bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Xenopus respiratory system reveals common tetrapod mechanisms for growth, regeneration and healing
Authors: Perry Shiri Kult , Shaidani Nikko-Ideen , Horb Marko E , Shubin Neil 
Published: October 2024

AbstractIn recent years, we have seen a significant increase in our understanding of the mechanisms of development, regeneration, and healing of the respiratory system. However, most of these studies have been limited by their focus on mammalian systems. Here, we aimed to identify the underlying molecular mechanisms that are active during lung growth and tissue repair in amphibians, specifically Xenopus tropicalis (X. tropicalis). First, we analyzed the stem cell composition and signaling pathways that are active in epithelial and mesenchymal cells during lung growth. Then, we established a protocol for lung injury to assess the types of stem cells underlying tissue repair. In mammals, Sftpc+ (AT2) cells are alveolar stem cells that can differentiate to Krt8+ cells during lung homeostasis and post-injury repair. In this study, we identified Sftpc+ cells and Krt8+ cells, along with the activity of key developmental signaling pathways, Hippo and Wnt, during lung maturation at post-metamorphosis stages. We then established a protocol for lung injury using chemically induced injury with bleomycin, which damages the lung through oxidative stress. The results show an elevation in collagen post-injury, indicating bleomycin’s effect in causing lung fibrosis.X. tropicalisfroglets survived 42 days post-injury, with a continuous decrease in fibrosis. To explore this effect, we analyzed the distribution of lung stem cells; Sox9 protein levels and Sftp gene expression were downregulated at the alveoli 42 days post-injury. The decrease in stem cell marker expression 42 days post-injury suggests they are differentiating as part of the healing process. Nevertheless, we could still detect them after a few weeks of healing. These results suggest thatX. tropicalishas a regenerative capacity for lung tissue repair and that the same signaling pathways and stem cells are active in both amphibians and mammalian lungs during lung growth, regeneration, and healing. These findings show for the first time the physiological similarities between the anuran and the mammalian lung during growth and tissue repair processes, suggestingX. tropicalisas a potential animal model to study lung regeneration.
Single-nucleus transcriptomics of wing sexual dimorphism and scale cell specialization in sulphur butterflies
Authors: Loh Ling S. , Hanly Joseph J. , Carter Alexander , Chatterjee Martik , Tsimba Martina , Shodja Donya N. , Livraghi Luca , Day Christopher R. , Reed Robert D. , McMillan W. Owen , Wray Gregory A. , Martin Arnaud 
Published: October 2024

AbstractThe evolution of sexual secondary characteristics necessitates regulatory factors that confer sexual identity to differentiating tissues and cells. InColias eurythemebutterflies, males exhibit two specialized wing scale types — UV-iridescent (UVI) and lanceolate scales — absent in females and likely integral to male courtship behavior. This study investigates the regulatory mechanisms and single-nucleus transcriptomics underlying these two sexually dimorphic cell types during wing development. We show that Doublesex (Dsx) expression is itself dimorphic and required to repress the UVI cell state in females, while unexpectedly, UVI activation in males is independent from Dsx. In the melanic marginal band, Dsx is required in each sex to enforce the presence of lanceolate scales in males, and their absence in females. Single-nucleus RNAseq reveals that UV-iridescent and lanceolate scale cell precursors each show distinctive gene expression profiles at 40% of pupal development, with marker genes that include regulators of transcription, cell signaling, cytoskeletal patterning, and chitin secretion. Both male-specific cell types share a low expression of theBric-a-brac(Bab) transcription factor, a key repressor of the UVI fate. Bab ChIP-seq profiling suggests that Bab binds the cis-regulatory regions of gene markers associated to UVI fate, including potential effector genes involved in the regulation of cytoskeletal processes and chitin secretion, and loci showing signatures of recent selective sweeps in an UVI-polymorphic population. These findings open new avenues for exploring wing patterning and scale development, shedding light on the mechanisms driving the specification of sex-specific cell states and the differentiation of specialized cell ultrastructures.
The potential impact of declining development assistance for healthcare on population health: projections for Malawi
Authors: Molaro Margherita , Revill Paul , Chalkley Martin , Mohan Sakshi , Mangal Tara , Colbourn Tim , Collins Joseph H. , Graham Matthew M. , Graham William , Janoušková Eva , Manthalu Gerald , Mnjowe Emmanuel , Mulwafu Watipaso , Murray-Watson Rachel , Twea Pakwanja D. , Phillips Andrew N. , She Bingling , Tamuri Asif U. , Nkhoma Dominic , Mfutso-Bengo Joseph , Hallett Timothy B. 
Published: October 2024

AbstractDevelopment assistance for health (DAH) to Malawi will likely decrease as a fraction of GDP in the next few decades. Given the country’s significant reliance on DAH for the delivery of its healthcare services, estimating the impact that this could have on health projections for the country is particularly urgent. We use the Malawi-specific, individual-based “all diseases – whole health-system”Thanzi La Onsemodel to estimate the impact this could have on health system capacities, proxied by the availability of human resources for health, and consequently on population health outcomes. We estimate that the projected changes in DAH could result in a 7-15.8% increase in disability-adjusted life years compared to a scenario where health spending as a percentage of GDP remains unchanged. This could cause a reversal of gains achieved to date in many areas of health, although progress against HIV/AIDS appears to be less vulnerable. The burden due to non-communicable diseases, on the other hand, is found to increase irrespective of yearly growth in health expenditure, if assuming current reach and scope of interventions. Finally, we find that greater health expenditure will improve population health outcomes, but at a diminishing rate.
How improvements to drug effectiveness impact mass drug administration for control and elimination of schistosomiasis
Authors: Ellis John R. , Mutono Nyamai , Vasconcelos Andreia , Thumbi SM , Hollingsworth T. Déirdre , Anderson Roy M. 
Published: October 2024

AbstractSchistosomiasis affects more than 230 million people worldwide. Control and elimination of this parasitic infection is based on mass drug administration of praziquantel (PZQ), which has been in use for several decades. Because of the limitations of the efficacy of PZQ especially against juvenile worms, and the threat of the emergence of resistance, there is a need to consider alternative formulations or delivery methods, or new drugs that could be more efficacious. We use an individual-based stochastic model of parasite transmission to investigate the effects of possible improvements to drug efficacy. We consider an increase in efficacy compared to PZQ, as well as additional efficacy against the juvenile life stage of schistosome parasites in the human host, and a slow-release formulation that would provide long-lasting efficacy for a period of time following treatment.Analyses suggest a drug with a high efficacy of 99%, or with efficacy lasting 24 weeks after treatment, are the two most effective individual improvements to the drug profile of PZQ. A drug with long lasting efficacy is most beneficial when MDA coverage is low. However, when prevalence of infection has already been reduced to a low level, a high efficacy is the most important factor to accelerate interruption of transmission. Our results indicate that increased efficacy against juvenile worms can only result in modest benefits, but the development of a new drug formulation with higher efficacy against adult worms or long-lasting efficacy would create an improvement to the community impact over the currently used formulation.Author summaryThe World Health Organization has set the target of elimination of schistosomiasis as a public health problem by 2030. Currently, praziquantel is the sole drug used in mass drug administration (MDA) for schistosomiasis, raising concerns about the potential evolution of resistance and whether an improved drug profile would be necessary to achieve elimination and the more ambitious goal of interruption of transmission. We present the results from an individual-based stochastic mathematical model that simulates schistosome transmission and the impact of MDA. Three potential improvements to the properties of the drug are considered: improved efficacy, long lasting efficacy post a single treatment and improved efficacy against the juvenile life stage of the schistosome. Our findings reveal that with good coverage, an improved drug efficacy is best at reducing prevalence and achieving interruption of transmission. However, when MDA quality is compromised due to low coverage, infrequent treatment or high rates of non-adherence, then a long-lasting efficacy performs best. There is only a modest benefit of improved drug efficacy against juvenile schistosomes. These results highlight the importance of good MDA program and inform future drug development aims.
High Prevalence of Unrecognized Actionable Cardiac Arrhythmias in Patients with Moderate to Severe Chronic Obstructive Pulmonary Disease
Authors: Coleman Kristie M. , Wolf RN. Elliot , Varrias Dimitrios , Schwartz Jacob , Garcia Brenda , Roselli Victoria , Lam Betty , Leavitt Jonas , Sharma Nikhil , Dumchin Gregory , Altschul Erica , Oks Margarita , Mina Bushra , Mountantonakis Stavros E. 
Published: October 2024

ABSTRACTBackgroundPatients with chronic obstructive pulmonary disease (COPD) are at high risk for developing arrhythmias due to hypoxemia, right heart failure, and the use of beta-agonist inhalers. Symptoms related to arrhythmias can often be masked or confounded by symptoms related to COPD exacerbation and remain undiagnosed. With this study, we identify the incidence of actionable arrhythmias in patients with no prior cardiology follow-up and moderate-severe COPD with continuous monitoring.MethodsAn automatic referral for electrophysiology (EP) consult was generated in patients with moderate-severe COPD if they endorsed one of the following: palpitations, dizziness, abnormal ECG, or near syncope. Eligible patients underwent ILR implantation after evaluation with an EP specialist and were followed via remote monitoring for 12 months. A control group of patients without COPD matched for age, sex, and implant indication were randomly selected in a 3:1 ratio. Actionable arrhythmias, defined as arrhythmias that correlated with symptoms triggered by the patient, necessitating EP intervention, were recorded for both groups.ResultsIn this prospective cohort study, 21 patients with COPD were enrolled and compared to 63 controls. COPD patients experienced a significantly higher rate of actionable arrhythmias compared to the controls (48% vs 11%, p<0.001). EP interventions in response to actionable arrhythmias included eight patients initiated on anticoagulation, three catheter ablations, one implantable cardiac defibrillator, and one permanent pacemaker implanted. In multivariate analysis, COPD was an independent predictor of actionable arrhythmias (aOR 4.3, 95% CI 1.2-15.2, p=0.02) when adjusting for chronic kidney disease and all-cause readmissions.ConclusionContinuous monitoring was highly effective in diagnosing significant arrhythmic events in patients with moderate-severe COPD. Awareness should be raised about the high arrhythmic risk in this population and the role of continuous monitoring should be evaluated in larger studies.Abstract FigureWHAT IS KNOWN?Patients with COPD are at greater risk for developing cardiac arrhythmias, which may propagate COPD exacerbations.WHAT THE STUDY ADDSQuantification of incidence of actionable arrhythmias in patients with moderate to severe COPD using continuous monitoring for the 1sttime.Multivariate analysis which determines whether this phenomenon is due to demographic confounders, comorbidities, treatment modalities or an independent association.Detailed presentation of the type or arrhythmias, COPD exacerbations and healthcare utilization, emphasizing the need for arrhytmia surveillance in this vulnerable patient population.
Prospective Quantification of Tricuspid Regurgitation with Echocardiography vs 4D Flow Cardiac Magnetic Resonance
Authors: Sularz Agata , Negm Ahmed S. , Chavez-Ponce Alejandra , El Shaer Ahmed , Liu Chia-Hao , Bird Jared , Oh Jae , Pislaru Sorin , Collins Jeremy D. , Alkhouli Mohamad 
Published: October 2024

AbstractIntroductionCardiac magnetic resonance (CMR) is a valuable tool in the assessment of valvular disease. However, its utilization in tricuspid regurgitation (TR) evaluation has been limited. We sought to compare TR grading with 4D-CMR and transthoracic echocardiography (TTE).MethodsWe prospectively recruited patients with ≥moderate TR on TTE to undergo multiparametric CMR with integrated cardiac function and 4D flow assessments using a 1.5-T scanner (Siemens Somatom Aera, Erlangen, Germany). Patients with other severe valvulopathy, end-stage renal disease, or pacemakers were excluded. TR was graded severe on CMR when TR volume ≥45 mL, and/or TR fraction ≥50%. The weighted kappa test was used to assess the agreement in overall TR grading on TTE and MR.ResultsFifty-two patients were enrolled (mean age 78.5±7.6 years, 53.8% men). The median interval between CMR and TTE was 2 days (IQR=1-37). The agreement between TTE and CMR-derived TR volume was fair (kappa = 0.28, 95%CI 0.13-0.45), with only 10 of 31 patients (32%) with ≥severe TR on TTE meeting severe TR volume criterion on CMR (TR volume ≥45 ml). There was no agreement between TTE and CMR-derived TR fraction (kappa=0.04, 95%CI 0.13-0.46) with only 3 of 31 patients (13%) with ≥severe TR on TTE meeting severe TR criterion on CMR (TR fraction ≥50%).ConclusionGrading of TR was frequently discordant between TEE and 4D-MRI. Further studies are needed to elucidate the clinical impact of concordant/discordant TR grading on multi-modality imaging.
Cochlear implants with dexamethasone-eluting electrode arrays reduce foreign body response in a murine model of cochlear implantation and human subjects
Authors: Rahman Muhammad Taifur , Mostaert Brian , Eckard Peter , Fatima Shakila Mahmuda , Scheperle Rachel , Razu Ibrahim , Hunger Bryce , Olszewski Rafal T. , Gu Shoujun , Garcia Cristina , Khan Nashwaan Ali , Bennion Douglas M , Oleson Jacob , Kirk Jonathon R. , Enke Ya Lang , Gay Robert D. , Morell Robert J. , Hirose Keiko , Hoa Michael , Claussen Alexander D. , Hansen Marlan R. 
Published: October 2024

AbstractThe inflammatory foreign body response (FBR) following cochlear implantation (CI) can negatively impact CI outcomes, including increased electrode impedances. This study aims to investigate the long-term efficacy of dexamethasone eluting cochlear implant and locally delivered dexamethasone, a potent anti-inflammatory glucocorticoid on the intracochlear FBR and electrical impedance post-implantation in a murine model and human subjects. The left ears of CX3CR1+/GFPThy1+/YFP(macrophage-neuron dual reporter) mice were implanted with dexamethasone-eluting cochlear implants (Dex-CI) or standard implant (Standard-CI) while the right ear served as unoperated control. Another group of dual reporter mice was implanted with a standard CI electrode array followed by injection of dexamethasone in the middle ear to mimic current clinical practice (Dex-local). Mouse implants were electrically stimulated with serial measurement of electrical impedance. Human subjects were implanted with either standard or Dex-CI followed by serial impedance measurements. Dex-CI reduced electrical impedance in the murine model and human subjects and inflammatory FBR in the murine model for an extended period. Dex-local in the murine model is ineffective for long-term reduction of FBR and electrode impedance. Our data suggest that dexamethasone eluting arrays are more effective than the current clinical practice of locally applied dexamethasone in reducing FBR and electrical impedance.
Integrative multi-ethnic Mendelian randomisation identifies tissue-specific causal genes for Coronary Artery Disease and interactions with post-acute Covid
Authors: Jaros Rachel , O’Sullivan Justin M. 
Published: October 2024

ABSTRACTCoronary artery disease (CAD) is highly heritable and remains the leading cause of mortality worldwide. Understanding the genetic and mechanistic underpinnings of CAD is crucial for early risk assessment and intervention. We conducted a transcriptome-wide Mendelian randomisation (MR) study, utilising unbiased tissue-specific gene regulatory networks, to identify genes causally associated with CAD in European and East Asian populations. We identified 291 tissue and ancestry-specific genes implicated in CAD, including 98 novel protein-coding genes across coronary artery, whole blood, and lung tissues. Genes involved in epigenetic processes (egPAXBPandKIAA0232) causally associated with CAD. Moreover, we identified genes related to the ubiquitin-proteasome system in the coronary artery and kinase signalling in the lung, as being causally related to CAD. The integration of protein interaction networks identified causal connections between CAD and HDL cholesterol levels, providing novel insights into CAD mechanisms, and potential actionable targets for people with this risk profile. The results also provide intriguing insights into the link between SARS-CoV-2 and CAD, unveiling mechanisms that may underlie the increased risk of cardiovascular disease following SARS-CoV-2 infection. The causal mechanisms we identified emphasise the tissue-agnostic and ancestrally unique pathways that underscore the complex interplay between CAD development, metabolic disturbances, and the immune system. Collectively, our results provide valuable insights into CAD pathogenesis and potential therapeutic targets.
Distinct neural alterations in schizophrenia and autism: A meta-analysis of social cognition and emotion processing
Authors: Boisvert Mélanie , Pilon Florence , Mottron Laurent , Potvin Stéphane 
Published: October 2024

AbstractObjectiveTwo conditions alter socio-communicative behaviors in humans: autism and schizophrenia. However, it is not well-known if these disorders share the same neural alterations during socio-emotional tasks. The main objective was to examine neural alterations in autism and schizophrenia during emotional and social cognition tasks. Our second objective was to determine if these alterations were common or distinct between disorders.MethodsFunctional neuroimaging studies using an emotional or a social cognition paradigm in schizophrenia or autism were queried from three databases. We selected articles if they reported whole brain coordinates of different activations between autism/schizophrenia participants and non-clinical controls. Using SDM, we analyzed the coordinates of brain activity differences between case and control groups, categorized by diagnosis and paradigm.ResultsThe meta-analysis aggregated 104 studies in schizophrenia and 80 studies in autism spectrum disorder. During emotional tasks, individuals with autism showed reduced activity in the left amygdala, while those with schizophrenia showed reduced activity in the right inferior frontal gyrus and the median cingulate gyrus. During social cognition tasks, alterations in both conditions did not survive corrected statistical thresholds. No spatial conjunction was observed between the alterations seen in each disorder during both emotional/social cognition tasks at both corrected and uncorrected thresholds.ConclusionsThese results suggest that the emotional processing in autism and schizophrenia in adulthood are characterized by alterations of bottom-up and top-down mechanisms of the emotional network, respectively. It should encourage the pursuit of functional neuroimaging studies on emotion processing using machine learning to differentiate these two conditions.
Privacy Fact Sheets mitigate Disease-related Privacy Concerns and Facilitate Equal Access to the Electronic Health Record: Randomized Controlled Trial
Authors: von Kalckreuth Niklas , Feufel Markus A. 
Published: October 2024

AbstractBackgroundThe German electronic health record (EHR) aims to enhance patient care and reduce costs, but users often worry about data security. To mitigate disease-related privacy concerns, for instance, surrounding stigmatized diseases, we test the effect of privacy fact sheets (PFS) - a concise but comprehensive transparency feature - on increasing EHR usage.ObjectiveWe investigate whether displaying a PFS shortly before upload decisions must be made mitigates disease-related privacy concerns and makes uploads more likely.MethodsIn an online user study, 393 German participants interacted with a randomly assigned medical report that varied systematically in terms of disease-related stigma (high vs. low) and time course (acute vs. chronic). They were then asked to decide whether to upload the report to the EHR, while we systematically varied the presentation of privacy information (PFS vs. no PFS).ResultsThe results show that, in general, upload behavior is negatively influenced by disease-related stigma (OR 0.130, p<.001) and positively influenced when a PFS is given (OR 4.527, p<.001). This increase was particularly pronounced for stigmatized diseases (OR 5.952, p=.006). Time course of diseases had no effect.ConclusionsOur results demonstrate that PFSs help to increase EHR uploads by mitigating privacy concerns related to stigmatized diseases. This indicates that a PFS is mainly relevant and effective for users with increased privacy risk perceptions, while they do not hurt other users. Thus, implementing PFSs can increase the likelihood that more patients, even those with increased privacy concerns due to stigmatized diseases, upload their data to the EHR, ultimately increasing health equity. That is, PFS may help to realize EHR benefits such as more efficient healthcare processes, improved treatment outcomes, and reduced costs for more users.Trial RegistrationDeutsches Register Klinischer Studien DRKS00033652,https://drks.de/search/de/trial/DRKS00033652