bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating Hepatotoxic Doses Using High-Content Imaging in Primary Hepatocytes
Authors: Shah Imran , Antonijevic Todor , Chambers Bryant , Harrill Joshua , Thomas Russell 
Published: July 2021

Abstract
Using in vitro data to estimate point of departure (POD) values is an essential component of new approach methodologies (NAMs)-based chemical risk assessments. In this case study, we evaluated a NAM for hepatotoxicity based on rat primary hepatocytes, high-content imaging (HCI), and toxicokinetic modeling. First, we treated rat primary hepatocytes with 10 concentrations (0.2–100 µM) of 51 chemicals that produced hepatotoxicity in repeat-dose subchronic and chronic exposures. Second, we used HCI to measure endoplasmic reticulum stress, mitochondrial function, lysosomal mass, steatosis, apoptosis, DNA texture, nuclear size, and cell number at 24, 48, and 72 h and calculated concentrations at 50% maximal activity (AC50). Third, we estimated administered equivalent doses (AEDs) from AC50 values using toxicokinetic modeling. AEDs using physiologically based toxicokinetic models were 4.1-fold (SD 6.3) and 8.1-fold (SD 15.5) lower than subchronic and chronic lowest observed adverse effect levels (LOAELs), respectively. In contrast, AEDs from ToxCast and Tox21 assays were 89.8-fold (SD 149.5) and 168-fold (SD 323.7) lower than subchronic and chronic LOAELs. Individual HCI endpoints also estimated AEDs for specific hepatic lesions that were lower than in vivo PODs. Lastly, AEDs were similar for different in vitro exposure durations, but steady-state toxicokinetic models produced 7.6-fold lower estimates than dynamic physiologically based ones. Our findings suggest that NAMs from diverse cell types provide conservative estimates of PODs. In contrast, NAMs based on the same species and cell type as the adverse outcome may produce estimates closer to the traditional in vivo PODs.
Turgor-limited predictions of tree growth, height and metabolic scaling over tree lifespans
Authors: Potkay Aaron , Hölttä Teemu , Trugman Anna T , Fan Ying 
Published: July 2021

Abstract
Increasing evidence suggests that tree growth is sink-limited by environmental and internal controls rather than by carbon availability. However, the mechanisms underlying sink-limitations are not fully understood and thus not represented in large-scale vegetation models. We develop a simple, analytically solved, mechanistic, turgor-driven growth model (TDGM) and a phloem transport model (PTM) to explore the mechanics of phloem transport and evaluate three hypotheses. First, phloem transport must be explicitly considered to accurately predict turgor distributions and thus growth. Second, turgor-limitations can explain growth-scaling with size (metabolic scaling). Third, turgor can explain realistic growth rates and increments. We show that mechanistic, sink-limited growth schemes based on plant turgor limitations are feasible for large-scale model implementations with minimal computational demands. Our PTM predicted nearly uniform sugar concentrations along the phloem transport path regardless of phloem conductance, stem water potential gradients and the strength of sink-demands contrary to our first hypothesis, suggesting that phloem transport is not limited generally by phloem transport capacity per se but rather by carbon demand for growth and respiration. These results enabled TDGM implementation without explicit coupling to the PTM, further simplifying computation. We test the TDGM by comparing predictions of whole-tree growth rate to well-established observations (site indices) and allometric theory. Our simple TDGM predicts realistic tree heights, growth rates and metabolic scaling over decadal to centurial timescales, suggesting that tree growth is generally sink and turgor limited. Like observed trees, our TDGM captures tree-size- and resource-based deviations from the classical ¾ power-law metabolic scaling for which turgor is responsible.
Bromodomain and extraterminal domain protein bromodomain inhibitor based cancer therapeutics
Authors: Halder Tithi Ghosh , Soldi Raffaella , Sharma Sunil 
Published: July 2021

Purpose of review
Bromodomain and extraterminal domain (BET) proteins are evolutionarily conserved, multifunctional super-regulators that specifically recognize acetyl-lysine on histones and other proteins controlling gene transcription. Several studies show that small molecules targeting these regulators preferentially suppress the transcription of cancer-promoting genes. Consequently, several BET inhibitors reached clinical trials and are in various stages for different kind of malignancies. In this review, we provide a concise summary of the molecular basis and preliminary clinical outcomes of BET inhibitors as anticancer therapeutics.

Recent findings
Results from early clinical trials with BET inhibitors confirmed their antitumor potential in both hematologic and solid tumours, but the evidence does not support the application of BET inhibitors as a monotherapy for cancer treatment. Treatment-emergent toxicities such as thrombocytopenia and gastrointestinal disorders are also reported. Preclinical data suggest that BET inhibitors may have a promising future in combination with other anticancer agents.

Summary
Despite of various challenges, BET inhibitors have high potential in combinatorial therapy and the future development of next-generation inhibitors could be promising. Further studies are needed to determine the predictive biomarkers for therapeutic response, which would translate into the long-term success of BET inhibitors as personalized medicines in cancer treatment.
Histopathologic Spectrum of Findings Associated With Tattoos: Multicenter Study Series of 230 Cases
Authors: Portilla Maya Nataly , Kempf Werner , Perez Muñoz Noelia , Rodríguez-Martínez Paula , Posada Rodolfo , Fernández-Figueras María Teresa 
Published: July 2021

Importance:
Reactions to tattoo may simulate common dermatosis or skin neoplasms. Histopathology allows diagnosis and helps determining the level and degree of inflammation associated, consequently orientating treatment.

Objective:
To describe the histological features found in biopsies of cutaneous reactions to tattoo.

Design:
This study was designed as a multicenter case series.

Setting:
All consecutive histopathological samples of tattoos referred from 1992 to 2019 to the Hospital General de Catalunya, Hospital Germans Trias i Pujol, and a private practice, all in Barcelona, Spain, and from the Kempf und Pfaltz Histologische Diagnostik in Zurich, Switzerland were retrieved from the files.

Participants and Exposure:
The inclusion criteria were all cosmetic/permanent makeup, artistic/professional, and traumatic tattoos associated with either inflammatory reactions alone and/or with tumors and/or infections. Exclusion criteria were cases without any associated pathologic finding in the place of the ink, amalgam tattoos, and medical or temporary tattoos.

Main Outcomes and Measures:
In all patients, clinical features (age, sex, location, tattoo color, and presentation) were recorded. Histological features evaluated included ink color, associated tumors or infections, and inflammatory reaction pattern. Inflammation was graded in low to moderate or severe.

Results:
From 477 biopsies diagnosed as tattoos, 230 cases from 226 patients met the inclusion criteria. Samples corresponded to 107 male and 120 female subjects and 3 of unknown gender. Median age was 39 years (ranging from 9 to 84 years). Fifty-three samples were referred from centers in Spain and 177 from the center in Switzerland. The series was analyzed in 2 parts: tattoos associated only with inflammatory reactions (117/230) and tattoos associated with tumors or infections (113/230). The most common form of inflammatory pattern associated with tattoo was the fibrosing reaction (79/117, 68%), followed by granulomatous reaction (56/117, 48%), lichenoid reaction (33/117, 28%), epithelial hyperplasia (28/117, 24%), pseudolymphoma (27/117, 23%) and spongiotic reaction (27/117, 23%). Combined features of 2 or more types of inflammatory patterns were seen in 64% cases.

Conclusions and Relevance:
Our series confirms that cutaneous reactions to tattoos are polymorphous. Inflammation tends to present with combined patterns. Infections are tending to decline, and pathologic findings are not specific to ink color or clinical features.
Comparison of Clinical, Ultrasound, and Electrophysiologic Changes in Chronic Inflammatory Demyelinating Polyneuropathy: A Prospective Study
Authors: Okhovat Ali Asghar , Nafissi Shahriar , Moradi Kamyar , Ziaadini Bentolhoda , Panahi Akram , Haghi Ashtiani Bahram , Fatehi Farzad 
Published: July 2021

Purpose:
The follow-up and monitoring of response to immunomodulatory therapy in patients with chronic inflammatory demyelinating polyneuropathy are still challenging. Various outcome measures have been proposed in recent years, and some are now frequently used in daily clinical practice; however, reliable biomarkers for the disease activity and treatment response are lacking.

Methods:
Cross-sectional nerve area of the bilateral vagus, fifth and the sixth cervical spinal, median, ulnar, tibial, peroneal, and sural nerves were measured at 2 time points with an interval of 6 months using nerve ultrasound. The results were used to calculate the ultrasound pattern sumscore (UPSS). The correlation between UPSS change (ΔUPSS) and changes in functional and nerve conduction studies measures over the study period were assessed.

Results:
Sixteen patients completed this prospective, observational study. General linear model showed that ΔUPSS is significantly associated with ΔMedical Research Council sumscore (β = −0.72, P = 0.003), Δhandgrip strength (β = −0.57, P = 0.014), ΔRasch-built overall disability scale (β = −0.57, P = 0.010), and Δoverall neuropathy limitations scale (β = 0.75, P < 0.001), after adjustment of confounding variables. Nevertheless, ΔUPSS was not correlated with other clinical measures, including Δpinch power, Δ9-hole peg test, Δ10-m walking test, and Δnerve conduction study sumscore (P values > 0.05).

Conclusions:
Nerve ultrasound might be an efficient method for monitoring the functional status of patients with chronic inflammatory demyelinating polyneuropathy over time because the alterations in its scores could significantly reflect clinical changes.
Ostwald ripening in the presence of simultaneous occurrence of various mass transfer mechanisms: an extension of the Lifshitz–Slyozov theory
Authors: Alexandrova Irina V. , Alexandrov Dmitri V. , Makoveeva Eugenya V. 
Published: July 2021

The Ostwald ripening stage of a phase transformation process with allowance for synchronous operation of various mass transfer mechanisms (volume diffusion and diffusion along the block boundaries and dislocations) and the initial condition for the particle-radius distribution function is theoretically studied. The initial condition is taken from the analytical solution describing the intermediate stage of a phase transition process. The present theory focuses on relaxation dynamics from the beginning of the ripening process to its final asymptotic state, which is described by the previously constructed theories (Slezov VV.et al.1978J. Phys. Chem. Solids39, 705–709. (doi:10.1016/0022-3697(78)90002-1) and Alexandrov & Alexandrova 2020Phil. Trans. R. Soc. A378, 20190247. (doi:10.1098/rsta.2019.0247)). An evolutionary behaviour of particle growth rates dependent on various mass transfer mechanisms and time is analytically described. The boundaries of the transition layer, which surround the blocking point, are found. The fundamental and relaxation contributions to the particle-radius distribution function are derived for the simultaneous occurrence of various mass transfer mechanisms. The left branch of this function is shifted to smaller particle radii whereas its right branch extends to the right of the blocking point as compared with the asymptotic universal distribution function. The theory under consideration well agrees with experimental data.This article is part of the theme issue ‘Transport phenomena in complex systems (part 1)’.
Evaporation kinetics of a polydisperse ensemble of drops
Authors: Ivanov Alexander A. , Alexandrova Irina V. , Alexandrov Dmitri V. 
Published: July 2021

A mathematical model of the evaporation of a polydisperse ensemble of drops, with allowance for a nonlinear ‘diffusion’ term in the kinetic equation for the population density distribution function, is developed. The model describes the interaction of a gas phase with vaporizing drops: it has great potential for application in condensed matter physics, thermophysics and engineering devices (e.g. spray drying, cooling, power engineering). The kinetics of heat transfer between phases is theoretically studied. An analytical solution to the integro-differential equations of the process of droplet evaporation is found in a parametric form. Analytical solutions in the presence and absence of the ‘diffusion’ term are compared. It is shown that the fluctuations in particle evaporation rates (‘diffusion’ term in the Fokker–Planck equation) play a decisive role in the evolutionary behaviour of a polydisperse ensemble of vaporizing liquid drops.This article is part of the theme issue ‘Transport phenomena in complex systems (part 1)’.
Variable-order fractional master equation and clustering of particles: non-uniform lysosome distribution
Authors: Fedotov Sergei , Han Daniel , Zubarev Andrey Yu , Johnston Mark , Allan Victoria J. 
Published: July 2021

In this paper, we formulate the space-dependent variable-order fractional master equation to model clustering of particles, organelles, inside living cells. We find its solution in the long-time limit describing non-uniform distribution due to a space-dependent fractional exponent. In the continuous space limit, the solution of this fractional master equation is found to be exactly the same as the space-dependent variable-order fractional diffusion equation. In addition, we show that the clustering of lysosomes, an essential organelle for healthy functioning of mammalian cells, exhibit space-dependent fractional exponents. Furthermore, we demonstrate that the non-uniform distribution of lysosomes in living cells is accurately described by the asymptotic solution of the space-dependent variable-order fractional master equation. Finally, Monte Carlo simulations of the fractional master equation validate our analytical solution.
This article is part of the theme issue ‘Transport phenomena in complex systems (part 1)’.
Kinetics of solid–liquid interface motion in molecular dynamics and phase-field models: crystallization of chromium and silicon
Authors: Karim Eaman T. , He Miao , Salhoumi Ahmed , Zhigilei Leonid V. , Galenko Peter K. 
Published: July 2021

The results of molecular dynamics (MD) simulations of the crystallization process in one-component materials and solid solution alloys reveal a complex temperature dependence of the velocity of the crystal–liquid interface featuring an increase up to a maximum at 10–30% undercooling below the equilibrium melting temperature followed by a gradual decrease of the velocity at deeper levels of undercooling. At the qualitative level, such non-monotonous behaviour of the crystallization front velocity is consistent with the diffusion-controlled crystallization process described by the Wilson–Frenkel model, where the almost linear increase of the interface velocity in the vicinity of melting temperature is defined by the growth of the thermodynamic driving force for the phase transformation, while the decrease in atomic mobility with further increase of the undercooling drives the velocity through the maximum and into a gradual decrease at lower temperatures. At the quantitative level, however, the diffusional model fails to describe the results of MD simulations in the whole range of temperatures with a single set of parameters for some of the model materials. The limited ability of the existing theoretical models to adequately describe the MD results is illustrated in the present work for two materials, chromium and silicon. It is also demonstrated that the MD results can be well described by the solution following from the hodograph equation, previously found from the kinetic phase-field model (kinetic PFM) in the sharp interface limit. The ability of the hodograph equation to describe the predictions of MD simulation in the whole range of temperatures is related to the introduction of slow (phase field) and fast (gradient flow) variables into the original kinetic PFM from which the hodograph equation is obtained. The slow phase-field variable is responsible for the description of data at small undercoolings and the fast gradient flow variable accounts for local non-equilibrium effects at high undercoolings. The introduction of these two types of variables makes the solution of the hodograph equation sufficiently flexible for a reliable description of all nonlinearities of the kinetic curves predicted in MD simulations of Cr and Si.
This article is part of the theme issue ‘Transport phenomena in complex systems (part 1)’.
Nonlinear theory of macroscopic flow induced in a drop of ferrofluid
Authors: Zubarev Andrey Yu. , Chirikov Dmitry , Musikhin Anton , Raboisson-Michel Maxime , Verger-Dubois Gregory , Kuzhir Pavel 
Published: July 2021

We present results of theoretical modelling of macroscopic circulating flow induced in a cloud of ferrofluid by an oscillating magnetic field. The cloud is placed in a cylindrical channel filled by a nonmagnetic liquid. The aim of this work is the development of a scientific basis for a progressive method of addressing drug delivery to thrombus clots in blood vessels with the help of the magnetically induced circulation flow. Our results show that the oscillating field can induce, inside and near the cloud, specific circulating flows with the velocity amplitude about several millimetres per second. These flows can significantly increase the rate of transport of the molecular non-magnetic impurity in the channel.
This article is part of the theme issue ‘Transport phenomena in complex systems (part 1)’.
The shape of dendritic tips: a test of theory with computations and experiments
Authors: Alexandrov Dmitri V. , Toropova Liubov V. , Titova Ekaterina A. , Kao Andrew , Demange Gilles , Galenko Peter K. , Rettenmayr Markus 
Published: July 2021

This article is devoted to the study of the tip shape of dendritic crystals grown from a supercooled liquid. The recently developed theory (Alexandrov & Galenko 2020Phil. Trans. R. Soc. A378, 20190243. (doi:10.1098/rsta.2019.0243)), which defines the shape function of dendrites, was tested against computational simulations and experimental data. For a detailed comparison, we performed calculations using two computational methods (phase-field and enthalpy-based methods), and also made a comparison with experimental data from various research groups. As a result, it is shown that the recently found shape function describes the tip region of dendritic crystals (at the crystal vertex and some distance from it) well.This article is part of the theme issue ‘Transport phenomena in complex systems (part 1)’.
The impact of a demand-side sanitation and hygiene promotion intervention on sustained behavior change and health in Amhara, Ethiopia: a cluster-randomized trial
Authors: Freeman Matthew C. , Delea Maryann G. , Snyder Jedidiah S. , Garn Joshua V. , Belew Mulusew , Caruso Bethany A. , Clasen Thomas F. , Sclar Gloria D. , Tesfaye Yihenew , Woreta Mulat , Zewudie Kassahun , Gebremariam Abebe 
Published: July 2021

ABSTRACTBackgroundBehaviors related to water, sanitation, and hygiene (WASH) are key drivers of infectious disease transmission, and experiences of WASH are potential influencers of mental well-being. Important knowledge gaps exist related to the content and delivery of effective WASH programs and their associated health impacts, particularly within the contexts of government programs implemented at scale.MethodsWe developed and tested a demand-side intervention calledAndilaye, which aimed to change behaviors related to sanitation, personal hygiene, and household environmental sanitation. This theory-informed intervention was delivered through the existing Ethiopian Health Extension Programme (HEP). It was a multilevel intervention with a catalyzing event at community level and behavior change activities at group and household level. We randomly selected and assigned 50kebeles(sub-districts) from threeworedas(districts), half to receive theAndilayeintervention, and half the standard of care sanitation and hygiene programming (i.e., community-led total sanitation and hygiene [CLTSH]). We collected data on WASH access, behavioral outcomes, and mental well-being.ResultsA total of 1,589 households were enrolled into the study at baseline; 1,472 households (94%) participated in an endline assessment two years after baseline, and approximately 14 months after the initiation of a multi-level intervention. The intervention did not improve construction of latrines (prevalence ratio [PR] 0.99; 95% CI: 0.82, 1.21) or handwashing stations with water (PR: 0.96; 95% CI: 0.72, 1.26), or the removal of animal feces from the compound (PR=1.10; 95% CI: 0.95, 1.28). Nor did it impact anxiety (PR 0.90; 95% CI: 0.72, 1.11), depression (PR: 0.83; 95% CI: 0.64, 1.07), emotional distress (PR: 0.86; 95% CI: 0.67,1.09) or well-being (PR: 0.90; 95% CI: 0.74, 1.10) scores.DiscussionWe report limited impact of the intervention, as delivered, on changes inbehavior and mental well-being. The effectiveness of the intervention was limited by poor intervention fidelity. While sanitation and hygiene improvements have been documented in Ethiopia, behavioral slippage, or regression to unimproved practices, in communities previously declared open defecation free is widespread. Evidence from this trial may help address knowledge gaps related to challenges associated with scalable alternatives to CLTSH and inform sanitation and hygiene programming and policy in Ethiopia and beyond.Trial registrationThis trial was registered with clinicaltrials.gov (NCT03075436) on March 9, 2017.