bluuebunny/crossref_metadata_2025 huggingface dataset:
Are there mortality improvements with newer interventions in adult cardiac surgery? Evidence from 73 meta-analyses
Authors: Parish Austin , Tolis George , Ioannidis John P.A.
Published: November 2024

Background

In the last two decades, many new interventions have been introduced with the ultimate goal of improving overall postoperative outcomes after cardiac operations in adults. We aimed to assess how often randomized controlled trials (RCTs) in adult cardiac surgery found significant mortality benefits for newer interventions versus older ones, whether observed treatment effect estimates changed over time and whether RCTs and non-randomized observational studies gave similar results.

Methods

We searched journals likely to publish systematic reviews on adult cardiac surgery for meta-analyses of mortality outcomes and that included at least one RCT, with or without observational studies. Relative treatment effect sizes were evaluated overall, over time, and per study design.

Results

73 meta-analysis comparisons (824 study outcomes on mortality, 519 from RCTs, 305 from observational studies) were eligible. The median mortality effect size was 1.00, IQR 0.54-1.30 (1.00 among RCTs, 0.91 among observational studies, p=0.039). 4 RCTs and 6 observational studies reached p<0.005 favoring newer interventions. 2/73 meta-analyses reached p<0.005 favoring the newer interventions. Effect size for experimental interventions relative to controls did not change over time overall (p=0.64) or for RCTs (p=0.30), and there was a trend for increase in observational studies (p=0.027). In 34 meta-analyses with both RCTs (n=95) and observational studies (n=305), the median relative summary effect (summary effect in observational studies divided by summary effect in RCTs) was 0.87 (IQR, 0.55-1.29); meta-analysis of the relative summary effects yielded a summary of 0.93 (95% CI, 0.74-1.18).

Conclusions

The vast majority of newer interventions had no mortality differences over older ones both overall and in RCTs in particular, while benefits for newer interventions were reported more frequently in observational studies.
Perceptions and willingness of patients and caregivers on the utilization of patient-generated health data: a cross-sectional survey
Authors: Park Ye-Eun , Beck Sang Sook , Lee Yura
Published: November 2024

Background

Patient-generated health data (PGHD) are increasingly recognized for their potential to complement traditional healthcare data by offering continuous monitoring and enhanced patient management. Despite the growing interest in PGHD however, the perceptions and willingness of patients and caregivers to utilize this information in a clinical setting remain underexplored.

Objective

This study aimed to assess the perceptions, expectations, and concerns of patients and caregivers regarding the clinical utilization of PGHD. The influence of demographic factors such as age and health status on these perceptions was also explored.

Methods

A cross-sectional survey was conducted of 400 participants, including both patients and caregivers. The survey collected data on attitudes towards PGHD, experiences with health information management, and the willingness to share PGHD for clinical and secondary purposes. Statistical analysis was used to identify significant differences in perceptions based on demographics and health-related roles.

Results

The analysis revealed significant variations in attitudes towards PGHD that were based on the participants’ health-related roles, age, and gender. Older patients and male caregivers exhibited higher concerns about data privacy and security, while younger participants showed greater enthusiasm for using PGHD in managing their health. These findings highlighted diverse needs and expectations across different demographic groups.

Conclusion

Consideration of demographics and role-based differences is very important when designing and implementing PGHD systems. Tailored approaches that address specific concerns and expectations can enhance the acceptance and effectiveness of PGHD in clinical practice, ultimately fostering more patient-centered care.
Evaluation of clinical characteristics of Legionella pneumophila pneumonia diagnosed by metagenomic Next-Generation Sequencing:A Retrospective Study
Authors: He Zhixiong , Chu Ruixiang , Ke Junyi , Li Qinglan , Wu Qi , Sheng Jiao , Liu Ping , Duan Minchao
Published: November 2024

Purpose

This study aimed to summarize the clinical characteristics and outcomes of Legionella pneumophila (L. pneumophila) pneumonia to assist clinicians in accurately and early identifying this disease. The findings provide evidence to guide decision-making for L. pneumophila infection and improve treatment success rates.

Patients and methods

A retrospective analysis of clinical data was conducted on 19 patients diagnosed with L. pneumophila infection at our hospital using Metagenomic next-generation sequencing (mNGS).

Results

The study included 16 male and 3 female participants, with an average age of 59.5±16.2 years. The majority of participants were immunocompromised (13/19). The most common symptoms included fever (n=11) with a median peak value of 39.5°C, cough (n = 15), expectoration (n = 14), dyspnea (n = 10), poor appetite (n = 9), fatigue (n = 8), and headache (n = 3). Elevated levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were observed in all patients, while procalcitonin (PCT) and lactate dehydrogenase (LDH) levels were significantly higher in the severe group compared to the non-severe group. Lymphocyte count levels were also significantly lower in the severe group (P<0.05). Common CT manifestations included flake high-density shadows (n = 17), pleural effusion (n = 11), consolidation (n = 4), ground-glass exudation (n = 4), and bronchial inflation signs (n = 3). The most prevalent underlying diseases were hypertension (n = 9), diabetes (n = 8), AIDS (n = 6), COPD (n = 5), and malignancies (n = 3). Common complications included acute liver injury (n=7), acute respiratory failure (n=6), electrolyte disorders (n=5), sepsis (n=3), MODS (n=2), and ARDS (n=1). The majority of patients received treatment with quinolones (16/19), with six patients requiring mechanical ventilation therapy. Tragically, 2 patients in the severe pneumonia group succumbed to sepsis and multiple organ failure.

Conclusion

L. pneumophila pneumonia is an acute respiratory infection. If not promptly diagnosed, patients may develop severe pneumonia, multiorgan failure, or face fatal outcomes. mNGS can be used for rapid and accurate diagnosis of L. pneumophila infections, thereby improving treatment outcomes. Early initiation of quinolones or combination therapy with other medications has demonstrated a significant therapeutic benefit for patients with L. pneumophila pneumonia.
Assessing phylogenetic information content and redundancy in hominin craniodental traits
Authors: Raskin Levi Yoder , Šešelj Maja , Bitarello Bárbara Domingues
Published: November 2024

Paleoanthropological phylogenetic inference is based on characters assumed to be phylogenetically informative and independent. Yet, our understanding of whether these criteria are met in published character supermatrices is limited. We assess the phylogenetic information content (PHIC) of 107 discrete craniodental traits from a widely-used hominin character matrix. We compare test topologies — inferred by permuting single traits or removing single traits, anatomical units (AUs), and operational taxonomic units — to the baseline topology, inferred from the unmodified matrix. In this dataset, only 31 traits have some degree of PHIC: 23 uniquely informative traits — sufficient, as a set, to closely approach the baseline topology — and eight redundant traits. No single AU, nor the combination of mandibular and dentition AUs, contains sufficient PHIC to approach the baseline topology, and only the maxilla contains more PHIC than expected. Therefore, phylogenetic placements of fossil hominins represented by isolated AUs should be regarded as putative until better-preserved specimens and more informative traits can be incorporated. Given the ubiquity of discrete morphological data in paleontology and that most of the history of life on Earth was only recorded through fossils, our methods should be broadly applicable to phylogenetic inference involving other paleontological clades.
Systematic dissection of epigenetic age acceleration in normal breast tissue reveals its link to estrogen signaling and cancer risk
Authors: Sehl Mary E. , Guo Wenbin , Farrell Collin , Marino Natascia , Henry Jill E. , Storniolo Anna Maria , Papp Jeanette , Li Jingyi Jessica , Horvath Steve , Pellegrini Matteo , Ganz Patricia A.
Published: November 2024

Breast aging encompasses intricate molecular and cellular changes that elevate cancer risk. Our study profiled DNA methylation and gene expression of 181 normal breast samples and systematically evaluated eight epigenetic clocks. We found that clocks trained using breast tissues demonstrate improved age prediction in normal breast tissue, and bias universally exists in epigenetic clocks, necessitating a proper definition of age acceleration. Cell composition analysis revealed significant age-related alterations and highlighted its distinct associations with age acceleration, including increased luminal epithelial and myoepithelial cells and reduced adipocytes and immune cells, connecting age acceleration to carcinogenesis from a cell compositional perspective. Additionally, CpG sites associated with age acceleration were enriched for estrogen receptor binding sites, providing a mechanistic link between estrogen exposure, accelerated aging, and cancer. These findings highlight the importance of cellular heterogeneity in epigenetic age estimates and the potential of age acceleration to guide for risk stratification and prevention strategies.
FOXM1 regulates platelet-induced anoikis resistance in pancreatic cancer cells
Authors: Ernesti Alissa , Heydel Beate , Blümke Juliane , Gutschner Tony , Hämmerle Monika
Published: November 2024

Anoikis resistance is a prerequisite for circulating tumor cells (CTC) to survive in the blood stream. Platelets can interact with these CTCs and protect them from cytokine and immune cell-mediated cell death. Whether platelets can regulate anoikis resistance by controlling tumor cell intrinsic gene expression changes has not been studied in pancreatic cancer cells in detail before. Here, we identified FOXM1 as a differentially regulated gene between attached and detached cells whose expression was controlled by platelets. Manipulating FOXM1 expression using FOXM1 knockdown and overexpression or by inhibiting its function using a small molecular inhibitor highlighted the role of FOXM1 in controlling platelet-mediated anoikis resistance in pancreatic cancer cells. Hence, targeting FOXM1 might be a novel therapeutic strategy in pancreatic cancer patients, especially in those with thrombocytosis.
London taxi drivers leverage regional boundaries to optimise route choices and improve their navigation skill across three decades
Authors: Gahnstrom Christoffer J. , Goodroe Sarah C. , de Silva Stephanie , Griesbauer Eva-Maria , Morley Jeremy , Manley Ed , Spiers Hugo J.
Published: November 2024

The world is defined by boundaries. They segment our experience of time and space, and in virtual environments have been shown to impact navigational choices. Here, we test the impact of boundaries on route choices in a real-world environment (London, UK) with a group of expert navigators: licensed London taxi drivers who are required to memorise the layout of over 26,000 streets to obtain their licence. After presenting photographs of a start location and a goal location, taxi drivers were asked to either accept or reject a third target street as forming part of the direct route or not. Performance increased across the adult life-span period in this group (age: 34 to 67). Taxi drivers were faster and more accurate when the target location formed part of a street network boundary (e.g. streets on the edge of the London neighbourhood Soho). Our results are consistent with taxi drivers exploiting the graph structure of the street network to plan routes, as well as consistent with the formation of hierarchical state representations to reduce the dimensionality of the planning problem. Taken together, we show that navigational skill can improve over decades of exposure and that experts exploit regional boundaries for optimal choices, providing a scaffolding over which to form action plans.
Cytotoxicity and Characterization of 3D-Printable Resins Using a Low-Cost Printer for Muscle-based Biohybrid Devices
Authors: Liao Ashlee S. , Dai Kevin , Irez Alaeddin Burak , Sun Anika , Bennington Michael J. , Schaffer Saul , Chopra Bhavya , Seok Ji Min , Adams Rebekah , Zhang Yongjie Jessica , Webster-Wood Victoria A.
Published: November 2024

Biohybrid devices integrate biological and synthetic materials. The selection of an appropriate synthetic material to interface with living cells and tissues is crucial due to cellular chemical and mechanical sensitivities. As such, the stiffness of the material and its biocompatibility while in direct contact must be considered. In this study, the material properties and biocompatibility of six commercially available, 3D printable resins (three rigid and three elastomeric) were assessed for their suitability for biohybrid actuators. To characterize the material, uniaxial tension and compression tests with post-hoc Hookean and Yeoh model analyses were conducted for both nonsterile and sterilized (ethanol-soaking or autoclaved) samples. The mechanical properties of the elastomeric resins were minimally impacted by the different sterilization techniques. However, both Phrozen AquaGray 8K and Liqcreate Bio-Med Clear rigid resins were significantly softer in tensile tests after sterilization, and AquaGray became far more ductile. Asiga DentaGUIDE was much more stable in its mechanical properties than the other rigid resins. It was also shown that long-term exposure to saline solutions leads to a decrease in the Young’s moduli of these rigid resins before any sterilization has occurred. The print fidelity was also assessed for nonsterile and sterilized samples via manual scoring to determine the impacts of the sterilization processes on the part fidelity. Sterilization techniques had a minimal impact on print fidelity for both elastomeric and ridged resins with two exceptions. In both Formlabs Silicone 40A IPA/BuOAc post-treatment and Phrozen AquaGrey 8K groups, ethanol/UV-sterilization caused more degradation compared to autoclave-sterilization. In addition to the material analyses, cytotoxicity analyses using calcein AM and ethidium homodimer-1 fluorescence markers were conducted by directly culturing C2C12, a common myoblast cell line used in bioactuators, with sterilized resin samples. Of the elastomeric resins, only Formlabs Silicone 40A was shown to have minimal impacts on cell viability. For the rigid resins, Asiga DentaGUIDE, Liqcreate Bio-Med Clear, and ethanol-sterilized Phrozen AquaGray 8K demonstrated minimal impacts on cell viability. Based on these analyses, Asiga DentaGUIDE and Formlabs Silicone 40A demonstrate potential for applications in biohybrid muscle-based actuators when using low-cost 3D printers.
Extreme fatigue-resistance in a brood parasite parallels a war of attrition in begging competition with hosts
Authors: Antonson Nicholas D. , Hauber Mark E. , Schelsky Wendy M. , Kallembach Carly , Fuxjager Matthew J.
Published: November 2024

Food-solicitation displays are critical to the survival of dependent young. These signals often evolve in extreme ways in response to familial conflict among siblings and between parents and offspring. Avian brood parasites demonstrate how these signals can become exaggerated by engaging in a begging arms race with host offspring. However, despite hypotheses about how begging displays in brood parasites are adapted to support the demands of early parasitic life, we know little about the physiological specializations that support exaggerated parasitic traits. Here, we investigate display performance in the begging competition between brood parasitic brown-headed cowbirds (Molothrus ater) and host prothonotary warblers (Protonotaria citrea). Usingin situmuscle stimulation, we test the performance limits of the musculus complexus (MC), which actuates begging displays. Our results show that nestlings of each species initiate their begging display at similar speeds, but cowbirds beg far longer than warblers. We trace these effects to species differences in muscle performance, with the cowbirdMCshowing dramatically greater fatigue-resistance than warblers, while other facets of muscle performance remained similar between species. Altogether, these findings suggest that intra-brood conflict in host-parasite interactions selects for extreme fatigue-resistance in skeletal muscles to support a “war of attrition” in begging behavior and nestling survival.
Adaptation and acclimation of gametophytic traits to heat stress in a widely distributed wild plant along a steep climatic gradient
Authors: Tushabe Donam , Altmann Franziska , Koehler Erik , Woods Sebastian , Kahl Sandra , Rosbakh Sergey
Published: November 2024

Climate change-induced heat waves often result in reduced seed yields and quality via high-temperature effects in the gametophytic phase. Surprisingly, the ability of pollen and ovules, particularly among wild plant populations, to adapt or acclimate to heat stress remains poorly understood.

To address this gap, we examined the adaptive and acclimation potential of six gametophytic traits in eleven distinct populations of wildSilene vulgarisacross a temperature gradient in Europe. First, we cultivated plants in a common garden to reveal differences in gametophytic traits indicative of adaptation. Next, we assessed the acclimation potential of these traits to heat stress by subjecting flowering plants to two chronic heat stress (CHS) treatments: moderate (35/30 °C) and severe (40/35 °C), for 18 days.

Findings from the common garden experiment indicated no intraspecific variation in gametophytic traits across the temperature gradient, suggesting that these traits may not influence the plant’s sexual adaptation to its local habitat. Plants originating from colder climates produced more and larger seeds than those from warmer climates. During CHS treatments, the female gametophyte was less temperature sensitive compared to the male gametophyte. Moderate CHS led to larger ovaries with more, large-sized ovules, while severe CHS reduced ovule numbers but increased their size. In contrast, both CHS treatments decreased pollen grain numbers, size, and anther length, with severe CHS causing more significant reductions. These reductions in gametophytic traits ultimately translated to lower seed yield and quality, which may threaten the sustained existence of natural plant populations over time. Under both CHS treatments, the acclimation potential did not vary among plant populations along the temperature gradient, except for pollen size under severe CHS, with larger pollen size in warmer climates than in colder regions.

Our findings suggest that the lack of adaptation and acclimation mechanisms in the gametophytic traits (except for pollen size) of wildSilene vulgarispopulations along the temperature gradient indicates that these plants may rely on alternative strategies, such as shifts in flowering time, to respond to thermal stress.
COSMOS: COmmunity and Single Microbe Optimisation System
Authors: Raajaraam Lavanya , Raman Karthik
Published: November 2024

Bioprocessing harnesses the potential of microbial communities and monocultures to convert renewable resources like agricultural by-products and wastewater into valuable products. While monocultures offer simplicity and control, microbial communities provide metabolic diversity, enabling complex substrate breakdown and cooperative biosynthesis. However, balancing efficiency with stability requires a nuanced approach, as each system presents unique advantages and limitations, particularly under different environmental conditions. To systematically explore the potential of these systems, we developed the COmmunity and Single Microbe Optimisation System (COSMOS), a dynamic computational framework that compares microbial monocultures and communities across diverse fermentation conditions. COSMOS identifies optimal microbial systems tailored to specific carbon sources and environments. Our findings highlight the impact of key factors such as environment, microbial interactions, and carbon sources on the biosynthetic capabilities of both communities and monocultures. A key result is the identification of theShewanella oneidensis–Klebsiella pneumoniaecommunity as the most efficient producer of 1,3-propanediol under anaerobic conditions. Notably, this aligns with previous experimental findings, with COSMOS accurately predicting the optimal carbon source concentration and inoculum ratio used. Additional findings highlight the value of communities for nutrient-limited processes and emphasise the importance of computational screening to balance productivity with ease of control. The insights gained from this study offer a roadmap toward optimising microbial systems for sustainable bioprocesses and circular bio-economies.

Importance

The transition to sustainable biomanufacturing is vital for reducing reliance on fossil-based resources in industries such as biofuels, wastewater treatment, and pharmaceuticals. While monocultures are preferred for their predictability, microbial communities offer greater metabolic versatility, particularly in nutrient-limited environments. However, their complexity and the lack of systematic evaluation tools have hindered wider adoption. Identifying the most efficient microbial system—whether monoculture or community—and optimizing it for resource efficiency is key to sustainability and aligns with the UN Sustainable Development Goals (SDG 9 and SDG 12). COSMOS addresses this gap by providing a computational framework to assess microbial systems, minimizing the need for extensive experimental testing. By enabling data-driven selection of scalable and efficient bioprocessing strategies, COSMOS supports the transition to circular bio-economies and sustainable manufacturing, ensuring resource-efficient production while reducing environmental impact.
Quantifying the success of prey crypsis, aposematism and evasiveness in avoiding predators’ attack
Authors: Linke Daniel , Mejia Jacqueline Hernandez , Navarro Valery N. P. Eche , Gohil Prapti , García César Ramírez , Salinas Letty , Elias Marianne , Matos-Maraví Pável
Published: November 2024

Antipredator defences typically act at distinct stages of the predation sequence—encounter, identification, approach, and subjugation. However, their effectiveness has rarely been quantified and compared simultaneously in wild predator-prey systems. We conducted a study in Peru, where we installed aviaries at two localities and recorded the responses of wild avian predators to three types of antipredator defences—crypsis, aposematism, and evasiveness—expressed by three butterfly species. The study included both immature and adult birds from insectivorous species in forest and urban environments. We tested the theoretical expectations that cryptic butterflies (Nymphalidae: Euptychiina) were rarely detected, aposematicHeliconius(Nymphalidae: Heliconiinae) were often sighted but seldom attacked, and evasiveSpicauda(Hesperiidae: Eudaminae) were frequently detected and attacked but evaded capture at higher rates. Despite these distinct defensive strategies, mortality rates among prey types were largely similar, but predator life stage strongly influenced defence effectiveness. Immature birds were more likely to attackHeliconius, possibly reflecting a lack of learned avoidance for aposematic signals. Additionally, predator family influenced predation patterns, with more skilled insectivores (e.g., Vireonidae) showing higher capture success against defended prey. These findings illuminate the evolutionary pressures that shape predator behaviour and prey defences in tropical ecosystems, where high predator diversity possibly maintains the coexistence of multiple defensive strategies. The observed similar mortality rates underscore the adaptive value of these defences, as they collectively distribute the total predation pressure across prey species.
An ultra-conserved ARF-DNA interface underlies auxin-triggered transcriptional response
Authors: Rienstra Juriaan , Carrillo Carrasco Polet Vanessa , Hernandez Garcia Jorge , Weijers Dolf
Published: November 2024

Auxin Response Factor (ARF) plant transcription factors are the key effectors in auxin signalling. Their DNA-Binding Domain (DBD) contains a B3 domain that allows base-specific interactions with Auxin Response Elements (AuxREs) in DNA target sites. Land plants encode three phylogenetically distinct ARF classes: the closely related A- and B-classes have overlapping DNA binding properties, contrasting with the different DNA-binding properties of the divergent C-class ARFs. ARF DNA-binding divergence likely occurred early in the evolution of the gene family, but the molecular determinants underlying it remain unclear. Here, we show that the B3 DNA-binding residues are deeply conserved in ARFs, and variability within these is only present in tracheophytes, correlating with greatly expanded ARF families. Using the liverwortMarchantia polymorpha, we confirm the essential role of conserved DNA-contacting residues for ARF function. We further show that ARF B3-AuxRE interfaces are not mutation-tolerant, suggesting low evolvability that has led to the ultra-conservation of the B3-DNA interface between ARF classes. Our data support the almost complete interchangeability between A/B-class ARF B3 by performing interspecies domain swaps, even between lineages that diverged over half a billion years ago. Our analysis further suggests that DNA-binding specificity diverged early during ARF evolution in a common streptophyte ancestor, followed by strong selection as part of a competition-based auxin response system

Significance Statement

Auxin response evolved nearly half a billion years ago in the earliest land plants. Auxin response is mediated by a family of DNA-binding ARF transcription factors. It has been unclear if and how the ARF family has evolved. In this paper, the authors show that the central protein-DNA interface that defines the genes that are under auxin control has remained essentially unchanged throughout auxin response evolution, explaining how auxin has become a dominant signal controlling growth and development in all land plants.
Synonymous codon usage defines functional gene families
Authors: Ghanegolmohammadi Farzan , Ohnuki Shinsuke , Byrne Shane , Begley Thomas J. , Dedon Peter C.
Published: November 2024

Background

The degeneracy of the genetic code is increasingly recognized for roles in regulating translation rate, protein folding, and cell response. However, the functional genomics of codon usage patterns remains poorly defined. We previously showed that prokaryotic and eukaryotic cells respond to individual stresses by uniquely reprogramming the tRNA pool and the dozens of tRNA modifications comprising the tRNA epitranscriptome to cause selective translation of mRNAs from codon-biased genes. Here, we systematically defined distinct values of codon bias in theSaccharomyces cerevisiaegenome by modeling isoacceptor codon distributions using a new statistical toolbox – analysis of synonymous codon signatures (ASCS).

Results

Application of ASCS to theS. cerevisiaegenome revealed linear relationships between patterns of codon bias and gene function using canonical correlation analysis. By mapping codon-biased open reading frames (ORFs) onto a functional network of Gene Ontology (GO) categories, we identified 115 gene families distinguished by unique codon usage signatures. The codon usage patterns were found to strongly predict functional clusters of genes, such as translational machinery, transcription, and metabolic processes.

Conclusions

The ASCS-derived model of codon usage patterns inS. cerevisiaereveals functional codon bias signatures and captures more biologically meaningful information when compared to other codon analytical approaches.
Selecting cacao clones with high productivity potential and tolerance to Black Pod Rot (BPR) and Frosty Pod Rot (FPR)
Authors: López Marlon Enrique , Ramírez Oscar Arnulfo , Dubón Aroldo , Díaz Javier
Published: November 2024

Cacao (Theobroma cacao) is affected annually by Frosty Pod Rot (FPR) (Moniliopthora roreri) and Black Pod Rot (BPR) (Phytophthorasp). The loss caused by both diseases is threatening cacao production worldwide. Therefore, cacao breeding programs focus on developing new cacao clones with high productivity potential and disease resistance. However, this challenge is not easy to achieve due to the long time required for selection, the influence of environmental conditions on the severity of the disease, and the avoidance of chemical control of diseases. Therefore, genetic resistance should be the best option for selecting and releasing new cacao clones to the farmers. In this study, 40 cacao clones, 20 from CATIE and 20 from FHIA breeding programs were evaluated from 2013 to 2017. Three criteria were used to select clones: Yield, Percentage Disease Pod (PDP), and Disease and Production Index (DPI). Results indicated that depending on the cacao breeding program objectives, it is possible to use those criteria to select new cacao clones that are highly productive and resistant to diseases because cacao clones with high productivity are not always the most resistant to diseases and vice versa; however, a combination of both criteria can be used to select cacao clones with high productivity potential and resistance to FPR and BPR.
Electroconvulsive therapy generates a postictal wave of spreading depolarization in mice and humans
Authors: Rosenthal Zachary P , Majeski Joseph B. , Somarowthu Ala , Quinn Davin K , Lindquist Britta E. , Putt Mary E. , Karaj Antoneta , Favilla Chris G , Baker Wesley B. , Hosseini Golkoo , Rodriguez Jenny P , Cristancho Mario A , Sheline Yvette I , Shuttleworth C. William , Abbott Christopher C. , Yodh Arjun G , Goldberg Ethan M
Published: November 2024

Electroconvulsive therapy (ECT) is a fast-acting, highly effective, and safe treatment for medication-resistant depression. Historically, the clinical benefits of ECT have been attributed to generating a controlled seizure; however, the underlying neurobiology is understudied and unresolved. Using optical neuroimaging of neural activity and hemodynamics in a mouse model of ECT, we demonstrated that a second brain event follows seizure: cortical spreading depolarization (CSD). We found that ECT pulse parameters and electrode configuration directly shaped the wave dynamics of seizure and subsequent CSD. To translate these findings to human patients, we used non-invasive diffuse optical monitoring of cerebral blood flow and oxygenation during routine ECT treatments. We observed that human brains reliably generate hyperemic waves after ECT seizure which are highly consistent with CSD. These results challenge a long-held assumption that seizure is the primary outcome of ECT and point to new opportunities for optimizing ECT stimulation parameters and treatment outcomes.
High-throughput, multiplexed quantification, and sorting of single EVs at single-molecule level
Authors: Park Juhwan , Feng Michelle , Yang Jingbo , Shen Hanfei , Qin Zhiyuan , Guo Wei , Issadore David A.
Published: November 2024

We have developed a platform for the high-throughput, multiplexed, and ultra-sensitive profiling of individual extracellular vesicles (EVs) directly in plasma, which we call BDEVS - AgaroseBead-basedDigital Single Molecule-SingleEV Sorting. Unlike conventional approaches, BDEVS achieves single molecule sensitivity and moderate multiplexing (demonstrated 3-plex) without sacrificing the throughput (processing ten thousand of EVs per minute) necessary to resolve EVs directly in human plasma. Our platform integrates rolling circle amplification (RCA) of EV surface proteins, which are cleaved from single EVs, and amplified within agarose droplets, followed by flow cytometry-based readout and sorting, overcoming steric hindrance, non-specific binding, and the lack of quantitation of multiple proteins on EVs that have plagued earlier approaches. We evaluated the analytical capabilities of BDEVS through head-to-head comparison with gold-standard technologies, and demonstrated a ∼100x improvement in the limit of detection of EV subpopulations. We demonstrate the high throughput (∼100k beads / minute) profiling of individual EVs for key immune markers PD-L1, CD155, and the melanoma tumor marker TYRP-1, and showed that BDEVS can precisely quantify and sort EVs, offering unprecedented resolution for analyzing tumor-immune interactions and detecting rare EV subpopulations in complex clinical specimens. We demonstrate BDEVS’s potential as a transformative tool for EV-based diagnostics and therapeutic monitoring in the context of cancer immunology by analyzing plasma samples from patients with melanoma, where EV heterogeneity plays a critical role in disease progression and response to therapy.

Graphical Abstract
Spatiotemporal regulation by downstream genes ofProk2in olfactory system: from development to function
Authors: Kim Bo-Ra , Rha Min-Seok , Cho Hyung-Ju , Yoon Joo-Heon , Kim Chang-Hoon
Published: November 2024

Olfaction is important for the quality of life; however, in Kallmann syndrome (KS), defective development results in olfactory dysfunction. The mechanism underlying olfactory development, especially in the olfactory epithelium (OE), which detects olfactory signals, remains unclear. Mutations inPROK2, which encodes prokineticin-2, occur in approximately 9% of the KS patients with olfactory defects. In this study, we examined olfactory function and analyzed the causes of olfactory dysfunction based on spatiotemporal development and gene expression changes inProk2knockout (KO) model mice with KS. AdultProk2KO mice exhibited reduced ability to detect olfactory signals. Maturation of olfactory sensory neurons (OSNs) in the OE and formation of glomeruli in the olfactory bulb (OB) in adultProk2KO mice were disrupted, thus causing olfactory dysfunction. Molecular analysis ofProk2KO mice during embryonic development revealed abnormal development of OB layers and reduced differentiation to mature OSNs in the OE, which caused defects in the entire olfactory system. Downstream signaling genes ofProk2, including intermediate filament genes and genes expressed in the putative OB, mediated olfactory system organization. Our findings reveal the role ofProk2in olfactory system organization, providing insights into the mechanisms through which olfactory development defects translate to olfactory function.
Building capacity among caregivers for managing children with Type 1 Diabetes Mellitus through a structured Interprofessional training program
Authors: Juhi Ayesha , Valladath Saleena Ummer , Mondal Himel , Kumar Rajan , Bhattacharya Sangita , Nath Santanu , Dhanvijay Anupkumar , Prabhu Mukhayprana
Published: November 2024

Background

Effective management of type 1 diabetes mellitus (T1DM) in children necessitates not only medical care but also substantial involvement from caregivers, who often encounter psychological, financial, and emotional challenges. This study aimed to develop and evaluate a structured educational program for caregivers of children with T1DM, facilitated by an interprofessional team.

Methods

This mixed-method study, conducted from May 15 to August 15, 2023, comprised two parts. First, a structured educational module was developed based on a needs assessment from semi-structured interviews with 20 caregivers. The module was created in English, Hindi, and Khortha (the local language of Deoghar, Jharkhand, India) and validated by a panel of 10 experts (CVI = 0.83). It was delivered using audio-visual aids, live demonstrations, posters, and booklets. The program’s effectiveness was evaluated through a pre-post-test questionnaire.

Results

The interviews revealed themes such as misunderstandings of treatment plans, distress from frequent insulin administration, fear of glucose monitoring, financial burdens, and psychological stress. Data from 68 of the 75 caregivers who participated in the educational program were analyzed. The Wilcoxon signed-rank test indicated a significant improvement in caregiver knowledge and management practices (P < 0.001), with a large effect size (Cohen’s d = 3.2).

Conclusion

This study demonstrates that structured educational interventions can significantly enhance caregivers’ knowledge and practices in managing T1DM. Multidisciplinary education and support are crucial for addressing the emotional and financial burdens caregivers face, ultimately improving the well-being of both caregivers and children.
A New Labelling Method of99mTc-PSMA-HBED-CC
Authors: Phromphao Benchamat , Shiratori Shuichi
Published: November 2024

Objective

68Ga-PSMA-HBED-CC (68Ga-PSMA-11) was approved by the US FDA as the first PSMA-targeted PET imaging drug for patients with prostate cancer. However, the utility of68Ga-PSMA-HBED-CC may be limited due to PET/CT or PET/MR accessibility and68GaCl3availability produced from68Ge/68Ga generator or cyclotron. Thus, in-house preparation of99mTc-PSMA-HBED-CC was developed as an alternative to68Ga-PSMA-HBED-CC to be ubiquitous and affordable in the worldwide population.

Methods

A solution of99mTc-pertechnetate was added to PSMA-HBED-CC and 4% SnCl2·2H2O in a 10 mL sterile vial. The mixture was heated at 100°C for 15 minutes and then allowed to cool to room temperature. Labeling conditions were optimized to maximize the radiochemical yield of99mTc-PSMA-HBED-CC. The chelation completeness was monitored using instant thin layer chromatography (iTLC), and the stability of99mTc-PSMA-HBED-CC was subsequently evaluated.

Results

The radiolabeling of99mTc-PSMA-HBED-CC was succeeded using the appropriate amount of 10 µg PSMA-HBED-CC 3 µg SnCl2·2H2O and99mTc-pertechnetate 370 MBq at 100 °C for 15 mins, yielded the best result in high radiochemical yield (71.49 ± 2.42%), radiochemical purity (98.29 ± 2.65%), specific activity of 37.84 ± 1.47 GBq/µmol.99mTc-PSMA-HBED-CC is stable with radiochemical purity of more than 95% within 4 hrs at room temperature.

Conclusion

A new labelling method of99mTc-PSMA-HBED-CC was developed. Quality control parameters of99mTc-PSMA-HBED-CC met the criteria in accordance with the European Pharmacopoeia.
Structure and evolution of Photosystem I in the early-branching cyanobacteriumAnthocerotibacter panamensis
Authors: Jiang Han-Wei , Gisriel Christopher J. , Cardona Tanai , Flesher David A. , Brudvig Gary W. , Ho Ming-Yang
Published: November 2024

Thylakoid-free cyanobacteria are thought to preserve ancestral traits of early-evolving organisms capable of oxygenic photosynthesis. However, and until recently, photosynthesis studies in thylakoid-free cyanobacteria were only possible in the model strain Gloeobacter violaceus. Here, we report the isolation, biochemical characterization, cryo-EM structure, and phylogenetic analysis of photosystem I from a newly-discovered thylakoid-free cyanobacterium, Anthocerotibacter panamensis, a distant relative of the genus Gloeobacter. We find that A. panamensis photosystem I exhibits a distinct carotenoid composition and has one conserved low-energy chlorophyll site, which was lost in G. violaceus. These features explain the capacity of A. panamensis to grow under high light intensity, unlike other Gloeobacteria. Furthermore, we find that, while at the sequence level photosystem I in thylakoid-free cyanobacteria has changed to a degree comparable to that of other strains, its subunit composition and oligomeric form might be identical to that of the most recent common ancestor of cyanobacteria.
A study protocol for an international registry observational study evaluating clinical outcomes of transcatheter versus standard surgical mitral valve operation for secondary mitral regurgitation: the TEERMISO study
Authors: Nappi Francesco , Avtaar Singh Sanjeet Singh , Salsano Antonio , Spadaccio Cristiano , Shingu Yasushige , Wakasa Satoru , Fiore Antonio
Published: November 2024

Background

Secondary mitral regurgitation (SMR) is a condition affecting the left ventricle (LV) rather than the mitral valve (MV). If the mitral valve (MV) remains structurally unchanged, enlargement of the left ventricle (LV) or impairment of the papillary muscles (PM) can occur. Several mechanical interventions are available to dictate the resolution of MR. However, there is a lack of robust data to compare mitral valve replacement, mitral valve repair (including subvalvular repair), and transcatheter mitral valve procedures (TMVp). This study aims to compare the effectiveness and clinical outcomes of TMVp using the edge-to-edge mitral valve repair (TEER) technique and standard surgical mitral valve procedures (S-SMVp) in patients with SMR.

Methods and analysis

Five cardiac surgery centres from four European countries and Japan have collaborated to create a multicentre observational registry (TEERMISO). The registry will enrol consecutive patients who underwent mechanical intervention for SMR between January 2007 and December 2023. The investigators assessed the difference between replacement and repair for both the standard surgical approach and the transcatheter procedure. The main clinical outcome will be the degree of LV remodelling as assessed by the Left Ventricular End-Diastolic Volume Index at 10 years. The study will measure several secondary endpoints, including all-cause mortality as the primary endpoint, followed by functional status, hospitalisation, neurocognition, physiological measures (echocardiographic assessment), adverse events and reoperation.

Ethics and dissemination

Ethics approval was obtained in Montpellier University Hospital on 24 May 2022 (Institutional Review Board (IRB) Approval Number: IRB-MTP_2022_05_202201143). The results of the main study and each sub-analysis will be submitted for publication in a peer-reviewed journal. ClinicalTrials.gov ID:NCT05090540; IRB ID: 202201143. (Supplementary material)

Strengths and limitations of this study

This study will be conducted as a large international registry concerning interventions to correct secondary mitral regurgitation; it will provide clinicians important information about transcatheter and surgical techniques in the specific field of the secondary mitral regurgitation.

The primary outcome will offer opportunity to better predict left ventricular remodeling after the procedures.

The secondary outcomes of this study will offer opportunity to provide important information abut survival

The retrospective nature of the study is a limitation to the study design.
The clots removed from ischaemic stroke patients by mechanical thrombectomy are amyloid in nature
Authors: Grixti Justine M. , Chandran Arun , Pretorius Jan-Hendrik , Walker Melanie , Sekhar Alakendu , Pretorius Etheresia , Kell Douglas B
Published: November 2024

Ischemic stroke due to large vessel occlusion results from the blockage of a major cerebral artery by a clot; however, the origins and molecular composition of these clots remain poorly understood. Mechanical thrombectomy has become a standard treatment to remove obstructive clots, providing a unique opportunity to analyze their properties. We previously demonstrated that blood can clot into an amyloid-like form, generating fibrinaloid microclots (2–200 μm) that are highly resistant to fibrinolysis. In this study, archived clots from eight ischemic stroke patients with large vessel occlusion were examined, using samples stored in the Walton Centre Clot Bank in Liverpool, UK. All clots exhibited strong, heterogeneous amyloid staining, revealing a pervasive amyloid component. These findings represent a previously unreported characteristic of stroke clots, highlighting the potential for amyloid-targeted therapies to overcome their fibrinolytic resistance and providing a foundational new insight into ischaemic stroke pathophysiology and treatment.
AI-enabled conversational agent increases engagement with cognitive-behavioral therapy: A randomized controlled trial
Authors: McFadyen Jessica , Habicht Johanna , Dina Larisa-Maria , Harper Ross , Hauser Tobias U. , Rollwage Max
Published: November 2024

Timely support after referral to mental healthcare is crucial, yet patients often face prolonged wait times without intervention. Digital mental health interventions offer scalable solutions, but many struggle to achieve acceptable patient engagement. Tailoring and personalizing materials to individual needs is paramount for driving engagement, a task that generative artificial intelligence AI (genAI) is potentially able to achieve. To examine this promise, we conducted a randomized controlled trial using a genAI-enabled therapy app, Limbic Care, which delivers personalized cognitive behavioral therapy (CBT) materials, against PDF workbooks delivering static CBT content, as commonly used in standard care. Adults with elevated symptoms of anxiety or depression (N = 540) were randomly assigned to the app or control group for six weeks. The app group exhibited a threefold increase in engagement (2.4 times higher usage frequency, 3.8 times longer usage durations). While both groups showed similar overall symptom improvement, participants who engaged with the app’s clinical personalization capabilities experienced significantly greater reductions in anxiety symptoms and enhanced well-being than those who engaged with the standard CBT materials. Importantly, the app was safe, with no increase in adverse events compared to standard care. Our findings suggest that genAI-enabled therapy apps can safely enhance patient engagement and improve clinical outcomes through clinically personalized interventions.
A Digital Diagnostic Pathway for Heart Failure: an economic evaluation
Authors: Mcmeekin Nicola , Davies Andrew , Petrie Mark C , Campbell Ross T , Lowe David J , Murphy Clare L , Macklin Leeanne , Brooksbank Katriona , Wu Olivia
Published: November 2024

Early diagnosis of heart failure improves patient outcomes, however diagnosis is complex and often delayed. This study evaluates a digital pathway for heart failure diagnosis, showing it reduces time to diagnosis and treatment initiation, with an incremental cost of £5,700 per quality adjusted life-year (QALY) gained over a lifetime. The pathway is cost-effective for the UK National Health Service at £20,000 per QALY threshold, however data uncertainties remain.

NPJ digital health 3000-4000 word limit plus abstract 70 words no sub-headings