doped hierarchical biochar. The incorporation of nitrogen element could not only tune the distribution of surface electrons on biochar, but optimize the ambient condition of adsorption active sites as well. The adsorption of MO might occur on the N-/O-containing functional groups through the electrostatic interaction, the π-π dispersion interaction, and the hydrogen bonding. The density functional theory showed that the graphitic-N and pyridinic-N were the dominant adsorption active sites.
Graphical Abstract
Antonio da Sangallo the Younger and St Peter’s Keys: Building Technology and Vitruvian Theory
Authors: Holzman Samuel , Yerkes Carolyn 
Published: November 2023

ABSTRACTThis article reconstructs an exceptional lifting device — a cruciform lewis — drawn by Antonio da Sangallo the Younger (1484–1546) at St Peter’s Basilica in Rome and connects it to the other drawings, mainly of Vitruvian theory, on the same sheet (now in the Uffizi in Florence). Elements of this sheet, dated to January 1542, have been studied in isolation, but this article connects them, underscoring how Sangallo’s theoretical interests in the art of building and the practicalities of masonry construction were inseparable. A question posed by the sheet is whether it documents Sangallo’s archaeological discoveries of ancient Roman tools or presents newly contrived ones — categories that Sangallo’s drawings move fluidly between. His studies should be understood in relation to the immediate problems that he faced on the building site of St Peter’s and within the broader context of other Renaissance drawings of machines, such as those by Francesco di Giorgio and Leonardo da Vinci.
A Dark Portrait: John Britton’s Denunciation of John Soane
Authors: Lukacher Brian 
Published: November 2023

ABSTRACTThis article presents hitherto overlooked documents at Vassar College in the United States relating to the character and reputation of the architect John Soane (1753–1837). The antiquarian and topographic author John Britton (1771–1857), a lifelong friend and associate of Soane, planned to write a ’tell-all’ biography in which he would reveal the malicious nature of the architect, and his obsession with remembrance and veneration, to scandalous effect. The scope and purpose of Britton’s intended exposé are established here through notes and correspondences that describe the resentful microclimate of the architects, writers, employees and family members in Soane’s orbit. A further manuscript by Britton, which satirises his devotion to Soane and the architect’s house museum, is also analysed. In the process, the article broaches the role of architectural journalism in fashioning the reputations of architects and their private and public personas in early Victorian London. It also considers the relationship of temperament to architectural invention and historiographic permutations in the controversial appraisal of Soane.
Women and the Construction Industry in Georgian Britain and Ireland
Authors: Lucey Conor 
Published: November 2023

ABSTRACTWhile the role of women as designers and/or patrons of architecture in eighteenth-century Britain and Ireland is increasingly recognised, their role in the making of architecture remains contested. This article sheds light on the subject by drawing not just on the extensive secondary literature, but also on records of livery companies and other primary sources in London and Dublin. It begins with the building site, focusing on female apprenticeship. Here substantial evidence is provided showing that girls bound to bricklayers, carpenters and plasterers as apprentices — the so-called ’lost labourers’ of recent scholarship, recorded in guild registers and court minutes — did not in fact acquire craft skills or work as on-site operatives in those trades. The article then turns to those areas of the building process to which women did make a substantial contribution: first the practical realm, including brickmaking, lime-burning and the cleaning and preparation of carved and moulded work for painters and decorators; then the organisational realm of business, including property development, house-building and estate management. Taken together, these stories from the margins of architectural and labour histories make clear the distinction between competence in skills and competence in business, giving a more accurate picture of the multifarious nature of female participation in the construction industry in the Georgian era.
Mental health symptoms and their associated factors among pharmacists in psychiatric hospitals during the early stage of the COVID-19 pandemic
Authors: Zhang Ling , Li Zhenkuo , Li Mengdie , Yang Yating , Hsu Michael , Xia Lei , Liu Tingfang , Liu Yuanli , Jiang Feng , Liu Huanzhong , Tang Yi-lang 
Published: November 2023

Abstract
As frontline workers, pharmacists often face significant work stress, especially in psychiatric settings. A multicenter cross-sectional design was conducted in 41 psychiatric hospitals. The Depression, Anxiety and Stress Scale–21 (DASS-21) was used to measure the mental health of 636 pharmacists. We also collected demographic data and work-related variables. The prevalence of depression, anxiety and stress was 20.60%, 22.96% and 8.96%, respectively. Multivariate logistic regression showed that several common factors were associated with depression, anxiety and stress, including professional identity (odds ratio [OR] = 0.132, 0.381 and 0.352) and verbal violence (OR = 2.068, 2.615 and 2.490). Those who were satisfied with their job were less likely to develop depression (OR = 0.234) or anxiety (OR = 0.328). We found specific factors associated with mental health. Older age (OR = 1.038) and perceived negative impact (OR = 2.398) of COVID-19 on medical work were associated with anxiety, and those with frontline experience with COVID-19 patients (OR = 2.306) were more likely to experience stress. More than one-fifth of pharmacists in psychiatric hospitals experienced symptoms of depression or anxiety during the pandemic, highlighting the need for policy change to improve workplace conditions and psychological well-being for this professional group.
Inviscid protostellar disc ring formation and high-density ring edges due to the ejection and subsequent infall of material onto a protostellar disc
Authors: Liffman Kurt 
Published: November 2023

Abstract
Discs of gas and dust are ubiquitous around protostars. Hypothetical viscous interactions within the disc are thought to cause the gas and dust to accrete onto the star. Turbulence within the disc is theorised to be the source of this disc viscosity. However, observed protostellar disc turbulence often appears to be small and not always conducive to disc accretion. In addition, theories for disc and planet evolution have difficulty in explaining the observed disc rings/gaps which form much earlier than expected.
Protostellar accretion discs are observed to contain significant quantities of dust and pebbles. Observations also show that some of this material is ejected from near the protostar, where it travels to the outer regions of the disc. Such solid infalling material has a relatively small amount of angular momentum compared to the material in the disc. This infalling material lowers the angular momentum of the disc and should drive a radial flow towards the protostar.
We show that the local radial accretion speed of the disc is proportional to the mass rate of infalling material onto the disc. Higher rates of infall onto the disc implies higher radial accretion disc speeds. As such, regions with high rates of infall of gas, dust, and pebbles onto the disc will produce gaps on relatively short timescales in the disc, while regions associated with relative low rates of infalling material will produce disc rings. As such, the inner edge of a disc gap will tend to have a higher surface density, which may enhance the probability of planet formation. In addition, the outer edge of a disc gap will act as a dust trap and may also become a site for planet formation.
For the early Solar System, such a process may have collected O

$^{16}$

-poor forsterite dust from the inner regions of the protosolar disc and O

$^{16}$

-rich CAIs and AOAs from the inner edge regions of the protosolar disc, thereby constructing a region favourable to the formation of pre-chondritic planetesimals.
Priority setting for health technology adoption at the national level: Lessons learned over 25 years’ experience
Authors: Luxenburg Osnat , Morginstin Tal , Myers Vicki , Saban Mor , Shemer Joshua , Wilf-Miron Rachel 
Published: November 2023

Abstract

Background
Limited health budgets and continual advancement of health technologies require mechanisms for prioritization. Israel, with a publicly funded health service basket, has implemented and optimized such a health technology assessment process since 1999.
We describe the process of evaluating technologies according to the Israeli model, analyze its outputs and benefits over two decades of implementation, and compare its key features with international experience.

Methods
Retrospective data were collected between 1998 and 2023, including work processes, committee composition, number of applications submitted and approved by a clinical domain, and yearly cost of the basket. Features were evaluated within the evidence-informed deliberative process (EDP) framework.

Results
This national model involves relevant stake holders in a participatory and transparent process, in a timely manner, and is accepted by the public, health professionals, and policy makers, facilitating early adoption of the newest medical technologies. Between 11 and 19 percent of applications are approved for reimbursement annually, mostly pharmaceuticals. On average 26 percent of approved technologies are added to the list without additional budget. Major domains of approved technologies were oncology, cardiology, and neurology.

Conclusions
Israel created a unique model for the expansion of the health service basket. Despite an increasing number of applications and rising costs, the mechanism enables a consensus to be reached on which technologies to fund, while remaining within budget constraints and facilitating immediate implementation. The process, which prioritizes transparency and stake holder involvement, allows just a resource allocation while maximizing the adoption of novel technologies, contributing to an outstanding national level of health despite relatively low health spending.
Leveraging the developmental neuroscience of caregiving to promote resilience among youth exposed to adversity
Authors: Gee Dylan G. , Cohodes Emily M. 
Published: November 2023

AbstractEarly adversity is a major risk factor for the emergence of psychopathology across development. Identifying mechanisms that support resilience, or favorable mental health outcomes despite exposure to adversity, is critical for informing clinical intervention and guiding policy to promote youth mental health. Here we propose that caregivers play a central role in fostering resilience among children exposed to adversity via caregiving influences on children’s corticolimbic circuitry and emotional functioning. We first delineate the numerous ways that caregivers support youth emotional learning and regulation and describe how early attachment lays the foundation for optimal caregiver support of youth emotional functioning in a developmental stage-specific manner. Second, we outline neural mechanisms by which caregivers foster resilience—namely, by modulating offspring corticolimbic circuitry to support emotion regulation and buffer stress reactivity. Next, we highlight the importance of developmental timing and sensitive periods in understanding caregiving-related mechanisms of resilience. Finally, we discuss clinical implications of this line of research and how findings can be translated to guide policy that promotes the well-being of youth and families.
Contract lenses: Reasoning about bidirectional programs via calculation
Authors: ZHANG HANLIANG , TANG WENHAO , XIE RUIFENG , WANG MENG , HU ZHENJIANG 
Published: November 2023

Abstract
Bidirectional transformations (BXs) are a mechanism for maintaining consistency between multiple representations of related data. The lens framework, which usually constructs BXs from lens combinators, has become the mainstream approach to BX programming because of its modularity and correctness by construction. However, the involved bidirectional behaviors of lenses make the equational reasoning and optimization of them much harder than unidirectional programs. We propose a novel approach to deriving efficient lenses from clear specifications via program calculation, a correct-by-construction approach to reasoning about functional programs by algebraic laws. To support bidirectional program calculation, we propose contract lenses, which extend conventional lenses with a pair of predicates to enable safe and modular composition of partial lenses. We define several contract-lens combinators capturing common computation patterns including

$\textit{fold}, \textit{filter},\textit{map}$

, and

$\textit{scan}$

, and develop several bidirectional calculation laws to reason about and optimize contract lenses. We demonstrate the effectiveness of our new calculation framework based on contract lenses with nontrivial examples.