bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering the temporal transcriptional landscape of human fetal leptomeninges
Authors: Sun Licheng , Liu Ping , Guo Jingjing , Fang Chuantao , Li Li , Liu Yi , Tan Yanfeng , Zhang Wei , Zhao Rui , Zhang Fayong , Xiao Jianbo , Dong Rui , Ma Shaojie , Mei Xinyu , Qi Dashi
Published: December 2024

The leptomeninges play a pivotal role in the central nervous system (CNS), serving both as a barrier and as a conduit for fluid and cellular transport. Despite their critical functions, our understanding of leptomeningeal development and maturation during human embryogenesis remains limited. This study seeks to bridge this gap.

We conducted single-nucleus RNA sequencing on leptomeningeal tissues from eight human embryos, capturing developmental stages from early fetal to late mid-fetal phases. Our bioinformatic analyses encompassed cell type classification, identification of layer-specific markers, mapping of the arachnoid barrier maturation trajectory, and joint analyses with mouse and aged human leptomeningeal scRNA datasets. Key bioinformatic findings were validated through immunostaining in selected samples.

Our study revealed a complex cellular heterogeneity within the developing leptomeninges, identifying distinct subpopulations of fibroblasts, immune cells, and vascular cells. We mapped the transcriptomic dynamics of fibroblast cell types throughout fetal brain development, highlighting a clear maturation process from early fetal to late mid-fetal stages. Comparative analysis with mouse data allowed us to distinguish human-specific layer markers while confirming several conserved markers shared between humans and mice. Joint analysis with aged human datasets identified two unique arachnoid clusters specific to aging leptomeninges. Moreover, we traced the developmental trajectory of the arachnoid barrier, detailing the transcriptomic shifts associated with its gradual formation. Notably, immune cells in early fetal stages were predominantly M2-type macrophages, underscoring a distinctive immune environment. Finally, we explored the molecular interactions between fibroblasts and other cell types, highlighting their coordinated roles in orchestrating leptomeningeal development.

Together, our findings provide a comprehensive overview of the cellular and molecular landscape of the developing human leptomeninges.
Alpha rhythm slowing in temporal lobe epilepsy across scalp EEG and MEG
Authors: Janiukstyte Vytene , Kozma Csaba , Owen Thomas W , Chaudhary Umair J , Diehl Beate , Lemieux Louis , Duncan John S , Rugg-Gunn Fergus , de Tisi Jane , Wang Yujiang , Taylor Peter N
Published: December 2024

EEG slowing is reported in various neurological disorders including Alzheimer’s, Parkinson’s and Epilepsy. Here, we investigate alpha rhythm slowing in individuals with refractory temporal lobe epilepsy compared with healthy controls, using scalp EEG and magnetoencephalography. We retrospectively analysed data from 17 (46) healthy controls and 22 (24) individuals with temporal lobe epilepsy who underwent scalp EEG and magnetoencephalography recordings as part of presurgical evaluation. Resting-state, eyes-closed recordings were source reconstructed using the standardized low-resolution brain electrographic tomography method. We extracted slow 6–9 Hz and fast 10–11 Hz alpha relative band power and calculated the alpha power ratio by dividing slow alpha by fast alpha. This ratio was computed for all brain regions in all individuals. Alpha oscillations were slower in individuals with temporal lobe epilepsy than controls (P<0.05). This effect was present in both the ipsilateral and contralateral hemispheres and across widespread brain regions. Alpha slowing in temporal lobe epilepsy was found in both EEG and magnetoencephalography recordings. We interpret greater slow alpha as greater deviation from health.
Crisaborole 2% ointment as an effective and safe option in mild to moderate atopic dermatitis: data from a pilot study
Authors: Sil Abheek , Sarkar Rashmi , Das Anupam
Published: December 2024

Crisaborole might emerge as a potential long-term therapeutic option in not only paediatric patients, but also adult patients with mild to moderate atopic dermatitis. Our pilot study, carried out on a cohort of Indian patients, emphasizes the safety, reliability and efficacy of this novel molecule on atopic dermatitis.
Audit and Feedback Interventions for Antibiotic Prescribing in Primary Care: A Systematic Review and Meta-analysis
Authors: Xu Alice X T , Brown Kevin , Schwartz Kevin L , Aghlmandi Soheila , Alderson Sarah , Brehaut Jamie C , Brown Benjamin C , Bucher Heiner C , Clarkson Janet , De Sutter An , Francis Nick A , Grimshaw Jeremy , Gunnarsson Ronny , Hallsworth Michael , Hemkens Lars , Høye Sigurd , Khan Tasneem , Lecky Donna M , Leung Felicia , Leung Jeremy , Lindbæk Morten , Linder Jeffrey A , Llor Carl , Little Paul , O’Connor Denise , Pulcini Céline , Ramlackhan Kalisha , Ramsay Craig R , Sundvall Pär-Daniel , Taljaard Monica , Touboul Lundgren Pia , Vellinga Akke , Verbakel Jan Y , Verheij Theo J , Wikberg Carl , Ivers Noah
Published: December 2024

Background

This systematic review evaluates the effect of audit and feedback (A&F) interventions targeting antibiotic prescribing in primary care and examines factors that may explain the variation in effectiveness.

Methods

Randomized controlled trials (RCTs) involving A&F interventions targeting antibiotic prescribing in primary care were included in the systematic review. Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, and ClinicalTrials.gov were searched up to May 2024. Trial, participant, and intervention characteristics were extracted independently by 2 researchers. Random effects meta-analyses of trials that compared interventions with and without A&F were conducted for 4 outcomes: (1) total antibiotic prescribing volume; (2) unnecessary antibiotic initiation; (3) excessive prescription duration, and (4) broad-spectrum antibiotic selection. A stratified analysis was also performed based on study characteristics and A&F intervention design features for total antibiotic volume.

Results

A total of 56 RCTs fit the eligibility criteria and were included in the meta-analysis. A&F was associated with an 11% relative reduction in antibiotic prescribing volume (N = 21 studies, rate ratio [RR] = 0.89; 95% confidence interval [CI]: .84, .95; I2 = 97); 23% relative reduction in unnecessary antibiotic initiation (N = 16 studies, RR = 0.77; 95% CI: .68, .87; I2 = 72); 13% relative reduction in prolonged duration of antibiotic course (N = 4 studies, RR = 0.87 95% CI: .81, .94; I2 = 86); and 17% relative reduction in broad-spectrum antibiotic selection (N = 17 studies, RR = 0.83 95% CI: .75, .93; I2 = 96).

Conclusions

A&F interventions reduce antibiotic prescribing in primary care. However, heterogeneity was substantial, outcome definitions were not standardized across the trials, and intervention fidelity was not consistently assessed.

Clinical Trials Registration. Prospero (CRD42022298297).
The use of SGLT2 inhibitors and GLP-1 receptor agonists in older patients: a debate on approaches in CKD and non-CKD populations
Authors: Liabeuf Sophie , Minutolo Roberto , Floege Jürgen , Zoccali Carmine
Published: December 2024

The management of CKD in older patients presents a significant challenge in modern medicine. As the global population ages, the prevalence of CKD among older adults is increasing, which demands effective and safe treatment strategies. The introduction of sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists has revolutionized the treatment of CKD, offering potential benefits beyond traditional therapies. However, their use in the older population raises essential questions about safety and efficacy, given the unique physiological changes and comorbidities associated with aging. In this CKJ controversy paper, Roberto Minutolo (PRO) and Sophie Liabeuf (CON) debate on the use of SGLT2 inhibitors and GLP-1 receptor agonists in older patients with CKD. Roberto Minutolo advocates the benefits of these medications, highlighting their role in improving cardiovascular outcomes and slowing CKD progression in older patients. He emphasizes the importance of personalized treatment plans based on the patient's cardio-renal risk profile and preferences. In contrast, Sophie Liabeuf expresses concerns about the safety of these drugs in older adults, citing risks such as fractures, acute kidney injury, and urinary tract infections. She argues that treatment decisions should be guided by patient frailty rather than chronological age, as frail individuals are more vulnerable to adverse drug effects. Both contenders agree on the need for more inclusive clinical trials to better understand the impact of these treatments on older populations. While Roberto Minutolo and Sophie Liabeuf present differing perspectives on the use of SGLT2 inhibitors and GLP-1 receptor agonists in older patients with CKD, their views can be seen as complementary rather than strictly opposing. Minutolo's focus on the benefits of these drugs underscores their potential to improve outcomes. Liabeuf's emphasis on caution and the consideration of frailty highlights the need for careful

patient assessment. Both agree on the importance of personalized treatment and the inclusion of older patients in future clinical trials, suggesting a shared goal of optimizing care for this vulnerable population. Their debate underscores the complexity of treatment decisions and the necessity of balancing risks and benefits in managing CKD in older adults.
NRF2 activation in the heart induces glucose metabolic reprogramming and reduces cardiac dysfunction via upregulation of the pentose phosphate pathway
Authors: Zoccarato Anna , Smyrnias Ioannis , Reumiller Christina M , Hafstad Anne D , Chong Mei , Richards Daniel A , Santos Celio X C , Visnagri Asjad , Verma Sharwari , Bromage Daniel I , Zhang Min , Zhang Xiaohong , Sawyer Greta , Thompson Richard , Shah Ajay M
Published: December 2024

Aims

The transcription factor nuclear factor erythroid–derived 2-like 2 (NRF2) is well recognized as a master regulator of antioxidant responses and cytoprotective genes. Previous studies showed that NRF2 enhances the resistance of mouse hearts to chronic haemodynamic overload, at least in part by reducing oxidative stress. Evidence from other tissues suggests that NRF2 may modulate glucose intermediary metabolism but whether NRF2 has such effects in the heart is unclear. Here, we investigate the role of NRF2 in regulating glucose intermediary metabolism and cardiac function during disease stress.

Methods and results

Cardiomyocyte-specific Keap1 knockout (csKeap1KO) mice, deficient in the endogenous inhibitor of NRF2, were used as a novel model of constitutively active NRF2 signalling. Targeted metabolomics and isotopomer analysis were employed in studies with 13C6-glucose in csKeap1KO and wild-type mice. Pharmacological and genetic approaches were utilized in neonatal rat ventricular myocytes (NRVMs) to explore molecular mechanisms. We found that cardiac-specific activation of NRF2 redirected glucose metabolism towards the pentose phosphate pathway (PPP), a branch pathway of glycolysis, and mitigated pressure overload-induced cardiomyocyte death and cardiac dysfunction. Activation of NRF2 also protected against myocardial infarction-induced DNA damage in remote myocardium and cardiac dysfunction. In vitro, knockdown of Keap1 upregulated PPP enzymes and reduced cell death in NRVM subjected to chronic neurohumoral stimulation. These pro-survival effects were abolished by pharmacological inhibition of the PPP or silencing of the PPP rate-limiting enzyme glucose-6-phosphate dehydrogenase. Knockdown of NRF2 in NRVM increased stress-induced DNA damage, which was rescued by supplementing the cells with either nicotinamide adenine dinucleotide phosphate (NADPH) or nucleosides, the two main products of the PPP.

Conclusion

These results indicate that NRF2 regulates cardiac metabolic reprogramming by stimulating the diversion of glucose into the PPP, thereby generating NADPH and providing nucleotides to prevent stress-induced DNA damage and cardiac dysfunction.
The role of artificial intelligence in standardizing global longitudinal strain measurements in echocardiography
Authors: Sveric Krunoslav M , Botan Roxana , Winkler Anna , Dindane Zouhir , Alothman Ghatafan , Cansiz Baris , Fassl Jens , Kaliske Michael , Linke Axel
Published: December 2024

Aims

To evaluate the accuracy and feasibility of artificial intelligence (AI) in left ventricular global longitudinal strain (GLS) analysis as compared to conventional (Manual) and semi-automated (SemiAuto) method in echocardiography (Echo).

Methods and results

GLS validation was performed on 550 standard Echo exams by expert cardiologists. The performance of a beginner cardiologist without experience of GLS analysis was assessed on a subset of 90 exams. The AI employs fully automated view selection, classification, endocardial border tracing, and calculation of GLS from an entire Echo exam, while SemiAuto requires manual chamber view selection, and Manual involves full user input. Interobserver agreement was assessed using the intraclass correlation coefficient (ICC) for all three methods. Agreement of measures included Pearson’s correlation (R) and Bland-Altman analysis [median bias; limits of agreement (LOA)]. With an 89% feasibility the AI showed good agreement with Manual (R = 0.92, bias = 0.7% and LOA: −3.5 to 4.8%) and with SemiAuto (r = 0.90, bias = 0.10% and LOA: −4.5 to 4%). ICCs for GLS were 1.0 for AI, 0.93 for SemiAuto, and 0.80 for Manual. After the 55th analysis, the beginner showed stable time performance with Manual (171 s), contrasting with the consistent performance of SemiAuto (85-69 s) from the beginning. The highest agreement between beginner and expert readers was achieved with AI (R = 1.00), followed by SemiAuto (R = 0.85) and Manual (R = 0.74).

Conclusion

Automated GLS analysis enhances efficiency and accuracy in cardiac diagnostics, particularly for novice users. Integration of automated solutions into routine clinical practice could yield more standardized results.
Intra-operative and post-operative management of conduits for coronary artery bypass grafting: a clinical consensus statement of the European Society of Cardiology Working Group on Cardiovascular Surgery and the European Association for Cardio-Thoracic Surgery Coronary Task Force
Authors: Sandner Sigrid , Antoniades Charalambos , Caliskan Etem , Czerny Martin , Dayan Victor , Fremes Stephen E , Glineur David , Lawton Jennifer S , Thielmann Matthias , Gaudino Mario
Published: December 2024

The structural and functional integrity of conduits used for coronary artery bypass grafting is critical for graft patency. Disruption of endothelial integrity and endothelial dysfunction are incurred during conduit harvesting subsequent to mechanical or thermal injury and during conduit storage prior to grafting, leading to acute thrombosis and early graft failure. Late graft failure, in particular that of vein grafts, is precipitated by progressive atherogenesis. Intra-operative management includes appropriate selection of conduit-specific harvesting techniques and storage solutions. Arterial grafts are prone to vasospasm subsequent to surgical manipulation, and application of intra-operative vasodilatory protocols is critical. Post-operative management includes continuation of oral vasodilator therapy and selection of antithrombotic and lipid-lowering agents to attenuate atherosclerotic disease progression in conduits. In this review, the scientific evidence underlying the key aspects of intra- and post-operative management of conduits for coronary artery bypass grafting is examined. Clinical consensus statements for best clinical practice are provided, and areas requiring further research are highlighted.
Calcific aortic stenosis: omics-based target discovery and therapy development
Authors: Blaser Mark C , Bäck Magnus , Lüscher Thomas F , Aikawa Elena
Published: December 2024

Calcific aortic valve disease (CAVD) resulting in aortic stenosis (AS) is the most common form of valvular heart disease, affecting 2% of those over age 65. Those who develop symptomatic severe AS have an average further lifespan of <2 years without valve replacement, and three-quarters of these patients will develop heart failure, undergo valve replacement, or die within 5 years. There are no approved pharmaceutical therapies for AS, due primarily to a limited understanding of the molecular mechanisms that direct CAVD progression in the complex haemodynamic environment. Here, advances in efforts to understand the pathogenesis of CAVD and to identify putative drug targets derived from recent multi-omics studies [including (epi)genomics, transcriptomics, proteomics, and metabolomics] of blood and valvular tissues are reviewed. The recent explosion of single-cell omics-based studies in CAVD and the pathobiological and potential drug discovery insights gained from the application of omics to this disease area are a primary focus. Lastly, the translation of knowledge gained in valvular pathobiology into clinical therapies is addressed, with a particular emphasis on treatment regimens that consider sex-specific, renal, and lipid-mediated contributors to CAVD, and ongoing Phase I/II/III trials aimed at the prevention/treatment of AS are described.
Analysis of the whole pharyngeal jaw adds nuance to the continental radiation of Neotropical cichlids
Authors: Nicholas Benjamin , López-Fernández Hernán
Published: December 2024

Understanding how continental assemblages have diversified can be difficult as they are products of extinction, biogeographical rearrangements, and changing environments over millions of years. Much of our knowledge of adaptive radiations stems from relatively recent, insular-like systems. However, increasing evidence supports the idea that adaptive radiations have a major role in hyperdiverse continental radiations such as Neotropical cichlids. This primarily riverine group has undergone adaptive diversification into many ecologically, morphologically, and behaviourally complex lineages. Surprisingly, the macroevolutionary patterns of the entire pharyngeal jaw is relatively understudied in Neotropical cichlids. In this study we use microcomputed tomography scans to characterize the entire pharyngeal system across Neotropical cichlids to test for signatures of adaptive radiation. We describe the morphological diversity of the upper and lower pharyngeal jaw, fit models of evolutionary divergence, and measure morphological disparity through time and among clades. Until now, studies of various axes of diversification in Cichlinae found congruent signals of an early burst of divergence in multiple trait dimensions, but we find no evidence of an early burst in the pharyngeal jaws. We find evidence of highly specialized pharyngeal jaws establishing early in the continental radiation and also evidence of recent morphological divergence in the three major tribes of Cichlinae. Our results further highlight the necessity to study adaptively radiating lineages in multiple trait dimensions as some axes of diversification may be otherwise overlooked.
The good, the bad, and the hazardous: comparative genomic analysis unveils cell wall features in the pathogen Candidozyma auris typical for both baker’s yeast and Candida
Authors: Alvarado María , Gómez-Navajas Jesús A , Blázquez-Muñoz María Teresa , Gómez-Molero Emilia , Fernández-Sánchez Sebastián , Eraso Elena , Munro Carol A , Valentín Eulogio , Mateo Estibaliz , de Groot Piet W J
Published: December 2024

The drug-resistant pathogenic yeast Candidozyma auris (formerly named Candida auris) is considered a critical health problem of global importance. As the cell wall plays a crucial role in pathobiology, here we performed a detailed bioinformatic analysis of its biosynthesis in C. auris and related Candidozyma haemuli complex species using Candida albicans and Saccharomyces cerevisiae as references. Our data indicate that the cell wall architecture described for these reference yeasts is largely conserved in Candidozyma spp.; however, expansions or reductions in gene families point to subtle alterations, particularly with respect to β­-1,3-­glucan synthesis and remodeling, phosphomannosylation, β-mannosylation, and glycosylphosphatidylinositol (GPI) proteins. In several aspects, C. auris holds a position in between C. albicans and S. cerevisiae, consistent with being classified in a separate genus. Strikingly, among the identified putative GPI proteins in C. auris are adhesins typical for both Candida (Als and Hyr/Iff) and Saccharomyces (Flo11 and Flo5-like flocculins). Further, 26 putative C. auris GPI proteins lack homologs in Candida genus species. Phenotypic analysis of one such gene, QG37_05701, showed mild phenotypes implicating a role associated with cell wall β-1,3-glucan. Altogether, our study uncovered a wealth of information relevant for the pathogenicity of C. auris as well as targets for follow-up studies.
Gendered Marital Power, Depression, and Cognition Among Older Adults in Mexico
Authors: Quashie Nekehia T , Saenz Joseph L , Sheehan Connor , Lopez Angelica
Published: December 2024

Objectives

As Mexico rapidly ages, population-level cognitive issues and Alzheimer's Disease and Related Dementia (AD/ADRD) are projected to increase. Limited social welfare positions family members-especially spouses- as the main support resource. While past research suggests marital power imbalances relate with increased depression among Mexican older adults, how marital power imbalance relates with cognition and gender differences therein remains understudied. Accordingly, we investigate how perceived marital power relates with cognitive ability with attention to depression and gender.

Methods

We use the 2012, 2015, and 2018 (n = 2,643 heterosexual dyads) waves of the Mexican Health and Aging Study (MHAS) and Actor Partner Interdependence Models (APIM). The APIM allows the cognitive function of each partner to be predicted by their own (actor effects) and partner’s (partner effects) perceived marital power imbalance, evaluates gender differences, and the mediating role of depression.

Results

Own reports of lower baseline marital power were directly negatively associated with subsequent cognition only among husbands. Partners’ baseline reports of marital power showed mixed direct associations with future cognition: husbands’ higher marital power negatively related with wives’ cognition whereas wives’ lower marital power positively related with husbands’ cognition. Wives’ marital power imbalance predicted higher depression in each partner, and both own and partner’s depression related with lower cognition, regardless of gender, suggesting that wives’ marital power imbalance impacts cognition indirectly through depression.

Discussion

Our findings suggest that gendered marital power relations is a novel area for future research in the context of Mexico's aging population, enduring marriages, and entrenched patriarchal structures.
Reclaiming the narrative: countering harmful commercial discourses
Authors: van Schalkwyk May C I , Maani Nason , Hawkins Benjamin , Petticrew Mark , Buse Kent
Published: December 2024

The discourses promoted by powerful commercial actors whose business activities are damaging to health undermine the potential for the transformational changes urgently needed to address pressing public health and environmental threats globally. This piece provides an analysis of corporate discursive practices and the mechanisms through which they contaminate scientific and policy debates and harm public and environmental health. We refer to this phenomenon as ‘discursive pollution’ to reflect the parallels between the effects of informational strategies and the commercial activities of harmful industries. It aims to contribute to the literature on the commercial determinants of health by offering a cross-industry perspective of discursive practices and the contradictions that underpin industry-favourable discourses. We propose how the health community can facilitate the construction of alternative discourses by revealing the contradictions and assumptions underpinning industry-favourable discourses.
Commercial influences on patient and public involvement: a renewed call for research and action
Authors: Hennessy Marita , Fahey Tom , Larkin James
Published: December 2024

Patient and public involvement is increasingly advocated in health policy, research and practice. Patients and people with lived experience, carers and the general public should have a say in how policy is generated, how services are delivered and how research is conducted. Through this perspective article, we hope to stimulate discussion and debate around industry influence in patient and public involvement, specifically pertaining to patient organizations, which often play a key role in patient and public involvement activities. As momentum gathers around patient and public involvement in many countries, it is timely to discuss the nature and extent of commercial influences in such activities, the (un)anticipated consequences of industry–patient interactions, including conflicts of interest and motivated bias, and how we might better manage, or negate, such interactions. Patient and public involvement must be integral to research, policy and practice. While further research is needed to examine the interactions, and consequences of pharmaceutical industry interactions with patients, several practical steps can be taken in the interim. Structures, processes and supports, which are fit for purpose, are needed to ensure independence, power and legitimacy within patient and public involvement activities, and that patient advocates have their voices heard, and ultimately acted upon.
Identification of hub genes and biological pathways related to central post-stroke pain in ischemic stroke
Authors: Liu Fude , Cheng Yawen , Han Xiangning , Zhu Ning , Jiang Shiliang , Li Jiahao , Ma Wenlong , Yu Jia
Published: December 2024

This investigation aims to screen ischemic stroke (IS)-related hub genes of central post-stroke pain (CPSP) from public databases and predict their potential roles through bioinformatics analysis to better interpret CPSP in IS. First, based on differential analysis, Venn analysis, and enrichment analyses, we identified 13 differently expressed genes in CPSP (CPSP-DEGs) related to the TNF signaling pathway, Vascular smooth muscle contraction, and IL-17 signaling pathway. Subsequently, through screening and analysis of the PPI network constructed by the Search Tool for the Retrieval of Interacting Genes (STRING) database, we obtained 3 CPSP-related hub genes (CD163, MMP9, and ARG1). They were all highly expressed in the IS group, exhibiting good diagnostic performance, with area under curve (AUC) value > 0.85. The immune-related analysis demonstrated that the infiltration levels of various immune cells in the IS group and the normal group were substantially different. In addition, by utilizing some online websites, we not only predicted some microRNAs (miRNAs) and transcription factors (TFs) that may target hub genes but also mined small molecular drugs that may target differentially expressed genes (DEGs) in IS. In conclusion, this project first investigated the role of CPSP-related genes in IS and identified 3 hub genes. At the same time, we predicted some miRNAs, TFs, and candidate drugs that may target hub genes. Our research uncovered the potential mechanism of CPSP-related genes in IS from multiple perspectives. Furthermore, it also laid a research foundation for the future study of the mechanisms of IS disease.
Repair of aortic coarctation in neonates less than two kilograms
Authors: Chen Qiang , Fleming Thomas , Caputo Massimo , Stoica Serban , Tometzki Andrew , Parry Andrew
Published: December 2024

OBJECTIVES

A significant number of low-birth-weight neonates are born with aortic coarctation. Previous studies of early operation on these patients have shown a high hospital mortality and recurrence at 1 year. We reviewed our data to ascertain whether modern approaches allow better outcomes for these children.

METHODS

Fourteen patients weighing <2 kg with isolated coarctation between January 2005 and December 2015 were studied by retrospective chart review to ensure >5 years follow-up. All patients underwent extended end-to-side surgical repair. In-hospital and medium-term follow-up data were collected. Data are expressed as median (range).

RESULTS

Weight at the time of surgery was 1.8 (1.5–1.9) kg. There were no deaths, in-hospital or during follow-up. In-hospital stay was 11 (4–47) days. At follow-up of 141 (80–207) months echocardiographic velocity across the repair was 1.6 (0.9–3.8) m/s. Two patients required balloon dilatations for recoarctation including 1 with William’s syndrome who required balloon coarctoplasty followed by stenting. This patient had grossly abnormal vessels at the time of initial surgery with aortic wall thickness >3 mm. There were no central neurological complications. Other complications included vocal cord dysfunction in 1, development of chylothorax requiring prolonged chest drainage in 2, pneumothorax following chest drain removal in 1 and wound dehiscence in 1 patient.

CONCLUSIONS

Neonates below 2 kg can undergo coarctation repair safely with low incidence of recurrence. Waiting for growth in this cohort of patients may not therefore be justified.
Development and confirmation of humanized plasma and epithelial lining fluid exposures of meropenem, cefiderocol and tobramycin in a standardized neutropenic murine pneumonia model
Authors: Fratoni Andrew J , Padgett Alissa M , Roenfanz Hanna F , Duffy Erin M , Nicolau David P
Published: December 2024

Background

Murine pneumonia models play a fundamental role in the preclinical development of novel compounds seeking an indication for the treatment of pneumonia. It is vital that plasma exposures in these models are not used as a surrogate for exposure in pulmonary epithelial lining fluid (ELF). Herein, human-simulated regimens (HSRs) in both plasma and ELF of meropenem, cefiderocol and tobramycin are described in the standardized COMBINE murine neutropenic pneumonia model.

Materials and methods

HSRs were developed in both plasma and ELF for meropenem and cefiderocol as 2 g q8h 3 h infusions, and tobramycin 7 mg/kg 30 min infusion. Pharmacokinetic studies were performed to confirm plasma and ELF exposures in mice that recapitulated %fT > MIC for meropenem and cefiderocol, and fCmax and fAUC0-24 for tobramycin in humans.

Results

Concentration–time profiles and relevant pharmacodynamic exposures for all three compounds were well matched in mice relative to humans. None of the plasma HSRs were able to appropriately humanize the ELF. Thus, modifications of the plasma HSRs were necessary to provide unique HSRs specific to ELF exposure for each compound.

Conclusions

It should not be assumed that lung penetration in mice relative to humans is equivalent. With HSRs confirmed for these three drugs with established clinical use in the treatment of patients with pneumonia, these humanized exposures within the standardized model will allow for back-translation of anticipated efficacy and provide purposeful quantitative benchmarks for cfu/lung assessments for researchers on an international scale.
Establishing best practices in large language model research: an application to repeat prompting
Authors: Gallo Robert J , Baiocchi Michael , Savage Thomas R , Chen Jonathan H
Published: December 2024

Objectives

We aimed to demonstrate the importance of establishing best practices in large language model research, using repeat prompting as an illustrative example.

Materials and Methods

Using data from a prior study investigating potential model bias in peer review of medical abstracts, we compared methods that ignore correlation in model outputs from repeated prompting with a random effects method that accounts for this correlation.

Results

High correlation within groups was found when repeatedly prompting the model, with intraclass correlation coefficient of 0.69. Ignoring the inherent correlation in the data led to over 100-fold inflation of effective sample size. After appropriately accounting for this issue, the authors’ results reverse from a small but highly significant finding to no evidence of model bias.

Discussion

The establishment of best practices for LLM research is urgently needed, as demonstrated in this case where accounting for repeat prompting in analyses was critical for accurate study conclusions.
Ambient artificial intelligence scribes: physician burnout and perspectives on usability and documentation burden
Authors: Shah Shreya J , Devon-Sand Anna , Ma Stephen P , Jeong Yejin , Crowell Trevor , Smith Margaret , Liang April S , Delahaie Clarissa , Hsia Caroline , Shanafelt Tait , Pfeffer Michael A , Sharp Christopher , Lin Steven , Garcia Patricia
Published: December 2024

Objective

This study evaluates the pilot implementation of ambient AI scribe technology to assess physician perspectives on usability and the impact on physician burden and burnout.

Materials and Methods

This prospective quality improvement study was conducted at Stanford Health Care with 48 physicians over a 3-month period. Outcome measures included burden, burnout, usability, and perceived time savings.

Results

Paired survey analysis (n = 38) revealed large statistically significant reductions in task load (−24.42, p <.001) and burnout (−1.94, p <.001), and moderate statistically significant improvements in usability scores (+10.9, p <.001). Post-survey responses (n = 46) indicated favorable utility with improved perceptions of efficiency, documentation quality, and ease of use.

Discussion

In one of the first pilot implementations of ambient AI scribe technology, improvements in physician task load, burnout, and usability were demonstrated.

Conclusion

Ambient AI scribes like DAX Copilot may enhance clinical workflows. Further research is needed to optimize widespread implementation and evaluate long-term impacts.
Regulation of artificial intelligence in healthcare: Clinical Laboratory Improvement Amendments (CLIA) as a model
Authors: Jackson Brian R , Sendak Mark P , Solomonides Anthony , Balu Suresh , Sittig Dean F
Published: December 2024

Objectives

To assess the potential to adapt an existing technology regulatory model, namely the Clinical Laboratory Improvement Amendments (CLIA), for clinical artificial intelligence (AI).

Materials and Methods

We identify overlap in the quality management requirements for laboratory testing and clinical AI.

Results

We propose modifications to the CLIA model that could make it suitable for oversight of clinical AI.

Discussion

In national discussions of clinical AI, there has been surprisingly little consideration of this longstanding model for local technology oversight. While CLIA was specifically designed for laboratory testing, most of its principles are applicable to other technologies in patient care.

Conclusion

A CLIA-like approach to regulating clinical AI would be complementary to the more centralized schemes currently under consideration, and it would ensure institutional and professional accountability for the longitudinal quality management of clinical AI.
Electrical properties as a tool for oil and gas exploration: a case study of Wadi Saal, East Central Sinai, Egypt
Authors: Gomaa Mohamed M
Published: December 2024

Some rock samples (39) have been obtained from Wadi Saal, East Central Sinai, Egypt, for studying electrical, petrographical, and petrophysical parameters. The petrographical analysis shows two major facies. Carbonate (limestone) facies with low porosity (11%) and permeability (69 mD), and sandstone facies with high porosity (28%) and permeability (5901 mD) indicate good reservoir characteristics. Porosity values are related to the bulk density, whereas permeability is controlled by rock porosity and irreducible water saturation. Alternating current (AC) electrical properties were measured with frequency (42 Hz–5 MHz) for samples. Electrical characteristic differences are affected with texture changes, mineralogy, porosity, tortuosity, pore-water salinity, mineral concentrations, permeability, and fluid content. Conductivity and impedance decrease whenever an insulator is existed. The dielectric constant increases with conductor composition (below the percolation) and falls with frequency beyond it. The conductivity expands with the number of conductor pathways connecting the electrodes. The primary objective of this work is to use laboratory AC electrical measurements to shed some light on the relationship between the texture, petrography, petrophysics, and geochemical composition of materials (sandstone and limestone). The goal is to study electrical properties of these mixtures at varying clay concentrations and saturation levels. These analyses could enhance oil and gas recovery by shedding light on reservoir rock electrical characteristics.
Haplotyped genome mapping and functional characterization of a blueberry anthocyanin acetyltransferase (AAT) controlling the accumulation of acylated anthocyanins
Authors: Dare Andrew P , Wu Chen , Carvajal Jose I , Nguyen Han M , Günther Catrin S , Hamiaux Cyril , Bailey Sarah , Deng Cecilia , Mengist Molla F , Iorizzo Massimo , Foster Toshi M , Chagné David , Montanari Sara , Espley Richard V
Published: December 2024

Blueberry has a diversity of anthocyanins that confer its characteristic blue-coloured skin. Whilst most cultivars produce only anthocyanin glycosides, some can add aliphatic or aromatic groups to the sugar moiety to create acylated anthocyanins. Due to their enhanced stability, acylated anthocyanins represent an attractive breeding target in blueberry. In this study, a haplotype-resolved assembly of a previously identified quantitative trait locus on chromosome 2 of ‘Hortblue Petite’ (Vaccinium corymbosum) was created to identify candidate anthocyanin acyltransferase genes. One full-length gene (VcAAT1a) was selected based on quantitative PCR expression profiling and transient expression in tobacco leaves and in strawberry and blueberry fruit flesh. In all three systems, VcAAT1a was able to produce a range of acylated anthocyanins in planta. Recombinant VcAAT1a protein demonstrated that, while VcAAT1a was able to act on both anthocyanin 3-O-glucosides and 3-O-galactosides, it could only utilize acetyl-CoA as an acyl donor. Protein modelling using AlphaFold suggested that this restricted range in acyl donors may be due to a spatially restricted sub-pocket in the acyl-binding site of VvAAT1. Finally, LUC/REN promoter activation assays revealed that the VcAAT1a promoter was transactivated by the VcMYBPA1 and VcMYBPA2 transcription factors, further expanding our knowledge of anthocyanin regulation in blueberry.
Simultaneous radio and X-ray observations of the transitional millisecond pulsar candidate 3FGL J1544.6−1125
Authors: Gusinskaia N V , Jaodand A D , Hessels J W T , Bogdanov S , Deller A T , Miller-Jones J C A , Russell T D , Patruno A , Archibald A M
Published: December 2024

Transitional millisecond pulsars (tMSPs) are neutron star systems that alternate between a rotation-powered radio millisecond pulsar state and an accretion disc-dominated low-mass X-ray binary (LMXB)-like state on multi-year time-scales. During the LMXB-like state, the X-ray emission from tMSPs switches between ‘low’ and ‘high’ X-ray brightness modes on a time-scale of seconds to minutes (or longer), while the radio emission shows variability on time-scales of roughly minutes. Coordinated Very Large Array (VLA) and Chandra observations of the nearby tMSP PSR J1023+0038 uncovered a clear anticorrelation between radio and X-ray luminosities such that the radio emission consistently peaks during the X-ray low modes. In addition, there are sometimes also radio/X-ray flares that show no obvious correlation. In this paper, we present simultaneous radio and X-ray observations of a promising tMSP candidate system, 3FGL J1544.6$-$1125, which shows optical, $\gamma$-ray, and X-ray phenomena similar to PSR J1023+0038, but which is challenging to study because of its greater distance. Using simultaneous VLA and Chandra observations, we find that the radio and X-ray emission are consistent with being anticorrelated in a manner similar to PSR J1023+0038. We discuss how our results help in understanding the origin of bright radio emission from tMSPs. The greater sensitivity of upcoming telescopes such as the Square Kilometre Array will be crucial for studying the correlated radio/X-ray phenomena of tMSP systems.
IFUM integrated field spectroscopy of ten M104 satellite galaxy candidates
Authors: Crosby Ethan , Mateo Mario , Escala Ivanna , Jerjen Helmut , Müller Oliver , Pawlowski Marcel S
Published: December 2024

We report the spectroscopic analysis of 10 satellite galaxy candidates in the sphere of influence of the Sombrero galaxy (M104, NGC4594), based on data obtained with IFUM (integral field units for Magellan). Based on their newly observed recessional velocities, we confirm that nine of these candidates are satellite galaxies of M104, with one being a background dwarf galaxy. All 10 dwarfs have stellar masses $2\times 10^{7}$ to $1\times 10^{9}\, {\rm M}_{\odot }$ and mean weighted metallicities $-1.7\lt \langle {[\mathrm{M/H}]}\rangle \lt -0.3$. Although these dwarfs are predominantly old, with stellar populations $\sim 5{\!-\!}11\,$ Gyr. However, this sample contains a local example of a low-mass ‘green pea’ candidate, it exhibits extreme optical emission features and broad emission line features ($\sigma \sim 250\, \mathrm{km\, s^{-1}}$) reminiscent of high-redshift Ly $\alpha$/Ly C photon leaking galaxies. Using the newly acquired recessional velocities of the nine satellites of M104, we find no evidence of coherent satellite motions unlike other nearby $L_*$ galaxy environments. Given the small sample, this result does not statistically rule out such coherent motions. There remain 60 satellite candidates of M104 for which future spectroscopy can more reliably test for such motion. Using the observed dwarf galaxies as tracers of the gravitational potential of M104, we estimate the dynamical mass of M104, $M_{\rm dyn}=(12.4\pm 6.5)\times 10^{12}\,{\rm M}_{\odot }$, and find that, making a reasonable estimate of M104’s gas mass, $\gt 90$ per cent of its baryons are missing. These results agree with previous measurements of M104’s dynamical mass.
Shock cooling emission from explosions of massive stars – III. Blue supergiants
Authors: Morag Jonathan , Sapir Nir , Waxman Eli
Published: December 2024

Light emission in the first hours and days following core-collapse supernovae is dominated by the escape of photons from the expanding shock-heated envelope. In preceding papers, we provided a simple analytic description of the time-dependent luminosity, L, and colour temperature, $T_{\rm col}$, as well as of the small (${\simeq} 10 {{\, \rm per\, cent}}$) deviations of the spectrum from a blackbody at low frequencies, $h\nu \lt 3T_{\rm col}$, and of ‘line dampening’ at $h\nu \gt 3T_{\rm col}$, for explosions of red supergiants (RSGs) with convective polytropic envelopes (without significant circumstellar medium). Here, we extend our work to provide similar analytic formulae for explosions of blue supergiants with radiative polytropic envelopes. The analytic formulae are calibrated against a large set of spherically symmetric multigroup (frequency-dependent) calculations for a wide range of progenitor parameters (mass, radius, and core/envelope mass ratios) and explosion energies. In these calculations, we use the opacity tables we constructed (and made publicly available), which include the contributions of bound–bound and bound–free transitions. The analytic formulae reproduce the numeric L and $T_{\rm col}$ to within 10 and 5 per cent accuracy, and the spectral energy distribution to within ${\sim} 20\!-\!40 {{\, \rm per\, cent}}$. The accuracy is similar to that achieved for RSG explosions.
The effect of radiation pressure on the dispersal of photoevaporating discs
Authors: Robinson Alfie , Owen James E , Booth Richard A
Published: December 2024

Observed infrared (IR) excesses indicate that protoplanetary discs evolve slowly for the majority of their lifetime before losing their near- and mid-IR excesses on short time-scales. Photoevaporation models can explain this ‘two-time-scale’ nature of disc evolution through the removal of inner regions of discs after a few million years. However, they also predict the existence of a population of non-accreting discs with large cavities. Such discs are scarce within the observed population, suggesting the models are incomplete. We explore whether radiation-pressure-driven outflows are able to remove enough dust to fit observations. We simulate these outflows using cudisc, including dust dynamics, growth/fragmentation, radiative transfer and a parametrization of internal photoevaporation. We find that, in most cases, dust mass-loss rates are around 5–10 times too small to meet observational constraints. Particles are launched from the disc inner rim, however grains larger than around a micron do not escape in the outflow, meaning mass-loss rates are too low for the initial dust masses at gap-opening. Only systems that have smooth photoevaporation profiles with gas mass-loss rates $\gt \sim$$5 \times 10^{-9}$$\mathrm{ M}_\odot$ yr$^{-1}$ and disc dust masses $\lt \sim$1 $\mathrm{ M}_{\oplus }$ at the time of gap opening can meet observational constraints; in the current models these manifest as EUV winds driven by atypically large high-energy photon fluxes. We also find that the height of the disc’s photosphere is controlled by small grains in the outflow as opposed to shadowing from a hot inner rim; the effect of this can be seen in synthetic scattered light observations.
Paradoxical pyoderma gangrenosum secondary to adalimumab successfully treated with methotrexate: A case report
Authors: El Morr Kristy , Rida Mohamad Ali
Published: December 2024

Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder, categorised under neutrophilic dermatoses. It can be idiopathic or associated with underlying conditions like inflammatory bowel disease, autoimmune diseases, and certain cancers. Some medications, including tumour necrosis factor-alpha inhibitors like adalimumab, can also induce this paradoxical reaction. We describe the case of a 19-year-old male with adalimumab-induced PG, which was successfully treated with methotrexate, contributing to the understanding of drug-induced PG and alternative treatment strategies.