bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of Dementia in Minority Ethnic Groups in Scotland
Authors: Tsai Somying , Ma Shuning , Nielsen Thomas Rune , Calia Clara 
Published: February 2024

Objective:
Minority ethnic groups (MEGs) in Europe receive suboptimal dementia evaluation, yet related research in Scotland is lacking. This research examined the evaluation of dementia in MEGs in Scotland and compared it with previous research to highlight the changes in the clinical evaluation of dementia over the decade.

Design and Setting:
A self-administered survey was created online and emailed to 14 Heads of the boards under the Scottish National Health Service and dementia-associated settings and organizations.

Results:
Most surveyed centers (85.6%) received MEG referrals. Although 92.9% of the centers used professional translators when needed, 85.7% thought assessing dementia in MEGs was difficult, mostly due to the suitability of test instruments and rating scales and patients’ linguistic abilities. Very few found their skills to be good in evaluating MEGs. There was no mention of specialized dementia services for MEGs.

Conclusions:
The lack of culturally appropriate instruments and specialized dementia services reveals that the services are not ready to meet the demand for evaluating patients from diverse cultural and language backgrounds. Inadequate clinical evaluation may lead to misdiagnoses. Therefore, although significant work has been carried out in the past few years, improvements must be continued to enhance the current practices and apply suitable evaluation methods for MEGs.
Climate change and its effects on body size and shape: the role of endocrine mechanisms
Authors: Names Gabrielle R. , Grindstaff Jennifer L. , Westneat David F. , Heidinger Britt J. 
Published: February 2024

In many organisms, rapidly changing environmental conditions are inducing dramatic shifts in diverse phenotypic traits with consequences for fitness and population viability. However, the mechanisms that underlie these responses remain poorly understood. Endocrine signalling systems often influence suites of traits and are sensitive to changes in environmental conditions; they are thus ideal candidates for uncovering both plastic and evolved consequences of climate change. Here, we use body size and shape, a set of integrated traits predicted to shift in response to rising temperatures with effects on fitness, and insulin-like growth factor-1 as a case study to explore these ideas. We review what is known about changes in body size and shape in response to rising temperatures and then illustrate why endocrine signalling systems are likely to be critical in mediating these effects. Lastly, we discuss research approaches that will advance understanding of the processes that underlie rapid responses to climate change and the role endocrine systems will have. Knowledge of the mechanisms involved in phenotypic responses to climate change will be essential for predicting both the ecological and the long-term evolutionary consequences of a warming climate.
This article is part of the theme issue ‘Endocrine responses to environmental variation: conceptual approaches and recent developments’.
Costs of molecular adaptation to the chemical exposome: a focus on xenobiotic metabolism pathways
Authors: Tomkiewicz Céline , Coumoul Xavier , Nioche Pierre , Barouki Robert , Blanc Etienne B. 
Published: February 2024

Organisms adapt to their environment through different pathways. In vertebrates, xenobiotics are detected, metabolized and eliminated through the inducible xenobiotic-metabolizing pathways (XMP) which can also generate reactive toxic intermediates. In this review, we will discuss the impacts of the chemical exposome complexity on the balance between detoxication and side effects. There is a large discrepancy between the limited number of proteins involved in these pathways (few dozens) and the diversity and complexity of the chemical exposome (tens of thousands of chemicals). Several XMP proteins have a low specificity which allows them to bind and/or metabolize a large number of chemicals. This leads to undesired consequences, such as cross-inhibition, inefficient metabolism, release of toxic intermediates, etc. Furthermore, several XMP proteins have endogenous functions that may be disrupted upon exposure to exogenous chemicals. The gut microbiome produces a very large number of metabolites that enter the body and are part of the chemical exposome. It can metabolize xenobiotics and either eliminate them or lead to toxic derivatives. The complex interactions between chemicals of different origins will be illustrated by the diverse roles of the aryl hydrocarbon receptor which binds and transduces the signals of a large number of xenobiotics, microbiome metabolites, dietary chemicals and endogenous compounds.
This article is part of the theme issue ‘Endocrine responses to environmental variation: conceptual approaches and recent developments’.
Modeling Normal Mouse Uterine Contraction and Placental Perfusion with Non-invasive Longitudinal Dynamic Contrast Enhancement MRI
Authors: Cortes Devin Raine Everaldo , Stapleton Margaret C. , Schwab Kristina E. , West Dalton , Coulson Noah W. , O’Donnell Mary Gemmel , Powers Robert W. , Wu Yijen L. 
Published: February 2024

ABSTRACTThe placenta is a transient organ critical for fetal development. Disruptions of normal placental functions can impact health throughout an individual’s entire life. Although being recognized by the NIH Human Placenta Project as an important organ, the placenta remains understudied, partly because of a lack of non-invasive tools for longitudinally evaluation for key aspects of placental functionalities. Non-invasive imaging that can longitudinally probe murine placental healthin vivoare critical to understanding placental development throughout pregnancy. We developed advanced imaging processing schemes to establish functional biomarkers for non-invasive longitudinal evaluation of placental development. We developed a dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) pipeline combined with advanced image process methods to model uterine contraction and placental perfusion dynamics. Our novel imaging pipeline uses subcutaneous administration of gadolinium for steepest-slope based perfusion evaluation. This enables non-invasive longitudinal monitoring. Additionally, we advance the placental perfusion chamber paradigm with a novel physiologically-based threshold model for chamber localization and demonstrate spatially varying placental chambers using multiple functional metrics that assess mouse placental development and continuing remodeling throughout gestation. Lastly, using optic flow to quantify placental motions arisen from uterine contractions in conjunction with time-frequency analysis, we demonstrated that the placenta exhibited asymmetric contractile motion.
Formation of a giant unilocular vacuole via macropinocytosis-like process confers anoikis resistance
Authors: Kim Jeongsik , Kim Dahyun , Kim Dong-Kyun , Lee Sang-Hee , Jang Wonyul , Lim Dae-Sik 
Published: February 2024

AbstractCell survival in metazoans depends on cell attachment to the extracellular matrix (ECM) or to neighboring cells. Loss of such attachment triggers a type of programmed cell death known as anoikis, the acquisition of resistance to which is a key step in cancer development. The mechanisms underlying anoikis resistance remain unclear, however. The intracellular F-actin cytoskeleton plays a key role in sensing the loss of cell-ECM attachment, but how its disruption affects cell fate during such stress is not well understood. Here, we reveal a cell survival strategy characterized by the formation of a giant unilocular vacuole (GUVac) in the cytoplasm of the cells whose actin cytoskeleton is disrupted during loss of matrix attachment. Time-lapse imaging and electron microscopy showed that large vacuoles with a diameter of >500 nm accumulated early after inhibition of actin polymerization in cells in suspension culture, and that these vacuoles subsequently coalesced to form a GUVac. GUVac formation was found to result from a variation of a macropinocytosis-like process, characterized by the presence of inwardly curved membrane invaginations. This phenomenon relies on both F-actin depolymerization and the recruitment of septin proteins for micron-sized plasma membrane invagination. The vacuole fusion step during GUVac formation requires PI(3)P produced by VPS34 and PI3K-C2α on the surface of vacuoles. Furthermore, its induction after loss of matrix attachment conferred anoikis resistance. Our results thus show that the formation of a previously unrecognized organelle promotes cell survival in the face of altered actin and matrix environments.
Germinal center BCR maturation in appendicitis reveals a role for antigen-specific adaptive immune responses during disease
Authors: Stewart Emma , Taghvaei Zainab , Leon Carmen , Shapiro Jason , Zhu Lisha , Alpert Lindsay , Turaga Kiran , Chowdhury Roshni Roy 
Published: February 2024

AbstractAppendicitis is one of the most common abdominal emergencies globally, yet little is understood about the inflammatory mechanisms or potential drivers of disease. Neutrophil inflammation and increased cytokine expression such as IL-6 and IL-8 are hallmarks of appendicitis inflammation. However, early histological studies identified increased T and B cell infiltration during appendicitis, providing support for adaptive immune activation as well, although this has never been investigated in depth. We hypothesized that antigen-dependent activation of the adaptive immune response contributes to appendicitis pathology, in addition to the known innate-mediated processes. Via a series of transcriptomic approaches and lymphocyte repertoire analysis in human appendiceal tissue, we identified evidence of antigen-dependent B cell activation. Increased somatic hypermutation in the germinal center and plasma cell compartment was comprised of presumed high-affinity IgG and IgA B cells. We propose that the appendiceal microbiome acts as a source of antigen, as significant microbial dysbiosis was observed during appendicitis. This dysbiosis was characterized by outgrowth of pathobionts such asParvimonasand oral biofilm-formers such asFretibacteriumandFusobacterium, in line with previous reports. We also identified potential loss of epithelial barrier integrity via spatial transcriptomic analysis of the appendiceal epithelium, supporting the possibility of microbial invasion into the tissue during appendicitis. This study provides insight into the inflammatory mechanisms of a common disease and helps to define the immune and microbial compartment of an often-ignored organ, the appendix.
Hyper-diverse antigenic variation and resilience to transmission-reducing intervention in falciparum malaria
Authors: Zhan Qi , He Qixin , Tiedje Kathryn E. , Day Karen P. , Pascual Mercedes 
Published: February 2024

AbstractIntervention against falciparum malaria in high transmission regions remains challenging, with relaxation of control efforts typically followed by rapid resurgence. Resilience to intervention co-occurs with incomplete immunity, whereby children eventually become protected from severe disease but not infection and a large transmission reservoir results from high asymptomatic prevalence across all ages. Incomplete immunity relates to the vast antigenic variation of the parasite, with the major surface antigen of the blood stage of infection encoded by the multigene family known asvar. Recent deep sampling ofvarsequences from individual isolates in northern Ghana showed that parasite population structure exhibited persistent features of high-transmission regions despite the considerable decrease in prevalence during transient intervention with indoor residual spraying (IRS). We ask whether despite such apparent limited impact, the transmission system had been brought close to a transition in both prevalence and resurgence ability. With a stochastic agent-based model, we investigate the existence of such a transition to pre-elimination with intervention intensity, and of molecular indicators informative of its approach. We show that resurgence ability decreases sharply and nonlinearly across a narrow region of intervention intensities in model simulations, and identify informative molecular indicators based onvargene sequences. Their application to the survey data indicates that the transmission system in northern Ghana was brought close to transition by IRS. These results suggest that sustaining and intensifying intervention would have pushed malaria dynamics to a slow-rebound regime with an increased probability of local parasite extinction.One Sentence SummaryPopulation genomics of hyper-diversevargenes inform resurgence dynamics in falciparum malaria.
Self-supervised Learning for Chest CT - Training Strategies and Effect on Downstream Applications
Authors: Tariq Amara , Patel Bhavik N. , Banerjee Imon 
Published: February 2024

AbstractSelf-supervised pretraining can reduce the amount of labeled training data needed by pre-learning fundamental visual characteristics of the medical imaging data. In this study, we investigate several self-supervised training strategies for chest computed tomography exams and their effects of downstream applications. we bench-mark five well-known self-supervision strategies (masked image region prediction, next slice prediction, rotation prediction, flip prediction and denoising) on 15M chest CT slices collected from four sites of Mayo Clinic enterprise. These models were evaluated for two downstream tasks on public datasets; pulmonary embolism (PE) detection (classification) and lung nodule segmentation. Image embeddings generated by these models were also evaluated for prediction of patient age, race, and gender to study inherent biases in models’ understanding of chest CT exams. Use of pretraining weights, especially masked regions prediction based weights, improved performance and reduced computational effort needed for downstream tasks compared to task-specific state-of-the-art (SOTA) models. Performance improvement for PE detection was observed for training dataset sizes as large aswith maximum gain of 5% over SOTA. Segmentation model initialized with pretraining weights learned twice as fast as randomly initialized model. While gender and age predictors built using self-supervised training weights showed no performance improvement over randomly initialized predictors, the race predictor experienced a 10% performance boost when using self-supervised training weights. We released models and weights under open-source academic license. These models can then be finetuned with limited task-specific annotated data for a variety of downstream imaging tasks thus accelerating research in biomedical imaging informatics.
Endothelial PHD2 deficiency induces apoptosis resistance and inflammation via AKT activation and AIP1 loss independent of HIF2α
Authors: Wang Shuibang , Awad Keytam S. , Chen Li-Yuan , Siddique Mohammad A. H. , Ferreyra Gabriela A. , Wang Caroline L. , Joseph Thea , Yu Zu-Xi , Takeda Kazuyo , Demirkale Cumhur Y. , Zhao You-Yang , Elinoff Jason M. , Danner Robert L. 
Published: February 2024

ABSTRACTBACKGROUNDIn hypoxic and pseudohypoxic rodent models of pulmonary arterial hypertension (PAH), hypoxia-inducible factor (HIF) inhibition reduces disease severity. However, HIF activation alone, due to genetic alterations or use of inhibitors of prolyl hydroxylase domain (PHD) enzymes, has not been definitively shown to cause PAH in humans, indicating the involvement of other mechanisms.METHODSPseudohypoxia was investigated in primary human lung endothelial cells by silencingPHD2,and inTie2-Cre/Phd2knockout mice, a rodent model of PAH. Lung vascular endothelial cells from PAH patients, and lung tissue from both SU5416/hypoxia PAH rats and PAH patients, were examined for validation.RESULTSPHD2silencing or inhibition, while activating HIF2α, induces apoptosis-resistance, hypo-proliferation, and IFN/STAT activation in endothelial cells, independent of HIF signaling. Mechanistically, PHD2 deficiency activates AKT and ERK, inhibits JNK, and reduces AIP1 (ASK1-interacting protein 1), all independent of HIF2α. Like PHD2,AIP1silencing affects these same kinase pathways and produces a similar dysfunctional endothelial cell phenotype, which can be partially reversed by AKT inhibition. These findings are corroborated in lung tissues of rodent PAH models and pulmonary vascular endothelial cells and tissues from PAH patients.CONCLUSIONSPHD2 deficiency in lung vascular endothelial cells induces an apoptosis-resistant, inflammatory, and hypo-proliferative phenotype. AKT activation and AIP1 loss, but not HIF signaling, drive these aberrant phenotypic changes. Our study suggests that HIF blockade alone may not suffice for PAH therapy; targeting PHD2, AKT, and AIP1 has the potential for developing more effective treatment.GRAPHIC ABSTRACTHighlightsPHD2silencing in human lung vascular endothelial cells suppresses apoptosis, inhibits proliferation, and activates STAT signaling, effects that persist despite HIF2α inhibition or knockdown.PHD2silencing activates AKT and ERK, inhibits JNK, and decreases AIP1, all independently of HIF2αLike PHD2,AIP1silencing led to similar alterations in kinase signaling and endothelial cell phenotypes, which are partially reversed by ATK inhibition.Thesein vitrofindings align with observations in lung vascular endothelial cells and tissues from rodent models of PAH as well as PAH patients.
Phosphoproteomic investigation of targets of protein phosphatases in EGFR signaling
Authors: Eguchi Akihiro , Olsen Jesper V. 
Published: February 2024

AbstractReceptor tyrosine kinases (RTKs) initiate cellular signaling pathways, which are regulated through a delicate balance of phosphorylation anddephosphorylation events. While many studies of RTKs have focused on downstream-activated kinases catalyzing the site-specific phosphorylation, few studies have focused on the phosphatases carrying out thedephosphorylation. In this study, we analyzed six protein phosphatase networks using chemical inhibitors in context of epidermal growth factor receptor (EGFR) signaling by mass spectrometry-based phosphoproteomics. Specifically, we focused on protein phosphatase 2C (PP2C), involved in attenuating p38-dependent signaling pathways in various cellular responses, and confirmed its effect in regulating p38 activity in EGFR signaling. Furthermore, utilizing a p38 inhibitor, we classified phosphosites whose phosphorylation status depends on PP2C inhibition into p38-dependent and p38-independent sites. This study provides a large-scale dataset of phosphatase-regulation of EGF-responsive phosphorylation sites, which serves as a useful resource to deepen our understanding of EGFR signaling.
Structured Peer Review: Pilot results from 23 Elsevier Journals
Authors: Malički Mario , Mehmani Bahar 
Published: February 2024

ABSTRACTBackgroundReviewers rarely comment on the same aspects of a manuscript, making it difficult to properly assess manuscripts’ quality and the quality of the peer review process. It was the goal of this pilot study to evaluate structured peer review implementation by: 1) exploring if and how reviewers answered structured peer review questions, 2) analysing reviewer agreement, 3) comparing that agreement to agreement before implementation of structured peer review, and 4) further enhancing the piloted set of structured peer review questions.MethodsStructured peer review consisting of 9 questions was piloted in August 2022 in 220 Elsevier journals. We randomly selected 10% of these journals across all fields and IF quartiles and included manuscripts that in the first 2 months of the pilot received 2 reviewer reports, leaving us with 107 manuscripts belonging to 23 journals. Eight questions had open ended fields, while the ninth question (on language editing) had only a yes/no option. Reviews could also leaveComments-to-AuthorandComments-to-Editor. Answers were qualitatively analysed by two raters independently.ResultsAlmost all reviewers (n=196, 92%) filled out the answers to all questions even though these questions were not mandatory in the system. The longest answer (Md 27 words, IQR 11 to 68) was for reporting methods with sufficient details for replicability or reproducibility. Reviewers had highest (partial) agreement (of 72%) for assessing the flow and structure of the manuscript, and lowest (of 53%) for assessing if interpretation of results are supported by data, and for assessing if statistical analyses were appropriate and reported in sufficient detail (also 52%). Two thirds of reviewers (n=145, 68%) filled out theComments-to-Authorsection, of which 105 (49%) resembled traditional peer review reports. Such reports contained a Md of 4 (IQR 3 to 5) topics covered by the structured questions. Absolute agreement regarding final recommendations (exact match of recommendation choice) was 41%, which was higher than what those journals had in the period of 2019 to 2021 (31% agreement, P=0.0275).ConclusionsOur preliminary results indicate that reviewers adapted to the new format of review successfully, and answered more topics than they covered in their traditional reports. Individual question analysis indicated highest disagreement regarding interpretation of results and conducting and reporting of statistical analyses. While structured peer review did lead to improvement in reviewer final recommendation agreements, this was not a randomized trial, and further studies should be done to corroborate this. Further research is also needed to determine if structured peer review leads to greater knowledge transfer or better improvement of manuscripts.
Detection of novel influenza viruses through community and healthcare testing: Implications for surveillance efforts in the United States
Authors: Morris Sinead E. , Gilmer Matthew , Threlkel Ryan , Brammer Lynnette , Budd Alicia P. , Iuliano A. Danielle , Reed Carrie , Biggerstaff Matthew 
Published: February 2024

AbstractBackgroundNovel influenza viruses pose a potential pandemic risk and rapid detection of infections in humans is critical to characterizing the virus and facilitating the implementation of public health response measures.MethodsWe use a probabilistic framework to estimate the likelihood that novel influenza virus cases would be detected through testing in different community and healthcare settings (urgent care, emergency department, hospital, and intensive care unit (ICU)) while at low frequencies in the United States. Parameters were informed by data on seasonal influenza virus activity and existing testing practices.ResultsIn a baseline scenario reflecting the presence of 100 novel virus infections with similar severity to seasonal influenza viruses, the median probability of detecting at least one infection per month was highest in urgent care settings (72%) and when community testing was conducted at random among the general population (77%). However, urgent care testing was over 15 times more efficient (estimated as the number of cases detected per 100,000 tests) due to the larger number of tests required for community testing. In scenarios that assumed increased clinical severity of novel virus infection, median detection probabilities increased across all healthcare settings, particularly in hospitals and ICUs (up to 100%) where testing also became more efficient.ConclusionsOur results suggest that novel influenza virus circulation is likely to be detected through existing healthcare surveillance, with the most efficient testing setting impacted by the disease severity profile. These analyses can help inform future testing strategies to maximize the likelihood of novel influenza detection.