bluuebunny/crossref_metadata_2025 huggingface dataset:
Hybrid spatial network disintegration strategy considering geographic and topological information
Authors: Ran Lin , Wu Guohua , Luo Qizhang
Published: June 2024

When considering disintegration of spatial networks, the topological relationships between nodes and their geographical positions are taken into account. In the case of regional attacks, the targeted nodes are determined based on the size of the region and the geographical relationships between nodes. In this paper, a new metric is proposed on top of region centrality (RC) to describe the importance of nodes within local regions in spatial networks. We define the weighted sum of the number of connections between nodes within a local region and the number of connections between nodes within the local region and nodes outside the local region as local connectivity. This metric integrates topological information with geographical information. From a mathematical perspective, RC is a special case of local connectivity. In addition, we propose a hybrid spatial network disintegration strategy based on two metrics, namely local connectivity and RC. From experimental results, our strategy outperforms traditional approaches and demonstrates a stronger ability to completely disintegrate the network.
Assessment of cone-beam CT technical image quality indicators and radiation dose for optimal STL model used in visual surgical planning
Authors: Koivisto Juha , Wolff Jan , Pauwels Ruben , Kaasalainen Touko , Suomalainen Anni , Stoor Patricia , Horelli Jani , Suojanen Juho
Published: June 2024

Objectives

The aim of this study was to identify cone-beam computed tomography (CBCT) protocols that offer an optimal balance between effective dose (ED) and 3D model for orthognathic virtual surgery planning, using CT as a reference, and to assess whether such protocols can be defined based on technical image quality metrics.

Methods

Eleven CBCT (VISO G7, Planmeca Oy, Helsinki, Finland) scan protocols were selected out of 32 candidate protocols, based on ED and technical image quality measurements. Next, an anthropomorphic RANDO SK150 phantom was scanned using these 11 CBCT protocols and 2 CT scanners for bone quantity assessments. The resulting DICOM (Digital Imaging and Communications in Medicine) files were converted into Standard Tessellation Language (STL) models that were used for bone volume and area measurements in the predefined orbital region to assess the validity of each CBCT protocol for virtual surgical planning.

Results

The highest CBCT bone volume and area of the STL models were obtained using normal dose protocol (F2) and ultra-low dose protocol (J13), which resulted in 48% and 96% of the mean STL bone volume and 48% and 95% of the bone area measured on CT scanners, respectively.

Conclusions

The normal dose CBCT protocol “F2” offered optimal bone area and volume balance for STL. The optimal CBCT protocol can be defined using contrast-to-noise ratio and modulation transfer function values that were similar to those of the reference CT scanners’. CBCT scanners with selected protocols can offer a viable alternative to CT scanners for acquiring STL models for virtual surgical planning at a lower effective dose.
Self-sealing atrio-oesophageal fistula as a complication of pulmonary vein isolation: a case report
Authors: Herrera-Parra Nicolás , García-Pretelt Enrique Carlos , Bonilla-Cortés Camilo Hernán , Ortíz Eduardo
Published: June 2024

Background

Atrio-oesophageal fistulas (AEFs) are an uncommon complication of pulmonary vein ablation, and its diagnosis is challenging. Multidisciplinary interventions and diagnostic imaging are usually required and may play a role in the initial assessment.

Case summary

A 69-year-old female with atrial fibrillation who had undergone recent pulmonary vein ablation consulted with unspecific symptoms and sudden hemiparesis. Brain imaging showed pneumocephalus and acute infarcts. Chest computed tomography (CT) was highly suspicious for AEF. Surgical exploration revealed a swollen mediastinum attached to the right inferior pulmonary vein.

Discussion

Non-specific symptoms after pulmonary vein ablation should prompt the suspicion of complications. In the presence of fever or neurological deficit, AEF must be suspected and assessed with a contrast-enhanced chest CT, which has become the gold standard. In brain imaging, pneumocephalus and multiple punctate acute infarcts might also indicate the presence of this complication.
Exploring differences in neophobia and anti-predator behaviour between urban and rural mountain chickadees
Authors: Heales Heather E , Flood Nancy J , Oud Madison D , Otter Ken A , Reudink Matthew W
Published: June 2024

Urbanization is changing natural landscapes worldwide, pushing species to quickly acclimate or adapt if they are to survive in urban environments. Mountain chickadees (Poecile gambeli) readily nest in both urban and rural environments without suffering apparent reproductive costs. However, whether urban-nesting chickadees are successful in these environments due to differences in behaviour between urban and rural birds remains untested. We examined the behavioural responses of urban and rural nesting mountain chickadee females when presented with a novel object (red plastic cup) or simulated predator (imitation squirrel model) at the nest. Behavioural responses depended on both the type of model and the habitat. As expected, mountain chickadees responded more strongly to squirrel models than novel objects; however, the magnitude of the difference in response depended on habitat. Urban birds seemingly ignored the novel object, spending little time investigating, and re-entering the nest box quickly. In contrast, rural birds spent more time reacting to the novel object and alarm calling within 5 m of the nest. When presented with a predator model, the urban birds reacted relatively more strongly (compared to the novel stimulus) than rural birds, spending more time within 5 m of the nest and alarm calling. These results suggest that either mountain chickadees in urban environments quickly acclimatize to the presence of novel objects or, potentially, that less neophobic birds disproportionately settle in urban environments or experience positive selection in urban areas. Either way, reduced neophobia may aid in mountain chickadees’ ability to readily and successfully nest in such habitats.
Analgesic effects of intraperitoneal lidocaine in adults undergoing surgery: a systematic review and meta-analysis with trial sequential analysis
Authors: Ng Ka Ting , Lim Wei En , Teoh Wan Yi , Zainal Abidin Mohd Fitry Bin
Published: June 2024

Objective

The administration of local anesthesia in intraperitoneal space as part of the multi-modal analgesic regimen has shown to be effective in reducing postoperative pain. Recent studies demonstrated that intraperitoneal lidocaine may provide analgesic effects. Primary objective was to determine the impact of intraperitoneal lidocaine on postoperative pain scores at rest.

Design

We carried out a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

Methods

Databases of MEDLINE, EMBASE, and CENTRAL were searched from their inception date until May 2023. Randomized clinical trials (RCT) comparing intraperitoneal lidocaine and placebo in adults undergoing surgery were included.

Results

Our systematic review included 24 RCTs (n = 1824). The intraperitoneal lidocaine group was significantly associated with lower postoperative pain scores at rest (MD, −0.87, 95% CI, −1.04 to −0.69) and at movement (MD, −0.50, 95% CI, −0.93 to −0.08) among adult patients after surgery. Its administration also significantly decreased morphine consumption (MD, −6.42 mg, 95% CI, −11.56 to −1.27) and lowered the incidence of needing analgesia (OR, 0.22, 95% CI, 0.14 to 0.35). Intraperitoneal lidocaine statistically reduced time to resume regular diet (MD, 0.16 days; 95% CI, −0.31 to −0.01) and lowered postoperative incidence of nausea and vomiting (OR, 0.54, 95% CI, 0.39 to 0.75).

Conclusions

In this review, our findings should be interpreted with caution. Future studies are warranted to determine the optimal dose of administering intraperitoneal lidocaine among adult patients undergoing surgery.
Recruitment and Retention Strategies for Randomized Clinical Trials Involving Family Members of ICU Patients
Authors: Samuels Aaron , Sygal Valeria , Burns Karen E. A. , Goldfarb Michael
Published: June 2024

OBJECTIVES:

To review recruitment and retention strategies of randomized family-centered interventional studies in adult ICUs.

DATA SOURCES:

The MEDLINE, Embase, PsycINFO, CINAHL, and the Cochrane Library database from inception to February 2023.

STUDY SELECTION:

Randomized controlled trials with family-centered interventions in the ICU setting that reported at least one family-centered outcome that were included in our previously published systematic review.

DATA EXTRACTION:

For recruitment: Number of family members approached and enrolled, type of approach, location, time of day approached, whether medical team approached first, compensation offered, and type of consent. For retention: Number of family members enrolled and completed initial follow-up visit, mode of follow-up, location of follow-up visit, data collection method, timing of follow-up visits, number of follow-up visits, and compensation offered. Recruitment (participants approached/enrolled) and retention (participants enrolled/completed initial follow-up) percentage were calculated.

DATA SYNTHESIS:

There were 51 studies in the analysis. The mean recruitment percentage was 49.3% ± 24.3%. There were no differences in recruitment percentage by study country, ICU type, recruitment approach, or whether the medical team approached the family member first (all p > 0.05). The mean retention percentage for the initial follow-up visit was 81.6% ± 18.0%. There were no differences in retention percentage by mode of participant contact, data collection type, or follow-up location (all p > 0.05). Minimal data were available to determine the impact of time of day approached and compensation on recruitment and retention outcomes.

CONCLUSIONS:

About half of family members of ICU patients approached participated in trials and more than eight in ten completed the initial follow-up visit. We did not identify specific factors that impacted family recruitment or retention. There is a strong need for further studies to characterize optimal strategies to ensure family participation in clinical trials.
Radiation Therapy–Induced Fibrous Histiocytoma, Mimicking Local Recurrence and Detected by 18F-FDG PET/CT in a Patient With Breast Cancer
Authors: Beytur Muhammet Fatih , Alçın Göksel , Cin Selçuk , Ergül Nurhan , Çermik Tevfik Fikret , Arslan Esra
Published: June 2024

A 76-year-old woman was diagnosed breast carcinoma and treated with breast-conserving surgery and chemoradiotherapy. A year after the treatment completion, restaging 18F-FDG PET/CT scan detected no any pathological finding. However, due to a lesion detected during physical examination on the right thoracic wall adjacent to the primary tumor bed, 18F-FDG PET/CT imaging was performed 9 months later for restaging. Highly intense FDG uptake was detected in an approximately 1-cm nodular lesion, and metastasis was reported as suspicious, and histopathological confirmation was recommended. Excision was performed and pathological examination diagnosed benign cellular fibrous histiocytoma.
Prostatic Utricle Cysts as a Potential Pitfall in PSMA PET/CT Interpretation
Authors: Girod Bradley J. , Nguyen Nghi C.
Published: June 2024

A 60-year-old man with T2aN0M0 prostate cancer underwent intensity-modulated radiotherapy targeting the prostate and seminal vesicles. Experiencing biochemical recurrence after 6 years, 68Ga-PSMA-11 PET/CT revealed focal radioactivity in the posterior midline of the prostate, identified as a prostatic utricle cyst on subsequent MRI. Similar findings appeared in a previous 18F-piflufolastat PET/CT, with negative biopsy results. The patient then received intensity-modulated radiotherapy directed to 2 PSMA-avid pelvic nodes and leuprolide acetate, achieving an undetectable PSA in 4 months. This case highlights a potential pitfall in PSMA PET interpretation associated with prostatic utricle cysts.
Left Atrial Appendage Closure Devices May Demonstrate Significant 18F-FDG Uptake in the Absence of Infection
Authors: Waring Harry J. , Bradley Kevin M.
Published: June 2024

A 79-year-old man found to have a pulmonary nodule and pleural effusion on CT went on to have an 18F-FDG PET/CT scan. The lung abnormality did not show FDG uptake and appeared benign. However, PET/CT detected moderately increased FDG uptake associated with a left atrial appendage closure device inserted 11 months prior to the PET/CT. Infection of a left atrial closure device has previously been demonstrated with FDG PET/CT. This case, in the absence of infection, with normal serum inflammatory markers, highlights that left atrial closure devices, in common with other foreign bodies/devices, may demonstrate significant, incidental FDG uptake.
Species interactions and eco-evolutionary dynamics of dispersal: the diversity dependence of dispersal
Authors: Bonte Dries , Keith Sally , Fronhofer Emanuel A.
Published: June 2024

Dispersal plays a pivotal role in the eco-evolutionary dynamics of spatially structured populations, communities and ecosystems. As an individual-based trait, dispersal is subject to both plasticity and evolution. Its dependence on conditions and context is well understood within single-species metapopulations. However, species do not exist in isolation; they interact locally through various horizontal and vertical interactions. While the significance of species interactions is recognized for species coexistence and food web functioning, our understanding of their influence on regional dynamics, such as their impact on spatial dynamics in metacommunities and meta-food webs, remains limited. Building upon insights from behavioural and community ecology, we aim to elucidate biodiversity as both a driver and an outcome of connectivity. By synthesizing conceptual, theoretical and empirical contributions from global experts in the field, we seek to explore how a more mechanistic understanding of diversity–dispersal relationships influences the distribution of species in spatially and temporally changing environments. Our findings highlight the importance of explicitly considering interspecific interactions as drivers of dispersal, thus reshaping our understanding of fundamental dynamics including species coexistence and the emergent dynamics of metacommunities and meta-ecosystems. We envision that this initiative will pave the way for advanced forecasting approaches to understanding biodiversity dynamics under the pressures of global change.

This article is part of the theme issue ‘Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics’.
Dispersal evolution alters evolution-mediated priority effects in a metacommunity
Authors: Fajgenblat Maxime , De Meester Luc , Urban Mark C.
Published: June 2024

Biologists have long sought to predict the distribution of species across landscapes to understand biodiversity patterns and dynamics. These efforts usually integrate ecological niche and dispersal dynamics, but evolution can also mediate these ecological dynamics. Species that disperse well and arrive early might adapt to local conditions, which creates an evolution-mediated priority effect that alters biodiversity patterns. Yet, dispersal is also a trait that can evolve and affect evolution-mediated priority effects. We developed an individual-based model where populations of competing species can adapt not only to local environments but also to different dispersal probabilities. We found that lower regional species diversity selects for populations with higher dispersal probabilities and stronger evolution-mediated priority effects. When all species evolved dispersal, they monopolized fewer patches and did so at the same rates. When only one of the species evolved dispersal, it evolved lower dispersal than highly dispersive species and monopolized habitats once freed from maladaptive gene flow. Overall, we demonstrate that dispersal evolution can shape evolution-mediated priority effects when provided with a greater ecological opportunity in species-poor communities. Dispersal- and evolution-mediated priority effects probably play greater roles in species-poor regions like the upper latitudes, isolated islands and in changing environments.

This article is part of the theme issue 'Diversity-dependence of dispersal: interspecific interactions determine spatial dynamics'.
Nucleolin acute degradation reveals novel functions in cell cycle progression and division in TNBC
Authors: Mills Joseph , Tessari Anna , Anastas Vollter , Kumar Damu Sunil , Rad Nastaran Samadi , Lamba Saranya , Cosentini Ilaria , Reers Ashley , Zhu Zirui , Miles Wayne O. , Coppola Vincenzo , Cocucci Emanuele , Magliery Thomas J. , Shive Heather , Davies Alexander E. , Rizzotto Lara , Croce Carlo M. , Palmieri Dario
Published: June 2024

Nucleoli are large nuclear sub-compartments where vital processes, such as ribosome assembly, take place. Technical obstacles still limit our understanding of the biological functions of nucleolar proteins in cell homeostasis and cancer pathogenesis. Since most nucleolar proteins are essential, their abrogation cannot be achieved through conventional approaches. Additionally, the biological activities of many nucleolar proteins are connected to their physiological concentration. Thus, artificial overexpression might not fully recapitulate their endogenous functions.

Proteolysis-based approaches, such as the Auxin Inducible Degron (AID) system paired with CRISPR/Cas9 knock-in gene-editing, have the potential to overcome these limitations, providing unprecedented characterization of the biological activities of endogenous nucleolar proteins.

We applied this system to endogenous nucleolin (NCL), one of the most abundant nucleolar proteins, and characterized the impact of its acute depletion on Triple-Negative Breast Cancer (TNBC) cell behavior.

Abrogation of endogenous NCL reduced proliferation and caused defective cytokinesis, resulting in bi-nucleated tetraploid cells. Bioinformatic analysis of patient data, and quantitative proteomics using our experimental NCL-depleted model, indicated that NCL levels are correlated with the abundance of proteins involved in chromosomal segregation. In conjunction with its effects on sister chromatid dynamics, NCL abrogation enhanced the anti-proliferative effects of chemical inhibitors of mitotic modulators such as the Anaphase Promoting Complex.

In summary, using the AID system in combination with CRISPR/Cas9 for endogenous gene editing, our findings indicate a novel role for NCL in supporting the completion of the cell division in TNBC models, and that its abrogation could enhance the therapeutic activity of mitotic-progression inhibitors.
Long-term single molecule localization microscopy uncovers dynamic co-assembly of Lrp6 and Ror2 into Wnt-signalosomes
Authors: Philippi Michael , Dohle Julia , Watrinet Isabelle , Holtmannspötter Michael , Li Jinye , Birkholz Oliver , Miao Yi , Rothbauer Ulrich , Christopher Garcia K. , Kurre Rainer , Piehler Jacob , You Changjiang
Published: June 2024

The conserved Wnt signaling has been classified as two categories of canonical and noncanonical Wnt signaling. With a high promiscuity of Wnt signaling, how receptors from the two distinct pathways re-arrange in multi-protein signalosomes remains elusive. We here developed single-molecule tracking and localization microscopy based on labeling with reversibly binding nanobodies (rbTALM) for imaging receptor dynamics in the plasma membrane for extended time periods. To this end, we engineered nanobody-tag pairs with fine-tuned binding stabilities ensuring single-molecule tracking with high fidelity, yet continuous exchange of photobleached labels. Multicolor rbTALM imaging enabled simultaneous tracking and super-resolution imaging of three different Wnt co-receptors in the same cell for more than one hour at video rate. Time-lapse correlation analyses uncovered cooperative association of canonical and noncanonical Wnt co-receptors into a common, hybrid Wnt signalosome, demonstrating the exciting possibilities of rbTALM imaging for exploring nanoscale dynamics across millisecond to hour timescales.
Cell of origin alters myeloid-mediated immunosuppression in lung adenocarcinoma
Authors: Yang Minxiao , Shulkin Noah , Gonzalez Edgar , Castillo Jonathan , Yan Chunli , Zhang Keqiang , Arvanitis Leonidas , Borok Zea , Wallace W. Dean , Raz Dan , Torres Evanthia T. Roussos , Marconett Crystal N.
Published: June 2024

Solid carcinomas are often highly heterogenous cancers, arising from multiple epithelial cells of origin. Yet, how the cell of origin influences the response of the tumor microenvironment is poorly understood. Lung adenocarcinoma (LUAD) arises in the distal alveolar epithelium which is populated primarily by alveolar epithelial type I (AT1) and type II (AT2) cells. It has been previously reported thatGramd2+AT1 cells can give rise to a histologically-defined LUAD that is distinct in pathology and transcriptomic identity from that arising fromSftpc+AT2 cells1,2. To determine how cells of origin influence the tumor immune microenvironment (TIME) landscape, we comprehensively characterized transcriptomic, molecular, and cellular states within the TIME ofGramd2+AT1 andSftpc+AT2-derived LUAD using KRASG12Doncogenic driver mouse models. Myeloid cells within theGramd2+AT1-derived LUAD TIME were increased, specifically, immunoreactive monocytes and tumor associated macrophages (TAMs). In contrast, theSftpc+AT2 LUAD TIME was enriched for Arginase-1+myeloid derived suppressor cells (MDSC) and TAMs expressing profiles suggestive of immunosuppressive function. Validation of immune infiltration was performed using flow cytometry, and intercellular interaction analysis between the cells of origin and major myeloid cell populations indicated that cell-type specific markers SFTPD in AT2 cells and CAV1 in AT1 cells mediated unique interactions with myeloid cells of the differential immunosuppressive states within each cell of origin mouse model. Taken together,Gramd2+AT1-derived LUAD presents with an anti-tumor, immunoreactive TIME, while the TIME ofSftpc+AT2-derived LUAD has hallmarks of immunosuppression. This study suggests that LUAD cell of origin influences the composition and suppression status of the TIME landscape and may hold critical implications for patient response to immunotherapy.
Modeling the dietary effects on bat viral shedding and potential consequences for pathogen spillover
Authors: Vanalli Chiara , Falvo Caylee , Crowley Dan , Schwarz Benjamin , Plowright Raina , Hudson Peter J. , Rynda-Apple Agnieszka , Cattadori Isabella M.
Published: June 2024

Changes in the quality and quantity of food resources can affect individuals’ health, the way they control infections and consequently the likelihood of onward transmission of pathogens. Dietary shifts have been proposed as one of the factors driving spillovers of zoonotic viruses from bats through a bridging host to humans. While there is a general understanding of the relationship between nutrition and infection in model systems, how diet affects pathogen shedding and the risk of spillover from bats is lacking. We used a data-driven mathematical modeling approach to disentangle the relation between diet, immunity, and viral shedding of Jamaican fruit bats infected with H18N11 and fed different dietary regimes. Model selection indicates that the synergistic interaction between the metabolite citrulline and the cytokine TNFα controls viral shedding in a diet-dependent manner. Bats on a sub-optimal fat diet are more successful in terminating shedding than bats on an optimal or sub-optimal sugar diet. However, when bat foraging behavior is considered, bats on the optimal diet show a lower spillover hazard, probably because of a feeding behavior less conducive to transmission. This study provides novel insights into the diet-driven mechanisms of viral shedding and how they can potentially contribute to spillover events.
Recovery after human bone marrow mesenchymal stem cells (hBM-MSCs)-derived extracellular vesicles (EVs) treatment in post-MCAO rats requires handling associated with repeated behavioral testing
Authors: Gomez-Galvez Yolanda , Gupta Malvika , Kaur Mandeep , Fusco Salvatore , Podda Maria Vittoria , Grassi Claudio , Srivastava Amit , Iacovitti Lorraine , Blanco-Suarez Elena
Published: June 2024

Rehabilitation is the only current intervention that improves sensorimotor function in ischemic stroke patients, similar to task-specific intensive training in animal models of stroke. Bone marrow mesenchymal stem cells (BM-MSCs)-derived extracellular vesicles (EVs) are promising in restoring brain damage and function in stroke models. Additionally, the non-invasive intranasal route allows EVs to reach the brain and target specific ischemic regions. Yet unclear is how handling might enhance recovery or influence other therapies such as EVs after stroke. We used the transient middle cerebral artery occlusion (MCAO) model of stroke in rats to assess how intensive handling alone, in the form of sensorimotor behavioral tests, or in combination with an intranasal multidose or single dose of EVs restored neurological function and ischemic damage. Handled rats were exposed to a battery of sensorimotor tests, including the modified Neurological Severity Score (mNSS), beam balance, corner, grid walking, forelimb placement, and cylinder tests, together with Magnetic Resonance Imaging (MRI) at 2, 7, 14, 21, and 28 days post-stroke (dps). Handled MCAO rats were also exposed to an intranasal multidose of EVs (8 doses in total across four weeks, each dose containing 0.8 × 109EVs in 120 µl) or a single dose of EVs (2.4 × 109EVs in 200 µl) at 2 dps. Non-handled rats were evaluated only by mNSS and MRI at 2, 28, and 56 dps and were treated with a single intranasal dose of EVs. Our results showed that handling animals after MCAO is necessary for EVs to work and that a single cumulative dose of EVs further improves the neurological function recovered during handling without affecting ischemic damage. These results show the importance of rehabilitation in combination with other treatments and highlight how intensive behavioral testing might influence functional recovery after stroke, especially when other treatments are also given.
Optimized Biomechanical Design of a Pulsatile Fontan Conduit for Congenital Heart Palliation
Authors: Emuna Nir , Marsden Alison L. , Humphrey Jay D.
Published: June 2024

The evolution of palliative surgical procedures for children born with congenital heart defects has proven remarkably successful in extending life, but the resulting non-physiological circulation predisposes to myriad sequelae that compromise quality of life and overall life span. Among these procedures, standard-of-care Fontan completion surgery bypasses the nonfunctional ventricle and provides steady flow of deoxygenated blood to the lungs via a synthetic conduit that typically connects the inferior vena cava to a pulmonary artery. This altered circulation reduces cardiac output, elevates central venous pressures, and possibly contributes to adverse remodeling of the pulmonary vessels. There is, therefore, strong motivation to develop a next generation Fontan conduit capable of serving as a sub-pulmonic pulsatile pump, and there are now several reports of initial attempts. None of these studies have been driven by biomechanical considerations, however, and none have achieved the desired functionality. We thus present a novel analytical framework to improve design and guide fabrication by focusing on the microstructure and material properties of the contractile myofibers and associated passive matrix. Our optimized designs simultaneously ensure desired levels of stroke volume, ejection fraction, and pressure generation given constraints on Frank-Starling myofiber contraction and the limited space within the thoracic cavity of a three-to four-year-old child. This analysis also highlights the need to minimize any associated axial force or torque generation that a pulsatile conduit could transmit to the host vessels at the requisite anastomoses.
From Cardiac Myosin to the Beta Receptor: Autoantibodies Promote a Fibrotic Transcriptome and Reduced Ventricular Recovery in Human Myocarditis
Authors: Myers Jennifer M. , Sandel Clayton , Alvarez Kathy , Garman Lori , Wiley Graham , Montgomery Courtney , Gaffney Patrick , Stavrakis Stavros , Fairweather DeLisa , Bruno Katelyn A. , Zhao Yan Daniel , Cooper Leslie T. , Cunningham Madeleine W.
Published: June 2024

Background

Myocarditis leads to dilated cardiomyopathy (DCM) with one-third failing to recover normal ejection fraction (EF50%), and there is a critical need for prognostic biomarkers to assess risk of nonrecovery. Cardiac myosin (CM) autoantibodies (AAbs) cross-reactive with the β−adrenergic receptor (βAR) are associated with myocarditis/DCM, but their potential for prognosis and functional relevance is not fully understood.

Methods

CM AAbs and myocarditis-derived human monoclonal antibodies (mAbs) were investigated to define pathogenic mechanisms and CM epitopes of nonrecovery. Myocarditis patients who do not recover ejection fraction (EF<50%) by one year were studied in a longitudinal (n=41) cohort. Sera IgG and human mAbs were investigated for autoreactivity with CM and CM peptides by ELISA, protein kinase A (PKA) activation, and transcriptomic analysis in H9c2 heart cell line.

Results

CM AAbs were significantly elevated in nonrecovered compared to recovered patients and correlated with reduced EF (<50%). CM epitopes specific to nonrecovery were identified. Transcriptomic analysis revealed serum IgG and mAb 2C.4 induced fibrosis/apoptosis pathwaysin vitrosimilar to isoproterenol treated cells. Sera IgG and 2C.4 activated PKA in an IgG and βAR-dependent manner. Endomyocardial biopsies from myocarditis/DCM revealed IgG+ trichrome+ tissues.

Conclusions

CM AAbs were significantly elevated in nonrecovered patients, suggesting novel prognostic relevance. CM AAbs correlated with lower EF, and Ab-induced fibrosis/apoptosis pathways suggested a role for CM AAbs in patients who do not recover and develop irreversible heart failure. Homology between CM and βARs supports mechanisms related to cross-reactivity of CM AAbs with the βAR, a potential AAb target in nonrecovery.
Distribution models predict climate-related range alteration or extinction of eleven threatened tropical rainforest trees in the Western Ghats
Authors: Madhavan A.P , Bhat Kshama , Kasinathan Srinivasan , Mudappa Divya , Page Navendu , Raman T. R. Shankar
Published: June 2024

Evidence for climate-change related alteration in distributions and ranges of forest trees is accumulating, but information from Asian tropical forests, particularly for threatened and endemic species, remains limited. Here, we examine landscape-level distribution-abundance patterns of 11 endemic and threatened tropical rainforest tree species in the Anamalai Hills and model their distribution and responses to future climate scenarios in the Southern Western Ghats (SWG), India. Six of the primarily low- and mid-elevation species were more abundant in protected reserves than forest fragments. Occurrence data from the Anamalais and SWG (N = 3004, range: 41-706 per species) were used to model distributions using maximum entropy (maxent) species distribution modelling in R. Maxent model performances indicated excellent fits for 9 of 11 species (AUC>0.90) with precipitation and temperature variables showing higher permutation importance. There was high interspecies variability in range size (197-12,221 km2) and niche width (0.04-0.50). Models of distribution under future climate in 2061-2080 predict range reductions in six species (including near-extinction for two species), increases for three species, and no substantial change for two species. Predicted southward and westward shifts in ranges and persistence in parts of the SWG indicate the importance of identifying and conserving micro-climatic zones or refugia to ensure the persistence of tree species under anticipated climate change.
Individual variation in meiotic crossover positioning, rate and interference are associated with distinct genetic processes in domestic pigs
Authors: Brekke Cathrine , Gjuvsland Arne B. , Berg Peer , Johnston Susan E.
Published: June 2024

Meiotic crossovers are essential for proper chromosome segregation, and provide an important mechanism for adaptation through linking beneficial alleles and purging deleterious mutations. However, crossovers can also break apart beneficial alleles and are themselves a source of new mutations within the genome. The rate and distribution of crossovers shows huge variation both within and between chromosomes, individuals and species, yet the molecular and evolutionary causes and consequences of this variation remain poorly understood. A key step in understanding this variation is to understand the genetic architecture of how many crossovers occur, where they occur, and how they interfere, as this allows us to identify the degree to which these factors are governed by common or distinct genetic processes. Here, we investigate individual variation in crossover count, crossover interference (ν), and crossover positioning measured as both intra-chromosomal allelic shuffling and distance to telomere (Mb), in a large genotyped breeding population of domestic pigs. Using measures from 82,474 gametes from 4,704 mothers and 271 fathers, we show that crossover traits are heritable within each sex (h2= 0.03 - 0.11), with the exception of male crossover interference. Crossover count and interference have a strongly shared genetic architecture in females, mostly driven by variants atRNF212. Female crossover positioning is mediated by variants atMEI4,PRDM9, andSYCP2. We also identify tentative associations at genomic regions corresponding toCTCFandREC114/REC8/CCNB1IP1(crossover count), andZCWPW1andZCWPW2(crossover positioning). Our results show that crossover count and crossover positioning in female pigs have the capacity to evolve somewhat independently in our dataset.
Nonlinear compliance of NompC gating spring and its implication in mechanotransduction
Authors: Wang Yukun , Jin Peng , Kumar Avinash , Jan Lily , Cheng Yifan , Jan Yuh-Nung , Zhang Yongli
Published: June 2024

Cytoskeleton-tethered mechanosensitive channels (MSCs) utilize compliant proteins or protein domains called gating springs to convert mechanical stimuli into electric signals, enabling sound and touch sensation and proprioception. The mechanical properties of these gating springs, however, remain elusive. Here, we explored the mechanical properties of the homotetrameric NompC complex containing long ankyrin-repeat domains (ARDs). We developed a toehold-mediated strand displacement approach to tether single membrane proteins, allowing us to exert force on them and precisely measure their absolute extension using optical tweezers. Our findings revealed that each ARD has a low stiffness of ∼0.7 pN/nm and begins to unfold stepwise at ∼7 pN, leading to nonlinear compliance. Our calculations indicate that this nonlinear compliance may help regulate NompC’s sensitivity, dynamic range, and kinetics to detect mechanical stimuli. Overall, our research highlights the importance of a compliant and unfolding-refolding gating spring in facilitating a graded response of MSC ion transduction across a wide spectrum of mechanical stimuli.
Altered connectome topology in newborns at risk for cognitive developmental delay: a cross-etiologic study
Authors: Speckert Anna , Payette Kelly , Knirsch Walter , von Rhein Michael , Grehten Patrice , Kottke Raimund , Hagmann Cornelia , Natalucci Giancarlo , Moehrlen Ueli , Mazzone Luca , Ochsenbein-Kölble Nicole , Padden Beth ,   SPINA BIFIDA STUDY GROUP ZURICH, Latal Beatrice , Jakab Andras
Published: June 2024

The human brain connectome is characterized by the duality of highly modular structure and efficient integration, supporting information processing. Newborns with congenital heart disease (CHD), prematurity, or spina bifida aperta (SBA) constitute a population at risk for altered brain development and developmental delay (DD). We hypothesize that, independent of etiology, alterations of connectomic organization reflect neural circuitry impairments in cognitive DD. Our study aim is to address this knowledge gap by using a multi-etiologic neonatal dataset to reveal potential commonalities and distinctions in the structural brain connectome and their associations with DD. We used diffusion tensor imaging (DTI) of 187 newborns (42 controls, 51 with CHD, 51 with prematurity, and 43 with SBA). Structural weighted connectomes were constructed using constrained spherical deconvolution based probabilistic tractography and the Edinburgh Neonatal Atlas. Assessment of brain network topology encompassed the analysis of global graph features, network-based statistics, and low-dimensional representation of global and local graph features. The Cognitive Composite Score of the Bayley Scales of Infant and Toddler Development 3rdedition was used as outcome measure at corrected 2 years for the preterm born individuals and SBA patients, and at 1 year for the healthy controls and CHD.

We revealed differences in the connectomic structure of newborns across the four groups after visualizing the connectomes in a two-dimensional space defined by network integration and segregation. Further, ANCOVA analyses revealed differences in global efficiency (p < 0.0001), modularity (p < 0.0001), mean rich club coefficient (p = 0.017) and small-worldness (p = 0.016) between groups after adjustment for postmenstrual age at scan and gestational age at birth. Moreover, small-worldness was significantly associated with poorer cognitive outcome, specifically in the CHD cohort (r = -0.41, p = 0.005).

Our cross-etiologic study identified divergent structural brain connectome profiles linked to deviations from optimal network integration and segregation in newborns at risk for DD. Small-worldness emerges as a key feature, associating with early cognitive outcomes, especially within the CHD cohort, emphasizing small-worldness’ crucial role in shaping neurodevelopmental trajectories. Neonatal connectomic alterations associated with DD may serve as a marker identifying newborns at-risk for DD and provide early therapeutic interventions.
Postmortem tissue biomarkers of menopausal transition
Authors: Tickerhoof Maria , Cham Heining , Ger Anaya , Burrja Sonola , Auluck Pavan , Schmidt Peter J. , Marenco Stefano , Kundakovic Marija
Published: June 2024

The menopausal transition (MT) is associated with an increased risk for many disorders including neurological and mental disorders. Brain imaging studies in living humans show changes in brain metabolism and structure that may contribute to the MT-associated brain disease risk. Although deficits in ovarian hormones have been implicated, cellular and molecular studies of the brain undergoing MT are currently lacking, mostly due to a difficulty in studying MT in postmortem human brain. To enable this research, we explored 39 candidate biomarkers for menopausal status in 42 pre-, peri-, and post-menopausal subjects across three postmortem tissues: blood, the hypothalamus, and pituitary gland. We identified thirteen significant and seven strongest menopausal biomarkers across the three tissues. Using these biomarkers, we generated multi-tissue and tissue-specific composite measures that allow the postmortem identification of the menopausal status across different age ranges, including the “perimenopausal”, 45-55-year-old group. Our findings enable the study of cellular and molecular mechanisms underlying increased neuropsychiatric risk during the MT, opening the path for hormone status-informed, precision medicine approach in women’s mental health.
Serum D-dimer level in women with polycystic ovary syndrome
Authors: Hossan S , Morshed MS , Banu H , Hasanat MA
Published: June 2024

Background

Women with polycystic ovarian syndrome (PCOS) have hyperandrogenemia and insulin resistance, which predispose them to prothrombotic conditions. D-dimer is a global marker of hemostatic dysfunction that has a contentious relationship with PCOS.

Objective

To assess the association of D-dimer with PCOS and its manifestations

Methods

This case-control study enrolled 44 women with PCOS based on the International Evidence-based Guideline, 2018, and an equal number of matched healthy controls by convenient sampling. After obtaining informed consent, participants’ clinical data was taken, and fasting blood was drawn to measure glucose, lipid profile, hormones, and D-dimer. D-dimer was analyzed by latex immunofluorescence assay.

Results

The D-dimer levels and status were statistically similar between the study groups [PCOS vs. control: 0.11 (0.10-0.17) vs. 0.13 (0.10-0.22), median (IQR), p= 0.673]. D-dimer levels did not vary according to the different characteristics of women with PCOS (p>0.05). D-dimer levels had no significant correlations with various clinical and biochemical characteristics among women with PCOS (p>0.05).

Conclusion

D-dimer has no significant association with PCOS or its manifestations.
Complementary value of molecular, phenotypic and functional aging biomarkers in dementia prediction
Authors: Engvig Andreas , Kalleberg Karl Trygve , Westlye Lars T. , Leonardsen Esten Høyland ,   Alzheimer’s Disease Neuroimaging Initiative
Published: June 2024

DNA methylation age (MA), brain age (BA), and frailty index (FI) are putative aging biomarkers linked to dementia risk. We investigated their relationship and combined potential for prediction of stages of cognitive impairment and future risk of dementia using the ADNI database. Of several MA algorithms, DunedinPACE had the strongest association with neuropsychological tests and was included alongside BA and FI in predictive analyses.

The pairwise correlations between age- and sex-adjusted measures for MA (aDundedinPACE), brain age (aBA), and frailty (aFI) were low (all <0.15). In a prediction model including age, sex, and aFI, we achieved an area under the curve (AUC) of 0.95 for differentiating cognitively normal controls (CN) from dementia patients in a held-out test set. The best models for CN vs. mild cognitive impairment (MCI) and MCI vs. dementia contained age, sex, aFI and aBA as predictors, and achieved out-of-sample AUCs of 0.82 and 0.83 respectively. When combined with clinical biomarkers (apolipoprotein E ε4 allele count, memory, executive function), a model including aBA and aFI predicted 5-year dementia risk among MCI patients with an out-of-sample AUC of 0.83. aDunedinPACE did not improve the predictions. FI had a stronger adverse effect on prognosis in males, while BA’s impact was greater in females.

Our findings highlight complementary value of BA and FI in dementia prediction. The results support a multidimensional view of dementia, including an intertwined relationship between the biomarkers, sex, and prognosis. The tested MA’s limited contribution suggests caution in their use for individual risk assessment of dementia.
Determining the optimal hematoma volume-based thresholds for surgical and medical strategies in basal ganglia hemorrhage
Authors: Chaisawasthomrong Chonnawee , Boongird Atthaporn
Published: June 2024

Background

The indication for surgical intervention in spontaneous intracerebral hemorrhage remains controversial, particularly regarding the benefits of early hematoma drainage via open craniotomy. This study aimed to identify the maximum hematoma volume suitable for conservative treatment and the volume that represents an absolute indication for surgery in patients with basal ganglia hemorrhage.

Methods

A retrospective analysis was performed on the medical records of patients admitted for basal ganglia hemorrhage from 2019 to 2021. The data encompassed personal history, general information and diagnostic imaging records, particularly CT brain scans from the initial ER visit, were examined to ascertain hematoma volume. The comparison focused on evaluating the outcomes of patients who received medical treatment compared to those who underwent surgical intervention, mainly considering various hematoma volumes, and was conducted using multivariate logistic analysis.

Results

In a study of 387 cases of basal ganglia hemorrhage, analysis of medical treatment alone across various hematoma volumes revealed that the group with volumes between 10 and 39.9 ml showed no significant difference in mortality compared to the group with volumes less than 10 ml. The Receiver Operating Characteristics (ROC) curve identified a 45.3 ml cutoff for survival prediction with medical treatment alone. Notably, patients in the subgroup undergoing surgical intervention with a hematoma volume less than 30 ml exhibited significantly higher mortality than those who did not undergo surgery. Conversely, there was a pronounced and statistically significant trend toward increased survival in the group with a hematoma volume of at least 60 ml.

Conclusions

The application of medical treatment alone is suitable for hematoma volumes ranging from 0 to 45.3 ml, whereas volumes of 60 ml or more serve as a clear indication for surgical intervention in patients with basal ganglia hemorrhage.
Insulin-AKT1-YBX1 Regulation of ANGPTL8 Promote Lipogenesis in Obstructive Sleep Apnea-Associated Dyslipidemia
Authors: Liu Yuenan , Yuan Haolin , Wang Anzhao , Wang Shengming , Xu Xu , Hu Junhui , Shen Jinhong , Hu Yiming , Li Xinyi , Li Niannian , Gao Zhenfei , Zhang Xiaoxu , Zhang Xiaoman , Liu Yupu , Xu Huajun , Yi Hongliang , Guan Jian , Li Zhiqiang , Zhao Yongxu , Yin Shankai , Liu Feng
Published: June 2024

Dyslipidemia is a hallmark of obstructive sleep apnea (OSA)-induced metabolic syndrome, yet the mechanisms remain poorly understood. We conducted a genome-wide association study on lipid traits in the OSA cohorts, identifying the SNP rs3745683 inANGPTL8, significantly associated with reductions in multiple lipid traits. ANGPTL8, an essential lipogenic hormone and potential therapeutic target for metabolic syndrome, showed elevated expression in OSA patients compared to healthy controls, strongly correlated with increased insulin levels. Notably,ANGPTL8expression can be upregulated by insulin stimulation, indicating it as an insulin-responsive hormone regulating dyslipidemia in OSA. Mechanistically, SNP rs3745683 attenuatedANGPTL8transcription by inhibiting its binding to transcription factor YBX1. Insulin prompted AKT1 to phosphorylate YBX1 at Ser102, facilitating YBX1’s nuclear translocation and subsequent regulation ofANGPTL8expression and lipid synthesis. Specific knockdown of YBX1 in mouse liver confirmed its necessity forANGPTL8expression and hepatic lipid synthesis in vivo. Our findings highlightANGPTL8as a critical regulator of dyslipidemia in OSA patients, offering a promising therapeutic avenue for managing metabolic syndrome in OSA.