bluuebunny/crossref_metadata_2025 huggingface dataset:
The Unique Role of Intracellular Perinuclear β-Adrenergic Receptors in defining Signaling Compartmentation and Pathological Cardiac Remodeling
Authors: Turcotte Moriah Gildart , Samuelsson Anne-Maj , Possidento Sofia M. , Li Jinliang , Qin Zhuyun , Kapiloff Michael S. , Dodge-Kafka Kimberly L.
Published: October 2024

The β-adrenergic receptor is a prototypical G-protein coupled receptor that initiates signaling from the plasma membrane. However, active receptors have been detected within intracellular compartments. The functional significance of these intracellular receptors remains unclear, including whether they regulate distinct cellular processes or function independently of plasma membrane receptors. We show using live cell imaging of primary cardiomyocytes that β-adrenergic receptors localized to Golgi apparatus opposing the outer nuclear membrane are sufficient and necessary for the stimulation of cAMP and calcium signaling within a nanometer scale compartment independent of receptors at other sites. Using compartment-specific activators and inhibitors, we show Golgi β-adrenergic receptors associated with the scaffold protein AKAP6β and the outer nuclear membrane protein nesprin-1α are responsible for pathological gene transcription and the induction of cardiomyocyte hypertrophy. The functional significance of Golgi-localized receptors is demonstrated in mice models of cardiomyopathy, providing proof-of-concept for a compartment-specific therapeutic intervention in Dilated Cardiomyopathy.
A Predictive Model for Compound-Protein Interactions Based on Concatenated Vectorization
Authors: Williams Gareth , Azim Kaz
Published: October 2024

Background

Large data sets of compound activity lend themselves to building predictive models based on compound and target structure. The simplest representation of structure is via vectorisation. Compound fingerprint vectorisation has been successfully employed in predicting compound activity classes.

Results

A vector representation of a protein-compound pair based on a concatenation of the compound fingerprint and the protein triplet vector has been used to train random forest and neural network models on multiple datasets of protein-compound interaction together with compound associated transcription and activity profiles. Results for compound-target predictability are comparable with more complex published methodologies.

Conclusion

A simple intuitive representation of a protein-compound pair can be employed in a variety of machine learning models to gain a predictive handle on the activity of compounds for which there is no activity data. It is hoped that this transparent approach will prove sufficiently portable and simple to implement that drug discovery will be opened up to the wider research community.
Pituitary adenylate cyclase-activating polypeptide (PACAP) overexpression in the paraventricular nucleus of the thalamus alters motivated and affective behavior in female rats
Authors: Carpenter Brody A. , Pirino Breanne E. , Jennings Malcolm C. , Samels Shanna B. , Shah Krisha S. , Maser Joya , Gupta Medha , Barson Jessica R.
Published: October 2024

Background

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been found to be involved in a wide range of motivated and affective behaviors. While the PACAP-38 isoform is more densely expressed than PACAP-27 in most of the brain, PACAP-27 is more highly expressed in the rodent paraventricular nucleus of the thalamus (PVT), where females also have greater expression than males. Notably, the role of PACAP-27 expression in cells of the PVT has not been explored.

Methods

Adult, female Long-Evans rats were injected in the PVT with an AAV to increase expression of PACAP or a control AAV. They were then investigated for subsequent gene and peptide levels of PACAP in the PVT; ethanol drinking and preference; sucrose drinking and preference; or locomotor activity in a novel chamber, behavior in a light-dark box, behavior in a novelty suppression of feeding test, locomotor activity in a familiar activity chamber, and behavior in a forced swim test.

Results

Gene expression of PACAP was significantly increased in the PVT by four weeks after injection with the PACAP AAV, and this resulted in a specific increase in levels of PACAP-27. Rats injected with the PACAP AAV demonstrated reduced drinking and preference for ethanol under the intermittent-access procedure compared to those injected with the control AAV. In contrast, rats injected with the PACAP AAV showed no significant difference in drinking or preference for sucrose, or in any affective behavior tested, except that they spent less time swimming in the forced swim test.

Conclusions

In light of the low overall level of expression of PACAP-27 in the brain, the ability of PACAP-27 in the PVT to control ethanol drinking, with minimal effects on other motivated or affective behaviors, supports the idea that compounds related to PACAP-27 should be investigated as potential therapeutics for the treatment of alcohol use disorder.
De novo discovery of conserved gene clusters in microbial genomes with Spacedust
Authors: Zhang Ruoshi , Mirdita Milot , Söding Johannes
Published: October 2024

Metagenomics has revolutionized environmental and human-associated microbiome studies. However, the limited fraction of proteins with known biological process and molecular functions presents a major bottleneck. In prokaryotes and viruses, evolution favors keeping genes participating in the same biological processes co-localized as conserved gene clusters. Conversely, conservation of gene neighborhood indicates functional association. Spacedust is a tool for systematic,de novodiscovery of conserved gene clusters. To find homologous protein matches it uses fast and sensitive structure comparison with Foldseek. Partially conserved clusters are detected using novel clustering and order conservation P-values. We demonstrate Spacedust’s sensitivity with an all-vs-all analysis of 1 308 bacterial genomes, identifying 72 843 conserved gene clusters containing 58% of the 4.2 million genes. It recovered recover 95% of antiviral defense system clusters annotated by a specialized tool. Spacedust’s high sensitivity and speed will facilitate the large-scale annotation of the huge numbers of sequenced bacterial, archaeal and viral genomes.
WITHDRAWN: Influence of Shading on the Behavioral Ecology of a Caribbean Alcyonacean Octocoral,Briareum asbestinum, in the Florida Keys, United States
Authors: Draud Savannah , Hoeksema Jason D. , Draud Matthew
Published: October 2024

Withdrawal Statement

The authors have withdrawn this manuscript because they are in the process of making revisions to the study/manuscript, and do not wish this paper to be considered as finalized at this point. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Enhanced Structural Brain Connectivity Analyses Using High Diffusion-weighting Strengths
Authors: Yu Leyao , Flinker Adeen , Veraart Jelle
Published: October 2024

Tractography is a unique modality for the in vivo measurement of structural connectivity, crucial for understanding brain networks and neurological conditions. With increasingb-value, the diffusion-weighting signal becomes primarily sensitive to the intra-axonal signal. However, it remains unclear how tractography is affected by this observation. Here, using open-source datasets, we showed that at highb-values, DWI reduces the uncertainty in estimating fiber orientations. Specifically, we found the ratio of biologically-meaningful longer-range connections increases, accompanied with downstream impact of redistribution of connectome and network metrics. However, when going beyondb=6000 s/mm2, the loss of SNR imposed a penalty. Lastly, we showed that the data reaches satisfactory reproducibility withb-value above 1200 s/mm2. Overall, the results suggest that usingb-values above 2500 s/mm2is essential for more accurate connectome reconstruction by reducing uncertainty in fiber orientation estimation, supporting the use of higherb-value protocols in standard diffusion MRI scans and pipelines.
Divergent changes in social stress-induced motivation in male and female mice
Authors: McGraw Megan , Christensen Cooper , Nelson Hailey , Li Ai-Jun , Qualls-Creekmore Emily
Published: October 2024

Exposure to stressors has been shown to dysregulate motivated behaviors in a bidirectional manner over time. The relationship between stress and motivation is relevant to psychological disorders, including depression, binge eating, and substance abuse; however, this relationship is not well characterized, especially in females, despite their increased risk of these disorders. Social defeat stress is a common model to study stress-induced motivation changes, however, historically this model excluded females due to lack of female-to-female aggression and unreliable male-to-female aggression. Additionally, changes in motivation are often assessed well after stress exposure ends, potentially missing or occluding changes to motivation during stress. Recently, the chronic non-discriminatory social defeat stress (CNSDS) model has demonstrated social defeat of male and female C57BL/6J mice by exposing both mice to an aggressive male CD-1 mouse simultaneously. Here we use this model to directly compare changes in the motivated behavior of male and female mice during and following chronic stress. We hypothesized that motivated behavioral responses would be dysregulated during stress and that the effects would worsen as the stress exposure continued. To monitor motivated behavior, mice had access to a Feeding Experimental Device.3 (FED3), a home cage device for operant responding. Operant responding was monitored prior to, during, and after stress by measuring nose pokes for sucrose pellets on a modified progressive ratio schedule of reinforcement. Our results demonstrated divergent behavioral outcomes between males and female mice in response to stress; where male mice increased motivated behavior during stress only, whereas female mice exhibited a decrease in motivation during and after stress. This study highlights the need to investigate the effects of stress-induced motivation over time, as well as the increased need to understand differences in the stress response in females.

Highlights

Operant behaviors were monitored continuously during and after stress exposure.

Chronic social stress produced opposite effects on motivation in males and females.

Susceptibility to stress only influenced outcomes on female motivated behaviors.
Susceptibility to auditory feedback manipulations and individual variability
Authors: Ozker Muge , Hagoort Peter
Published: October 2024

Monitoring auditory feedback from hearing one’s own voice is important for fluent speech production as it enables detection and correction of speech errors. The influence of auditory feedback is best illustrated by manipulating it during speech production. A common temporal manipulation technique, delaying auditory feedback (DAF), leads to disruptions in speech fluency, while a common spectral manipulation technique, perturbing the pitch of auditory feedback (PAF), results in vocal alterations.

Previous research involving clinical populations has revealed diverse susceptibility profiles to auditory feedback manipulations, yet the extent of such diversity within the neurotypical population remains unclear. Furthermore, different types of manipulations elicit distinct speech errors (i.e. fluency/coordination versus acoustic errors), which may be processed by distinct error correction mechanisms. It is yet to be understood whether individuals affected by one manipulation are similarly impacted by the other. Lastly, based on evidence from clinical studies, which demonstrated that visual feedback can improve impaired speech production, it is an open question whether visual feedback can alleviate the disruptive effects of altered auditory feedback.

We recorded voice samples from 40 neurotypical participants during both a DAF and a PAF task. DAF significantly prolonged articulation duration and increased voice pitch and intensity. In some trials, participants received immediate visual feedback, however visual feedback did not alleviate but rather strengthened the disruptive effects of DAF. During the PAF task, participants adjusted their voice pitch in the opposite direction of the perturbation in majority of the trials to compensate for the perturbation. We assessed susceptibility of the participants to the effects of DAF and PAF by examining articulation duration and compensatory vocal response magnitude, respectively. Susceptibility varied widely among participants for both manipulations, but individuals susceptible to one manipulation did not consistently exhibit susceptibility to the other, indicating distinct processing mechanisms for these different types of auditory feedback manipulations.
MORC-1 is a key component of theC. elegansCSR-1 germline gene licensing mechanism
Authors: Kirshner Jessica A. , Picard Colette L. , Weiser Natasha E. , Mehta Nicita , Feng Suhua , Murphy Victoria N. , Vakhnovetsky Anna , Alessi Amelia F. , Xiao Connie , Inoki Kai , Mouridi Sonia El , Frøkjær-Jensen Christian , Jacobsen Steven E. , Kim John K.
Published: October 2024

The Argonaute CSR-1 is essential for germline development inC. elegans. Mutation ofcsr-1downregulates thousands of germline-expressed genes, leading to the model that the CSR-1-mediated small RNA pathway promotes, or “licenses,” gene expression by an unknown mechanism. CSR-1 also silences a limited number of genes through its canonical endonucleolytic “slicer” activity. We show that the GHKL-type ATPase MORC-1, a CSR-1 slicing target, over-accumulates at CSR-1 “licensed” target genes incsr-1(-), which correlates with ectopic gain of H3K9me3, H3K36me3 loss, and gene downregulation. Loss ofmorc-1rescuescsr-1(-) defects, while overexpressing MORC-1 in the germline of wild-type worms is sufficient to cause sterility and downregulate CSR-1 targets. These results show that MORC-1 overexpression incsr-1(-) is a primary driver of the CSR-1-mediated gene licensing mechanism.

One-Sentence Summary

MORC-1 acts downstream of CSR-1 to regulate germline chromatin states and is a key component of the gene licensing mechanism.
Ultrasensitive in vivo infrared spectroscopic imaging via oblique photothermal microscopy
Authors: Li Mingsheng , Xiao Sheng , Ni Hongli , Ding Guangrui , Yuan Yuhao , Marar Carolyn , Mertz Jerome , Cheng Ji-Xin
Published: October 2024

In vivo IR spectroscopy faces challenges due to poor sensitivity in reflection mode and low resolution at micrometer scale. To break this barrier, we report an oblique photothermal microscope (OPTM) to enable ultrasensitive IR spectroscopic imaging of live subjects at sub-micron resolution. Classic photothermal measurement captures only a small fraction of probe photons through a pinhole to extract the photothermal signal. Instead, OPTM uses a differential split detector placed on the sample surface to collect 500-fold more photons and suppress the laser noise by 12 fold via balanced detection. Leveraging its improved sensitivity, OPTM enables low-dose IR imaging of skin without photodamage. Depth-resolved in vivo OPTM imaging of metabolic markers beneath mouse and human skin is shown. Furthermore, we demonstrate in vivo OPTM tracking of topical drug contents within mouse and human skin. Collectively, OPTM presents a highly sensitive imaging platform for in vivo and in situ molecular analysis.
A heteromeric nicotinic acetylcholine receptor promotes sleep by relaying GABAergic signals within a locus of motor and sensory integration
Authors: Yumita Tomohiro , Ahamed Hassan , Hatch Hayden A. M. , Cossentino Ian , Louka Charalambia , Stavropoulos Nicholas
Published: October 2024

Locomotor inactivity and reduced sensory responsiveness are defining attributes of sleep, yet the underlying mechanisms are not well understood. In particular, the molecular and circuit mechanisms by which sleep-regulatory signals from the brain restrict movement and sensation remain largely ill-defined. Here we identify a nicotinic acetylcholine receptor (nAChR) that promotes sleep inDrosophilathrough its expression in GABAergic neurons of the ventral nerve cord (VNC), a center for motor and sensory systems. Biochemical, genetic, and pharmacological manipulations indicate that a heteromeric nAChR containing the α1 and β1 subunits promotes sleep by coupling cholinergic input to GABA release in the VNC and the likely inhibition of motor neurons, sensory afferents, or both. The functional parallels of the VNC and the mammalian spinal cord suggest that disruptions of analogous inhibitory circuits in humans may impair suppression of behavioral activity and sensory inputs during sleep and contribute to sleep disorders.
CREATE: cell-type-specific cis-regulatory elements identification via discrete embedding
Authors: Cui Xuejian , Yin Qijin , Gao Zijing , Li Zhen , Chen Xiaoyang , Chen Shengquan , Liu Qiao , Zeng Wanwen , Jiang Rui
Published: October 2024

Identifying cis-regulatory elements (CREs) within non-coding genomic regions—such as enhancers, silencers, promoters, and insulators—is pivotal for elucidating the intricate gene regulatory mechanisms underlying complex biological traits. The current prevalent sequence-based methods often focus on singular CRE types, limiting insights into cell-type-specific biological implications. Here, we introduce CREATE, a multimodal deep learning model based on the Vector Quantized Variational AutoEncoder framework, designed to extract discrete CRE embeddings and classify multiple CRE classes using genomic sequences, chromatin accessibility, and chromatin interaction data. CREATE excels in accurate CRE identification and exhibits strong effectiveness and robustness. We showcase CREATE’s capability in generating comprehensive CRE-specific feature spectrum, offering quantitative and interpretable insights into CRE specificity. By enabling large-scale prediction of CREs in specific cell types, CREATE facilitates the recognition of disease- or phenotype-related biological variabilities of CREs, thereby expanding our understanding of gene regulation landscapes.
BaMBo: An Annotated Bone Marrow Biopsy Dataset for Segmentation Task
Authors: Singh Anilpreet , Dharamdasani Satyender , Sharma Praveen , Gupta Sukrit
Published: October 2024

Bone marrow examination has become increasingly important for the diagnosis and treatment of hematologic and other illnesses. The present methods for analyzing bone marrow biopsy samples involve subjective and inaccurate assessments by visual estimation by pathologists. Thus, there is a need to develop automated tools to assist in the analysis of bone marrow samples. However, there is a lack of publicly available standardized and high-quality datasets that can aid in the research and development of automated tools that can provide consistent and objective measurements. In this paper, we present a comprehensiveBoneMarrowBiopsy (BaMBo) dataset consisting 185 semantic-segmented bone marrow biopsy images, specifically designed for the automated calculation of bone marrow cellularity. Our dataset comprises high-resolution, generalized images of bone marrow biopsies, each annotated with precise semantic segmentation of different haematological components. These components are divided into 4 classes: Bony trabeculae, adipocytes, cellular region and Background (BG). The annotations were performed with the help of two experienced hematopathologists that were supported by state-of-the-art Deep Learning (DL) models and image processing techniques. We then used our dataset to train a custom U-Net based DL model that performs multi-class semantic segmentation of the images (Dice Score: 0.831±0.099) and predicts the cellularity of these images with an error of 5.9%±8.8%. This shows the applicability of our data for future research in this domain. Our code is available athttps://github.com/AI-in-Medicine-IIT-Ropar/BaMbo-Bone-Marrow-Biopsy.
Signatures of bulk neutrinos in the early Universe
Authors: McKeen David , Ng John N. , Shamma Michael
Published: October 2024

Neutrino masses and quantum gravity are strong reasons to extend the standard model of particle physics. A large extra dimension can be motivated by quantum gravity and can explain the small neutrino masses with new singlet states that propagate in the bulk. In such a case, a Kaluza-Klein tower of sterile neutrinos emerges. We revisit constraints on towers of sterile neutrinos that come from cosmological observables such as the effective number of noninteracting relativistic species and the dark matter density. These limits generically rule out micron-sized extra dimensions. We explore the weakening of these constraints to accommodate an extra dimension close to the micron size by assuming that the Universe is reheated after inflation to a low temperature. We discuss how such a possibility can be distinguished in the event of a positive signal in a cosmological observable.

Published by the American Physical Society
2024
Why and how do suppliers develop environmental management capabilities in response to buyer-led development initiatives?
Authors: Qiao Jianqi , Li Suicheng , Capaldo Antonio
Published: October 2024

Purpose

Although buying firms increasingly adopt supplier development to help suppliers enhance their ability to deal with environmental issues, little is known about the mechanisms by which buyer-led environmental supplier development (ESD) affects the environmental management capabilities (EMC) of suppliers. Focusing on the supplier perspective and specifically on the role of psychological mechanisms at the supplier level, the authors adopt the stimulus–organism–response framework from functionalist psychology to investigate the mediating role of environment-related supplier perceived relationship value in the association between ESD, in the form of environmental requirements and audits (indirect development – ID) vs. direct development projects (direct development – DD), and supplier EMC.

Design/methodology/approach

The authors used structural equation modeling and regression analysis to test the hypotheses using survey data from 221 supplying organizations in China.

Findings

Results reveal that each of the three considered dimensions of the environment-related supplier perceived relationship value (i.e. economic, strategic and co-creation) helps enhance EMC. However, while DD influences positively all three dimensions, ID has a positive effect on only the economic and strategic dimensions. Moreover, the mediation analysis suggests that, while DD affects EMC both directly and via the three dimensions of environment-related supplier perceived relationship value (partial mediation), ID affects EMC only through its impact on environment-related supplier perceived relationship economic and strategic value (full mediation).

Originality/value

The study sheds light on the psychological mechanisms that drive suppliers’ involvement in green supplier development activities. By doing so, it contributes to the understanding of ESD practices and processes and their effectiveness.
The Scope of the Medical Exception in Criminal Law
Authors: Forsberg Lisa
Published: October 2024

Many medical procedures involve the causation of serious injury by doctors to their patients. Yet when accepted as ‘proper medical treatment’, doctors incur no criminal liability for their actions, per the ‘medical exception’ in criminal law. This exception is well established; its scope much less so. This article seeks to clarify the scope of the medical exception. First, it examines whether legal authority provides an explicit principle for determining the scope of the exception, arguing that no such explicit principle can be found. Second, it seeks to identify an implicit principle: a property shared by interventions that fall within the medical exception, which distinguishes them from interventions without. It considers three candidates, based on physiological, objective psychological, and broad welfare benefit, arguing that none fully succeeds in accounting for the medical exception's scope. The article then considers some implications, an objection, and some remaining problems for future research to consider.
Labour market and income inequalities in the Netherlands, 1977–2022
Authors: Jongen Egbert , Been Jim , Caminada Koen , Vethaak Heike
Published: October 2024

We study how changes in labour market outcomes and household composition translate into changes in household incomes in the Netherlands over the period 1977–2022. During this period, the Netherlands witnessed a vast increase in female employment and earnings. This was also the key driver of household income growth. Male employment hardly changed, and male earnings growth was limited, and hence contributed little to household income growth. The increase in employment and earnings was the most pronounced for lower‐educated women and women with relatively low earnings. The resulting drop in earnings inequality among women also put a drag on the rise in household income inequality, together with an increase in social benefits and a reduction in taxes for the bottom of the household income distribution. However, overall there was still a small increase in disposable household income inequality because inequality in male earnings increased, with earnings falling in real terms for men with low earnings and rising somewhat for men with high earnings. Furthermore, the proportion of singles increased, in particular among low‐earning men and women, and assortative matching on earnings in couples increased. We further show that despite still having relatively low household income inequality overall, a large gap remains between immigrants and natives.
Labour market trends and income inequality in Germany, 1983–2020
Authors: Blömer Maximilian , Herold Elena , Lay Max , Peichl Andreas , Rathje Ann‐Christin , Schüle Paul , Steuernagel Anne
Published: October 2024

This study analyses the development of inequality in Germany from 1983 to 2020, focusing on labour market trends and income inequality. Using data from the German Socio‐Economic Panel, we show that one of the most important trends in the German labour market in recent decades has been the increasing participation of women in the labour market. In addition, we confirm previous findings that inequality in earnings and household disposable income increased from the 1990s to 2005. Since then, inequality has not increased further despite changes in the composition of the labour force that tend to increase inequality, such as increased assortative matching and high net migration rates.
Machine learning‐based classification of varicocoele grading: A promising approach for diagnosis and treatment optimization
Authors: Kayra Mehmet Vehbi , Şahin Ali , Toksöz Serdar , Serindere Mehmet , Altıntaş Emre , Özer Halil , Gül Murat
Published: October 2024

Background

Varicocoele is a correctable cause of male infertility. Although physical examination is still being used in diagnosis and grading, it gives conflicting results when compared to ultrasonography‐based varicocoele grading.

Objectives

We aimed to develop a multi‐class machine learning model for the grading of varicocoeles based on ultrasonographic measurements.

Method

Between January and May 2024, we enrolled unilateral varicocoele patients at an infertility clinic, assessing their varicocoele stages using the Dubin and Amelar system. We measured vascular diameter and reflux time at the testicular apex and the subinguinal region ultrasonography in both the supine and standing positions. Using these measurements, we developed four multi‐class machine learning models, evaluating their performance metrics and determining which patient position and projection were most influential in varicocoele grading.

Results

We included 248 patients with unilateral varicocoele in the study, their average age was 26.61 ± 4.95 years old. Of these, 212 had left‐sided and 36 had right‐sided varicocoeles. According to the Dubin and Amelar system, there were 66 grade I, 96 grade II, and 86 grade III varicocoeles. Among the models we created, the random forest (RF) model performed best, with an overall accuracy of 0.81 ± 0.06, an F1 score of 0.79 ± 0.02, a sensitivity of 0.69 ± 0.02, and a specificity of 0.8 ± 0.03.

Vascular diameter measurement at the testicular apex in the supine position had the most impact on grading across all models. In support vector machine and multi‐layer perceptron models, reflux time measurements from the subinguinal projection in the standing position contributed the most, while in RF and k‐nearest neighbors models, measurements from the subinguinal projection in the supine position were the most influential.

Conclusions

Machine learning methods have demonstrated superior accuracy in predicting disease compared to traditional statistical regressions and nomograms. These advancements hold promise for clinically automated prediction of varicocoele grades in patients. Tailored varicocoele grading for individuals has the potential to enhance treatment effectiveness and overall quality of life.
Characteristics and outcomes of children and young adults with sickle cell disease supported with extracorporeal membrane oxygenation (ECMO): An updated analysis of the ELSO registry
Authors: Remy Tancrède , Jegard Julien , Chenouard Alexis , Maminirina Pierre , Liet Jean Michel , Couec Marie‐Laure , Joram Nicolas , Bourgoin Pierre
Published: October 2024

Background

Sickle cell disease (SCD) is a global hemoglobinopathy; approximately 300 000 individuals are diagnosed annually. Acute chest syndrome (ACS), a common complication, leads to significant hospitalization and mortality, particularly in cases of severe respiratory distress. ECMO outcomes in this specific population are poorly described.

Methods

This retrospective observational study, utilizing data from the Extracorporeal Life Support Organization (ELSO) registry, focuses on children and young adults (<40 years) with SCD undergoing ECMO from 1998 to 2022.

Results

We observed a growing trend in ECMO cases over the last 15 years, with 210 SCD patients identified in the registry (five neonates, 95 children, 110 adults). ECMO was predominantly initiated for pulmonary support (62%), and most of the primary diagnoses were related to SCD (reported as “SCD” or “acute chest syndrome”). The global survival rate was 55.8% (59% for children and 52.7% for adults). None of the children supported for extracorporeal cardiopulmonary resuscitation survived, and only 2/18 (11%) of adults cannulated for ECPR survived. Complication rates, including acute renal failure (33.8%) neurological events (13%), thrombotic (23.3%), or bleeding events (22.9%) were not noticeably different from reported outcomes in the ELSO registry.

Conclusion

Our findings suggest that ECMO outcomes in SCD patients align with general ECMO trends and may not be limited by suspected unfavorable results in children and young adults. Despite limitations, our study contributes valuable insights into using ECMO in SCD, emphasizing the need for further research and understanding in this underexplored domain.
Piecing together the intricate puzzle of organ recovery in AL amyloidosis
Authors: Nuvolone Mario , Palladini Giovanni
Published: October 2024

In AL amyloidosis, the factors hindering organ recovery despite deep haematological responses to anti‐clonal therapy remain elusive. The study by Staron and colleagues identifies tissue‐specific factors influencing the lack of organ response, including host‐related characteristics, the properties of the amyloidogenic precursor, the extent of organ compromise at diagnosis and the dynamics and depth of haematological response. While this study begins to unravel the complex mechanisms underlying organ recovery in AL amyloidosis, it also raises critical questions that warrant further investigation through future collaborative research.

Commentary on: Staron et al. Factors impeding organ recovery despite a deep haematological response in patients with systemic AL amyloidosis. Br J Haematol 2024; 205:2268‐2272.
Young children's perceptions and experiences of school readiness during the transition from preschool to primary school in China
Authors: Luo Shilan , Yuan Shanshan
Published: October 2024

School readiness has a profound educational value for children's positive adjustment to primary school and holistic development. However, little research sufficiently addresses how young children view multifaceted components of learning, such as cognitive, affective and behavioural experiences on school readiness. A timely understanding of children's perceptions and experiences is crucial to shed light on how to promote transition and improve children's school readiness. This study investigated the perceptions and experiences of 41 children in China (5–6 years of age, 23 girls) regarding their school readiness based on Mosaic approach methods. The results indicated that young children have their own unique perceptions, emotional and behavioural experiences of school readiness. The perceptions of school readiness include four aspects of material supplies, subjects knowledge, interests and specialties and behavioural habits, which has similarities to that of adults in aspects of academic knowledge and social rules. Nevertheless, findings revealed young children view interests and strengths as important part of school readiness, reflecting their personal preferences and abilities. The emotional experiences could be considered positive or negative, with positive emotional experiences expressing children's curiosity and expectation, fulfilment and pleasure, and negative emotional experiences expressing academic burden, rules pressure and social worries, which need to be addressed. Young children's behavioural experiences with school readiness present two patterns of passive acceptance and active participation, they are eager to participate in activities and have a strong desire to explore and learn. Our findings extend beyond existing conception of school readiness, and give greater weight to children's interests and strengths, positive experiences and active participation. It is important to focus on children's intrinsic interests and strengths, accept children's ideas and choices, care for their emotional state and provide positive support.
Cytology Is No Longer ‘Just Cytology’: The Clear Message of the XII. Congress of Molecular Cytopathology in Naples
Authors: Ryška Aleš
Published: October 2024

The editorial summarises the key messages of the very successful XII. Congress of Molecular Cytopathology in Naples. The programme of this meeting covered many burning issues from all areas of cytology—from molecular testing to the role of liquid biopsy to the unification of terminology and its impact on patient management.
iGlarLixi effectively reduces residual hyperglycaemia in Chinese people with type 2 diabetes on basal insulin: A post hoc analysis of the LixiLan‐L‐CN study
Authors: Yuan Xiaoyong , Li Dongmei , Wang Kun , Lauand Felipe , Zhang Minlu , Fang Hexin , Du Qin , Kang Lei , Alvarez Agustina , Guo Xiaohui
Published: October 2024

Aim

To compare the effects of iGlarLixi versus insulin glargine 100 U/mL (iGlar) on residual hyperglycaemia in Chinese people with uncontrolled type 2 diabetes (T2D) on prior basal insulin (BI) therapy ± oral antidiabetic drugs in the LixiLan‐L‐CN study (NCT03798080).

Materials and Methods

In this post hoc analysis, residual hyperglycaemia (i.e. HbA1c ≥ 7.0% [≥ 53 mmol/mol] and fasting plasma glucose [FPG] < 7.0 mmol/L) were assessed over 30 weeks. Outcomes were assessed at week 30 in participants with baseline residual hyperglycaemia, including changes from baseline in HbA1c, FPG, 2‐hour postprandial glucose (PPG) and daily BI dose, the proportion of participants with HbA1c less than 7.0% (< 53 mmol/mol) and FPG less than 7.0 mmol/L and the incidence of hypoglycaemia.

Results

Of 421 participants, 124 (29.5%) had baseline residual hyperglycaemia (iGlarLixi, n = 64 [31.7%]; iGlar, n = 60 [29.1%]). At week 30, the residual hyperglycaemia rate decreased to 7.0% with iGlarLixi and increased to 43.3% with iGlar. Among participants with baseline residual hyperglycaemia, a greater proportion achieved both HbA1c and FPG targets at week 30 with iGlarLixi versus iGlar (43.8% vs. 16.7%), and iGlarLixi provided greater reductions in HbA1c (least squares mean [LSM] difference, −0.9% [−9.4 mmol/mol]) and 2‐hour PPG (LSM difference, −4.7 mmol/L; both P < .001). Daily BI dose and incidence of hypoglycaemia were similar in the two groups.

Conclusions

The findings of this post hoc analysis suggest that iGlarLixi had greater benefits than iGlar in reducing the rate of residual hyperglycaemia over 30 weeks in Chinese people with suboptimally controlled T2D on prior BI‐based therapy.
Glycaemic sugar metabolism and the gut microbiota: past, present and future
Authors: Westerbeke Florine H. M. , Attaye Ilias , Rios‐Morales Melany , Nieuwdorp Max
Published: October 2024

Non‐communicable diseases (NCDs), such as type 2 diabetes (T2D) and metabolic dysfunction‐associated fatty liver disease, have reached epidemic proportions worldwide. The global increase in dietary sugar consumption, which is largely attributed to the production and widespread use of cheap alternatives such as high‐fructose corn syrup, is a major driving factor of NCDs. Therefore, a comprehensive understanding of sugar metabolism and its impact on host health is imperative to rise to the challenge of reducing NCDs. Notably, fructose appears to exert more pronounced deleterious effects than glucose, as hepatic fructose metabolism induces de novo lipogenesis and insulin resistance through distinct mechanisms. Furthermore, recent studies have demonstrated an intricate relationship between sugar metabolism and the small intestinal microbiota (SIM). In contrast to the beneficial role of colonic microbiota in complex carbohydrate metabolism, sugar metabolism by the SIM appears to be less beneficial to the host as it can generate toxic metabolites. These fermentation products can serve as a substrate for fatty acid synthesis, imposing negative health effects on the host. Nevertheless, due to the challenging accessibility of the small intestine, our knowledge of the SIM and its involvement in sugar metabolism remains limited. This review presents an overview of the current knowledge in this field along with implications for future research, ultimately offering potential therapeutic avenues for addressing NCDs.
How Do Australians Manage Diagnostic Testing Risks? Focus Groups Linked to a Model of Behaviour Change
Authors: Rozbroj Tomas , Parker Catriona , Haas Romi , Wallis Jason A. , Buchbinder Rachelle , O'Connor Denise A.
Published: October 2024

Background

Diagnostic tests carry significant risks, and communications are needed to help lay people consider these. The development of communications has been hindered by poor knowledge about how lay people understand and negotiate testing risks. We examined lay Australians' perceptions of diagnostic testing risks and how these risks are managed.

Method

We completed 12 semistructured online focus groups with 61 Australian adults (18+) between April and June 2022. Participants were divided into younger/older (> 50 years) and male/female groups. Using semistructured discussion and exploring two hypothetical scenarios, we examined attitudes to diagnostic tests, their risks and how test risks were managed. Themes were identified, subanalysed to identify age and gender differences and mapped to the COM‐B model of behaviour change.

Results

The six themes provided detailed accounts of how participants considered themselves able, empowered and assertive when negotiating testing risks and of complex ways in which relationships with health workers, personal experiences and structural factors influenced negotiating testing risks. COM‐B identified multiple opportunities for leveraging these lay beliefs in health promotion. It also identified barriers, including narrow concepts of testing risks, challenges during shared decision‐making and overestimation of personal influence on testing decisions.

Significance

Our findings matter because they are a novel, detailed account of testing risk beliefs, linked to a model for behaviour change. This will directly inform development of test risk/benefit communications, which are a research priority.

Public Contribution

The study design enabled participants to influence the discussion agenda, and they could comment on the analysis. Participants contributed insights about their needs, beliefs and experiences related to medical testing, and these will be used to shape future patient‐centred decision tools.
Deep learning predicted perceived age is a reliable approach for analysis of facial ageing: A proof of principle study
Authors: Turner Conor , Pardo Luba M. , Gunn David A. , Zillmer Ruediger , Mekić Selma , Liu Fan , Ikram M. Arfan , Klaver Caroline C. W. , Croll Pauline H. , Goedegebure André , Trajanoska Katerina , Rivadeneira Fernando , Kavousi Maryam , Brusselle Guy G. O. , Kayser Manfred , Nijsten Tamar , Bacardit Jaume
Published: October 2024

Background

Perceived age (PA) has been associated with mortality, genetic variants linked to ageing and several age‐related morbidities. However, estimating PA in large datasets is laborious and costly to generate, limiting its practical applicability.

Objectives

To determine if estimating PA using deep learning‐based algorithms results in the same associations with morbidities and genetic variants as human‐estimated perceived age.

Methods

Self‐supervised learning (SSL) and deep feature transfer (DFT) deep learning (DL) approaches were trained and tested on human‐estimated PAs and their corresponding frontal face images of middle‐aged to elderly Dutch participants (n = 2679) from a population‐based study in the Netherlands. We compared the DL‐estimated PAs with morbidities previously associated with human‐estimated PA as well as genetic variants in the gene MC1R; we additionally tested the PA associations with MC1R in a new validation cohort (n = 1158).

Results

The DL approaches predicted PA in this population with a mean absolute error of 2.84 years (DFT) and 2.39 years (SSL). In the training–test dataset, we found the same significant (p < 0.05) associations for DL PA with osteoporosis, ARHL, cognition, COPD and cataracts and MC1R, as with human PA. We also found a similar but less significant association for SSL and DFT PAs (0.69 and 0.71 years per allele,p = 0.008 and 0.011, respectively) with MC1R variants in the validation dataset as that found with human, SSL and DFT PAs in the training–test dataset (0.79, 0.78 and 0.71 years per allele respectively; allp < 0.0001).

Conclusions

Deep learning methods can automatically estimate PA from facial images with enough accuracy to replicate known links between human‐estimated perceived age and several age‐related morbidities. Furthermore, DL predicted perceived age associated with MC1R gene variants in a validation cohort. Hence, such DL PA techniques may be used instead of human estimations in perceived age studies thereby reducing time and costs.
Hand eczema and changes in the skin microbiome after 2 weeks of topical corticosteroid treatment
Authors: Nørreslet Line Brok , Ingham Anna Cäcilia , Agner Tove , Olesen Caroline Meyer , Bregnhøj Anne , Sommerlund Mette , Andersen Paal Skytt , Stegger Marc , Mørtz Charlotte Gotthard , Edslev Sofie Marie
Published: October 2024

Background

More than 50% of patients with hand eczema (HE) are colonized with Staphylococcus aureus. Comprehensive knowledge of the skin microbiome and its changes in patients with HE may provide insights into future potential therapeutical targets.

Objective

To describe the skin microbiome in patients with moderate‐to‐severe chronic HE and assess its changes following treatment with topical corticosteroids (TCS).

Methods

Bacterial samples were collected from lesional and nonlesional skin before and after 2 weeks of TCS treatment using ESwabs and analysed by 16S rRNA and tuf gene sequencing. Clinically, the disease severity was assessed by the Hand Eczema Severity Index (HECSI).

Results

A cohort of 31 patients with HE were included and followed up. Compared to nonlesional skin, lesional skin differed in overall bacterial community composition (p = 0.02), displayed higher relative abundance of Staphylococcus, in particular S. aureus (p = 0.01) and lower abundance of Micrococcus (p = 0.02). As disease severity improved with treatment, these microbial characteristics on lesional skin shifted towards that of nonlesional skin on the hands.

Conclusion

The bacterial skin microbiome was altered in lesions of HE and partly driven by S. aureus colonization, however, shifted towards nonlesional skin following treatment. Our results emphasize the future possibilities for anti‐S. aureus treatment strategies.
Effect of evidence‐based nursing practices on individualised care: A cross‐sectional descriptive study
Authors: Ozdemir Cevriye , Sendir Merdiye , Eren Rabia , Bakir Gizem Kubat , Kizil Hamiyet
Published: October 2024

Aim

This study was conducted to determine the effect of nurses' attitudes towards evidence‐based practices on individualised nursing care.

Methods

This study is a cross‐sectional descriptive trial. The descriptive analysis included 200 clinical nurses working in a private hospital between April and September 2022. Data were collected with a personal information form, Individualised Care Scale (A‐Nurse Version), and Evidence‐Based Nursing Attitude Questionnaire. The relationship between the scales and effect was examined by Pearson correlation and linear regression analyses. T‐test, one‐way analysis of variance (ANOVA), and post hoc (Tukey, LSD) analysis were used in the statistical analysis of nurses according to their descriptive characteristics. This study has adhered to the STROBE checklist for reporting.

Results

They had high mean scores on Individualised Care Scale total (3.68 ± 1.25) and from Clinical Situation (3.78 ± 1.30) and Decisional Control (3.82 ± 1.35) subscales and average score from the Personal Life (3.32 ± 1.29) subscale. Their mean score from the Evidence‐Based Nursing Attitude Questionnaire was average (47.64 ± 10.99). There was a positive moderate (r = 0.50, p = 0.000 < 0.05) significant correlation between the scales.

Conclusion

Positive attitude towards evidence‐based nursing practices positively affects individualised care. Variables such as professional experience positively affect nurses' attitudes towards evidence‐based nursing. A positive and significant relationship was found between nurses' attitudes towards evidence‐based practice and their attitudes towards individualised care.
Best Before? Expiring Central Bank Digital Currency and Loss Recovery
Authors: KAHN CHARLES M. , VAN OORDT MAARTEN R.C. , ZHU YU
Published: October 2024

Physical cash enables payments in the absence of electricity or network coverage. Such offline payment functionality promotes the operational resilience and, particularly in developing countries, the accessibility of payments. Central banks are exploring issuing digital cash substitutes with similar offline payment functionality. Such substitutes could incorporate novel features, making them more desirable than physical cash. This paper considers automating personal loss recovery for offline digital currency balances through the introduction of an expiry date. Our results show this functionality could have a substantial positive impact on consumer demand for offline digital currency balances. We find an asymmetric impact on welfare of adjustments to the expiry date: small increases from the optimum cause little damage, but small decreases from the optimal expiry date can have a large negative impact. More information‐sharing between user devices and the central bank can improve loss recovery but has an ambiguous impact on social welfare.