bluuebunny/crossref_metadata_2025 huggingface dataset:
GNN4DM: a graph neural network-based method to identify overlapping functional disease modules
Authors: Gézsi András , Antal Péter
Published: September 2024

Motivation

Identifying disease modules within molecular interaction networks is an essential exploratory step in computational biology, offering insights into disease mechanisms and potential therapeutic targets. Traditional methods often struggle with the inherent complexity and overlapping nature of biological networks, and they are limited in effectively leveraging the vast amount of available genomic data and biological knowledge. This limitation underscores the need for more effective, automated approaches to integrate these rich data sources.

Results

In this work, we propose GNN4DM, a novel graph neural network-based structured model that automates the discovery of overlapping functional disease modules. GNN4DM effectively integrates network topology with genomic data to learn the representations of the genes corresponding to functional modules and align these with known biological pathways for enhanced interpretability. Following the DREAM benchmark evaluation setting and extending with three independent data sources (GWAS Atlas, FinnGen, and DisGeNET), we show that GNN4DM performs better than several state-of-the-art methods in detecting biologically meaningful modules. Moreover, we demonstrate the method’s applicability by discovering two novel multimorbidity modules significantly enriched across a diverse range of seemingly unrelated diseases.

Availability and implementation

Source code, all training data, and all identified disease modules are freely available for download at https://github.com/gezsi/gnn4dm. GNN4DM was implemented in Python.
Multiple lines of evidence for disruption of nuclear lamina and nucleoporins in FUS amyotrophic lateral sclerosis
Authors: Okada Kensuke , Ito Daisuke , Morimoto Satoru , Kato Chris , Oguma Yuki , Warita Hitoshi , Suzuki Naoki , Aoki Masashi , Kuramoto Junko , Kobayashi Reona , Shinozaki Munehisa , Ikawa Masahito , Nakahara Jin , Takahashi Shinichi , Nishimoto Yoshinori , Shibata Shinsuke , Okano Hideyuki
Published: September 2024

Advanced pathological and genetic approaches have revealed that mutations in fused in sarcoma/translated in liposarcoma (FUS/TLS), which is pivotal for DNA repair, alternative splicing, translation and RNA transport, cause familial amyotrophic lateral sclerosis (ALS). The generation of suitable animal models for ALS is essential for understanding its pathogenesis and developing therapies. Therefore, we used CRISPR-Cas9 to generate FUS-ALS mutation in the non-classical nuclear localization signal (NLS), H517D (mouse position: H509D) and genome-edited mice.

Fus WT/H509D mice showed progressive motor impairment (accelerating rotarod and DigiGait system) with age, which was associated with the loss of motor neurons and disruption of the nuclear lamina and nucleoporins and DNA damage in spinal cord motor neurons. We confirmed the validity of our model by showing that nuclear lamina and nucleoporin disruption were observed in lower motor neurons differentiated from patient-derived human induced pluripotent stem cells (hiPSC-LMNs) with FUS-H517D and in the post-mortem spinal cord of patients with ALS. RNA sequence analysis revealed that most nuclear lamina and nucleoporin-linking genes were significantly decreased in FUS-H517D hiPSC-LMNs.

This evidence suggests that disruption of the nuclear lamina and nucleoporins is crucial for ALS pathomechanisms. Combined with patient-derived hiPSC-LMNs and autopsy samples, this mouse model might provide a more reliable understanding of ALS pathogenesis and might aid in the development of therapeutic strategies.
Strategic Conformity or Anti-Conformity to Avoid Punishment and Attract Reward
Authors: Dvorak Fabian , Fischbacher Urs , Schmelz Katrin
Published: September 2024

We provide systematic insights on strategic conformist—as well as anti-conformist—behaviour in situations where people are evaluated, i.e., where an individual has to be selected for reward (e.g., promotion) or punishment (e.g., layoffs). To affect the probability of being selected, people may attempt to fit in or stand out in order to affect the chances of being noticed or liked by the evaluator. We investigate such strategic incentives for conformity or anti-conformity experimentally in three different domains: facts, taste and creativity. To distinguish conformity and anti-conformity from independence, we introduce a new experimental design that allows us to predict participants’ independent choices based on transitivity. We find that the prospect of punishment increases conformity, while the prospect of reward reduces it. Anti-conformity emerges in the prospect of reward, but only under specific circumstances. Similarity-based selection (i.e., homophily) is much more important for the evaluators’ decisions than salience. We also employ a theoretical approach to illustrate strategic key mechanisms of our experimental setting.
Disentangling evolutionary, geometric and ecological components of the elevational gradient of diversity
Authors: Herrera-Alsina Leonel , Parvanova Rossina , Guirguis Jacinta , Bocedi Greta , Trethowan Liam , Lancaster Lesley T , Travis Justin M J
Published: September 2024

Despite the high importance and risk of mountain ecosystems in global biodiversity conservation, the mechanisms giving rise to and maintaining elevational biodiversity gradients are poorly understood, limiting predictions of future responses. Species richness peaks at lowlands for many taxa, which might be a consequence of mountain shape, reducing available area in highlands. For other taxa, diversity can be highest at mid elevations, suggesting the presence of mechanisms that counteract the influence of geometry. Here, we mechanistically investigate the role of mountain geometry (smaller at the peak) interaction with ecological niche width, diversification, and altitudinal dispersal to investigate the relative roles of these processes in shaping elevational biodiversity gradients. We simulated landscapes and lineages until species richness stop increasing and showed that the disproportionately large area of lowlands provides opportunity for higher species accumulation than any other elevation, even when available niche width and per-capita diversification rate are uniform across altitudes. Regardless of the underlying Elevational Diversity Gradient, altitudinal dispersal always plays a stronger role in maintaining highland than lowland diversity, due to unequal areas involved. To empirically test these predictions resulting from our model, we fit dynamic models of diversification and altitudinal dispersal to three mountainous endemic radiations whose species richness peaks in mid and high-elevation. We find that highland diversity is explained by increased diversification rates with elevation in Fijian bees, whereas niche availability is more likely to explain high altitude diversity in frailejon bushes and earless frogs, suggesting these clades are still growing. Our model and findings provide a new framework for distinguishing drivers of diversity dynamics on mountainsides and allow to detect the presence of clade-specific mechanisms underlying the geometry-diversity relationship. Understanding of these ecological and evolutionary forces can allow increased predictability of how ongoing land use and climate changes will impact future highland biodiversity.
Cross potential selection: a proposal for optimizing crossing combinations in recurrent selection using the usefulness criterion of future inbred lines
Authors: Sakurai Kengo , Hamazaki Kosuke , Inamori Minoru , Kaga Akito , Iwata Hiroyoshi
Published: September 2024

In plant breeding programs, rapid production of novel varieties is highly desirable. Genomic selection allows the selection of superior individuals based on genomic estimated breeding values. However, it is worth noting that superior individuals may not always be superior parents. The choice of the crossing pair significantly influences the genotypic value of the resulting progeny. This study has introduced a new crossing strategy, termed cross potential selection, designed to expedite the production of novel varieties of inbred crops. Cross potential selection integrates fast recurrent selection and usefulness criterion to generate novel varieties. It considers the segregation of each crossing pair and computes the expected genotypic values of the top-performing individuals, assuming that the progeny distribution of genotypic values follows a normal distribution. It does not consider genetic diversity and focuses only on producing a novel variety as soon as possible. We simulated a 30-year breeding program in 2 scenarios, low heritability (h2=0.3) and high heritability (h2=0.6), to compare cross potential selection with 2 other selection strategies. Cross potential selection consistently demonstrated the highest genetic gains among the 3 strategies in early cycles. In the 3rd year of the breeding program with a high heritability (h2=0.6), cross potential selection exhibited the highest genetic gains, 138 times that of 300 independent breeding simulations. Regarding long-term improvement, the other selection strategies outperformed cross potential selection. Nevertheless, compared with the other 2 strategies, cross potential selection achieved significant short-term genetic improvements. Cross potential selection is a suitable breeding strategy for the rapid production of varieties within limited time and cost.
Virus Infection Induces Immune Gene Activation with CTCF-anchored Enhancers and Chromatin Interactions in Pig Genome
Authors: Cao Jianhua , Ren Ruimin , Li Xiaolong , Zhang Xiaoqian , Sun Yan , Tian Xiaohuan , Liu Ru , Liu Xiangdong , Ruan Yijun , Li Guoliang , Zhao Shuhong
Published: September 2024

Chromatin organization is important for gene transcription in pig genome. However, its three-dimensional (3D) structure and dynamics are much less investigated than those in human. Here, we applied the long-read chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) method to map the whole-genome chromatin interactions mediated by CCCTC-binding factor (CTCF) and RNA polymerase II (RNAPII) in porcine macrophage cells before and after polyinosinic-polycytidylic acid [Poly(I:C)] induction. Our results reveal that Poly(I:C) induction impacts the 3D genome organization in the 3D4/21 cells at the fine-scale chromatin loop level rather than at the large-scale domain level. Furthermore, our findings underscore the pivotal role of CTCF-anchored chromatin interactions in reshaping chromatin architecture during immune responses. Knockout of the CTCF-binding locus further confirms that the CTCF-anchored enhancers are associated with the activation of immune genes via long-range interactions. Notably, the ChIA-PET data also support the spatial relationship between single nucleotide polymorphisms (SNPs) and related gene transcription in 3D genome aspect. Our findings in this study provide new clues and potential targets to explore key elements related to diseases in pigs and are also likely to shed light on elucidating chromatin organization and dynamics underlying the process of mammalian infectious diseases.
Real-world public health interventions demonstrate how research evidence informs program scale-up
Authors: Crane Melanie , Lee Karen , Wolfenden Luke , Phongsavan Philayrath , Bauman Adrian
Published: September 2024

Evidence-based population interventions rely on intervention testing (efficacy and effectiveness trials) to determine what works to improve public health. We investigated the characteristics of real-world public health interventions to address obesity and explored the extent to which research testing was undertaken prior to scale-up. We identified 90 population health interventions targeting physical activity, nutrition or obesity-related health behaviours and collected publicly available information on their key characteristics and outcomes. We then assessed the differences between interventions that followed a research pathway and those that did not. Two-thirds (n = 60) of the interventions were reported as having followed a research pathway. Univariate logistic regression analysis revealed that these interventions were more likely to be health education interventions [odds ratio (OR): 5.56; 95% confidence interval (CI): 1.38–22.38], developed by research institutes (OR: 12.81; 95% CI: 3.47–47.34), delivered in North America (OR: 4.13; 95% CI: 1.61–10.62), and less likely to be owned (OR: 0.35; 95% CI: 0.14–0.88) or funded by government organizations (OR: 0.37; 95% CI: 0.14–0.95). Interventions that followed a research pathway were nearly three times more likely to have a positive impact on population health (OR: 2.72; 95% CI: 1.04–7.14). Interventions that followed a research pathway to scale-up were no more likely to be sustained longer than those that did not. Differences exist across real-world interventions between those that follow a research pathway to population-scale delivery and those that do not, regarding organizational and environmental context. A key benefit of research pathway to scale-up is the impact it has on health outcomes.
Fourier Dimension Estimates for Sets of Exact Approximation Order: The Case of Small Approximation Exponents
Authors: Fraser Robert , Wheeler Reuben
Published: September 2024

We show for decreasing, positive approximation functions $\psi $ such that $\tau = \lim _{q \to \infty } -\frac{\log \psi (q)}{\log q} < \frac{13 + \sqrt{73}}{8}$ and such that $q^{2} \psi (q) \to 0$ that the set $\operatorname{Exact}(\psi )$ of numbers approximable to the exact order $\psi $ has positive Fourier dimension. This implies that the set $\operatorname{Exact}(\psi )$ contains normal numbers.
Improved Nucleic Acid Amplification Test for the Diagnosis of Onchocerciasis and Its Use for Detection of Circulating Cell-free DNA
Authors: Bennuru Sasisekhar , Kodua Frimpong , Dahlstrom Eric , Nutman Thomas B
Published: September 2024

Background

The coendemicity of onchocerciasis with other filariae warrants a better diagnostic tool for elimination efforts that are highly sensitive and specific for use in surveillance and xenomonitoring.

Methods

Based on next-generation sequencing data, quantitative polymerase chain reaction (qPCR) assays were designed for 15 highly repeated targets from Onchocerca volvulus (Ov) and 11 from Onchocerca ochengi. The 2 most promising repeats Ov15R and Ov16R from Ov and OoR1 and OoR5 from O. ochengi, were selected for further testing.

Results

The analytic sensitivity of Ov15R and Ov16R was similar, with limits of detection at 1 fg and specificity approaching 100%. Using DNA obtained previously from skin snips of participants infected with Ov, Ov16R identified 17 additional samples as positive for Ov infections when compared with the gold standard O-150. Although Ov16R failed to detect circulating cell-free DNA (ccfDNA) in the plasma of individuals infected with Ov, 1-mL urine samples were variably positive for ccfDNA. Interestingly, plasma levels of ccfDNA were shown to be easily measurable as early as 12 to 24 hours following treatment. To enable processing of larger volumes of urine for better sensitivity, a chitosan-based filter technique was developed that efficiently captured ccfDNA from 1 to 15 mL of urine. Interestingly, Ov15R, Ov16R, and O-150 map to the same region(s) of the Ov genome, prompting a redesign of the standard O-150 qPCR. This resulted in a new O-150 assay that performs on par with Ov15R/Ov16R.

Conclusions

Each of these assays dramatically improve detection of Ov DNA and can easily be configured to field-friendly isothermal formats.
EDP-938 Has a High Barrier to Resistance in Healthy Adults Experimentally Infected with Respiratory Syncytial Virus
Authors: Levene Rachel Emily , DeVincenzo John , Conery Annie L , Ahmad Alaa , Or Yat Sun , Rhodin Michael H J
Published: September 2024

Background

EDP-938 is an oral once-daily RSV nucleoprotein (N) inhibitor with potent antiviral activity. In a human RSV challenge trial, EDP-938 significantly reduced viral load and symptom severity. During antiviral development, it is critical to understand the propensity for resistance to develop. In vitro studies of EDP-938 suggest a higher barrier to resistance as compared to RSV fusion inhibitors. We evaluated the development of viral resistance to EDP-938 in a human challenge trial.

Methods

A subset of the 124 participants with RSV infection were chosen for genetic analysis; 159 nasal wash samples from 48 participants were analyzed using next-generation sequencing of the N gene of RSV. Of the 48 participant sampled, 37 were from EDP-938–treated and 11 were placebo-treated participants, representing 45% and 26% of the participants, respectively. The effects of treatment-emergent mutations on viral load, EDP-938 efficacy, and viral fitness were evaluated.

Results

Two of the 37 EDP-938–treated participants with samples sequenced had treatment-emergent mutations: N:L139I and N:E112G. From in vitro analysis, N:L139I reduced sensitivity to EDP-938 by approximately 10-fold, while N:E112G had no effect. However, N:L139I was associated with a reduction in viral fitness, suggesting clinical resistance is associated with fitness costs. Neither of these variants were associated with reduced viral clearance.

Conclusions

In human RSV infections treated with EDP-938, emergence of RSV variants with reduced sensitivity to EDP-938 occurred in only 1 participant and was associated with reduced viral fitness. EDP-938's high barrier to resistance highlights its robust mechanism of action.

Clinical Trials Registration

NCT03691623.
Predatory protists impact plant performance by promoting plant growth-promoting rhizobacterial consortia
Authors: Guo Sai , Geisen Stefan , Mo Yani , Yan Xinyue , Huang Ruoling , Liu Hongjun , Gao Zhilei , Tao Chengyuan , Deng Xuhui , Xiong Wu , Shen Qirong , Kowalchuk George A , Li Rong
Published: September 2024

Plant performance is impacted by rhizosphere bacteria. These bacteria are subjected to both bottom-up control by root exudates as well as top-down control by predators, particularly protists. Protists stimulate plant growth-promoting microbes resulting in improved plant performance. However, knowledge of the mechanisms that determine the interconnections within such tripartite protist–bacteria–plant interactions remains limited. We conducted experiments examining the effects of different densities of the predatory protist Cercomonas lenta on rhizosphere bacterial communities, specifically zooming on interactions between Cercomonas lenta and key bacterial taxa, as well as interactions among key bacterial taxa. We tracked rhizosphere bacterial community composition, potential microbial interactions, and plant performance. We found that Cercomonas lenta inoculation led to an average increase in plant biomass of 92.0%. This effect was linked to an increase in plant growth-promoting rhizobacteria (Pseudomonas and Sphingomonas) and a decrease in bacteria (Chitinophaga) that negatively impact on plant growth-promoting rhizobacteria. We also found evidence for cooperative enhancements in biofilm formation within the plant growth-promoting rhizobacterial consortium. Cercomonas lenta enhanced a plant growth-promoting rhizobacterial consortium colonization by promoting its cooperative biofilm formation in the rhizosphere, leading to a 14.5% increase in phosphate solubilization that benefits plant growth. Taken together, we provide mechanistic insights into how the predatory protist Cercomonas lenta impacts plant growth, namely by stimulating plant beneficial microbes and enhancing their interactive activities such as biofilm formation. Predatory protists may therefore represent promising biological agents that can contribute to sustainable agricultural practices by promoting interactions between the plant and its microbiome.
Abiotic factors shape mosquito microbiomes that enhance host development
Authors: Kriefall Nicola G , Seabourn Priscilla S , Yoneishi Nicole M , Davis Kahiwahiwa , Nakayama Kirsten K , Weber Danya E , Hynson Nicole A , Medeiros Matthew C I
Published: September 2024

Metazoans rely on interactions with microorganisms through multiple life stages. For example, developmental trajectories of mosquitoes can vary depending on the microorganisms available during their aquatic larval phase. However, the role that the local environment plays in shaping such host-microbe dynamics and the consequences for the host organism remain inadequately understood. Here, we examine the influence of abiotic factors, locally available bacteria, and their interactions on the development and associated microbiota of the mosquito Aedes albopictus. Our findings reveal that leaf detritus infused into the larval habitat water, sourced from native Hawaiian tree ‘ōhi‘a lehua Metrosideros polymorpha, invasive strawberry guava Psidium cattleianum, or a pure water control, displayed a more substantial influence than either temperature variations or simulated microbial dispersal regimes on bacterial community composition in adult mosquitoes. However, specific bacteria exhibited divergent patterns within mosquitoes across detrital infusions that did not align with their abundance in the larval habitat. Specifically, we observed a higher relative abundance of a Chryseobacterium sp. strain in mosquitoes from the strawberry guava infusion than the pure water control, whereas the opposite trend was observed for a Pseudomonas sp. strain. In a follow-up experiment, we manipulated the presence of these two bacterial strains and found larval developmental success was enhanced by including the Chryseobacterium sp. strain in the strawberry guava infusion and the Pseudomonas sp. strain in the pure water control. Collectively, these data suggest that interactions between abiotic factors and microbes of the larval environment can help shape mosquito populations' success.
Spatiotemporal dynamics of giant viruses within a deep freshwater lake reveal a distinct dark-water community
Authors: Zhang Liwen , Meng Lingjie , Fang Yue , Ogata Hiroyuki , Okazaki Yusuke
Published: September 2024

Giant viruses (GVs) significantly regulate the ecological dynamics of diverse ecosystems. Although metagenomics has expanded our understanding of their diversity and ecological roles played in marine environments, little is known about GVs of freshwater ecosystems. Most previous studies have employed short-read sequencing and therefore resulted in fragmented genomes, hampering accurate assessment of genetic diversity. We sought to bridge this knowledge gap and overcome previous technical limitations. We subjected spatiotemporal (2 depths × 12 months) samples from Lake Biwa to metagenome–assembled genome reconstruction enhanced by long-read metagenomics. This yielded 293 GV metagenome-assembled genomes. Of these, 285 included previously unknown species in five orders of nucleocytoviruses and the first representatives of freshwater mirusviruses, which exhibited marked divergence from marine-derived lineages. The good performance of our long-read metagenomic assembly was demonstrated by the detection of 42 (14.3%) genomes composed of single contigs with completeness values >90%. GVs were partitioned across water depths, with most species specific to either the sunlit epilimnion or the dark hypolimnion. Epilimnion-specific members tended to be transient and exhibit short and intense abundance peaks, in line with the fact that they regulate the surface algal blooms. During the spring bloom, mirusviruses and members of three nucleocytovirus families were among the most abundant viruses. In contrast, hypolimnion-specific ones, including a mirusvirus genome, were typically more persistent in the hypolimnion throughout the water-stratified period, suggesting that they infect hosts specific to the hypolimnion and play previously unexplored ecological roles in dark water microbial ecosystems.
Chloramphenicol versus ceftriaxone for the treatment of pneumonia and sepsis in elderly patients with advanced dementia and functional disability. A propensity-weighted retrospective cohort study
Authors: Eynath Y , McNeil R , Buchrits S , Guz D , Fredman D , Gafter-Gvili A , Avni T
Published: September 2024

Background

Sepsis and pneumonia in the elderly comprise a significant portion of medical admissions. Chloramphenicol has been used in Israel for treatment of bacterial infections, without evidence regarding its efficacy and safety.

Objectives

We aimed to examine whether chloramphenicol was associated with similar outcomes to ceftriaxone, for treatment of sepsis and pneumonia in the elderly with dementia and functional disability.

Methods

Patients over 75, with dementia and functional disability, admitted to the internal medicine ward at Beilinson Hospital between 2011 and 2021, with community-acquired aspiration pneumonia or sepsis of undetermined source were included. Patients with mild dementia and independent in their activities of daily living were excluded. Primary outcome was 30- and 90-day all-cause mortality. A propensity-weighted multivariable model was constructed using inverse probability of treatment weighting. Results were expressed as OR with 95% CI.

Results

In total, 1558 patients were included: 512 treated with chloramphenicol and 1046 with ceftriaxone. The cohort consisted of elderly patients (mean age 87 ± 6.2 years) with comorbidities; 30- and 90-day all-cause mortality were similar [222/512 (43.3%) versus 439/1046 (41.9%) P = 0.602, and 261/512 (50.9%) versus 556/1046 (53.1%) P = 0.419, respectively]. Propensity-weighted, logistic multivariable analysis for 30- and 90-day all-cause mortality revealed similar mortality rates for chloramphenicol and ceftriaxone (OR 1.049 95% CI 0.217–1.158, OR 0.923 95% CI 0.734–1.112, respectively).

Conclusion

In this retrospective cohort of elderly debilitated patients hospitalized with pneumonia and sepsis, we found no difference in 30- and 90-day mortality between those treated with chloramphenicol or ceftriaxone. Further studies should determine the efficacy and safety of chloramphenicol in this population.
Using the electronic health record to provide audit and feedback in medical student clerkships
Authors: Xu Jacqueline , Silver Matthew A , Kim Jung , Mazotti Lindsay
Published: September 2024

Objectives

This article focuses on the role of the electronic health record (EHR) to generate meaningful formative feedback for medical students in the clinical setting. Despite the scores of clinical data housed within the EHR, medical educators have only just begun to tap into this data to enhance student learning. Literature to-date has focused almost exclusively on resident education.

Materials and Methods

Development of EHR auto-logging and triggered notifications are discussed as specific use cases in providing enhanced feedback for medical students.

Results

By incorporating predictive and prescriptive analytics into the EHR, there is an opportunity to create powerful educational tools which may also support general clinical activity.

Discussion

This article explores the possibilities of EHR as an educational resource. This serves as a call to action for educators and technology developers to work together on creating health record user-centric tools, acknowledging the ongoing work done to improve student-level attribution to patients.

Conclusion

EHR analytics and tools present a novel approach to enhancing clinical clerkship education for medical students.
Wnt7b overexpression in osteoblasts stimulates bone formation and reduces obesity in mice on a high-fat diet
Authors: Song Fangfang , Marmo Tyler , Song Chao , Liao Xueyang , Long Fanxin
Published: September 2024

Previous studies have shown that Wnt7b potently stimulates bone formation by promoting osteoblast differentiation and activity. As high-fat feeding leads to obesity and systemic metabolic dysregulation, here we investigate the potential benefit of Wnt7b overexpression in osteoblasts on both bone and whole-body metabolism in mice fed with a high-fat diet (HFD). Wnt7b overexpression elicited massive overgrowth of trabecular and cortical bone but seemed to ameliorate body fat accumulation in mice with prolonged HFD feeding. In addition, Wnt7b overexpression modestly improved glucose tolerance in male mice on HFD. Collectively, the results indicate that targeted overexpression of Wnt7b in osteoblasts not only stimulates bone formation but also improves certain aspects of global metabolism in overnourished mice.
Surgical explantation of the WATCHMAN device and right atrial thrombus: a case report
Authors: Mukasa Kotaro , Nishiori Hironobu , Ikeuchi Hiroki , Inui Tomohiko , Matsumiya Goro
Published: September 2024

A 74-year-old male with a history of cardioembolic stroke, chronic atrial fibrillation, and cerebral hemorrhage, who had undergone left atrial appendage closure using the WATCHMAN device 1 year prior, was diagnosed with a 25-mm intra-cardiac mass in the right atrium. The patient underwent the surgical removal of the right atrial mass and the explantation of the WATCHMAN device. The WATCHMAN device was explanted with an external incision at the base of the left atrial appendage, facilitating the removal of the device and the closure of the appendage through direct suturing. The pathological examination confirmed the right atrial mass to be a thrombus. The patient was discharged on postoperative Day 13. From the perspectives of simplicity and radicality, the external approach could be a good option.
Laparoscopic excision of an incidental vascular tumor
Authors: Boligo Sofia , Santos Cláudia , Branco Cláudia , Contente Helena
Published: September 2024

Anastomosing hemangioma (AH) is an exceedingly rare benign vascular tumor, often mistaken for malignant neoplasms due to its histological features. First described in 2009, AH has been documented in various sites, including the kidney, liver, and adrenal gland. This report presents a 64-year-old man who, following a bicycle accident, underwent imaging that revealed a nodule suspicious for a paraganglioma in the right para-caval region. Despite the high radiotracer uptake on 68Ga-DOTANOC PET scan, which suggested paraganglioma, the patient remained asymptomatic and laboratory tests ruled out excessive catecholamine secretion. Surgical excision led to a diagnosis of AH, distinguished by its unique anastomosing vascular pattern and histological similarity to angiosarcoma. This case underlines the diagnostic challenges and potential for overtreatment of AH, highlighting the need for heightened awareness and careful histopathological and imaging evaluation to avoid misdiagnosis and ensure appropriate management.
Sperm-carried IGF2: towards the discovery of a spark contributing to embryo growth and development
Authors: Cannarella Rossella , Rando Oliver J , Condorelli Rosita A , Chamayou Sandrine , Romano Simona , Guglielmino Antonino , Yin Qiangzong , Hans Tobias Gustafsson , Mancuso Francesca , Arato Iva , Bellucci Catia , Luca Giovanni , Lundy Scott D , La Vignera Sandro , Calogero Aldo E
Published: September 2024

Spermatozoa have been shown to carry key RNAs which, according to animal evidence, seem to play a role in early embryo development. In this context, a potential key growth regulator is insulin-like growth factor 2 (IGF2), a highly conserved paternally expressed imprinted gene involved in cell growth and proliferation which, recent observations indicate, is expressed in human spermatozoa. We herein hypothesized that sperm IGF2 gene expression and transmission at fertilization is required to support early embryo development. To test this hypothesis, we analyzed sperm IGF2 mRNA levels in the same semen aliquot used for homologous assisted reproductive technique (ART) in infertile couples and correlated these levels with embryo morphokinetics. To find a mechanistic explanation for the observed results, the transcriptomes of blastocysts obtained after injection of Igf2 mRNA in mouse parthenotes were analyzed. Sperm IGF2 mRNA negatively correlated with time of 2-cell stage (t2), t3, t4, t5, and time of expanded blastocyst (tEB), independently of maternal age, body mass index, anti-Müllerian hormone levels, and oocyte quality. An IGF2 mRNA index >4.9 predicted the ability of the embryos to reach the blastocyst stage on Day 5, with a sensitivity of 100% and a specificity of 71.6% (AUC 0.845; P < 0.001). In the animal study, transcriptome analysis demonstrated that 65 and 36 genes were, respectively, up- and down-regulated in the experimental group compared to the control group. These genes belong to pathways that regulate early embryo development, thus supporting the findings found in humans. This study has the potential to challenge the longstanding tenet that spermatozoa are simply vehicles carrying paternal DNA. Instead, it suggests that IGF2 mRNA in healthy spermatozoa provides critical support for early embryo development. Pre-ART sperm-carried IGF2 mRNA levels may be used as a marker to predict the chances of obtaining blastocysts to be transferred for infertile couples undergoing ART.
Estimating the Effect of Coronavirus Disease 2019 (COVID-19) Vaccination and Infection Variant on Post-COVID-19 Venous Thrombosis or Embolism Risk
Authors: O’Carroll Andrew , Richard Stephanie A , Byrne Celia , Rusiecki Jennifer , Wier Ben , Berjohn Catherine M , Fries Anthony C , Lalani Tahaniyat , Smith Alfred G , Mody Rupal M , Ganesan Anuradha , Huprikar Nikhil , Colombo Rhonda E , Schofield Christina , Lindholm David A , Mende Katrin , Jones Milissa U , Flanagan Ryan , Larson Derek T , Ewers Evan C , Saunders David , Maves Ryan C , Maldonado Carlos J , Sanchez Edwards Margaret , O’Connell Robert J , Simons Mark P , Tribble David R , Agan Brian K , Burgess Timothy H , Pollett Simon D
Published: September 2024

Background

Previous research has shown that vaccination reduces risk of post–coronavirus disease 2019 (COVID-19) venous thrombosis or embolism (VTE), but the effect of vaccine boosting on post-COVID-19 VTE risk reduction is unclear. We sought to estimate the effect of COVID-19 vaccination on the risk of post-COVID-19 VTE and to examine if the magnitude of this association differed among variant eras.

Methods

We performed a case-control study of Military Health System (MHS) beneficiaries who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2020–2022. Cases were defined as those with medically attended VTE within 90 days after their first positive SARS-CoV-2 test; controls were defined as SARS-CoV-2 infections without incident VTE by 90 days. Multivariate logistic regression estimated the odds of post-SARS-CoV-2 VTE based on pre-COVID-19 vaccine status, adjusting for other VTE risk factors.

Results

A total of 4646 MHS beneficiaries were included in this analysis; 1370 received a primary vaccine series and a further 790 received at least 1 booster at time of infection; 71 had VTE within 90 days of SARS-CoV-2 infection. Those who were vaccinated had lower odds of VTE (adjusted odds ratio [95% confidence interval]) compared to the unvaccinated following infection (primary series: 0.28 [.13–.62]; booster dose: 0.06 [.01–.46]). Post-COVID-19 VTE risk was lowest during the Omicron era, but VTEs were too rare to examine for an interaction of variant era and vaccine effect.

Conclusions

Among MHS beneficiaries, COVID-19 vaccination was associated with a reduced risk of post-COVID-19 VTE diagnosis; estimated risk reduction was larger among those who received a booster.
Nature as infrastructure to improve health: drawing on gardening and Indigenous health and connection to land research
Authors: Kingsley Jonathan
Published: September 2024

The world is currently grappling with several public health issues (like the increase in urbanization, chronic diseases and social isolation). Increased connection with nature has been identified as a possible solution to many of these concerns. This perspective paper draws on recent empirical evidence around the health and wellbeing benefits of nature. To highlight these benefits I will draw on insights from my own research focused on Indigenous people’s connection to land (known as Country in Australia) and gardening as a mechanism for engaging people in nature. This will be applied to support the notion that nature is critical infrastructure that has significant potential to improve public health outcomes. In doing this it must be acknowledged that these are only a few aspects of the relationship between nature and health based on my own expertise and paradigms developed from my research. I will conclude this perspective essay by providing five overarching recommendations to mainstream the evidence substantiating the health and wellbeing benefits of nature into policy and practice.
Structural neuroanatomy of human facial behaviors
Authors: Noohi Fate , Kosik Eena L , Veziris Christina , Perry David C , Rosen Howard J , Kramer Joel H , Miller Bruce L , Holley Sarah R , Seeley William W , Sturm Virginia E
Published: September 2024

The human face plays a central role in emotions and social communication. The emotional and somatic motor networks generate facial behaviors, but whether facial behaviors have representations in the structural anatomy of the human brain is unknown. We coded 16 facial behaviors in 55 healthy older adults who viewed five videos that elicited emotions and examined whether individual differences in facial behavior were related to regional variation in gray matter volume. Voxel-based morphometry analyses revealed that greater emotional facial behavior during the disgust trial (i.e. greater brow furrowing and eye tightening as well as nose wrinkling and upper lip raising) and the amusement trial (i.e. greater smiling and eye tightening) was associated with larger gray matter volume in midcingulate cortex, supplementary motor area, and precentral gyrus, areas spanning both the emotional and somatic motor networks. When measured across trials, however, these facial behaviors (and others) only related to gray matter volume in the precentral gyrus, a somatic motor network hub. These findings suggest that the emotional and somatic motor networks store structural representations of facial behavior and that the midcingulate cortex is critical for generating the predictable movements in the face that arise during emotions.
Relationships Between Hearing Status, Cognitive Abilities, and Reliance on Visual and Contextual Cues
Authors: Micula Andreea , Holmer Emil , Ning Ruijing , Danielsson Henrik
Published: September 2024

Objectives:

Visual and contextual cues facilitate speech recognition in suboptimal listening conditions (e.g., background noise, hearing loss, hearing aid signal processing). Moreover, successful speech recognition in challenging listening conditions is linked to cognitive abilities such as working memory and fluid intelligence. However, it is unclear which cognitive abilities facilitate the use of visual and contextual cues in individuals with normal hearing and hearing aid users. The first aim was to investigate whether individuals with hearing aid users rely on visual and contextual cues to a higher degree than individuals with normal hearing in a speech-in-noise recognition task. The second aim was to investigate whether working memory and fluid intelligence are associated with the use of visual and contextual cues in these groups.

Design:

Groups of participants with normal hearing and hearing aid users with bilateral, symmetrical mild to severe sensorineural hearing loss were included (n = 169 per group). The Samuelsson and Rönnberg task was administered to measure speech recognition in speech-shaped noise. The task consists of an equal number of sentences administered in the auditory and audiovisual modalities, as well as without and with contextual cues (visually presented word preceding the sentence, e.g.,: “Restaurant”). The signal to noise ratio was individually set to 1 dB below the level obtained for 50% correct speech recognition in the hearing-in-noise test administered in the auditory modality. The Reading Span test was used to measure working memory capacity and the Raven test was used to measure fluid intelligence. The data were analyzed using linear mixed-effects modeling.

Results:

Both groups exhibited significantly higher speech recognition performance when visual and contextual cues were available. Although the hearing aid users performed significantly worse compared to those with normal hearing in the auditory modality, both groups reached similar performance levels in the audiovisual modality. In addition, a significant positive relationship was found between the Raven test score and speech recognition performance only for the hearing aid users in the audiovisual modality. There was no significant relationship between Reading Span test score and performance.

Conclusions:

Both participants with normal hearing and hearing aid users benefitted from contextual cues, regardless of cognitive abilities. The hearing aid users relied on visual cues to compensate for the perceptual difficulties, reaching a similar performance level as the participants with normal hearing when visual cues were available, despite worse performance in the auditory modality. It is important to note that the hearing aid users who had higher fluid intelligence were able to capitalize on visual cues more successfully than those with poorer fluid intelligence, resulting in better speech-in-noise recognition performance.
Online Utilization of the Nominal Group Technique to Gather Consensus Opinion Across Geographically Disparate Locations
Authors: Fallon Anthony Bruce , O'Connell Christine
Published: September 2024

Introduction:

The nominal group technique (NGT) is a structured focus group that gathers opinion and generates consensus from groups on topics of interest. Previous studies using online NGTs (ONGTs) in health have been conducted in regions of high population density and internet connectivity. This activity aimed to determine the feasibility and utility of ONGTs in gathering opinion and reaching consensus on curriculum topics for a continuing research education program for health professionals dispersed across various locations in Southern Queensland.

Methods:

Fifteen clinical education academics from a range of health professions participated in 1-hour ONGT sessions from 2 University Department of Rural Health sites or their home offices. The traditional NGT was adapted for online use, using two free online platforms (Zoom for videoconferencing and Wooclap for voting and response collation).

Results:

The chosen platforms were effective in presenting ONGTs, allowing active and effective contributions to research topic ideas from all participants, including those with low internet connectivity. Silent generation enabled sharing, open discussion, and clarification of generated ideas. Wooclap was effective in reviewing and voting on generated responses and providing real-time feedback on voting outcomes. Outcomes were consistent with group consensus and useful in prioritizing research training topics.

Discussion:

The modified ONGT is effective in gathering opinion and gaining consensus from a geographically dispersed health workforce with varied levels of internet connectivity and experience with online platforms. It represents a cost-effective and time-effective alternative to face-to-face NGTs that is less likely to be affected by workforce disruptions.
Advances in mechanism and management of bone homeostasis in osteonecrosis: a review article from basic to clinical applications
Authors: Xiang Xiao-Na , He Hong-Chen , He Cheng-Qi
Published: September 2024

Osteonecrosis, characterized by bone cell death leading to impaired bone recovery, causes challenges in bone homeostasis maintenance. Bone homeostasis relies on the delicate balance between osteoclasts and osteoblasts, encompassing a series of complex and strictly regulated biological functions. Current treatments, including conservative therapies and surgeries, often fall short of expected outcomes, necessitating a reorientation towards more effective therapeutic strategies according to the pathogenesis. In this review, the authors hierarchically outlined risk factors, emerging mechanisms, and last-decade treatment approaches in osteonecrosis. By connecting mechanisms of bone homeostasis, the authors proposed future research directions should be focused on elucidating risk factors and key molecules, performing high-quality clinical trial, updating practice, and accelerating translational potential.
Porto-sinusoidal vascular disorder in surgical candidates for liver metastases: Prevalence, noninvasive diagnosis, and burden on surgical outcomes
Authors: Dajti Elton , Serenari Matteo , Malvi Deborah , Dajti Gerti , Ravaioli Federico , Colecchia Luigi , Marasco Giovanni , Caputo Francesca , Renzulli Matteo , Vasuri Francesco , Vestito Amanda , Azzaroli Francesco , Barbara Giovanni , Ravaioli Matteo , Festi Davide , D’Errico Antonietta , Cescon Matteo , Colecchia Antonio
Published: September 2024

Chemotherapy can cause vascular and metabolic liver injury in patients with liver metastases, but scarce data are available. We aimed to (i) describe the prevalence of porto-sinusoidal vascular disorder (PSVD) among patients undergoing resection for liver metastases; and (ii) assess whether liver (LSM) and spleen stiffness measurements could diagnose PSVD and predict postoperative complications. This is a prospective single-center study enrolling consecutive patients undergoing hepatic resection for metastases at a tertiary center. For each patient, we evaluated previous exposure to chemotherapy, comorbidities, elastography, type of surgery, histological features at the resection specimen, morbidity (post-hepatectomy liver failure and major complications according to Clavien-Dindo), and 90-day survival. Sixty-eight patients were included, of whom 60 (88%) had received chemotherapy. Twenty-nine (44%) patients had PSVD. Spleen stiffness measurements <21 kPa (negative predictive value 87%) and >40 kPa (positive predictive value 100%) could accurately diagnose PSVD. PSVD significantly increased the risk of post-hepatectomy liver failure (22% vs. 45%) and major complications (11% vs. 31%). Preoperative LSM was associated with postoperative morbidity. The cutoff LSMs <4.5 and >8 kPa predicted the risk of clinically significant post-hepatectomy liver failure (0%, 11%, and 33% in LSM <4.5, 4.5–8, and >8 kPa, respectively) and major complications (0%, 25%, 44% in LSM <4.5, 4.5–8, and >8 kPa, respectively). PSVD is very common among patients undergoing liver surgery for metastases, and it is associated with increased morbidity. LSM and spleen stiffness measurements can correctly identify patients with PSVD and those at risk of clinically relevant postoperative complications.