bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between non-scarring alopecia and hypothyroidism: a bidirectional two-sample Mendelian randomization study
Authors: Yang Jiankang , Zhu Zhenlai , Zhang Chen , Guo Yanyang , Wang Gang , Fu Meng
Published: March 2024

Background

Non-scarring alopecia is typically represented by two main types: alopecia areata (AA) and androgenetic alopecia (AGA). While previous observational studies have indicated a link between non-scarring alopecia and hypothyroidism, the precise causal relationship remains uncertain. To determine the potential links between non-scarring alopecia and hypothyroidism, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis.

Methods

We used independent genetic instruments from the FinnGen consortium for AA (682 cases, 361,140 controls) and AGA (195 cases, 201,019 controls) to investigate the association with hypothyroidism in the UK Biobank study (22,687 cases, 440,246 controls). The primary analysis was performed using the inverse variance-weighted method. Complementary approaches were employed to evaluate the pleiotropy and heterogeneity.

Results

Genetically predicted AA exhibited a positive causal effect on hypothyroidism (odds ratio [OR], 1.0017; 95% confidence interval [CI], 1.0004-1.0029; P = 0.0101). Additionally, hypothyroidism was found to be strongly correlated with an increase in the risk of AA (OR, 45.6839; 95% CI, 1.8446-1131.4271, P = 0.0196). However, no causal relationship was demonstrated between AGA and hypothyroidism. A sensitivity analysis validated the integrity of these causal relationships.

Conclusion

This MR study supports a bidirectional causal link between AA and hypothyroidism. Nevertheless, additional research is needed to gain a more thorough comprehension of the causal relationship between non-scarring alopecia and hypothyroidism.
Challenges and opportunities for the built environment in a carbon-constrained world for the next 100 years and beyond
Authors: Park Ah-Hyung Alissa , Williams Jonah M. , Friedmann Julio , Hanson David , Kawashima Shiho , Sick Volker , Taha Mahmoud Reda , Wilcox Jennifer
Published: March 2024

Today, the built environment, including infrastructure for tunnels, bridges, highways, subways, railroads, harbors, buildings and airports, is responsible for a significant portion of the energy consumption, natural resource utilization, waste generation as well as CO2 and other environmentally harmful emissions in the United States and around the world. There is no silver bullet solution to achieve the ambitious goal of zero carbon buildings and a city infrastructure with significantly reduced CO2 emissions. Thus, multifaceted solutions should be developed. Another challenge associated with the built environment is aging and a large economic burden to upgrade and maintain the outdated infrastructure. The current status of the U.S. built environment is far below sustainable condition. Rapidly deteriorating infrastructure that must be replaced provides us with the unique opportunity to rethink where and how we should live in the future. In addition, current challenges related to economic and societal inequality in the United States and other global communities also force us to re-evaluate how humanity is connected and how we share resources for a sustainable and healthy future while keeping the Earth safe. The engineering solutions for our future built environment include, but are not limited to, the design and synthesis of new infrastructure materials with low carbon intensity, the development of new manufacturing options and technologies, and the integration of innovative functionalities into building envelopes.
A division-of-labor mode contributes to the cardioprotective potential of mesenchymal stem/stromal cells in heart failure post myocardial infarction
Authors: Wang Xicheng , Yang Chao , Ma Xiaoxue , Li Xiuhua , Qi Yiyao , Bai Zhihui , Xu Ying , Ma Keming , Luo Yi , Song Jiyang , Jia Wenwen , He Zhiying , Liu Zhongmin
Published: March 2024

Background

Treatment of heart failure post myocardial infarction (post-MI HF) with mesenchymal stem/stromal cells (MSCs) holds great promise. Nevertheless, 2-dimensional (2D) GMP-grade MSCs from different labs and donor sources have different therapeutic efficacy and still in a low yield. Therefore, it is crucial to increase the production and find novel ways to assess the therapeutic efficacy of MSCs.

Materials and methods

hUC-MSCs were cultured in 3-dimensional (3D) expansion system for obtaining enough cells for clinical use, named as 3D MSCs. A post-MI HF mouse model was employed to conduct in vivo and in vitro experiments. Single-cell and bulk RNA-seq analyses were performed on 3D MSCs. A total of 125 combination algorithms were leveraged to screen for core ligand genes. Shinyapp and shinycell workflows were used for deploying web-server.

Result

3D GMP-grade MSCs can significantly and stably reduce the extent of post-MI HF. To understand the stable potential cardioprotective mechanism, scRNA-seq revealed the heterogeneity and division-of-labor mode of 3D MSCs at the cellular level. Specifically, scissor phenotypic analysis identified a reported wound-healing CD142+ MSCs subpopulation that is also associated with cardiac protection ability and CD142- MSCs that is in proliferative state, contributing to the cardioprotective function and self-renewal, respectively. Differential expression analysis was conducted on CD142+ MSCs and CD142- MSCs and the differentially expressed ligand-related model was achieved by employing 125 combination algorithms. The present study developed a machine learning predictive model based on 13 ligands. Further analysis using CellChat demonstrated that CD142+ MSCs have a stronger secretion capacity compared to CD142- MSCs and Flow cytometry sorting of the CD142+ MSCs and qRT-PCR validation confirmed the significant upregulation of these 13 ligand factors in CD142+ MSCs.

Conclusion

Clinical GMP-grade 3D MSCs could serve as a stable cardioprotective cell product. Using scissor analysis on scRNA-seq data, we have clarified the potential functional and proliferative subpopulation, which cooperatively contributed to self-renewal and functional maintenance for 3D MSCs, named as “division of labor” mode of MSCs. Moreover, a ligand model was robustly developed for predicting the secretory efficacy of MSCs. A user-friendly web-server and a predictive model were constructed and available (https://wangxc.shinyapps.io/3D_MSCs/).
Comprehensive investigation into the influence of glycosylation on head and neck squamous cell carcinoma and development of a prognostic model for risk assessment and anticipating immunotherapy
Authors: Ma Heng , Xiong Ludan , Zhao Bohui , Hahan Zhuledesi , Wei Minghui , Shi Hengmei , Yang Susu , Ren Qianhe
Published: March 2024

Background

It has been well established that glycosylation plays a pivotal role in initiation, progression, and therapy resistance of several cancers. However, the correlations between glycosylation and head and neck squamous cell carcinoma (HNSCC) have not been elucidated in detail.

Methods

The paramount genes governing glycosylation were discerned via the utilization of the Protein-Protein Interaction (PPI) network and correlation analysis, coupled with single-cell RNA sequencing (scRNA-seq) analysis. To construct risk models exhibiting heightened predictive efficacy, cox- and lasso-regression methodologies were employed, and the veracity of these models was substantiated across both internal and external datasets. Subsequently, an exploration into the distinctions within the tumor microenvironment (TME), immunotherapy responses, and enriched pathways among disparate risk cohorts ensued. Ultimately, cell experiments were conducted to validate the consequential impact of SMS in Head and Neck Squamous Cell Carcinoma (HNSCC).

Results

A total of 184 genes orchestrating glycosylation were delineated for subsequent scrutiny. Employing cox- and lasso-regression methodologies, we fashioned a 3-gene signature, proficient in prognosticating the outcomes for patients afflicted with HNSCC. Noteworthy observations encompassed distinctions in the Tumor Microenvironment (TME), levels of immune cell infiltration, and the presence of immune checkpoint markers among divergent risk cohorts, holding potentially consequential implications for the clinical management of HNSCC patients.

Conclusion

The prognosis of HNSCC can be proficiently anticipated through risk signatures based on Glycosylation-related genes (GRGs). A thorough delineation of the GRGs signature in HNSCC holds the potential to facilitate the interpretation of HNSCC’s responsiveness to immunotherapy and provide innovative strategies for cancer treatment.
Single-cell RNA sequencing reveals Immune Education promotes T cell survival in mice subjected to the cecal ligation and puncture sepsis model
Authors: Ham Steven D. , Abraham Mabel N. , Deutschman Clifford S. , Taylor Matthew D.
Published: March 2024

Background

Individual T cell responses vary significantly based on the microenvironment present at the time of immune response and on prior induced T cell memory. While the cecal ligation and puncture (CLP) model is the most commonly used murine sepsis model, the contribution of diverse T cell responses has not been explored. We defined T cell subset responses to CLP using single-cell RNA sequencing and examined the effects of prior induced T cell memory (Immune Education) on these responses. We hypothesized that Immune Education prior to CLP would alter T cell responses at the single cell level at a single, early post-CLP time point.

Methods

Splenic T cells were isolated from C57BL/6 mice. Four cohorts were studied: Control, Immune-Educated, CLP, and Immune-Educated CLP. At age 8 weeks, Immune-Educated and Immune-Educated CLP mice received anti-CD3ϵ antibody; Control and CLP mice were administered an isotype control. CLP (two punctures with a 22-gauge needle) was performed at 12-13 weeks of life. Mice were sacrificed at baseline or 24-hours post-CLP. Unsupervised clustering of the transcriptome library identified six distinct T cell subsets: quiescent naïve CD4+, primed naïve CD4+, memory CD4+, naïve CD8+, activated CD8+, and CD8+ cytotoxic T cell subsets. T cell subset specific gene set enrichment analysis and Hurdle analysis for differentially expressed genes (DEGs) were performed.

Results

T cell responses to CLP were not uniform – subsets of activated and suppressed T cells were identified. Immune Education augmented specific T cell subsets and led to genomic signatures favoring T cell survival in unoperated and CLP mice. Additionally, the combination of Immune Education and CLP effected the expression of genes related to T cell activity in ways that differed from CLP alone. Validating our finding that IL7R pathway markers were upregulated in Immune-Educated CLP mice, we found that Immune Education increased T cell surface IL7R expression in post-CLP mice.

Conclusion

Immune Education enhanced the expression of genes associated with T cell survival in unoperated and CLP mice. Induction of memory T cell compartments via Immune Education combined with CLP may increase the model’s concordance to human sepsis.
Alpha1-antitrypsin improves survival in murine abdominal sepsis model by decreasing inflammation and sequestration of free heme
Authors: Zemtsovski Jan D. , Tumpara Srinu , Schmidt Sonja , Vijayan Vijith , Klos Andreas , Laudeley Robert , Held Julia , Immenschuh Stephan , Wurm Florian M. , Welte Tobias , Haller Hermann , Janciauskiene Sabina , Shushakova Nelli
Published: March 2024

Background

Excessive inflammation, hemolysis, and accumulation of labile heme play an essential role in the pathophysiology of multi-organ dysfunction syndrome (MODS) in sepsis. Alpha1-antitrypsin (AAT), an acute phase protein with heme binding capacity, is one of the essential modulators of host responses to inflammation. In this study, we evaluate the putative protective effect of AAT against MODS and mortality in a mouse model of polymicrobial abdominal sepsis.

Methods

Polymicrobial abdominal sepsis was induced in C57BL/6N mice by cecal ligation and puncture (CLP). Immediately after CLP surgery, mice were treated intraperitoneally with three different forms of human AAT—plasma-derived native (nAAT), oxidized nAAT (oxAAT), or recombinant AAT (recAAT)—or were injected with vehicle. Sham-operated mice served as controls. Mouse survival, bacterial load, kidney and liver function, immune cell profiles, cytokines/chemokines, and free (labile) heme levels were assessed. In parallel, in vitro experiments were carried out with resident peritoneal macrophages (MPMΦ) and mouse peritoneal mesothelial cells (MPMC).

Results

All AAT preparations used reduced mortality in septic mice. Treatment with AAT significantly reduced plasma lactate dehydrogenase and s-creatinine levels, vascular leakage, and systemic inflammation. Specifically, AAT reduced intraperitoneal accumulation of free heme, production of cytokines/chemokines, and neutrophil infiltration into the peritoneal cavity compared to septic mice not treated with AAT. In vitro experiments performed using MPMC and primary MPMΦ confirmed that AAT not only significantly decreases lipopolysaccharide (LPS)-induced pro-inflammatory cell activation but also prevents the enhancement of cellular responses to LPS by free heme. In addition, AAT inhibits cell death caused by free heme in vitro.

Conclusion

Data from the septic CLP mouse model suggest that intraperitoneal AAT treatment alone is sufficient to improve sepsis-associated organ dysfunctions, preserve endothelial barrier function, and reduce mortality, likely by preventing hyper-inflammatory responses and by neutralizing free heme.
Advancing ecological assessment of the Arabian Gulf through eDNA metabarcoding: opportunities, prospects, and challenges
Authors: Joydas Thadickal V. , Manokaran Seerangan , Gopi Jayanath , Rajakumar Jayachandran P. , Yu-Jia Lin , Heinle Moritz , Nazal Mazen K. , Manikandan Karuppasamy P. , Qashqari Maryam , Mohandas Sowmya P. , Hussain Syed A. , Maneja Rommel H. , Qasem Ali M. , Lozano-Cortés Diego , Abuzaid Nabil S.
Published: March 2024

The Arabian Gulf (hereafter ‘the Gulf’) is renowned for its unique ecological characteristics and distinct marine life. It offers a diverse range of ecosystems that have adapted to the impacts posed by natural stress and human activities. Regular biomonitoring and diversity assessments are necessary to document the health of the Gulf ecosystem and to implement appropriate measures for effective conservation and management. Recently, environmental DNA (eDNA), a total pool of DNA isolated from environmental samples, has emerged as a highly effective tool for ecological studies. This review explores the opportunities, prospects, and challenges associated with employing eDNA metabarcoding in the ecological assessment and biomonitoring of the Gulf. It provides an overview of the status of the Gulf ecosystem and discusses the potential applications of eDNA metabarcoding in assessing biodiversity, monitoring invasive species, and evaluating ecosystem health. Additionally, the investigation addresses the challenges inherent in implementing this technique, considering environmental complexities, methodological intricacies, and data interpretation. Overall, this review emphasizes the immense potential of eDNA metabarcoding in advancing ecological assessment in the Gulf and calls for further research and collaboration to harness its benefits in this unique marine ecosystem.
Utilization of response surface methodology to optimize the mechanical behaviour of flax/nano TiO2/Epoxy based hybrid composites under liquid nitrogen environment
Authors: Mohammed Ajmal Sheriff F. , Natrayan L. , Giri Jayant , Makki Emad , Shah Mohd Asif , Mallik Saurav
Published: March 2024

Linum usitatissimum commonly known as flax fibers, emerges as a promising reinforcement phase for artificial polymer resins, boasting ecological benefits, low density, and easy accessibility. However, the mechanical behavior of such composites hinges crucially on factors such as fiber mat thickness, nanoTiO2 filler content, and the application of cryogenic treatment. Addressing this complex interplay, this study employs a hand lay-up technique for composite construction, subjecting nanocomposite plates to the challenging liquid nitrogen conditions at 77 K post-manufacture. Recognizing the need for an optimized approach, Response Surface Methodology (RSM) based on Box-Benhken designs is employed to enhance the mixing features of linum usitatissimum polymer composites. The study calculates anticipated mechanical strength values through rigorous ANOVA inferential analysis, uncovering the pivotal roles played by fiber mat thickness, nanofiller content, and cryogenic treatment in the two feature interactions (2FI) model components. The methodology proves robust with high R2 values (0.9670 for tensile, 0.9845 for flexural, and 0.9670 for interlaminar shear strength) consistently aligning with experimental findings. The study culminates in identifying optimized parameters for maximal mechanical properties—300 gsm flax fiber thickness, 5 wt.% nano TiO2 concentration, and a 15-min cryogenic treatment—a result that advances our understanding of fundamental factors influencing composite performance and provides practical guidelines for applications in fields requiring superior mechanical strength in challenging environments.
Robust and accurate corneal interfaces segmentation in 2D and 3D OCT images
Authors: Zhu Xueli , Huang Wei , Ma Shaodong , Yi Quanyong
Published: March 2024

Segmentation of corneal layer interfaces in optical coherence tomography (OCT) images is important for diagnostic and surgical purposes, while manual segmentation is a time-consuming and tedious process. This paper presents a novel technique for the automatic segmentation of corneal layer interfaces using customized initial layer estimation and a gradient-based segmentation method. The proposed method was also extended to three-dimensional OCT images. Validation was performed on two corneal datasets, one with 37 B-scan images of healthy human eyes and the other with a 3D volume scan of a porcine eye. The approach showed robustness in extracting different layer boundaries in the low-SNR region with lower computational cost but higher accuracy compared to existing techniques. It achieved segmentation errors below 2.1 pixels for both the anterior and posterior layer boundaries in terms of mean unsigned surface positioning error for the first dataset and 2.6 pixels (5.2 μm) for segmenting all three layers that can be resolved in the second dataset. On average, it takes 0.7 and 0.4 seconds to process a cross-sectional B-scan image for datasets one and two, respectively. Our comparative study also showed that it outperforms state-of-the-art methods for quantifying layer interfaces in terms of accuracy and time efficiency.
Differences in diversity and community composition of the shell microbiome of apparently healthy lobsters Homarus americanus across Atlantic Canada
Authors: Koepper Svenja , Clark K. Fraser , McClure J. T. , Revie Crawford W. , Stryhn Henrik , Thakur Krishna K.
Published: March 2024

Host-microbe dynamics are of increasing interest in marine research due to their role in host health and productivity. Changes in the shell microbiome of American lobsters have been associated with epizootic shell disease, a syndrome that is spreading northwards across the eastern U.S. and Canadian Atlantic coast. This study analyzed differences in alpha and beta diversity, as well as differentially abundant taxa, in the shell-associated bacterial community of apparently healthy lobsters from four lobster fishing areas (LFAs) in Atlantic Canada. Over 180 lobsters from New Brunswick, Nova Scotia and Prince Edward Island (PEI) were sampled during seven sampling events over four sampling months. The bacterial community was identified using novel PacBio long-read sequencing, while alpha and beta diversity parameters were analyzed using linear regression models and weighted UniFrac distances. The bacterial richness, diversity and evenness differed by sampling location, sampling month, and molt stage, but not by lobster sex or size, nor sampling depth. Similarly, based on LFA, sampling month, year and lobster molt stage, the shell microbiome differed in microbial community composition with up to 34 out of 162 taxa differing significantly in abundance between sampling groups. This large-scale microbial survey suggests that the shell microbial diversity of apparently healthy lobsters is influenced by spatial and temporal factors such as geographic location, as well as the length of time the carapace is exposed to the surrounding seawater.
Sortase-encoding genes, srtA and srtC, mediate Enterococcus faecalis OG1RF persistence in the Helicoverpa zea gastrointestinal tract
Authors: Jackson Jerreme J. , Heyer Samantha , Bell Geneva
Published: March 2024

Enterococcus faecalis is a commensal and opportunistic pathogen in the gastrointestinal (GI) tract of mammals and insects. To investigate mechanisms of bacterial persistence in the gastrointestinal tract (GIT), we developed a non-destructive sampling model using Helicoverpa zea, a destructive agricultural pest, as host to study the role of bacterial sortase enzymes in mitigating persistence in the gastrointestinal tract. E. faecalis OG1RF ΔsrtA and E. faecalis OG1RF ΔsrtC, isogenic E. faecalis OG1RF sortase mutants grew similarly under planktonic growth conditions relative to a streptomycin-resistant E. faecalis OG1RFS WT in vitro but displayed impaired biofilm formation under, both, physiological and alkaline conditions. In the H. zea GI model, both mutants displayed impaired persistence relative to the WT. This represents one of the initial reports in which a non-destructive insect model has been used to characterize mechanisms of bacterial persistence in the Lepidopteran midgut and, furthermore, sheds light on new molecular mechanisms employed by diverse microorganisms to associate with invertebrate hosts.
Comparative transcriptomics and proteomics analysis of the symbiotic germination of Paphiopedilum barbigerum with Epulorhiza sp. FQXY019
Authors: Tian Fan , Wang Juncai , Ding Fangjun , Wang Lianhui , Yang Yanbing , Bai Xinxiang , Tan Chengjiang , Liao Xiaofeng
Published: March 2024

Introduction

Paphiopedilum barbigerum is currently the rarest and most endangered species of orchids in China and has significant ornamental value. The mature seeds of P. barbigerum are difficult to germinate owing to the absence of an endosperm and are highly dependent on mycorrhizal fungi for germination and subsequent development. However, little is known about the regulation mechanisms of symbiosis and symbiotic germination of P. barbigerum seeds.

Methods

Herein, transcriptomics and proteomics were used to explore the changes in the P. barbigerum seeds after inoculation with (FQXY019 treatment group) or without (control group) Epulorhiza sp. FQXY019 at 90 days after germination.

Results

Transcriptome sequencing revealed that a total of 10,961 differentially expressed genes (DEGs; 2,599 upregulated and 8,402 downregulated) were identified in the control and FQXY019 treatment groups. These DEGs were mainly involved in carbohydrate, fatty acid, and amino acid metabolism. Furthermore, the expression levels of candidate DEGs related to nodulin, Ca2+ signaling, and plant lectins were significantly affected in P. barbigerum in the FQXY019 treatment groups. Subsequently, tandem mass tag-based quantitative proteomics was performed to recognize the differentially expressed proteins (DEPs), and a total of 537 DEPs (220 upregulated and 317 downregulated) were identified that were enriched in processes including photosynthesis, photosynthesis-antenna proteins, and fatty acid biosynthesis and metabolism.

Discussion

This study provides novel insight on the mechanisms underlying the in vitro seed germination and protocorm development of P. barbigerum by using a compatible fungal symbiont and will benefit the reintroduction and mycorrhizal symbiotic germination of endangered orchids.
Spectral exponent assessment and neurofilament light chain: a comprehensive approach to describe recovery patterns in stroke
Authors: Lanzone Jacopo , Zulueta Aida , Boscarino Marilisa , Gallotta Matteo , Argentieri Maria Rosaria , Viganò Alessandro , Sarasso Simone , Colombo Michele A. , D’Ambrosio Sasha , Lunetta Christian , Parati Eugenio
Published: March 2024

Introduction

Understanding the residual recovery potential in stroke patients is crucial for tailoring effective neurorehabilitation programs. We propose using EEG and plasmatic Neurofilament light chain (NfL) levels as a model to depict longitudinal patterns of stroke recovery.

Methods

We enrolled 13 patients (4 female, mean age 74.7 ± 8.8) who underwent stroke in the previous month and were hospitalized for 2-months rehabilitation. Patients underwent blood withdrawal, clinical evaluation and high-definition EEG at T1 (first week of rehabilitation) and at T2 (53 ± 10 days after). We assessed the levels of NfL and we analyzed the EEG signal extracting Spectral Exponent (SE) values. We compared our variables between the two timepoint and between cortical and non-cortical strokes.

Results

We found a significant difference in the symmetry of SE values between cortical and non-cortical stroke at both T1 (p = 0.005) and T2 (p = 0.01). SE in the affected hemisphere showed significantly steeper values at T1 when compared with T2 (p = 0.001). EEG measures were consistently related to clinical scores, while NfL at T1 was related to the volume of ischemic lesions (r = 0.75; p = 0.003). Additionally, the combined use of NfL and SE indicated varying trends in longitudinal clinical recovery.

Conclusion

We present proof of concept of a promising approach for the characterization of different recovery patterns in stroke patients.
The “psychiatric” neuron: the psychic neuron of the cerebral cortex, revisited
Authors: Flynn L. Taylor , Bouras Nadia N. , Migovich Volodar M. , Clarin Jacob D. , Gao Wen-Jun
Published: March 2024

Nearly 25 years ago, Dr. Patricia Goldman-Rakic published her review paper, “The ‘Psychic’ Neuron of the Cerebral Cortex,” outlining the circuit-level dynamics, neurotransmitter systems, and behavioral correlates of pyramidal neurons in the cerebral cortex, particularly as they relate to working memory. In the decades since the release of this paper, the existing literature and our understanding of the pyramidal neuron have increased tremendously, and research is still underway to better characterize the role of the pyramidal neuron in both healthy and psychiatric disease states. In this review, we revisit Dr. Goldman-Rakic’s characterization of the pyramidal neuron, focusing on the pyramidal neurons of the prefrontal cortex (PFC) and their role in working memory. Specifically, we examine the role of PFC pyramidal neurons in the intersection of working memory and social function and describe how deficits in working memory may actually underlie the pathophysiology of social dysfunction in psychiatric disease states. We briefly describe the cortico-cortical and corticothalamic connections between the PFC and non-PFC brain regions, as well the microcircuit dynamics of the pyramidal neuron and interneurons, and the role of both these macro- and microcircuits in the maintenance of the excitatory/inhibitory balance of the cerebral cortex for working memory function. Finally, we discuss the consequences to working memory when pyramidal neurons and their circuits are dysfunctional, emphasizing the resulting social deficits in psychiatric disease states with known working memory dysfunction.
Greater white matter degeneration and lower structural connectivity in non-amnestic vs. amnestic Alzheimer’s disease
Authors: Phillips Jeffrey S. , Adluru Nagesh , Chung Moo K. , Radhakrishnan Hamsanandini , Olm Christopher A. , Cook Philip A. , Gee James C. , Cousins Katheryn A. Q. , Arezoumandan Sanaz , Wolk David A. , McMillan Corey T. , Grossman Murray , Irwin David J.
Published: March 2024

Introduction

Multimodal evidence indicates Alzheimer’s disease (AD) is characterized by early white matter (WM) changes that precede overt cognitive impairment. WM changes have overwhelmingly been investigated in typical, amnestic mild cognitive impairment and AD; fewer studies have addressed WM change in atypical, non-amnestic syndromes. We hypothesized each non-amnestic AD syndrome would exhibit WM differences from amnestic and other non-amnestic syndromes.

Materials and methods

Participants included 45 cognitively normal (CN) individuals; 41 amnestic AD patients; and 67 patients with non-amnestic AD syndromes including logopenic-variant primary progressive aphasia (lvPPA, n = 32), posterior cortical atrophy (PCA, n = 17), behavioral variant AD (bvAD, n = 10), and corticobasal syndrome (CBS, n = 8). All had T1-weighted MRI and 30-direction diffusion-weighted imaging (DWI). We performed whole-brain deterministic tractography between 148 cortical and subcortical regions; connection strength was quantified by tractwise mean generalized fractional anisotropy. Regression models assessed effects of group and phenotype as well as associations with grey matter volume. Topological analyses assessed differences in persistent homology (numbers of graph components and cycles). Additionally, we tested associations of topological metrics with global cognition, disease duration, and DWI microstructural metrics.

Results

Both amnestic and non-amnestic patients exhibited lower WM connection strength than CN participants in corpus callosum, cingulum, and inferior and superior longitudinal fasciculi. Overall, non-amnestic patients had more WM disease than amnestic patients. LvPPA patients had left-lateralized WM degeneration; PCA patients had reductions in connections to bilateral posterior parietal, occipital, and temporal areas. Topological analysis showed the non-amnestic but not the amnestic group had more connected components than controls, indicating persistently lower connectivity. Longer disease duration and cognitive impairment were associated with more connected components and fewer cycles in individuals’ brain graphs.

Discussion

We have previously reported syndromic differences in GM degeneration and tau accumulation between AD syndromes; here we find corresponding differences in WM tracts connecting syndrome-specific epicenters. Determining the reasons for selective WM degeneration in non-amnestic AD is a research priority that will require integration of knowledge from neuroimaging, biomarker, autopsy, and functional genetic studies. Furthermore, longitudinal studies to determine the chronology of WM vs. GM degeneration will be key to assessing evidence for WM-mediated tau spread.
Effects of hyperbaric oxygen therapy on autistic behaviors and GRIN2B gene expression in valproic acid-exposed rats
Authors: Mohtaj Khorassani Yalda , Moghimi Ali , Khakzad Mohammad Reza , Fereidoni Masoud , Hassani Delaram , Torbati Gah Javad
Published: March 2024

Introduction

Autism is a complex neurodevelopmental condition characterized by deficits in social interaction, communication, and restricted repetitive behaviors. Hyperbaric oxygen therapy (HBOT) has emerged as a potential treatment for autism, although its effects on behavior and gene expression are not well understood. The GRIN2B gene, known for its involvement in encoding a glutamate receptor subunit crucial for neuron communication and associated with autism, was a focus of this study.

Methods

Using a rat model induced by prenatal exposure to valproic acid, we examined the impact of HBOT on autism-like behaviors and GRIN2B gene expression. Male Wistar rats were categorized into four groups: control, VPA (valproic acid-exposed), VPA+HBOT [2 atmosphere absolute (ATA)], and VPA+HBOT (2.5 ATA). The rats underwent several behavioral tests to assess social behavior, anxiety, stereotype and exploratory behaviors, and learning. Following the behavioral tests, the HBOT groups received 15 sessions of HBOT at pressures of 2 and 2.5 (ATA), and their behaviors were re-evaluated. Subsequently, real-time PCR was employed to measure GRIN2B gene expression in the frontal lobe.

Results

Our results indicated that HBOT significantly increased social interaction and exploratory behaviors in VPA-exposed rats, alongside elevated GRIN2B gene expression in their frontal lobe.

Discussion

Our findings imply that HBOT might have a potential role in ameliorating autism-related behaviors in the VPA rat model of autism through potential modulation of GRIN2B gene expression. However, additional research is essential to fully comprehend the underlying mechanisms and refine the HBOT protocol for optimizing its effectiveness in improving autism-related symptoms.
Cross-talk between the gut microbiota and hypothyroidism: a bidirectional two-sample Mendelian randomization study
Authors: Shi Chao , Chen Jie , He Siying , Zhang Yingying , Zhang Yanyue , Yu Lisha
Published: March 2024

Background

Multiple observational studies suggest a connection between the composition of the gut microbiota and hypothyroidism. However, it has yet to be determined whether the gut microbiota has a causal effect on hypothyroidism.

Methods

To investigate the connection between the gut microbiota and hypothyroidism, two-sample Mendelian randomization was performed using data from a genome-wide association study meta-analysis (n = 18,430) conducted by the MiBioGen consortium. Summary statistics for hypothyroidism (26,342 cases and 59,827 controls) were obtained using the data from the FinnGen consortium R8 release data. To investigate the causal link between the gut microbiota and hypothyroidism, various methods, including MR-Egger, weighted median, weighted model, simple model, MR-PRESSO, and inverse variance weighted (IVW), were employed. The bacteria that were causally linked to hypothyroidism in forward Mendelian randomization analysis were subjected to reverse Mendelian randomization analysis. Cochran’s Q statistics were utilized to gauge the heterogeneity of the instrumental variables.

Results

The results indicated that Akkermansia had a positive impact on hypothyroidism, with an odds ratio of 0.84 (95% CI 0.74–0.95, p = 0.01) based on the inverse variance-weighted estimates. Additionally, Anaerostipes (OR = 1.17, 95% CI 1.01–1.36, p = 0.04), Butyrivibrio (OR = 0.93, 95% CI 0.88–0.99, p = 0.02), Holdemania (OR = 0.89, 95% CI 0.81–0.99, p = 0.03), Intestinimonas (OR = 1.13, 95% CI 1.02–1.26, p = 0.03), Ruminiclostridium5 (OR = 1.19, 95% CI 1.01–1.41, p = 0.04), and Ruminococcaceae UCG-011 (OR = 0.91, 95% CI 0.84–0.99, p = 0.03) were identified. The gut microbiota was not significantly affected by hypothyroidism, as indicated by the results of the reverse MR analysis. There was no significant variation in the instrumental variables or horizontal pleiotropy.

Conclusion

The findings of this study using two-sample Mendelian randomization indicate a causal relationship between Akkermansia and hypothyroidism. Increased Akkermansia inhibits the onset and progression of hypothyroidism. Additional randomized controlled experiments are necessary to elucidate the beneficial impact of probiotics on hypothyroidism and their distinct protective mechanisms.
UPLC-ESI-MS/MS-based widely targeted metabolomics reveals differences in metabolite composition among four Ganoderma species
Authors: Wei-Ye Liu , Hong-Bo Guo , Rui-Heng Yang , Ai-Guo Xu , Jia-Chen Zhao , Zhao-Qian Yang , Wen-Jun Han , Xiao-Dan Yu
Published: March 2024

The Chinese name “Lingzhi” refers to Ganoderma genus, which are increasingly used in the food and medical industries. Ganoderma species are often used interchangeably since the differences in their composition are not known. To find compositional metabolite differences among Ganoderma species, we conducted a widely targeted metabolomics analysis of four commonly used edible and medicinal Ganoderma species based on ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry. Through pairwise comparisons, we identified 575–764 significant differential metabolites among the species, most of which exhibited large fold differences. We screened and analyzed the composition and functionality of the advantageous metabolites in each species. Ganoderma lingzhi advantageous metabolites were mostly related to amino acids and derivatives, as well as terpenes, G. sinense to terpenes, and G. leucocontextum and G. tsugae to nucleotides and derivatives, alkaloids, and lipids. Network pharmacological analysis showed that SRC, GAPDH, TNF, and AKT1 were the key targets of high-degree advantage metabolites among the four Ganoderma species. Analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes demonstrated that the advantage metabolites in the four Ganoderma species may regulate and participate in signaling pathways associated with diverse cancers, Alzheimer’s disease, and diabetes. Our findings contribute to more targeted development of Ganoderma products in the food and medical industries.
Association of multiple serum minerals and vitamins with metabolic dysfunction-associated fatty liver disease in US adults: National Health and Nutrition Examination Survey 2017–2018
Authors: Guo Peisen , Yu Jiahui
Published: March 2024

Background

Despite the rapid increase in the global prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), there are no approved therapeutic drugs for MAFLD yet. Nutrient supplementation might mitigate the risk of MAFLD. It is more typical for individuals to consume multiple nutrients simultaneously. However, the studies exploring the combined effects of multiple nutrients on MAFLD are limited. This study aimed to investigate the relationship between both individual nutrients and their combined influence on the risk of MAFLD.

Methods

Data were obtained from National Health and Nutrition Examination Survey (NHANES), and 18 types of nutrients were considered in this study. Logistic regression analysis was performed to evaluate the correlation between single nutrients and the risk of MAFLD. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was performed to pinpoint the most relevant nutrient associated with the risk of MAFLD. Subsequently, both Weighted Quantile Sum (WQS) regression and Quantile g-computation (Qgcomp) were used to assess the combined effects of multiple nutrients on the risk of MAFLD.

Results

A total of 3,069 participants were included in this study. LASSO regression analysis showed that Se, α-tocopherol, and γ-tocopherol exhibited a positive association with the risk of MAFLD. In contrast, the serum levels of Co, P, α-cryptoxanthin, LZ, and trans-β-carotene were inversely associated with the prevalence of MAFLD. When Se and two types of vitamin E were excluded, the WQS index showed a significant inverse relationship between the remaining 15 nutrients and the risk of MAFLD; α-cryptoxanthin showed the most substantial contribution. Similarly, Qgcomp suggested that the combined effects of these 15 nutrients were associated with a lower risk of MAFLD, with α-cryptoxanthin possessing the most significant negative weights.

Conclusion

This study suggested that the complex nutrients with either a low proportion of Se, α-tocopherol, and γ-tocopherol or without them should be recommended for patients with MAFLD to reduce its risk.
The frequency of NUDT15 rs116855232 and its impact on mercaptopurine-induced toxicity in Syrian children with acute lymphoblastic leukemia
Authors: Muhammad Muhammad , Saifo Maher , Aljamali Majd , Alali Mousa , Ghanem Khaled M.
Published: March 2024

Introduction

Polymorphisms in NUDT15 may result in differences in mercaptopurine-induced toxicity. This study aimed to identify the frequency of the NUDT15 (c.415C>T; rs116855232) polymorphism and investigate the effect of this polymorphism on mercaptopurine-induced toxicity in a population of Syrian patients with childhood acute lymphoblastic leukemia (ALL).

Methods

This is a retrospective study that included children with ALL reaching at least 6 months of maintenance therapy. The NUDT15 genotyping was determined using standard targeted sequencing of polymerase chain reaction products. The odds ratio (OR) for the association between toxicity and genotype was evaluated.

Results

A total of 92 patients were enrolled. The majority of the patients in the study population were low-risk (63.04%), followed by intermediate-risk (25%), and high-risk (11.96%). There were 5 patients (5.4%) with NUDT15 (c.415C>T; rs116855232) CT genotype, and 1 patient (1.08%) with NUDT15 TT genotype, with allele frequencies of C=0.962 and T=0.038. The mercaptopurine median dose intensity was 100%, 54.69%, and 5% for the genotypes CC, CT, and TT, respectively (P=0.009). Early onset leukopenia was significantly associated with the NUDT15 polymorphism (OR: 6.16, 95% CI: 1.11-34.18, P=0.037). There was no association between the NUDT15 genotype and hepatotoxicity.

Conclusion

Approximately 6.5% of the study population exhibited reduced NUDT15 activity. The mercaptopurine dose intensity was considerably low in NUDT15 rs116855232 TT genotype compared with CT and CC. The dosage of mercaptopurine should be adjusted according to the NUDT15 genotype in pediatric patients with ALL.
Assessment of knowledge and perceptions of human papillomavirus vaccine and its determinants among women who have eligible daughters in Debre Berhan City, Ethiopia: a cross-sectional study
Authors: Tsige Abate Wondesen , Ayenew Kassahun Dires , Ayele Siraye Genzeb
Published: March 2024

Introduction

Globally, cervical cancer(CC) is the second most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths in women. Human papillomavirus (HPV) infection is the leading cause of CC. Persistent infection with HPV accounts for 90% of all CC cases. The human papillomavirus vaccine has the great potential to prevent HPV-related infections for millions of women and men. The current study aimed to assess knowledge and perceptions towards the HPV vaccine and its determinants among women who have eligible daughters in Debre Berhan City, Ethiopia.

Methods

A cross-sectional study was conducted from April 2, 2023, to May 15, 2023. A multistage sampling procedure was used to recruit 607 women participants. Descriptive statistics were used to summarize socio-demographic data. Univariable and multivariable binary logistic regression analyses were performed to measure the associations between the dependent and independent variables. A p-value of <0.05 was considered statistically significant.

Results

More than three-fourths of the participants, 479 individuals (80%) were currently married, and 243(40.1%) had a diploma or higher education level. Of 456(75.12) participants reported, they had information about cervical cancer. For 449(73.9%) of the participants, television was the main evidence. The majority of 352(59.99%) participants knew the HPV vaccine could be offered to a female child aged 9-14 years old. Only 215(35.4%) participants think the HPV vaccine was safe and effective. Women who had a degree and above educational level were about 9 times more likely to have good knowledge about the HPV vaccine than study participants who did not read and write (AOR=9.21; 95% CI=2.82-12.16; p=0.004). Women who did not have information about the HPV vaccine before this study were about 80% less likely to have a positive perception of the HPV vaccine than participants who had earlier information about the HPV vaccine (AOR=0.8; 95%CI=0.63-0.49; P=003).

Conclusion

Women had poor knowledge and perceptions about the HPV vaccine. Maternal marital status, age, and having information about the HPV vaccine were the only predictors of women’s knowledge of the HPV vaccine.
Case report: Anesthetic management for removal of tumor thrombus in the inferior vena cava and pulmonary artery in renal cell carcinoma
Authors: Chen Suli , Lu Liangyuan , Zheng Xiangli , Lin Yanjun , Bao Liming , Zhang Bao , Yang Zhanmin
Published: March 2024

Anesthetic management of patients with renal cell carcinoma with tumor thrombus in the inferior vena cava (IVC) is challenging. This paper reports the experience of anesthesia management in a patient with advanced renal cell carcinoma with thrombus accumulation in the IVC, right atrium, and pulmonary artery who underwent radical nephrectomy and tumor thrombus removal assisted by cardiopulmonary bypass. The emboli, measuring approximately 3 × 6 cm in the left inferior pulmonary artery and 4 × 13 cm in the right main pulmonary artery, were removed completely. During incision of the IVC under systemic heparinization, significant blood loss occurred in the surgical field. The surgery took 724 min, and cardiopulmonary bypass took 396 min. Intraoperative blood loss was 22,000 ml. The patient was extubated 39 hours after surgery and stayed in intensive care unit for 3 days. At 1 year follow-up, the patient was in good health and leading a normal life.
Clinical characteristic, common sites, and geographical distribution of pediatric tuberculosis patients in Southwest China
Authors: Wang Dong-Mei , Wang Chuan , An Qi , Yang Qing , Liao Yi
Published: March 2024

Background

The data report of a large sample, dynamic epidemiology, and characteristic analysis of pediatric tuberculosis (TB) in Southwest China is not clear. Herein, we conducted descriptive dynamic epidemiology, characteristic analysis and geographical distribution study of pediatric TB inpatients in Southwest China for more than 20 years.

Methods

Patients with pediatric TB were recruited from October 2002 to September 2022 in Southwest of China based on etiology or clinical confirmation. Extract hospitalization medical record information for each patient. The geographical distribution chart of cases is used to display the trend of case flow segmented every 5 years.

Results

Among 3,024 pediatric TB patients with an average age of 9.11 ± 4.39, 17.49% (529) had pulmonary tuberculosis (PTB), 9.06% (274) had extrapulmonary tuberculosis (EPTB), and 73.45% (2,221) had combined TB. The most common form of EPTB is disseminated TB (28.98%), followed by TB lymphadenitis (20.56%), pleural TB (19.72%), and TB meningitis (19.68%). Children aged 0–4 years had a high risk of TB meningitis and a severe symptoms, while children in the elderly age group had a high risk of pleural TB. In the past 20 years, hospitalized TB pediatric cases mainly came from Sichuan, Tibet, Qinghai, Yunnan and other places. The number of patients from ethnic minorities, especially Tibetans, showed an upward trend on a yearly basis (χ2 = 401.43, P < 0.001).

Conclusions

Public health investment and effective management in pediatric TB should be further strengthened.