bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in and characteristics of drug overdose morbidity among pregnant and postpartum individuals in California, 2010-2018
Authors: Goldman-Mellor Sidra , Jensen Jordan , Cruz Shaina Sta , Olfson Mark , Gemmill Alison , Yan Yueqi , Margerison Claire
Published: July 2024

Fatal drug overdoses among pregnant and postpartum individuals have risen dramatically over the past 10 years. Trends in and characteristics of nonfatal drug overdoses in this population, however, remain unknown, despite the importance of this outcome for maternal and infant health. We used statewide, longitudinally linked hospital and emergency department administrative claims data from California to characterize the incidence, trends, drug type involvement, and sociodemographic disparities in pregnancy-associated drug overdose between 2010 and 2019. Generalized linear models accounting for multiple deliveries per individual were used to test for trends; descriptive statistics were used for other study analyses. Of California individuals with a live delivery between 2010 and 2018, approximately 0.2% had a pregnancy-associated drug overdose. Nonfatal overdoses were nearly 60 times more common than fatal overdoses. Incidence of overdoses involving stimulants increased in frequency, while incidence of overdoses involving sedative/hypnotic drugs and psychotropic medications decreased in frequency. Risk of overdose was substantially higher among delivering individuals who were young, non-Hispanic Black, Medicaid patients, or who lived in nonmetropolitan areas. Ongoing public health surveillance of pregnancy-associated nonfatal drug overdose events and clinical interventions to reduce these events are critical for prevention efforts.
Parity, faultlessness and relativism: A response to Wright and Ferrari
Authors: Zeman Dan
Published: July 2024

Crispin Wright and Filippo Ferrari have accused relativism of not accounting for ‘parity’ – the idea that, when we argue over matters of taste, we take our opponents’ opinions to be ‘as good as ours’ from our own committed perspective. In this paper, I show that (i) explaining parity has not been taken to be a desideratum by relativists and thus they cannot be accused of failing to fulfil a promise; (ii) Wright’s and Ferrari’s reasons for claiming that parity should be a desideratum are unconvincing.
Barking up the wrong frog: global prevalence of misdirected amplexus in anuran amphibians
Authors: Soni Shubham P , Apte Vaishnavi , Joshi Pranav , Cyriac Vivek P
Published: July 2024

Reproduction is an energy-expensive life process in many organisms, and accurate conspecific recognition is crucial to successful reproduction. Nonetheless, misdirected attempts at amplexus towards heterospecifics appear to be common in many anuran amphibians. Such reproductive interference can have significant ecological and evolutionary consequences, but its prevalence remains unknown. Here, we compile a global dataset of anuran misdirected amplexus and test how phylogenetic relatedness, ecological niche, breeding phenology, and geography influence the prevalence of anuran misdirected amplexus. We find misdirected amplexus to be significantly higher among more closely related heterospecific pairs than between random pairs, but still occurred between species of different families. Misdirected amplexus was also significantly more common in arboreal and terrestrial anurans, and among species pairs with similar body sizes or with similar microhabitat use. We also show that misdirected amplexus is significantly more common among explosive breeders compared with prolonged breeders and is more prevalent in temperate regions compared with the tropics. Overall, we show that misdirected amplexus among anuran amphibians is not a rare phenomenon and that its prevalence is influenced by evolutionary relatedness, microhabitat use, ecological similarity, and breeding phenology. These interactions have the potential to cause species decline, hence understanding them is crucial.
A case of IgG4-related disease manifesting as a spinal epidural mass
Authors: Chau Hatty Hoi Ting , Lo Bill Archie , Chu Wai Pong , Ho Ho Nam , Tsui Wilson Man-shan
Published: July 2024

IgG4-related disease is an immune-mediated fibroinflammatory condition. Isolated manifestation in the spine as hypertrophic pachymeningitis is very rare and the mass-like lesion on MRI often mimic tumour or infection. Patients would present with symptoms that result from mass effect or neurovascular compression. Studies showed that serum and CSF IgG4 levels are rarely informative, and therefore, tissue biopsy is crucial for accurate diagnosis. Apart from supporting the diagnosis, MRI is helpful in delineating the extent of disease and follow-up after treatment. A 18F-FDG PET/CT scan is useful in detecting systemic manifestations of IgG4-related disease. Although IgG4-related disease generally responds well to corticosteroid at inflammatory state, relapse is not uncommon. Current treatment strategies for IgG4-related hypertrophic pachymeningitis are high dose corticosteroid therapy and early decompressive surgery to avoid chronic neurological complications. We described a case of a 27-year-old gentleman complaining of lower limb weakness and numbness. MRI showed a mass-like epidural lesion at the thoracic spine causing cord compression. Open biopsy of the epidural mass demonstrated histopathological characteristics of IgG4-related disease. Patient responded well to early surgical decompression of the spinal cord and corticosteroid as evidenced by symptom improvement and resolving mass on subsequent MRI study. However, a follow-up MRI revealed disease recurrence years later.
A prefrontal–habenular circuitry regulates social fear behaviour
Authors: Tian Yuanyuan , Zheng Junqiang , Zhu Xiao , Liu Xue , Li Haoyang , Wang Jun , Yang Qian , Zeng Ling-Hui , Shi Zhiguo , Gong Mengyuan , Hu Yuzheng , Xu Han
Published: July 2024

The medial prefrontal cortex (mPFC) has been implicated in the pathophysiology of social impairments, including social fear. However, the precise subcortical partners that mediate mPFC dysfunction on social fear behaviour have not been identified.

Using a social fear conditioning paradigm, we induced robust social fear in mice and found that the lateral habenula (LHb) neurons and LHb-projecting mPFC neurons are activated synchronously during social fear expression. Moreover, optogenetic inhibition of the mPFC–LHb projection significantly reduced social fear responses. Importantly, consistent with animal studies, we observed an elevated prefrontal–habenular functional connectivity in subclinical individuals with higher social anxiety characterized by heightened social fear.

These results unravel a crucial role of the prefrontal–habenular circuitry in social fear regulation and suggest that this pathway could serve as a potential target for the treatment of social fear symptoms often observed in many psychiatric disorders.
Neural dysfunction underlying working memory processing at different stages of the illness course in schizophrenia: a comparative meta-analysis
Authors: Yao Yuhao , Zhang Shufang , Wang Boyao , Lin Xiaoyong , Zhao Gaofeng , Deng Hong , Chen Ying
Published: July 2024

Schizophrenia, as a chronic and persistent disorder, exhibits working memory deficits across various stages of the disorder, yet the neural mechanisms underlying these deficits remain elusive with inconsistent neuroimaging findings. We aimed to compare the brain functional changes of working memory in patients at different stages: clinical high risk, first-episode psychosis, and long-term schizophrenia, using meta-analyses of functional magnetic resonance imaging studies. Following a systematic literature search, 56 whole-brain task-based functional magnetic resonance imaging studies (15 for clinical high risk, 16 for first-episode psychosis, and 25 for long-term schizophrenia) were included. The separate and pooled neurofunctional mechanisms among clinical high risk, first-episode psychosis, and long-term schizophrenia were generated by Seed-based d Mapping toolbox. The clinical high risk and first-episode psychosis groups exhibited overlapping hypoactivation in the right inferior parietal lobule, right middle frontal gyrus, and left superior parietal lobule, indicating key lesion sites in the early phase of schizophrenia. Individuals with first-episode psychosis showed lower activation in left inferior parietal lobule than those with long-term schizophrenia, reflecting a possible recovery process or more neural inefficiency. We concluded that SCZ represent as a continuum in the early stage of illness progression, while the neural bases are inversely changed with the development of illness course to long-term course.
Polycomb repressive complex 2 is critical for mouse cortical glutamatergic neuron development
Authors: Currey Laura , Mitchell Benjamin , Al-Khalily Majd , McElnea Sarah-Jayne , Kozulin Peter , Harkins Danyon , Pelenyi Alexandra , Fenlon Laura , Suarez Rodrigo , Kurniawan Nyoman D , Burne Thomas H , Harris Lachlan , Thor Stefan , Piper Michael
Published: July 2024

The Polycomb Repressive Complex 2 (PRC2) regulates corticogenesis, yet the consequences of mutations to this epigenetic modifier in the mature brain are poorly defined. Importantly, PRC2 core genes are haploinsufficient and causative of several human neurodevelopmental disorders. To address the role of PRC2 in mature cortical structure and function, we conditionally deleted the PRC2 gene Eed from the developing mouse dorsal telencephalon. Adult homozygotes displayed smaller forebrain structures. Single-nucleus transcriptomics revealed that glutamatergic neurons were particularly affected, exhibiting dysregulated gene expression profiles, accompanied by aberrations in neuronal morphology and connectivity. Remarkably, homozygous mice performed well on challenging cognitive tasks. In contrast, while heterozygous mice did not exhibit clear anatomical or behavioral differences, they displayed dysregulation of neuronal genes and altered neuronal morphology that was strikingly different from homozygous phenotypes. Collectively, these data reveal how alterations to PRC2 function shape the mature brain and reveal a dose-specific role for PRC2 in determining glutamatergic neuron identity.
2024 Clinical Practice Guideline Update by the Infectious Diseases Society of America on Complicated Intra-abdominal Infections: Utility of Blood Cultures in Adults, Children, and Pregnant People
Authors: Bonomo Robert A , Humphries Romney , Abrahamian Fredrick M , Bessesen Mary , Chow Anthony W , Dellinger E Patchen , Edwards Morven S , Goldstein Ellie , Hayden Mary K , Kaye Keith S , Potoski Brian A , Rodríguez-Baño Jesús , Sawyer Robert , Skalweit Marion , Snydman David R , Tamma Pranita D , Pahlke Sarah , Donnelly Katelyn , Loveless Jennifer
Published: July 2024

This article is part of a clinical practice guideline update on the risk assessment, diagnostic imaging, and microbiological evaluation of complicated intra-abdominal infections in adults, children, and pregnant people, developed by the Infectious Diseases Society of America. In this guideline, the panel provides recommendations for obtaining blood cultures in patients with known or suspected intra-abdominal infection. The panel's recommendations are based on evidence derived from systematic literature reviews and adhere to a standardized methodology for rating the certainty of evidence and strength of recommendation according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.
Making a Pathogen? Evaluating the Impact of Protist Predation on the Evolution of Virulence in Serratia marcescens
Authors: Hopkins Heather A , Lopezguerra Christian , Lau Meng-Jia , Raymann Kasie
Published: July 2024

Opportunistic pathogens are environmental microbes that are generally harmless and only occasionally cause disease. Unlike obligate pathogens, the growth and survival of opportunistic pathogens do not rely on host infection or transmission. Their versatile lifestyles make it challenging to decipher how and why virulence has evolved in opportunistic pathogens. The coincidental evolution hypothesis postulates that virulence results from exaptation or pleiotropy, i.e. traits evolved for adaptation to living in one environment that have a different function in another. In particular, adaptation to avoid or survive protist predation has been suggested to contribute to the evolution of bacterial virulence (the training ground hypothesis). Here, we used experimental evolution to determine how the selective pressure imposed by a protist predator impacts the virulence and fitness of a ubiquitous environmental opportunistic bacterial pathogen that has acquired multidrug resistance: Serratia marcescens. To this aim, we evolved S. marcescens in the presence or absence of generalist protist predator, Tetrahymena thermophila. After 60 d of evolution, we evaluated genotypic and phenotypic changes by comparing evolved S. marcescens with the ancestral strain. Whole-genome shotgun sequencing of the entire evolved populations and individual isolates revealed numerous cases of parallel evolution, many more than statistically expected by chance, in genes associated with virulence. Our phenotypic assays suggested that evolution in the presence of a predator maintained virulence, whereas evolution in the absence of a predator resulted in attenuated virulence. We also found a significant correlation between virulence, biofilm formation, growth, and grazing resistance. Overall, our results provide evidence that bacterial virulence and virulence-related traits are maintained by selective pressures imposed by protist predation.
Assessment of unmeasured confounding in the association between perceived discrimination and mental health in a predominantly African American cohort using g-estimation
Authors: Luo Jiajun , Saulsberry Loren , Krakowka William Isaac , Ahsan Habibul , Aschebrook-Kilfoy Briseis
Published: July 2024

Background

Perceived discrimination in health care settings can have adverse consequences on mental health in minority groups. However, the association between perceived discrimination and mental health is prone to unmeasured confounding. The study aims to quantitatively evaluate the influence of unmeasured confounding in this association, using g-estimation.

Methods

In a predominantly African American cohort, we applied g-estimation to estimate the association between perceived discrimination and mental health, adjusted and unadjusted for measured confounders. Mental health was measured using clinical diagnoses of anxiety, depression and bipolar disorder. Perceived discrimination was measured as the number of patient-reported discrimination events in health care settings. Measured confounders included demographic, socioeconomic, residential and health characteristics. The influence of confounding was denoted as α1 from g-estimation. We compared α1 for measured and unmeasured confounding.

Results

Strong associations between perceived discrimination in health care settings and mental health outcomes were observed. For anxiety, the odds ratio (95% confidence interval) unadjusted and adjusted for measured confounders were 1.30 (1.21, 1.39) and 1.26 (1.17, 1.36), respectively. The α1 for measured confounding was –0.066. Unmeasured confounding with α1=0.200, which was over three times that of measured confounding, corresponds to an odds ratio of 1.12 (1.01, 1.24). Similar results were observed for other mental health outcomes.

Conclusion

Compared with measured confounding, unmeasured that was three times measured confounding was not enough to explain away the association between perceived discrimination and mental health, suggesting that this association is robust to unmeasured confounding. This study provides a novel framework to quantitatively evaluate unmeasured confounding.
The Simplicial Coalgebra of Chains Under Three Different Notions of Weak Equivalence
Authors: Raptis George , Rivera Manuel
Published: July 2024

We study the simplicial coalgebra of chains on a simplicial set with respect to three notions of weak equivalence. To this end, we construct three model structures on the category of reduced simplicial sets for any commutative ring $R$. The weak equivalences are given by: (1) an $R$-linearized version of categorical equivalences, (2) maps inducing an isomorphism on fundamental groups and an $R$-homology equivalence between universal covers, and (3) $R$-homology equivalences. Analogously, for any field ${\mathbb{F}}$, we construct three model structures on the category of connected simplicial cocommutative ${\mathbb{F}}$-coalgebras. The weak equivalences in this context are (1′) maps inducing a quasi-isomorphism of dg algebras after applying the cobar functor, (2′) maps inducing a quasi-isomorphism of dg algebras after applying a localized version of the cobar functor, and (3′) quasi-isomorphisms. Building on a previous work of Goerss in the context of (3)–(3′), we prove that, when ${\mathbb{F}}$ is algebraically closed, the simplicial ${\mathbb{F}}$-coalgebra of chains defines a homotopically full and faithful left Quillen functor for each one of these pairs of model categories. More generally, when ${\mathbb{F}}$ is a perfect field, we compare the three pairs of model categories in terms of suitable notions of homotopy fixed points with respect to the absolute Galois group of ${\mathbb{F}}$.
Laboratory capacity expansion: lessons from establishing molecular testing in regional referral laboratories in Ethiopia
Authors: Chekol Leulseged , Waktola Ebba , Nawaz Saira , Tadesse Lehageru , Muluye Samuel , Bonger Zelalem , Bogale Addisu , Eshetu Frehywot , Degefaw Desalegne , Tayachew Adamu , Delelegn Hulemenaw , Daves Sharon , Seyoum Eyasu , Moon Kyle , Melese Daniel , Balada Joan-Miquel , Wang Shu-Hua , Williams Desmond , Gebreyes Wondwossen , Mekuria Zelalem
Published: July 2024

Respiratory viruses contribute to high morbidity and mortality in Africa. In 2020, the Ohio State University's Global One Health Initiative, in collaboration with the Ethiopian Public Health Institute and the US Centers for Disease Control and Prevention, took action to strengthen Ethiopia's existing respiratory virus surveillance system through decentralization of laboratory testing and scale-up of national and regional capacity for detecting respiratory viruses. In August 2022, four regional laboratories were established, thereby raising the number of reference laboratories conducting respiratory virus surveillance to five. This article highlights lessons learned during implementation and outlines processes undertaken for laboratory scale-up and decentralization.
Ruptures in Depiction—Recognition and Political Cartoons of Putin: From a Strategic Mastermind to the Object of Contempt and Mockery
Authors: Kopper Akos
Published: July 2024

This article contributes to discussions over the role of recognition in international relations by focusing on an aspect of popular culture, specifically political cartoons. It argues that studying political cartoons may contribute to capturing aspects of recognition that go beyond those rooted in formal interactions between states and thereby enhance our understanding of what Ringmar called the recognition game. The article focuses on political cartoons about Russia/Putin in two periods. The first is after the annexation of Crimea, while the second is after the outbreak of the war in Ukraine. The tones of caricatures in these two periods differ radically. Images in the first depict a transgressive Putin to be feared. While not necessarily a flattering image, the article argues that this set of images can be interpreted as a form of recognition of Russia being a great power to be reckoned with and could encourage Russia’s reckless moves later. Once we get to the second period, however, there is a rupture. The tone of depiction changes, showing a pathetic, deplorable Putin. These images do not simply convey misrecognition, but convey humiliation, a difference somewhat overlooked by the discipline.
Fair prediction of 2-year stroke risk in patients with atrial fibrillation
Authors: Gao Jifan , Mar Philip , Tang Zheng-Zheng , Chen Guanhua
Published: July 2024

Objective

This study aims to develop machine learning models that provide both accurate and equitable predictions of 2-year stroke risk for patients with atrial fibrillation across diverse racial groups.

Materials and Methods

Our study utilized structured electronic health records (EHR) data from the All of Us Research Program. Machine learning models (LightGBM) were utilized to capture the relations between stroke risks and the predictors used by the widely recognized CHADS2 and CHA2DS2-VASc scores. We mitigated the racial disparity by creating a representative tuning set, customizing tuning criteria, and setting binary thresholds separately for subgroups. We constructed a hold-out test set that not only supports temporal validation but also includes a larger proportion of Black/African Americans for fairness validation.

Results

Compared to the original CHADS2 and CHA2DS2-VASc scores, significant improvements were achieved by modeling their predictors using machine learning models (Area Under the Receiver Operating Characteristic curve from near 0.70 to above 0.80). Furthermore, applying our disparity mitigation strategies can effectively enhance model fairness compared to the conventional cross-validation approach.

Discussion

Modeling CHADS2 and CHA2DS2-VASc risk factors with LightGBM and our disparity mitigation strategies achieved decent discriminative performance and excellent fairness performance. In addition, this approach can provide a complete interpretation of each predictor. These highlight its potential utility in clinical practice.

Conclusions

Our research presents a practical example of addressing clinical challenges through the All of Us Research Program data. The disparity mitigation framework we proposed is adaptable across various models and data modalities, demonstrating broad potential in clinical informatics.
Leveraging GPT-4 for identifying cancer phenotypes in electronic health records: a performance comparison between GPT-4, GPT-3.5-turbo, Flan-T5, Llama-3-8B, and spaCy’s rule-based and machine learning-based methods
Authors: Bhattarai Kriti , Oh Inez Y , Sierra Jonathan Moran , Tang Jonathan , Payne Philip R O , Abrams Zach , Lai Albert M
Published: July 2024

Objective

Accurately identifying clinical phenotypes from Electronic Health Records (EHRs) provides additional insights into patients’ health, especially when such information is unavailable in structured data. This study evaluates the application of OpenAI’s Generative Pre-trained Transformer (GPT)-4 model to identify clinical phenotypes from EHR text in non-small cell lung cancer (NSCLC) patients. The goal was to identify disease stages, treatments and progression utilizing GPT-4, and compare its performance against GPT-3.5-turbo, Flan-T5-xl, Flan-T5-xxl, Llama-3-8B, and 2 rule-based and machine learning-based methods, namely, scispaCy and medspaCy.

Materials and Methods

Phenotypes such as initial cancer stage, initial treatment, evidence of cancer recurrence, and affected organs during recurrence were identified from 13 646 clinical notes for 63 NSCLC patients from Washington University in St. Louis, Missouri. The performance of the GPT-4 model is evaluated against GPT-3.5-turbo, Flan-T5-xxl, Flan-T5-xl, Llama-3-8B, medspaCy, and scispaCy by comparing precision, recall, and micro-F1 scores.

Results

GPT-4 achieved higher F1 score, precision, and recall compared to Flan-T5-xl, Flan-T5-xxl, Llama-3-8B, medspaCy, and scispaCy’s models. GPT-3.5-turbo performed similarly to that of GPT-4. GPT, Flan-T5, and Llama models were not constrained by explicit rule requirements for contextual pattern recognition. spaCy models relied on predefined patterns, leading to their suboptimal performance.

Discussion and Conclusion

GPT-4 improves clinical phenotype identification due to its robust pre-training and remarkable pattern recognition capability on the embedded tokens. It demonstrates data-driven effectiveness even with limited context in the input. While rule-based models remain useful for some tasks, GPT models offer improved contextual understanding of the text, and robust clinical phenotype extraction.
The only purple-flower species in Actaea L. is pollinated by a hornet
Authors: Qiu Lin-Feng , Zhang Jiu-Dong , Li Ying , Liu Xiao-Ying , Zhang Dan-Qing , Huang Long , Yang Ya-Peng , Wang Shi-Yu , Li Yue-Yi , Ma Zi-Wei , Sui Jie , Wang Lin , Che Xiao-Fen , Tian Xian-Hua , Ren Yi , Zhang Jian-Qiang
Published: July 2024

Examining the pollination biology of plant species is not only crucial for enhancing our understanding of their reproductive biology, but also essential for elucidating their adaptation and evolutionary history. Here, we investigated the breeding system and pollination biology of two closely related species in Actaea. The flower of A. purpurea is unique in the genus with purple and chartaceous (paper-like) sepals, fewer stamens with yellow anthers and purple filaments. Through three seasons of field observation and exclusion experiments, we determined that A. purpurea was primarily pollinated by a hornet species, Vespa bicolor, which also served as the most efficient pollinator. In contrast, A. japonica was primarily pollinated by large flies. Actaea purpurea exhibited a significantly higher cumulative nectar volume than A. japonica, which could be a crucial factor in attracting V. bicolor. A control experiment further demonstrated that removing the nectar leaf (petal) significantly decreased the visiting frequency of V. bicolor. Breeding system studies revealed that both species were self-compatible, yet they primarily underwent outcrossing in natural habitats. Our study presents a compelling case of possible pollinator shift in A. purpurea accompanied by morphological divergence. A more in-depth investigation of this system would offer crucial insights into the extent to which pollinators are involved in the plant speciation process and whether they contribute to reproductive isolation between closely related species.
Exploring molecular glioblastoma: Insights from advanced imaging for a nuanced understanding of the molecularly defined malignant biology
Authors: Griessmair Michael , Delbridge Claire , Ziegenfeuter Julian , Jung Kirsten , Mueller Tobias , Schramm Severin , Bernhardt Denise , Schmidt-Graf Friederike , Kertels Olivia , Thomas Marie , Zimmer Claus , Meyer Bernhard , Combs Stephanie E , Yakushev Igor , Wiestler Benedikt , Metz Marie-Christin
Published: July 2024

Background

Molecular glioblastoma (molGB) does not exhibit the histologic hallmarks of a grade 4 glioma but is nevertheless diagnosed as glioblastoma when harboring specific molecular markers. MolGB can easily be mistaken for similar-appearing lower-grade astrocytomas. Here, we investigated how advanced imaging could reflect the underlying tumor biology.

Methods

Clinical and imaging data were collected for 7 molGB grade 4, 9 astrocytomas grade 2, and 12 astrocytomas grade 3. Four neuroradiologists performed VASARI-scoring of conventional imaging, and their inter-reader agreement was assessed using Fleiss κ coefficient. To evaluate the potential of advanced imaging, 2-sample t test, 1-way ANOVA, Mann–Whitney U, and Kruskal–Wallis test were performed to test for significant differences between apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) that were extracted fully automatically from the whole tumor volume.

Results

While conventional VASARI imaging features did not allow for reliable differentiation between glioma entities, rCBV was significantly higher in molGB compared to astrocytomas for the 5th and 95th percentile, mean, and median values (P < .05). ADC values were significantly lower in molGB than in astrocytomas for mean, median, and the 95th percentile (P < .05). Although no molGB showed contrast enhancement initially, we observed enhancement in the short-term follow-up of 1 patient.

Discussion

Quantitative analysis of diffusion and perfusion parameters shows potential in reflecting the malignant tumor biology of molGB. It may increase awareness of molGB in a nonenhancing, “benign” appearing tumor. Our results support the emerging hypothesis that molGB might present glioblastoma captured at an early stage of gliomagenesis.
Nano-laponite encapsulated coaxial fiber scaffold promotes endochondral osteogenesis
Authors: Yuan Li , Wei Jiawei , Xiao Shiqi , Jin Shue , Xia Xue , Liu Huan , Liu Jiangshan , Hu Jiaxin , Zuo Yi , Li Yubao , Yang Fang , Li Jidong
Published: July 2024

Osteoinductive supplements without side effects stand out from the growth factors and drugs widely used in bone tissue engineering. Lithium magnesium sodium silicate hydrate (laponite) nanoflake is a promising bioactive component for bone regeneration, attributed to its inherent biosafety and effective osteoinductivity. Up to now, the in vivo osteogenic potential and mechanisms of laponite-encapsulated fibrous membranes remain largely unexplored. This study presents a unique method for homogeneously integrating high concentrations of laponite RDS into a polycaprolactone (PCL) matrix by dispersing laponite RDS sol into the polymer solution. Subsequently, a core-shell fibrous membrane (10RP-PG), embedding laponite-loaded PCL in its core, was crafted using coaxial electrospinning. The PCL core’s slow degradation and the shell’s gradient degradation enabled the sustained release of bioactive ions (Si and Mg) from laponite. In vivo studies on a critical-sized calvarial bone defect model demonstrated that the 10RP-PG membrane markedly enhanced bone formation and remodeling by accelerating the process of endochondral ossification. Further transcriptome analysis suggested that osteogenesis in the 10RP-PG membrane is driven by Mg and Si from endocytosed laponite, activating pathways related to ossification and endochondral ossification, including Hippo, Wnt and Notch. The fabricated nanocomposite fibrous membranes hold great promise in the fields of critical-sized bone defect repair.
Corticosteroids alter kidney development and increase glomerular filtration rate in larval zebrafish (Danio rerio)
Authors: Heigwer Jana , Steenbergen Petrus J , Gehrig Jochen , Westhoff Jens H
Published: July 2024

Pharmaceutical drugs and other chemicals can impact organogenesis, either during pregnancy or by postnatal exposure of very preterm infants. Corticosteroids are administered to pregnant women at risk of preterm delivery in order to reduce neonatal morbidity and mortality. In addition, high-dose corticosteroid exposure of very preterm infants regularly serves to maintain blood pressure and to prevent and treat bronchopulmonary dysplasia, a form of chronic lung disease in prematurely born infants. Despite clinical benefits, there is increasing evidence of corticosteroid-mediated short- and long-term detrimental developmental effects, especially in the kidney. Here, we performed a detailed morphological and functional analysis of corticosteroid-mediated effects on pronephros development in larval zebrafish. About 24-h postfertilization (hpf) transgenic Tg(wt1b: EGFP) zebrafish larvae were exposed to a set of natural and synthetic corticosteroids (hydrocortisone, dexamethasone, 6α-methylprednisolone, betamethasone, prednisolone, fludrocortisone, 11-deoxycorticosterone) with varying glucocorticoid and mineralocorticoid potency for 24 h at different concentrations. A semiautomated, multiparametric in vivo workflow enabled simultaneous assessment of kidney morphology, renal FITC-inulin clearance, and heart rate within the same larva. All corticosteroids exerted significant morphological and functional effects on pronephros development, including a significant hypertrophy of the pronephric glomeruli as well as dose-dependent increases in FITC-inulin clearance as a marker of glomerular filtration rate. In conclusion, the present study demonstrates a significant impact of corticosteroid exposure on kidney development and function in larval zebrafish. Hence, these studies underline that corticosteroid exposure of the fetus and the preterm neonate should be carefully considered due to potential short- and long-term harm to the kidney.
The impact of diversity statements on age diversity: More than just window-dressing?
Authors: de Saint Priest Oriana , Krings Franciska
Published: July 2024

Many organizations are committed to age diversity and inclusion, aiming for a fair treatment and balanced representation of younger and older employees in all units of the organization. However, the continuing workplace discrimination against mature workers demonstrates that older employees are often excluded and remain underrepresented. Hence, organizations still struggle to reach their diversity goals and finding ways to effectively foster employee behaviors that result in more age diversity is therefore crucial. We investigate the impact of age diversity statements on selecting older and younger individuals into teams in 3 experimental studies. We find consistent evidence that when building teams, short diversity statements increase the selection rates of older individuals so that teams become more age balanced. With no age diversity statement in place, older teammates are hardly chosen, showing that diversity statements can help overcome negative age bias. We found no evidence that age diversity statements produce unintended negative side-effects in terms of increased bias based on dimensions other than age. Overall, this research provides a first examination and encouraging conclusions regarding the effectiveness of age diversity statements, laying the groundwork for more field research in this area.
Migrating Mobile Applications to the Web
Authors: Formella Kyle T. , Borissov Edouard K. , Cordes Karyn , Wright Amy , Klute Ryan M.
Published: July 2024

Nurses and clinicians require knowledge and training of their facilities' code blue response cart to manage emergency scenarios. However, the nurses who access the carts change frequently through turnover and role changes. An augmented reality training solution was built for mobile devices, but encountered distribution and access challenges. This study evaluated the conversion of the mobile application to a desktop-based version deployed via a learning management system. Eight hundred fifty clinicians were assigned the interactive learning product, which collected anonymous usage data and an optional feedback survey within the module. Of 850 assigned users, 468 completed the module, and 338 completed the feedback survey. Respondents indicated a positive difference of 25.3% in retrospective pre/post confidence and an appreciation for the features of the product. Performance measured by decreasing total item search time appeared to level off after three plays. The format transition was successful, allowing the same widespread distribution as the mobile versions of [X]. Feedback gathered will drive improvements in the module.
Concurrent Use of Radiotherapy and Ribociclib
Authors: Bouziane Jihane , Loap Pierre , Cottu Paul , Escalup Laurence , Kirova Youlia
Published: July 2024

Objectives:

In the recent MONALEESA-2, MONALEESA-3, and MONALEESA-7 clinical trials, the addition of ribociclib, a CDK4/6 inhibitor, to standard endocrine therapy significantly improved progression-free survival (PFS) compared with hormone therapy alone in the treatment of locally advanced or metastatic estrogen receptor-positive (ER) and HER2-negative breast cancer. However, its toxicity raises concerns when administered concomitantly with radiotherapy, leading most radiotherapists and medical oncologists to prefer to discontinue Ribociclib during radiotherapy (RT). Although there are insufficient published data on this combination, our preliminary experience with the first 2 patients treated at Institut Curie suggests promising results when using Ribociclib with Letrozole or Fulvestrant concurrently with palliative radiotherapy in the treatment of metastatic breast cancer. Our study aimed to evaluate the safety of combining Ribociclib with palliative radiotherapy in patients with metastatic breast cancer, providing crucial insights for clinical decision-making.

Methods:

A retrospective analysis was conducted on patients treated for hormone receptor-positive metastatic breast cancer with Ribociclib and concurrent radiotherapy at the Institut Curie (Paris, France) between September 2023 and April 2024. Among 38 patients who received Ribociclib and underwent irradiation, 36 temporarily suspended Ribociclib during radiotherapy, while 2 continued Ribociclib concurrently and were included in the analysis. Palliative radiotherapy was administered using volumetric modulated arc therapy, delivering 20 Gy in 5 fractions to bone metastatic sites. Ribociclib was given at 600 mg/day with hormonotherapy. Follow-up was conducted from the last day of RT until the last medical consultation. Toxicities were graded using CTCAE V5.0.

Results:

Two patients received Ribociclib concomitantly with radiotherapy, experiencing pain relief without interruptions in RT. However, Ribociclib treatment was halted in both cases due to grade 3 neutropenia and grade 1 QTc interval prolongation, respectively. One patient had a dose reduction to 400 mg due to neutropenia, with favorable outcomes observed. Both patients continued Ribociclib treatment, with one achieving complete remission and the other partial remission of bone disease. No late toxicities were observed.

Conclusion:

Despite the need for further investigation, our results suggest safety consistent with pivotal trials, advocating for a prospective cooperative data collection initiative to explore this combined strategy further, potentially revolutionizing metastatic breast cancer management.
Cardiac magnetic resonance findings in cardiac amyloidosis
Authors: Dhore-patil Aneesh , Modi Vivek , Gabr El-Moatasem , Bersali Akila , Darwish Amr , Shah Dipan
Published: July 2024

Purpose of review

The purpose of this review is to highlight the increasing importance of cardiac magnetic resonance (CMR) imaging in diagnosing and managing cardiac amyloidosis, especially given the recent advancements in treatment options.

Recent findings

This review emphasizes the crucial role of late gadolinium enhancement (LGE) with phase-sensitive inversion recovery (PSIR) techniques in both diagnosing and predicting patient outcomes in cardiac amyloidosis. The review also explores promising new techniques for diagnosing early-stage disease, such as native T1 mapping and ECV quantification. Additionally, it delves into experimental techniques like diffusion tensor imaging, MR elastography, and spectroscopy.

This review underscores CMR as a powerful tool for diagnosing cardiac amyloidosis, assessing risk factors, and monitoring treatment response. While LGE imaging remains the current best practice for diagnosis, emerging techniques such as T1 mapping and ECV quantification offer promise for improved detection, particularly in early stages of the disease. This has significant implications for patient management as newer therapeutic options become available for cardiac amyloidosis.
Unlocking the therapeutic potential: odyssey of induced pluripotent stem cells in precision cell therapies
Authors: Mohite Popat , Puri Abhijeet , Dave Roshan , Budar Aarati , Munde Shubham , Ghosh Shruti Bagchi , Alqahtani Taha , Shmrany Humood Al , Kumer Ajoy , Dhara Bikram
Published: July 2024

This review explores the application of induced pluripotent stem cells (iPSCs) in regenerative medicine. The therapeutic significance of iPSC-derived cell therapy within regenerative medicine, emphasizes their reprogramming process and crucial role in cellular differentiation while setting the purpose and scope for the comprehensive exploration of iPSC-derived cell therapy. The subsequent sections intricately examine iPSC-derived cell therapy, unraveling the diverse derivatives of iPSCs and striking a delicate balance between advantages and limitations in therapeutic applications. Mechanisms of action, revealing how iPSC-derived cells seamlessly integrate into tissues, induce regeneration, and contribute to disease modeling and drug screening advancements is discussed. The analysis extends to clinical trials, shedding light on outcomes, safety considerations, and ethical dimensions. Challenges and concerns, including the risk of tumorigenesis and scalability issues, are explored. The focus extends to disease-specific applications, showcasing iPSC-derived cell therapy as a promising avenue for various medical conditions, supported by illustrative case studies. Future directions and research needs are outlined, identifying areas for further exploration, safety considerations and potential enhancements that will shape the future landscape of iPSC-derived therapies. In conclusion, this review provides a significant understanding of iPSC-derived cell therapy’s status that contemplates the implications for regenerative medicine and personalized treatment using iPSCs, offering a comprehensive perspective on the evolving field within the confines of a dynamic and promising scientific frontier.
Clinical trials in pulmonary sarcoidosis; what is needed, what is happening and what is next?
Authors: Veltkamp Marcel
Published: July 2024

Purpose of review

There is a clinical unmet need to improve treatment for patients with pulmonary sarcoidosis. Both retrospective and prospective drug trials are hampered by the fact that patients with sarcoidosis are characterized by a heterogeneous presentation and disease course. In this review, an overview is given of different drug trials in pulmonary sarcoidosis with an emphasis on different primary endpoints and the problems related to them.

Recent findings

In recent years, using significant input from patients with sarcoidosis, different task-forces/studies tried to develop a core set of most important outcomes to measure in future studies on treatment of sarcoidosis. Furthermore, at present, three major clinical trials are being conducted on new drugs for treatment of pulmonary sarcoidosis.

Progress has been made to develop a core set of outcomes measures that can be used in making a combined primary endpoint in future drug trials in sarcoidosis.
Management of large head and neck defects in the vessel-depleted neck
Authors: Shehee Lindsey , Bottalico Danielle , Prendes Brandon
Published: July 2024

Purpose of review

Surgery, radiation, and chemotherapy are often utilized in the treatment of head and neck cancer. These treatments can cause extensive scarring within the neck and can limit the viability of recipient vessels for further microvascular reconstruction. Patients with vessel-depleted necks provide a significant challenge for microvascular surgeons and are a topic of much discussion in the field.

Recent findings

While reconstruction in the vessel-depleted neck is an active area of interest, the patient population is rare. Therefore, single institution series with small numbers comprise the majority of published literature. Recent publications describe techniques for identifying adequate recipient vessel options outside of the field of treatment with excellent free flap outcomes. Further, recent summary articles describe techniques for addressing issues with pedicle length that can arise when using vessels that are far from the defect to be reconstructed.

When viable vessel options are available within the treatment field, these recipient vessels can be used with good reliability and free flap success. If in-field recipient vessels are not available, minimal access incisions can be used to identify superficial temporal, angular, contralateral facial, or transverse cervical vessels. Further away from the treatment field, internal mammary vessels can be harvested through open or robotic approaches. If the use of these distant vessels creates issues with pedicle length, interposition vein grafts, arteriovenous (AV) loops, or flow-through flaps can be used to augment vessel length.
Effectiveness of remote ischemic preconditioning in patients undergoing transplant surgery: meta-analysis of randomized control studies
Authors: Abbas Ameer Fadhel , Shahbaz Haania , Gumera Armand , Al-Shammari Ali Saad , Alchamaley Mohanad Mahdey Salih , Hashim Hashim Talib , Abdeltawwab Mohannad , Amin Mahmoud
Published: July 2024

Introduction:

Remote ischemic preconditioning (RIPC) is a phenomenon in which the induction of shortened periods of ischemia prior to surgical procedures within a distant tissue preserves other tissues or organs of concern, such as the liver or kidney in transplant surgery, in the event of prolonged ischemic insults. The authors aim to evaluate the effectiveness of RIPC in patients undergoing transplant surgery, specifically kidney and liver transplants.

Materials and methods:

PubMed, Embase, and Scopus were searched until 19 December 2023 for trials evaluating RIPC in patients undergoing transplant surgery. A total of 9364 search articles were obtained, which yielded 10 eligible studies. Data analysis was done using RevMan 5.4 software. The risk of bias was done using Cochrane risk of bias tool.

Results and discussion:

For graft rejection, the study observed a relative risk of 0.99 (95% CI, 0.49–1.98, P=0.97) from 5 trials, indicating no significant effect of RIPC on graft survival in both kidney and liver transplants. The length of hospital stay also showed no significant decrease for those undergoing RIPC, with mean difference (MD) of -0.58 (95% CI, −1.38 to 0.23, P=0.16). GFR at 1-year post-kidney transplant did not significantly change in the RIPC group compared to controls, as evidenced by an MD of -0.13 (95% CI, −3.79 to 3.54, P=0.95). These results collectively suggest that RIPC may not be effective in reducing patient, or graft, outcomes.
Creation of a Common Framework to Evaluate Initial Registered Nurse Role Competency
Authors: Scortzaru Michelle , Larkin Troy , Luttrell Julianne , Parazin Julia
Published: July 2024

Assessment of initial nursing competency is essential to safe nursing practice yet often focuses on psychomotor skill acquisition. A multistate health system created a competency strategy based on a comprehensive conceptualization of competency using the American Nursing Association scope and standards of nursing practice. This approach allows for the broad application of a standard competency assessment tool across diverse nursing specialties and provides a framework for nursing professional development practitioners to implement in their organizations.
Exploring interaction between genetically predicted body mass index and serum 25-hydroxyvitamin D levels on the odds for psoriasis in UK Biobank and the HUNT Study: A factorial Mendelian randomisation study
Authors: Jenssen Marita , Arora Nikhil , Løset Mari , Åsvold Bjørn Olav , Thomas Laurent , Gangsø Bekkevold Ole-Jørgen , Mai Xiao-Mei , Sun Yi-Qian , Furberg Anne-Sofie , Jorde Rolf , Wilsgaard Tom , Danielsen Kjersti , Brumpton Ben Michael
Published: July 2024

Background

Mendelian randomisation (MR) studies show that higher body mass index (BMI) and lower 25-hydroxyvitamin D (25[OH]D) increase psoriasis risk. The combined effect of these factors has not been explored using factorial MR.

Methods

Using cross-sectional data from UK Biobank (UKB, n=398 404) and the Trøndelag Health Study (HUNT, n=86 648), we calculated polygenic risk scores for BMI and 25(OH)D to estimate odds ratios for psoriasis using 2×2 and continuous factorial MR. We quantified additive interaction by relative excess risk due to interaction (RERI)-estimates. We also performed traditional observational analyses in UKB.

Results

There were 12 207 (3.1%) participants with psoriasis in UKB and 7794 (9.0%) in HUNT. In 2×2 factorial MR, we found no evidence of relative excess risk for psoriasis due to interaction between genetically predicted higher BMI and lower 25(OH)D, neither in UKB (RERI −0.01, 95% confidence interval (CI) −0.08, 0.07) nor in HUNT (RERI −0.04, 95% CI −0.14, 0.06). The same was observed in the continuous factorial MR and observational analyses.

Conclusions

This study did not find evidence of interaction between BMI and 25(OH)D on the risk of psoriasis. Given minor differences in measured BMI and 25(OH)D between groups, small effects may have been undetected.