bluuebunny/crossref_metadata_2025 huggingface dataset:
DoUBLing up: ubiquitin and ubiquitin-like proteases in genome stability
Authors: Foster Benjamin M. , Wang Zijuan , Schmidt Christine K.
Published: April 2024

Maintaining stability of the genome requires dedicated DNA repair and signalling processes that are essential for the faithful duplication and propagation of chromosomes. These DNA damage response (DDR) mechanisms counteract the potentially mutagenic impact of daily genotoxic stresses from both exogenous and endogenous sources. Inherent to these DNA repair pathways is the activity of protein factors that instigate repair processes in response to DNA lesions. The regulation, coordination, and orchestration of these DDR factors is carried out, in a large part, by post-translational modifications, such as phosphorylation, ubiquitylation, and modification with ubiquitin-like proteins (UBLs). The importance of ubiquitylation and UBLylation with SUMO in DNA repair is well established, with the modified targets and downstream signalling consequences relatively well characterised. However, the role of dedicated erasers for ubiquitin and UBLs, known as deubiquitylases (DUBs) and ubiquitin-like proteases (ULPs) respectively, in genome stability is less well established, particularly for emerging UBLs such as ISG15 and UFM1. In this review, we provide an overview of the known regulatory roles and mechanisms of DUBs and ULPs involved in genome stability pathways. Expanding our understanding of the molecular agents and mechanisms underlying the removal of ubiquitin and UBL modifications will be fundamental for progressing our knowledge of the DDR and likely provide new therapeutic avenues for relevant human diseases, such as cancer.
Long-range electron proton coupling in respiratory complex I — insights from molecular simulations of the quinone chamber and antiporter-like subunits
Authors: Djurabekova Amina , Lasham Jonathan , Zdorevskyi Oleksii , Zickermann Volker , Sharma Vivek
Published: April 2024

Respiratory complex I is a redox-driven proton pump. Several high-resolution structures of complex I have been determined providing important information about the putative proton transfer paths and conformational transitions that may occur during catalysis. However, how redox energy is coupled to the pumping of protons remains unclear. In this article, we review biochemical, structural and molecular simulation data on complex I and discuss several coupling models, including the key unresolved mechanistic questions. Focusing both on the quinone-reductase domain as well as the proton-pumping membrane-bound domain of complex I, we discuss a molecular mechanism of proton pumping that satisfies most experimental and theoretical constraints. We suggest that protonation reactions play an important role not only in catalysis, but also in the physiologically-relevant active/deactive transition of complex I.
The SWI/SNF ATP-dependent chromatin remodeling complex in cell lineage priming and early development
Authors: Saha Dhurjhoti , Animireddy Srinivas , Bartholomew Blaine
Published: April 2024

ATP dependent chromatin remodelers have pivotal roles in transcription, DNA replication and repair, and maintaining genome integrity. SWI/SNF remodelers were first discovered in yeast genetic screens for factors involved in mating type switching or for using alternative energy sources therefore termed SWI/SNF complex (short for SWItch/Sucrose NonFermentable). The SWI/SNF complexes utilize energy from ATP hydrolysis to disrupt histone-DNA interactions and shift, eject, or reposition nucleosomes making the underlying DNA more accessible to specific transcription factors and other regulatory proteins. In development, SWI/SNF orchestrates the precise activation and repression of genes at different stages, safe guards the formation of specific cell lineages and tissues. Dysregulation of SWI/SNF have been implicated in diseases such as cancer, where they can drive uncontrolled cell proliferation and tumor metastasis. Additionally, SWI/SNF defects are associated with neurodevelopmental disorders, leading to disruption of neural development and function. This review offers insights into recent developments regarding the roles of the SWI/SNF complex in pluripotency and cell lineage primining and the approaches that have helped delineate its importance. Understanding these molecular mechanisms is crucial for unraveling the intricate processes governing embryonic stem cell biology and developmental transitions and may potentially apply to human diseases linked to mutations in the SWI/SNF complex.
Decoding the ubiquitin landscape by cutting-edge ubiquitinomic approaches
Authors: P T Brindhavanam , Sahu Indrajit
Published: April 2024

Functional consequences of protein ubiquitination have gone far beyond the degradation regulation as was initially imagined during its discovery 40 years back. The state-of-the-art has revealed the plethora of signaling pathways that are largely regulated by ubiquitination process in eukaryotes. To no surprise, ubiquitination is often dysregulated in many human diseases, including cancer, neurodegeneration and infection. Hence it has become a major focus with high-gain research value for many investigators to unravel new proteoforms, that are the targets of this ubiquitination modification. Despite many biochemical or proteomic approaches available for ubiquitination detection, mass-spectrometry stood out to be the most efficient and transformative technology to read this complex modification script. Here in this review, we have discussed how different ubiquitin codes can be decoded qualitatively and quantitatively following various sequential proteomic approaches to date reported and indicated the current limitations with scope for improvements.
Reduced Tolerance for Risky Play in Primary Caregivers of Children With Hearing Loss
Authors: Deniz Burcu , Kara Halide Çetin , Çögen Talha
Published: April 2024

Purpose:

It is known that taking appropriate risks during play is crucial for the development of a child's creativity, problem-solving abilities, resilience, self-confidence, and skills in evaluating risky situations. However, communication problems resulting from hearing loss (HL) can affect a child's ability to hear danger and warning signals during play, potentially leading to injury. This study investigates the attitudes of parents or caregivers with children with HL toward risky play.

Method:

The study included 170 caregivers of children with normal hearing (NH;
n
= 103) and cochlear implant and/or hearing aids users (
n
= 67) aged 3–13 years. The primary caregiver completed the Tolerance for Risk in Play Scale (TRIPS), and the caregivers of children with HL also completed the Auditory Behavior in Everyday Life (ABEL) questionnaire.

Results:

TRIPS total scores were significantly higher in the NH group (
p
< .05). Mothers of children with HL had lower TRIPS scores than mothers of children with NH (
p
< .05). Similarly, lower TRIPS scores were found in the lower income group with HL (
p
< .05). A weak positive correlation was observed between TRIPS and both the ABEL total score (
p
< .05,
r
= .207) and ABEL auditory awareness score (
p
< .05,
r
= .204) in the hard of hearing group.

Conclusions:

The study found that caregivers of children with HL have less tolerance for risky play. Additionally, caregivers of children with better auditory skills were more tolerant of risky play. Therefore, it is suggested that caregivers of children using appropriate hearing devices should be informed that they do not need to be overly restrictive during play, and these children should be encouraged to engage in risky play.
Written Language Practice, Self-Efficacy, and Beliefs: A Survey of Speech-Language Pathologists Working With School-Aged Clients
Authors: Yi Julia J. , Erickson Karen A.
Published: April 2024

Purpose:

This study examined the clinical practice, self-efficacy, and beliefs about assessing and treating written language among speech-language pathologists (SLPs) working with school-aged clients (aged 5–21 years) in school and nonschool settings in the United States.

Method:

A survey was completed by a nationwide sample of 344 SLPs working with school-aged clients in the United States. Statistical analyses were conducted to determine differences between (a) SLPs' self-efficacy in assessing and treating spoken versus written language and (b) school-based and non–school-based SLPs' clinical practice, self-efficacy, and beliefs about their roles with written language.

Results:

All respondents reported significantly lower rates of self-efficacy in assessing and treating written language compared to spoken language, and their self-efficacy had a significant, positive relationship with the amount of clinical time devoted to written language. School-based SLPs devoted a significantly lower percentage of clinical time to written language, had significantly lower self-efficacy in addressing written language, and had lower rates of agreement on statements about their roles and responsibilities with written language compared to non–school-based SLPs. These differences were not found with spoken language. The most prevalent written language needs on respondents' workloads were reported as written expression (69.3%) and reading comprehension (66%).

Conclusions:

School-based and non–school-based SLPs report different levels of clinical time devoted to written language, self-efficacy in addressing written language, and beliefs about their roles in addressing written language. There is a need to investigate the reasons for these differences and the potential impact of preservice and in-service training in ameliorating them.

Supplemental Material:

https://doi.org/10.23641/asha.25511047
Zweizeitige Arthrodese bei knöchernen Fingergelenkdefekten –
Langfristige Ergebnisse
Authors: Moeller Richard-Tobias , Mentzel Martin , Vergote Daniel , Bauknecht Simon
Published: April 2024

Hintergrund Knöcherne Defekte bei Fingerverletzungen und -infekten stellen
durch die engen anatomischen Beziehungen hohe Anforderungen an ihre Behandlung.
Bedingt durch den Unfallmechanismus liegen vielfach kontaminierte und
kompromittierte Weichgewebe vor und setzen einer einzeitigen operativen
Behandlung Grenzen. Vorgestellt werden die langfristigen subjektiven und
funktionellen Ergebnisse nach zweizeitiger Rekonstruktion von knöchernen
Defektverletzungen an Fingergelenken.

Patienten und Methoden Im Zeitraum von 15 Jahren wurden insgesamt 40
Patienten mit 43 Fingern aufgrund einer Defektverletzung an den Phalangen
behandelt. Initial wurde der Finger nach Debridement mit Kirschnerdrähten
stabilisiert. Nach Konsolidierung oder Rekonstruktion des Weichgewebes wurde in
einer weiteren Operation der Knochen durch Interposition eines Beckenkamspans
unter Arthrodese von mindestens einem Fingergelenk rekonstruiert. Bei 9
Patienten traten Komplikationen auf. 25 Patienten mit 27 Fingern konnten im
Median 10,3 Jahre nachuntersucht werden. Erhoben wurde der Bewegungsumfang, die
Länge des betroffenen Fingers und die Kraftentwicklung jeweils im Verhältnis zur
Gegenseite. Neben einer subjektiven Einschätzung des Gesamtergebnisses wurde die
Alltagsfunktion mittels Disabilities of the Arm, Shoulder and Hand (DASH)
Fragebogen ermittelt.

Ergebnisse Signifikante Unterschiede zur Gegenseite (p<0,05) fanden
sich in der Länge (70 mm; 91,0%) und der Gesamtbeweglichkeit des betroffenen
Fingers (95°; 46,0%), der Handspanne bei Beteiligung des Daumens (202,5 mm;
93,4%) und im Kraftgriff bei Verletzung von einem der dreigliedrigen Fingern
(30 kg; 84,1%). Der DASH-Wert lag bei 4,2 Punkten (0–55,8). Subjektiv waren die
Patienten zu 88% mit dem Behandlungsergebnis zufrieden.

Schlussfolgerung Ein zweizeitiges Vorgehen bei ausgedehnten knöchernen
Defektverletzungen im Fingergelenkbereich unter Arthrodese des Gelenkes ist eine
verlässliche Versorgungsstrategie. Sie ergibt langfristig trotz messtechnisch
signifikanter Unterschiede zur Gegenseite eine subjektiv sehr gute Funktion der
Hand im Alltag.
Wege in den Krankenversicherungsschutz – Das Pilotprojekt
Clearingstelle 1.0 am Gesundheitsamt Frankfurt am Main
Authors: Lang Sarah Alexandra , Tinnemann Peter , Zöllner Rebecca
Published: April 2024

Bundesweit haben schätzungsweise 500 000 bis 1 Million Menschen keinen
Krankenversicherungsschutz und damit keinen Zugang zu regulären
Versorgungsstrukturen – oft mit fatalen Folgen für die Gesundheit der
Betroffenen. Vor allem in Großstädten gibt es niederschwellige medizinische
Ambulanzen, die eine Basisgesundheitsversorgung parallel zum Regelsystem
anbieten. Es fehlt an nachhaltigen Lösungen zu Absicherung einer
bedarfsgerechten Gesundheitsversorgung. Clearingstellen als Anlaufstellen für
Menschen ohne Krankenversicherungsschutz und das Konzept Anonymer
Behandlungsschein (ABS) bauen eine Brücke zwischen gesundheitlichem Parallel-
und Regelsystem. Mit der Pilotierung der „Clearingstelle 1.0“ am Gesundheitsamt
Frankfurt am Main 2020 bis 2022 wurde die medizinische Basisversorgung der
Humanitären Sprechstunden durch fachliche Sozialberatung ergänzt, mit dem Ziel,
möglichst viele Personen ins gesetzliche Regelsystem zu vermitteln. Neben der
Ausweitung des Beratungsangebots, ist die dauerhafte Verankerung der
Clearingstelle in Frankfurt am Main für das Gesundheitsamt ein erklärtes
Ziel.
Descemet Membrane Endothelial Keratoplasty (DMEK) Anesthesia Analysis
Authors: Andres Christoph , Trouvain André Maurice , Szurman Peter , Seitz Berthold , Fries Fabian Norbert , Rickmann Annekatrin
Published: April 2024

Purpose Comparison of safety and clinical results of Descemet membrane endothelial keratoplasty (DMEK) in topical, peribulbar, or general anesthesia.

Methods Retrospective, post hoc matched study of 346 patients who received DMEK surgery with different types of anesthesia (n = 54 topical, n = 137 peribulbar, n = 155 general anesthesia). Outcome criteria were intraoperative complications, endothelial cell count (ECC), central corneal thickness (CCT) and graft rejection rate, rebubbling rate, and visual acuity (VA). Mean follow-up time was 9.4 ± 2.8 months.

Results The group with topical anesthesia showed intraoperative difficulties such as vitreous pressure (p = 0.01) and difficult graft unfolding (p = 0.4), possibly leading to a higher rebubbling rate (p = 0.03) and therefore graft failure (p = 0.39). However, rebubbling and graft failure occurred more often when the graft preparation was more difficult (p = 0.2, p = 0.13, respectively), which was independent of anesthesia. All three groups achieved comparable functional results regarding VA, ECC, and CCT after 6 months.

Conclusion DMEK under topical anesthesia is feasible and shows comparable final visual outcomes but should be limited to selected cooperative patients and performed by experienced surgeons due to the potential for increased intraoperative challenges.
Emerging Roles of Spatial Transcriptomics in Liver Research
Authors: Fujiwara Naoto , Kimura Genki , Nakagawa Hayato
Published: April 2024

Spatial transcriptomics, leveraging sequencing- and imaging-based techniques, has emerged as a groundbreaking technology for mapping gene expression within the complex architectures of tissues. This approach provides an in-depth understanding of cellular and molecular dynamics across various states of healthy and diseased livers. Through the integration of sophisticated bioinformatics strategies, it enables detailed exploration of cellular heterogeneity, transitions in cell states, and intricate cell–cell interactions with remarkable precision. In liver research, spatial transcriptomics has been particularly revelatory, identifying distinct zonated functions of hepatocytes that are crucial for understanding the metabolic and detoxification processes of the liver. Moreover, this technology has unveiled new insights into the pathogenesis of liver diseases, such as the role of lipid-associated macrophages in steatosis and endothelial cell signals in liver regeneration and repair. In the domain of liver cancer, spatial transcriptomics has proven instrumental in delineating intratumor heterogeneity, identifying supportive microenvironmental niches and revealing the complex interplay between tumor cells and the immune system as well as susceptibility to immune checkpoint inhibitors. In conclusion, spatial transcriptomics represents a significant advance in hepatology, promising to enhance our understanding and treatment of liver diseases.
Enhancing predictive capabilities in data-driven dynamical modeling with automatic differentiation: Koopman and neural ODE approaches
Authors: Ricardo Constante-Amores C. , Linot Alec J. , Graham Michael D.
Published: April 2024

Data-driven approximations of the Koopman operator are promising for predicting the time evolution of systems characterized by complex dynamics. Among these methods, the approach known as extended dynamic mode decomposition with dictionary learning (EDMD-DL) has garnered significant attention. Here, we present a modification of EDMD-DL that concurrently determines both the dictionary of observables and the corresponding approximation of the Koopman operator. This innovation leverages automatic differentiation to facilitate gradient descent computations through the pseudoinverse. We also address the performance of several alternative methodologies. We assess a “pure” Koopman approach, which involves the direct time-integration of a linear, high-dimensional system governing the dynamics within the space of observables. Additionally, we explore a modified approach where the system alternates between spaces of states and observables at each time step—this approach no longer satisfies the linearity of the true Koopman operator representation. For further comparisons, we also apply a state-space approach (neural ordinary differential equations). We consider systems encompassing two- and three-dimensional ordinary differential equation systems featuring steady, oscillatory, and chaotic attractors, as well as partial differential equations exhibiting increasingly complex and intricate behaviors. Our framework significantly outperforms EDMD-DL. Furthermore, the state-space approach offers superior performance compared to the “pure” Koopman approach where the entire time evolution occurs in the space of observables. When the temporal evolution of the Koopman approach alternates between states and observables at each time step, however, its predictions become comparable to those of the state-space approach.
Effects of mRNA conformational switching on translational noise in gene circuits
Authors: Sinzger-D’Angelo Mark , Hanst Maleen , Reinhardt Felix , Koeppl Heinz
Published: April 2024

Intragenic translational heterogeneity describes the variation in translation at the level of transcripts for an individual gene. A factor that contributes to this source of variation is the mRNA structure. Both the composition of the thermodynamic ensemble, i.e., the stationary distribution of mRNA structures, and the switching dynamics between those play a role. The effect of the switching dynamics on intragenic translational heterogeneity remains poorly understood. We present a stochastic translation model that accounts for mRNA structure switching and is derived from a Markov model via approximate stochastic filtering. We assess the approximation on various timescales and provide a method to quantify how mRNA structure dynamics contributes to translational heterogeneity. With our approach, we allow quantitative information on mRNA switching from biophysical experiments or coarse-grain molecular dynamics simulations of mRNA structures to be included in gene regulatory chemical reaction network models without an increase in the number of species. Thereby, our model bridges a gap between mRNA structure kinetics and gene expression models, which we hope will further improve our understanding of gene regulatory networks and facilitate genetic circuit design.
Microsecond fast, battery powered, 100 kV modular pulse charger utilizing pulse transformers
Authors: Klein Tyler , Eulenbach Andrew , Neuber Andreas , Dickens James
Published: April 2024

Multiple pulse charging modules were designed and tested for synchronous use in scaled experiments. The pulse chargers are each capable of charging a nanofarad-sized capacitive load to 100 kV in less than 10 µs. This is achieved by initially charging a microfarad-sized capacitor to a maximum of 3 kV, then, using a thyristor switch, discharging the capacitor into two transformers paralleled on the primary side. Each transformer steps the voltage up to 50 kV, with the transformer having opposing polarities and a common neutral on the secondary. Thus, the full 100 kV is obtained by placing the nanofarad-sized capacitor between the +50 and −50 kV terminals. The pulse chargers use a microcontroller to monitor and control the pulse charger in addition to communicating with the user as well as other pulse chargers. For increased battery life, each pulse charger is kept in a low-power state while not in use. Upon startup, the pulse chargers automatically detect the number of modules in the system, the position of itself in the system, and the timing delays associated with each pulse charger in the system. This information is essential for synchronous charging and provides individual information and controls for the pulse chargers.
Deformable polarization singularity array by superimposed Ince–Gaussian beams
Authors: Wang Jinwen , Chen Yun , Cisowski Claire Marie , Yang Xin , Wang Chengyuan , Han Lei , Li Fuli , Gao Hong , Franke-Arnold Sonja
Published: April 2024

We present a numerical and experimental study of polarization singularity arrays, which are generated by the coherent superposition of orthogonal, linearly polarized, even and odd Ince–Gaussian (IG) beams. The generated array consists of multiple polarization singularities of different types. The type of the polarization singularities can be adjusted effectively by switching the linear polarization states of two IG modes and by modifying the relative phase factor. In addition, we study the evolution of the arrays with the ellipticity parameter, which leads to the splitting and spatial rearrangement of polarization singularities. This work may have implications for material processing, optical trapping, and manipulation.
Longitudinal and transverse piezoelectric effects of ferroelectret metamaterials with positive and negative Poisson's ratios
Authors: Hu Qianqian , Zhang Tongyan , Sessler Gerhard M. , von Seggern Heinz , Altmann Alexander A. , Kupnik Mario , Shi Zhiming , Zhang Xiaoqing
Published: April 2024

A theoretical model has been developed to express the longitudinal and transverse piezoelectric effects in ferro/piezoelectrets. This model is an extension of the classic model based on layer-dielectric structures that focuses on the longitudinal piezoelectric effect. The improved model reveals that the relation between the longitudinal piezoelectric d33 coefficient and the transverse piezoelectric d31 coefficient is associated with Poisson's ratio μ13 (or μ31) and Young's moduli Y1 and Y3. The polarity of the two coefficients is opposite for materials with a positive Poisson's ratio as normally observed in conventional piezoelectric materials, and the same for materials with a negative Poisson's ratio, i.e., auxetic materials. The experimental results available in the literature and obtained from ferroelectret metamaterials with a honeycomb cross-sectional structure and two-dimensional (2D) symmetric structure, called 2D ferroelectret metamaterials, designed and prepared in this study reasonably agree with theoretical predictions. This study not only extends the scope of the metamaterials by inducing the concept of ferroelectret metamaterials but also provides a strategy for designing ferroelectrets with designable properties.
Nonempirical semilocal density functionals for correcting the self-interaction of polaronic states
Authors: Falletta Stefano , Pasquarello Alfredo
Published: April 2024

Through the use of the piecewise-linearity condition of the total energy, we correct the self-interaction for the study of polarons by constructing nonempirical functionals at the semilocal level of theory. We consider two functionals, the γDFT and μDFT functionals, both of which are based on the addition of a weak local potential to the semilocal Hamiltonian to enforce the piecewise-linearity condition. We show that the resulting polaron properties are in good agreement with reference hybrid functional calculations. This supports the use of semilocal functionals for calculating polaron properties.
Optically induced dielectrophoresis for continuous separation and purification of C. vulgaris and H. pluvialis
Authors: Bian Qin , Wu Tao , Wu Zhihao , He Jixin , Wang Tianyi , Liu Zhiyuan , Liu Xiaomei , Yan Hong , Zhou Teng , Shi Liuyong
Published: April 2024

Marine microalgae are widely present in the natural environment, exhibiting a significant economic value. However, during the inoculation and cultivation process of microalgae, the introduction of unwanted algae is bound to trigger nutrient competition, leading to a decrease in the growth rate of microalgae and consequently impacting their economic value in production. To address this issue, this study integrates the optically induced dielectrophoresis (ODEP) manipulation technology based on the continuous flow in a microfluidic system. A two-stage cell filter, utilizing two virtual optical spots, is designed and manufactured. Leveraging the size differences between microalgae, continuous separation and purification of mixed samples containing Chlorella vulgaris and Haematococcus pluvialis are achieved within microchannels. Additionally, optimal ODEP manipulation conditions for mixed algal liquid samples, comprising C. vulgaris and H. pluvialis, are demonstrated, including appropriate alternating current voltage (6 V), alternating current frequency (100 kHz), light spot width (40 μm), and sample flow rate (0.9 μl/min). Analysis of mixed liquid samples collected at the chip's outlet reveals a reduction in the proportion of H. pluvialis from 37.5% to 1.2% after separation. In summary, this study proposes an ODEP microfluidic system capable of continuously separating and purifying microalgae with different biological characteristics, showcasing its potential as an alternative to traditional labor-intensive microalgae separation techniques.
Replicator–mutator dynamics with evolutionary public goods game-environmental feedbacks
Authors: Du Chunpeng , Lu Yikang , Zhang Yali , Shen Chen , Shi Lei , Guo Hao
Published: April 2024

Feedback loops between strategies and the environment are commonly observed in socio-ecological, evolution-ecological, and psychology-economic systems. However, the impact of mutations in these feedback processes is often overlooked. This study proposes a novel model that integrates the public goods game with environmental feedback, considering the presence of mutations. In our model, the enhancement factor of the public goods game combines positive and negative incentives from the environment. By employing replicator–mutator (RM) equations, we provide an objective understanding of the system’s evolutionary state, focusing on identifying conditions that foster cooperation and prevent the tragedy of the commons. Specifically, mutations play a crucial role in the RM dynamics, leading to the emergence of an oscillatory tragedy of the commons. By verifying the Hopf bifurcation condition, we establish the existence of a stable limit cycle, providing valuable insights into sustained oscillation strategies. Moreover, the feedback mechanism inherent in the public goods game model offers a fresh perspective on effectively addressing the classic dilemma of the tragedy of the commons.
Surface engineered nanodiamonds: mechanistic intervention in biomedical applications for diagnosis and treatment of cancer
Authors: Dey Tanima , Ghosh Anushikha , Sanyal Arka , Charles Chelsea Josephine , Pokharel Sahas , Nair Lakshmi , Singh Manjari , Kaity Santanu , Ravichandiran Velayutham , Kaur Kulwinder , Roy Subhadeep
Published: April 2024

In terms of biomedical tools, nanodiamonds (ND) are a more recent innovation. Their size typically ranges between 4 to 100 nm. ND are produced via a variety of methods and are known for their physical toughness, durability, and chemical stability. Studies have revealed that surface modifications and functionalization have a significant influence on the optical and electrical properties of the nanomaterial. Consequently, surface functional groups of NDs have applications in a variety of domains, including drug administration, gene delivery, immunotherapy for cancer treatment, and bio-imaging to diagnose cancer. Additionally, their biocompatibility is a critical requisite for their in vivo and in vitro interventions. This review delves into these aspects and focuses on the recent advances in surface modification strategies of NDs for various biomedical applications surrounding cancer diagnosis and treatment. Furthermore, the prognosis of its clinical translation has also been discussed.
How to allocate mitigation efforts between home insulation, fuel switch and fuel decarbonization? Insights from the French residential sector
Authors: Escribe Célia , Vivier Lucas , Giraudet Louis-Gaëtan , Quirion Philippe
Published: April 2024

Reducing greenhouse gas emissions in residential buildings relies on three channels that are rarely assessed together—insulating homes, switching to low-carbon heating systems and decarbonizing heating fuels. Their combination results from an interplay between top-down planning of the energy system and decentralized policies for the residential sector—insulation subsidies in particular. In this paper, we examine how the design of insulation subsidies influences the allocation of efforts between these three channels. To do so, we use an innovative framework coupling a highly detailed model of residential energy demand with a highly detailed model of the energy system, both focused on France. We find that the most cost-effective effort allocation to reach carbon neutrality implies 19% emission reductions from home insulation, 36% from fuel switch and 45% from fuel decarbonization. This however requires perfectly targeted subsidies. In three alternative, arguably more realistic subsidy scenarios, we find that total system cost is increased by 11%–16%. Our results highlight the key role played by subsidy specifications in determining the trade-off between insulation and fuel switch, e.g. insulation investments doubles, and heat pump adoption is 19% lower, when subsidies are restricted to the most comprehensive measures. Finally, alternative assumptions regarding the availability of renewable energy sources—biogas in particular—imply stronger energy efficiency efforts.
The
u(2|2)1
WZW model
Authors: Gaberdiel Matthias R , Mazzucchelli Elia
Published: April 2024

WZW models based on super Lie algebras play an important role for the description of string theory on AdS spaces. In particular, for the case of

AdS
3

×

S
3

with pure NS–NS flux the super Lie algebra of

psu

(
1
,
1

|

2

)
k

appears in the hybrid formalism, and higher dimensional AdS spaces can be described in terms of related supergroup cosets. In this paper we study the WZW models based on

u

(
2

|

2

)
1

and

psu

(
2

|

2

)
1

that may play a role for the worldsheet theory that is dual to free super Yang–Mills in 4D.
A 3D bioprinted hydrogel gut-on-chip with integrated electrodes for transepithelial electrical resistance (TEER) measurements
Authors: Vera Daniel , García-Díaz María , Torras Núria , Castillo Óscar , Illa Xavi , Villa Rosa , Alvarez Mar , Martinez Elena
Published: April 2024

Conventional gut-on-chip (GOC) models typically represent the epithelial layer of the gut tissue, neglecting other important components such as the stromal compartment and the extracellular matrix (ECM) that play crucial roles in maintaining intestinal barrier integrity and function. These models often employ hard, flat porous membranes for cell culture, thus failing to recapitulate the soft environment and complex 3D architecture of the intestinal mucosa. Alternatively, hydrogels have been recently introduced in GOCs as ECM analogs to support the co-culture of intestinal cells in in vivo-like configurations, and thus opening new opportunities in the organ-on-chip field. In this work, we present an innovative GOC device that includes a 3D bioprinted hydrogel channel replicating the intestinal villi architecture containing both the epithelial and stromal compartments of the gut mucosa. The bioprinted hydrogels successfully support both the encapsulation of fibroblasts and their co-culture with intestinal epithelial cells under physiological flow conditions. Moreover, we successfully integrated electrodes into the microfluidic system to monitor the barrier formation in real time via transepithelial electrical resistance measurements.
Steering cell orientation through light-based spatiotemporal modulation of the mechanical environment
Authors: Jorba Ignasi , Gussenhoven Sil , van der Pol Atze , Groenen Bart GW , van Zon Maarten , Goumans Marie José , Kurniawan Nicholas A , Ristori Tommaso , Bouten Carlijn VC
Published: April 2024

The anisotropic organization of cells and the extracellular matrix (ECM) is essential for the physiological function of numerous biological tissues, including the myocardium. This organization changes gradually in space and time, during disease progression such as myocardial infarction. The role of mechanical stimuli has been demonstrated to be essential in obtaining, maintaining and de-railing this organization, but the underlying mechanisms are scarcely known. To enable the study of the mechanobiological mechanisms involved, in vitro techniques able to spatiotemporally control the multiscale tissue mechanical environment are thus necessary. Here, by using light-sensitive materials combined with light-illumination techniques, we fabricated 2D and 3D in vitro model systems exposing cells to multiscale, spatiotemporally resolved stiffness anisotropies. Specifically, spatial stiffness anisotropies spanning from micron-sized (cellular) to millimeter-sized (tissue) were achieved. Moreover, the light-sensitive materials allowed to introduce the stiffness anisotropies at defined timepoints (hours) after cell seeding, facilitating the study of their temporal effects on cell and tissue orientation. The systems were tested using cardiac fibroblasts (cFBs), which are known to be crucial for the remodeling of anisotropic cardiac tissue. We observed that 2D stiffness micropatterns induced cFBs anisotropic alignment, independent of the stimulus timing, but dependent on the micropattern spacing. cFBs exhibited organized alignment also in response to 3D stiffness macropatterns, dependent on the stimulus timing and temporally followed by (slower) ECM co-alignment. In conclusion, the developed model systems allow improved fundamental understanding of the underlying mechanobiological factors that steer cell and ECM orientation, such as stiffness guidance and boundary constraints.
How frequently is alcohol advertised on television in Canada?: A cross-sectional study
Authors: Pauzé Elise , Pinto Adena , Potvin Kent Monique
Published: April 2024

Aims

Alcohol marketing is a commercial driver of alcohol use, including among youth. This study sought to quantify and characterize alcohol advertising on broadcast television in Canada.

Methods

Open-source television program logs for January to December 2018 submitted to the Canadian Radio-television and Telecommunications Commission by 147 stations with alcohol advertisements were analyzed.

Results

Overall, 501 628 alcohol advertisements were broadcast. Four companies accounted for 83% of advertisements, namely, Anheuser-Busch in Bev (33.7%), Molson Coors (22.7%), Diageo (16.1%), and Arterra Wines Canada (10.8%). On conventional stations, advertising was highest on French-language stations [Median (Mdn) = 3224; interquartile range (IQR) = 2262] followed by those with programming in foreign/mixed languages (Mdn = 2679; IQR = 219) and English-language stations (Mdn = 1955; IQR = 1563). On speciality stations, advertising was most frequent on those primarily focused on sports programming (Mdn = 8036; IQR = 7393), movies and scripted shows (Mdn = 7463; IQR = 5937), and cooking (Mdn = 5498; IQR = 4032). On weekdays, 33% of alcohol ads aired from 6 to 9 a.m. and 3 to 9 p.m. and on weekends, 52% aired from 6 a.m. to 9 p.m. when children or adolescents are more likely to be watching television. On youth-oriented stations (n = 4), 7937 alcohol advertisements were broadcast with most airing from 9 p.m. to midnight (44–45%) or 12–6 a.m. (50%) on both weekdays and weekends.

Conclusions

While few alcohol advertisements were broadcast on youth-oriented stations, young people in Canada are likely exposed to such advertising on programming intended for older or general audiences (e.g. sports). More research is needed to ascertain the extent to which broadcast television constitutes a source of alcohol advertising exposure among youth and to inform policies aimed at protecting them from the influence of such exposure.
Autofluorescence-guided hemithyroidectomy in a low-volume thyroid institution with no experience in parathyroid surgery: randomized clinical trial
Authors: Abood Ali , Rolighed Lars , Ovesen Therese , Madsen Stine H , Vestergaard Peter , Triponez Frédéric
Published: April 2024

Background

Recent studies suggest that low-volume surgeons with no experience in parathyroid surgery are at increased risk of causing parathyroid gland damage during thyroid surgery. The aim of this RCT was to evaluate the impact of using autofluorescence in hemithyroidectomy on parathyroid gland identification and preservation in a low-volume institution with no experience in parathyroid surgery.

Methods

Patients referred for hemithyroidectomy were randomized 1 : 1 to either autofluorescence-guided hemithyroidectomy (the near-infrared autofluorescence group) or conventional hemithyroidectomy (the control group). The primary outcome was parathyroid gland identification rate. Secondary outcomes were the rate of parathyroid gland autotransplantation and the rate of inadvertent parathyroid gland excision.

Results

A total of 170 patients were randomized to either autofluorescence-guided hemithyroidectomy (84 patients) or conventional hemithyroidectomy (86 patients). In the near-infrared autofluorescence group, 81.0% of parathyroid glands were identified, compared with 57.0% in the control group (P < 0.001). Autofluorescence enabled parathyroid gland visualization before the naked eye in 46.3% of cases. Surgeons had lower confidence in the parathyroid gland identification process in the control group than in the near-infrared autofluorescence group (59.1% versus 87.5% respectively; P < 0.001). In the near-infrared autofluorescence group, the parathyroid gland autotransplantation rate was initially high, but declined over time. There was no difference in the rate of inadvertent parathyroid gland excision.

Conclusion

Autofluorescence guidance significantly improved the parathyroid gland identification rate in hemithyroidectomy in a low-volume institution with no experience in parathyroid surgery and provided an increase in surgical confidence. The pattern of parathyroid gland autotransplantation in autofluorescence-guided surgery indicates the presence of a learning curve.

Registration number

NCT05044351 (http://www.clinicaltrials.gov).
Predictors of cognition after glioma surgery: connectotomy, structure-function phenotype, plasticity
Authors: Herbet Guillaume , Duffau Hugues , Mandonnet Emmanuel
Published: April 2024

Determining preoperatively the maximal extent of resection that would preserve cognitive functions is the core challenge of brain tumour surgery. Over the past decade, the methodological framework to achieve this goal has been thoroughly renewed: the population-level topographically-focused voxel-based lesion-symptom mapping has been progressively overshadowed by machine learning (ML) algorithmics, in which the problem is framed as predicting cognitive outcomes in a patient-specific manner from a typically large set of variables. However, the choice of these predictors is of utmost importance, as they should be both informative and parsimonious.

In this perspective, we first introduce the concept of connectotomy: instead of parameterizing resection topography through the status (intact/resected) of a huge number of voxels (or parcels) paving the whole brain in the Cartesian 3D-space, the connectotomy models the resection in the connectivity space, by computing a handful number of networks disconnection indices, measuring how the structural connectivity sustaining each network of interest was hit by the resection. This connectivity-informed reduction of dimensionality is a necessary step for efficiently implementing ML tools, given the relatively small number of patient-examples in available training datasets.

We further argue that two other major sources of interindividual variability must be considered to improve the accuracy with which outcomes are predicted: the underlying structure-function phenotype and neuroplasticity, for which we provide an in-depth review and propose new ways of determining relevant predictors. We finally discuss the benefits of our approach for precision surgery of glioma.
Conditioning and pseudoconditioning differently change intrinsic excitability of inhibitory interneurons in the neocortex
Authors: Kanigowski Dominik , Urban-Ciecko Joanna
Published: April 2024

Many studies indicate a broad role of various classes of GABAergic interneurons in the processes related to learning. However, little is known about how the learning process affects intrinsic excitability of specific classes of interneurons in the neocortex. To determine this, we employed a simple model of conditional learning in mice where vibrissae stimulation was used as a conditioned stimulus and a tail shock as an unconditioned one. In vitro whole-cell patch-clamp recordings showed an increase in intrinsic excitability of low-threshold spiking somatostatin-expressing interneurons (SST-INs) in layer 4 (L4) of the somatosensory (barrel) cortex after the conditioning paradigm. In contrast, pseudoconditioning reduced intrinsic excitability of SST-LTS, parvalbumin-expressing interneurons (PV-INs), and vasoactive intestinal polypeptide-expressing interneurons (VIP-INs) with accommodating pattern in L4 of the barrel cortex. In general, increased intrinsic excitability was accompanied by narrowing of action potentials (APs), whereas decreased intrinsic excitability coincided with AP broadening. Altogether, these results show that both conditioning and pseudoconditioning lead to plastic changes in intrinsic excitability of GABAergic interneurons in a cell-specific manner. In this way, changes in intrinsic excitability can be perceived as a common mechanism of learning-induced plasticity in the GABAergic system.
Clinical Predictors and Outcomes of Invasive Anal Cancer for People With HIV in an Inception Cohort
Authors: Cachay Edward R , Gilbert Tari , Qin Huifang , Mathews Wm Christopher
Published: April 2024

Background

Due to the heterogeneity of risk for invasive anal cancer (IAC) among people with human immunodeficiency virus (PWH), we investigated predictors of IAC and described outcomes among those with a cancer diagnosis.

Methods

Using a longitudinal inception cohort of anal cancer screening, we evaluated risk factors and outcome probabilities for incident IAC in Cox models. Screening included anal cytology and digital anorectal examination, and, if results of either were abnormal, high-resolution anoscopy.

Results

Between 30 November 2006 and 3 March 2021, a total of 8139 PWH received care at the University of California, San Diego, with 4105 individuals undergoing screening and subsequently followed up over a median of 5.5 years. Anal cancer developed in 33 of them. IAC was more likely to develop in patients with anal high-grade squamous intraepithelial lesions (aHSILs) on initial or subsequent follow-up cytology (hazard ratio, 4.54) and a nadir CD4 cell count ≤200/µL (2.99). The joint effect of aHSILs and nadir CD4 cell count ≤200/µL amplified the hazard of IAC by 9-fold compared with the absence of both. PWH with time-updated cytology aHSIL and CD4 cell counts ≤200/µL had 5- and 10-year probabilities of IAC of 3.40% and 4.27%, respectively. Twelve individuals with cancer died, 7 (21% of the total 33) due to cancer progression, and they had clinical stage IIIA or higher cancer at initial diagnosis.

Conclusions

PWH with both aHSIL and a nadir CD4 cell count ≤200/µL have the highest risk of IAC. PWH who died due to IAC progression had clinical stage IIIA cancer or higher at diagnosis, highlighting the importance of early diagnosis through high-resolution anoscopic screening.
Mid-term results of a prospective study for aortic dissection with a gutter-plugging chimney stent graft
Authors: Shu Chang , Wan Zicheng , Luo Mingyao , Fang Kun , Hu Jia , Zuo Jian , Li Xiaoqiang , Li Quanming , He Hao , Li Xin
Published: April 2024

OBJECTIVES

Our goal was to access early and mid-term outcomes of a gutter-plugging chimney stent graft for treatment of Stanford type B aortic dissections in the clinical trial Prospective Study for Aortic Arch Therapy with stENt-graft for Chimney technology (PATENCY).

METHODS

Between October 2018 and March 2022, patients with Stanford type B aortic dissections were treated with the Longuette chimney stent graft in 26 vascular centres. The efficiency and the incidence of adverse events over 12 months were investigated.

RESULTS

A total of 150 patients were included. The technical success rate was 99.33% (149/150). The incidence of immediate postoperative endoleak was 5.33% (8/150, type I, n = 6; type II, n = 1; type IV, n = 1) neurologic complications (stroke or spinal cord ischaemia); the 30-day mortality was 0.67% (1/150) and 1.33% (2/150), respectively. During the follow-up period, the median follow-up time was 11.67 (5–16) months. The patent rate of the Longuette graft was 97.87%. Two patients with type I endoleak underwent reintervention. The follow-up rate of the incidence of retrograde A type aortic dissection was 0.67% (1/150). There was no paraplegia, left arm ischaemia or stent migration.

CONCLUSIONS

For revascularization of the left subclavian artery, the Longuette chimney stent graft can provide an easily manipulated, safe and effective endovascular treatment. It should be considered a more efficient technique to prevent type Ia endoleak. Longer follow-up and a larger cohort are needed to validate these results.

CLINICAL TRIAL REGISTRY NUMBER

NCT03767777