bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling the mystery: a Mendelian randomized exploration of gut microbiota and different types of obesity
Authors: Liu Siyuan , Li Fan , Cai Yunjia , Ren Linan , Sun Lin , Gang Xiaokun , Wang Guixia
Published: February 2024

Background

Numerous studies have demonstrated the influence of gut microbiota on the development of obesity. In this study, we utilized Mendelian randomization (MR) analysis to investigate the gut microbiota characteristics among different types of obese patients, aiming to elucidate the underlying mechanisms and provide novel insights for obesity treatment.

Methods

Two-sample multivariable Mendelian randomization (MR) analysis was employed to assess causal relationships between gut microbiota and various obesity subtypes. Gut microbiota data were obtained from the international consortium MiBioGen, and data on obese individuals were sourced from the Finnish National Biobank FinnGen. Eligible single-nucleotide polymorphisms (SNPs) were selected as instrumental variables. Various analytical methods, including inverse variance weighted (IVW), MR-Egger regression, weighted median, MR-RAPS, and Lasso regression, were applied. Sensitivity analyses for quality control included MR-Egger intercept tests, Cochran’s Q tests, and leave-one-out analyses and others.

Results

Mendelian randomization studies revealed distinct gut microbiota profiles among European populations with different obesity subtypes. Following multivariable MR analysis, we found that Ruminococcaceae UCG010 [Odds Ratio (OR): 0.842, 95% confidence interval (CI): 0.766-0.926, Adjusted P value: 0.028] independently reduced the risk of obesity induced by excessive calorie intake, while Butyricimonas [OR: 4.252, 95% CI: 2.177-8.307, Adjusted P value: 0.002] independently increased the risk of medication-induced obesity. For localized adiposity, Pasteurellaceae [OR: 0.213, 95% CI: 0.115-0.395, Adjusted P value: <0.001] acted as a protective factor. In the case of extreme obesity with alveolar hypoventilation, lactobacillus [OR: 0.724, 95% CI: 0.609-0.860, Adjusted P value: 0.035] reduced the risk of its occurrence. Additionally, six gut microbiota may have potential roles in the onset of different types of obesity. Specifically, the Ruminococcus torques group may increase the risk of its occurrence. Desulfovibrio and Catenabacterium may serve as protective factors in the onset of Drug-induced obesity. Oxalobacteraceae, Actinomycetaceae, and Ruminiclostridium 9, on the other hand, could potentially increase the risk of Drug-induced obesity. No evidence of heterogeneity or horizontal pleiotropy among SNPs was found in the above studies (all P values for Q test and MR-Egger intercept > 0.05).

Conclusion

Gut microbiota abundance is causally related to obesity, with distinct gut microbiota profiles observed among different obesity subtypes. Four bacterial species, including Ruminococcaceae UCG010, Butyricimonas, Pasteurellaceae and lactobacillus independently influence the development of various types of obesity. Probiotic and prebiotic supplementation may represent a novel approach in future obesity management.
Toward a transformative climate change adaptation from local to global perspective—A transdisciplinary challenge by Kyoto Climate Change Adaptation Center
Authors: Ichihara Masako , Nakagawa Yoshinori , Ishii Reiichiro , Saijo Tatsuyoshi , Yasunari Tetsuzo
Published: February 2024

Policies for climate change adaptation differ from those for climate change mitigation, both of which share the common aim of maintaining a sustainable climate system that enables humankind to survive while enjoying wellbeing. Considering the variability in regional conditions, they must be diverse throughout the policymaking process, with the participation of multiple stakeholders, to place the livelihood of residents as the central issue. Simultaneously, these regional diversities must also be realized in a manner consistent with the global goal of climate change mitigation. To that end, comprehensive and transformative adaptation measures are essential, rather than responding to imminent issues on an ad-hoc basis. As the literature shows, a transdisciplinary approach involving researchers across different fields and multiple non-academic sectors can fill the gaps in transformative adaptation. Still, it has yet to be implemented because of the lack of experience of this issue. Here, we present key findings that affect the generation of synergies and tradeoffs among issues through our novel transdisciplinary approach in Kyoto, Japan, via a series of Future Design workshops in agriculture in collaboration with local farmers, regional policymakers, and researchers with diverse backgrounds. These results provide a direction for future research to secure a methodological foundation that will facilitate the sustainability of these efforts.
Therapeutic strategies based on non-ionizing radiation to prevent venous neointimal hyperplasia: the relevance for stenosed arteriovenous fistula, and the role of vascular compliance
Authors: Russu Eliza , Arbanasi Emil-Marian , Chirila Traian V. , Muresan Adrian V.
Published: February 2024

We have reviewed the development and current status of therapies based on exposure to non-ionizing radiation (with a photon energy less than 10 eV) aimed at suppressing the venous neointimal hyperplasia, and consequentially at avoiding stenosis in arteriovenous grafts. Due to the drawbacks associated with the medical use of ionizing radiation, prominently the radiation-induced cardiovascular disease, the availability of procedures using non-ionizing radiation is becoming a noteworthy objective for the current research. Further, the focus of the review was the use of such procedures for improving the vascular access function and assuring the clinical success of arteriovenous fistulae in hemodialysis patients. Following a brief discussion of the physical principles underlying radiotherapy, the current methods based on non-ionizing radiation, either in use or under development, were described in detail. There are currently five such techniques, including photodynamic therapy (PDT), far-infrared therapy, photochemical tissue passivation (PTP), Alucent vascular scaffolding, and adventitial photocrosslinking. The last three are contingent on the mechanical stiffening achievable by the exogenous photochemical crosslinking of tissular collagen, a process that leads to the decrease of venous compliance. As there are conflicting opinions on the role of compliance mismatch between arterial and venous conduits in a graft, this aspect was also considered in our review.
Inflammation mediates the relationship between diet quality assessed by healthy eating index-2015 and metabolic syndrome
Authors: Yuguang Li , Chang Yu , Li Hongwei , Li Fangqi , Zou Qing , Liu Xiangliang , Chen Xiao , Cui Jiuwei
Published: February 2024

Background

Metabolic syndrome is a cluster of metabolic disorders, including obesity, hypertension, hyperglycemia, and abnormal lipid levels. However, researches on the association between overall dietary quality measured by the Healthy Eating Index-2015 (HEI-2015) and the risk of metabolic syndrome is still lacking.

Methods

This study utilized data from four cycles (2011-2018) of the National Health and Nutrition Examination Survey (NHANES) database, including 17,582 participants. Logistic regression analysis was employed to explore the correlation between HEI and the risk of metabolic syndrome. Additionally, mediation analysis was conducted to examine the effects of Systemic Immune-Inflammation Index (SII) and serum uric acid as potential mediators between HEI and metabolic syndrome risk. Weighted quantile sum (WQS) regression evaluated the composite exposure impact of the 13 components of the HEI on metabolic syndrome, as well as the proportion of their weights.

Results

Higher dietary quality measured by HEI-2015 (at the 75th percentile) was negatively correlated with the risk of metabolic syndrome (OR=0.80, 95%CI=0.72-0.89, P=0.003). Higher SII and serum uric acid levels were identified as risk factors for metabolic syndrome (P for trend<0.001). Approximately 37.5% of the effect of HEI on metabolic syndrome occurrence was mediated by SII (Indirect effect=-0.002, 95%CI (-0.003,-0.001), Direct effect=-0.022, 95%CI (-0.0273,-0.015)). Additionally, 25% of the effect of HEI on metabolic syndrome occurrence was mediated by serum uric acid levels (Indirect effect=-0.006, 95%CI (-0.010,-0.012), Direct effect=-0.024, 95%CI (-0.041,-0.009)). WQS regression analysis revealed the highest weighted proportions for seafood and plant proteins (25.20%) and sodium (17.79%), while the weight for whole fruit was the lowest (0.25%).

Conclusion

Better dietary quality measured by HEI-2015 was associated with a lower likelihood of metabolic syndrome. Higher SII and serum uric acid levels were identified as risk factors for metabolic syndrome and potential mediators.
Effects of menstrual disorders and dysmenorrhea on cardiovascular disease: a Mendelian randomization study
Authors: Lai Sijia , Jin Qiubai , Wang Dayang , Li Tianli , Wang Xian
Published: February 2024

Background

Observational studies have demonstrated associations between menstrual disorders, dysmenorrhea, and cardiovascular disease (CVD). However, it remains unclear whether these associations are causal. This study is to investigate whether menstrual disorders and dysmenorrhea causally affect the risk of CVD.

Methods

The summary data for menstrual disorders (excessive menstruation and irregular menses) and dysmenorrhea were obtained from FinnGen study, summary data for CVD were obtained from UK Biobank and meta-analysis. The inverse-variance-weighted method was mainly used in the Mendelian randomization for causality analysis. Sensitivity analyses were performed by several methods under different model assumptions.

Results

Genetic liability to excessive menstruation was associated with higher risk of atrial fibrillation (odds ratio (OR), 1.078 [95% confidence interval (CI), 1.015-1.145]; P=0.014), but a lower risk of hypertension (OR, 0.994 [95% CI: 0.989-0.999]; P=0.016). Irregular menses was associated with higher risk of atrial fibrillation (OR, 1.095 [95% CI: 1.015-1.182]; P=0.02), hypertension (OR, 1.007 [95% CI: 1.000-1.013]; P=0.047), myocardial infarction (OR, 1.172 [95% CI: 1.060-1.295]; P=0.02), ischemic heart disease, (OR, 1.005 [95% CI: 1.000-1.010]; P=0.037) and coronary heart disease (OR, 1.004 [95% CI: 1.001-1.008]; P=0.026). Dysmenorrhea was associated with higher risk of atrial fibrillation (OR, 1.052 [95% CI: 1.014-1.092]; P=0.008) and Ischemic stroke (cardioembolic) (OR, 1.122 [95% CI: 1.002-1.257]; P=0.046). After Benjamini-Hochberg correction, irregular menses was associated with higher risk of myocardial infarction.

Conclusion

We confirmed a causal relationship of excessive menstruation, irregular menses and dysmenorrhea on cardiovascular outcomes independent of sex hormone levels, with an emphasis on the link between irregular menses and myocardial infarction. These clinical features can be utilized as markers to identify women at higher risk of developing CVD in the future, recommending early clinical intervention of menstrual diseases.
The metabolic profiles and body composition of non-obese metabolic associated fatty liver disease
Authors: Zhang Yujuan , Xiang Liulan , Qi Fang , Cao Yutian , Zhang Wenhui , Lv Tiansu , Zhou Xiqiao
Published: February 2024

Background/purpose

Metabolic-associated fatty liver disease (MAFLD) is a major cause of chronic liver disease worldwide and is generally thought to be closely related to obesity and diabetes. However, it also affects non-obese individuals, particularly in Asian cultures.

Methods

Healthy physical examination subjects and MAFLD patients were included in the endocrinology department of Jiangsu Provincial Hospital of Traditional Chinese Medicine. MAFLD was defined as fatty liver in imaging without virus infection, drug, alcohol, or other known causes of chronic liver disease. Non-obese MAFLD was defined as MAFLD in non-obese subjects (BMI<25 kg/m2).

Results

The final analysis comprised 1047 participants in total. Of 946 MAFLD patients, 162 (17.12%) were diagnosed with non-obese MAFLD. Non-obese MAFLD patients were older, had lower alanine aminotransferase (ALT), triglyceride, and waist circumference, but had higher high density lipoprotein cholesterol (HDL-c) than obese MAFLD patients. Compared with non-obese healthy controls, non-obese MAFLD patients had higher BMI, ALT, gamma-glutamyl transferase (GGT), uric acid (UA), triglycerides (TG), and low density lipoprotein cholesterol (LDL-c). In terms of body composition, body fat mass (BFM), waist-hip ratio (WHR), percent body fat (PBF), visceral fat area (VFA), and fat mass index (FMI) were lower in non-obese healthy controls than non-obese MAFLD patients. A binary logistic regression analysis revealed that non-obese MAFLD was linked with lower GGT and higher HDL-c.

Conclusion

In this study cohort, non-obese MAFLD was present at a prevalence of 13.90%. In contrast to non-obese healthy controls, non-obese MAFLD patients exhibited different metabolic profiles, but they also had different body compositions.
Who can benefit from postmastectomy radiotherapy among HR+/HER2- T1-2 N1M0 breast cancer patients? An explainable machine learning mortality prediction based approach
Authors: Jin Long , Zhao Qifan , Fu Shenbo , Zhang Yuan , Wu Shuhan , Li Xiao , Cao Fei
Published: February 2024

Objective

The necessity of postmastectomy radiotherapy(PMRT) for patients with HR+/HER2 T1-2 N1M0 breast cancer remains controversial. We want to use explainable machine learning to learn the feature importance of the patients and identify the subgroup of the patients who may benefit from the PMRT. Additionally, develop tools to provide guidance to the doctors.

Methods

In this study, we trained and validated 2 machine learning survival models: deep learning neural network and Cox proportional hazard model. The training dataset consisted of 35,347 patients with HR+/HER2- T1-2 N1M0 breast cancer who received mastectomies from the SEER database from 2013 to 2018. The performance of survival models were assessed using a concordance index (c-index).Then we did subgroup analysis to identify the subgroup who could benefit from PMRT. We also analyzed the global feature importance for the model and individual feature importance for individual survival prediction. Finally, we developed a Cloud-based recommendation system for PMRT to visualize the survival curve of each treatment plan and deployed it on the Internet.

Results

A total of 35,347 patients were included in this study. We identified that radiotherapy improved the OS in patients with tumor size >14mm and age older than 54: 5-year OS rates of 91.9 versus 87.2% (radio vs. nonradio, P <0.001) and cohort with tumor size >14mm and grade worse than well-differentiated, 5-year OS rates of 90.8 versus 82.3% (radio vs. nonradio, P <0.001).The deep learning network performed more stably and accurately in predicting patients survival than the random survival forest and Cox proportional hazard model on the internal test dataset (C-index=0.776 vs 0.641) and in the external validation(C-index=0.769 vs 0.650).Besides, the deep learning model identified several key factors that significantly influence patient survival, including tumor size, examined regional nodes, age at 45-49 years old and positive regional nodes (PRN).

Conclusion

Patients with tumor size >14mm and age older than 54 and cohort with tumor size >14mm and grade worse than well-differentiated could benefit from the PMRT. The deep learning network performed more stably and accurately in predicting patients survival than Cox proportional hazard model on the internal test. Besides, tumor size, examined regional nodes, age at 45-49 years old and PRN are the most significant factors to the overall survival (OS).
New mechanistic insights of anti-obesity by sleeve gastrectomy-altered gut microbiota and lipid metabolism
Authors: Liu Chuxuan , Xu Qian , Dong Shuohui , Ding Huanxin , Li Bingjun , Zhang Dexu , Liang Yongjuan , Li Linchuan , Liu Qiaoran , Cheng Yugang , Wu Jing , Zhu Jiankang , Zhong Mingwei , Cao Yihai , Zhang Guangyong
Published: February 2024

Background

The obesity epidemic has been on the rise due to changes in living standards and lifestyles. To combat this issue, sleeve gastrectomy (SG) has emerged as a prominent bariatric surgery technique, offering substantial weight reduction. Nevertheless, the mechanisms that underlie SG-related bodyweight loss are not fully understood.

Methods

In this study, we conducted a collection of preoperative and 3-month postoperative serum and fecal samples from patients who underwent laparoscopic SG at the First Affiliated Hospital of Shandong First Medical University (Jinan, China). Here, we took an unbiased approach of multi-omics to investigate the role of SG-altered gut microbiota in anti-obesity of these patients. Non-target metabolome sequencing was performed using the fecal and serum samples.

Results

Our data show that SG markedly increased microbiota diversity and Rikenellaceae, Alistipes, Parabacteroides, Bactreoidales, and Enterobacteraies robustly increased. These compositional changes were positively correlated with lipid metabolites, including sphingolipids, glycerophospholipids, and unsaturated fatty acids. Increases of Rikenellaceae, Alistipes, and Parabacteroide were reversely correlated with body mass index (BMI).

Conclusion

In conclusion, our findings provide evidence that SG induces significant alterations in the abundances of Rikenellaceae, Alistipes, Parabacteroides, and Bacteroidales, as well as changes in lipid metabolism-related metabolites. Importantly, these changes were found to be closely linked to the alleviation of obesity. On the basis of these findings, we have identified a number of microbiotas that could be potential targets for treatment of obesity.
Study on the spillover effect of digital economy development on CO2 emissions
Authors: Hou Jianchao , Fu Yu
Published: February 2024

To study the spillover effect of the digital economy development on carbon emissions, this study innovatively constructs different spatial weight matrices, based on 2011–2020 panel data covering 30 Chinese provinces, and it explores the direct spillovers, conducted spillovers, and spillovers from different spillover channels, such as human capital, service industry development, and information development of digital economy development on carbon emissions through the spatial Durbin model combined with a mediating effect model. The results show that there is significant spatial heterogeneity in digital economy development; in terms of regions, the eastern region has the highest average development level and the central region has the highest average annual growth rate. Digital economy development can directly suppress carbon emissions, and it can also indirectly suppress carbon emissions by driving technological innovation and optimizing the energy consumption structure, and there exists a spatial spillover effect. Under human capital, service industry development and information development matrices, the spatial spillover effect of digital economy development on carbon emissions is significantly negative. Regions with the same level of information development are more likely to exert a spatial spillover effect of digital economy development on carbon emissions.
Irreversible bonds for higher stability of COF materials in photocatalytic reactions
Authors: Ma Fang , Ye Liqun
Published: February 2024

Covalent organic frameworks (COFs), one of a multitude of advanced mainstream materials in photocatalysts, are crystalline porous materials with tunable topology and high porosity and are connected by dynamic covalent bonds. We sought to achieve efficient photocatalytic yields, making the stability of the bond energy crucial. Stable bond energy will enable our products to be more economically efficient. At present, the main photocatalysts are reversible imine bonds and other 2D COFs, but irreversibly stable COFs are seldom involved. Therefore, this review surveys the relevant literature to explore the stability of irreversible bond energy, elaborating the synthesis schemes of irreversible bonds. Irreversibly connected bonds will improve the stability and durability of our synthesized catalyst in practical applications, so we seek to explore the stability of bond energy for our practical applications. In this review, we offer a detailed summary of the irreversible bonding pattern, explore the stability of COFs, and summarize classic highly crystalline ordered semiconductor COFs with irreversible bonding methods.
Women's preconception psychological stress and birth outcomes in a fertility clinic: the EARTH study
Authors: Mínguez-Alarcón Lidia , Williams Paige L. , Souter Irene , Ford Jennifer B. , Hauser Russ , Chavarro Jorge E.
Published: February 2024

Background

The epidemiologic literature on women's perceived stress in relation to perinatal outcomes has been inconclusive and does not consider the preconception window of exposure.

Objective

To evaluate whether women's preconception perceived stress is related to live birth, gestational age, and birthweight in a cohort receiving fertility treatment.

Methods

This observational study included women seeking fertility care at the Massachusetts General Hospital (2004–2019). During preconception, women provided information on their psychological stress using the short version of the validated Perceived Stress Scale 4 (PSS-4). We used regression models to evaluate the associations of stress with live birth (N = 768 attempting to conceive) and perinatal outcomes (N = 413 live births) while adjusting for confounders. Stratified analyses by mode of conception [natural, intrauterine insemination (IUI), and IVF (in vitrofertilization)] and selected socioeconomic factors (race, education, and income) were also conducted.

Results

Higher psychological stress was negatively associated with the overall probability of live birth (adjusted RR = 0.95, 95% CI: 0.92, 0.98), particularly among women conceiving using IVF. However, we found no association between women's psychological stress and gestational age and birth weight in the overall analyses and also stratified by mode of conception. Similarly, we observed no differences in women's psychological stress with any of the measured outcomes by socioeconomic factors.

Discussion

These results highlight the importance of considering the preconception window and mode of conception when evaluating the relationship between women's preconception stress and live birth.
Location versus ID: what matters to lung-resident memory T cells?
Authors: Macedo Bruna Gois , Masuda Mia Y. , Borges da Silva Henrique
Published: February 2024

Tissue-resident memory T cells (TRM cells) are vital for the promotion of barrier immunity. The lung, a tissue constantly exposed to foreign pathogenic or non-pathogenic antigens, is not devoid of these cells. Lung TRM cells have been considered major players in either the protection against respiratory viral infections or the pathogenesis of lung allergies. Establishment of lung TRM cells rely on intrinsic and extrinsic factors. Among the extrinsic regulators of lung TRM cells, the magnitude of the impact of factors such as the route of antigen entry or the antigen natural tropism for the lung is not entirely clear. In this perspective, we provide a summary of the literature covering this subject and present some preliminary results on this potential dichotomy between antigen location versus antigen type. Finally, we propose a hypothesis to synthesize the potential contributions of these two variables for lung TRM cell development.
Actions to prevent and identify fetal alcohol spectrum disorders to be implemented in general practice: a consensus
Authors: Leruste Sébastien , Pouilley-Bax Alice , Doray Bérénice , Maillard Thierry , Monin Frédérick , Loubaresse Coralie , Marimoutou Catherine , Spodenkiewicz Michel
Published: February 2024

Introduction

Fetal alcohol exposure is the most common preventable cause of non-genetic intellectual disability. Fetal Alcohol Syndrome (FAS) is characterized by intellectual disability and distinctive facial features and affects 0.1% of live births, representing approximately 800 cases per year in France. Fetal Alcohol Spectrum Disorder (FASD) are 10 times more common than FAS, with an estimated 8,000 cases per year, and are associated with behavioral and social maladjustment in both children and adults, as well as various malformations. General practitioners play a key role in preventing and identifying FASD through their involvement in pregnancy and child monitoring.

Methods

Qualitative study using the Delphi method. Items were developed from the literature and semi-structured interviews with field professionals and health institutions. A panel of multi-professional experts, mostly general practitioners, was recruited.

Results

24 initial actions were submitted to the experts. At the end of the first round, six actions reached a consensus and six were reformulated for the second round. At the end of the second round, three actions reached a consensus, for a total of 11 consensus actions. Four of these actions seem particularly relevant for rapid implementation, namely systematic proposal of pre-conceptional consultations for women planning pregnancy, systematic identification of environmental factors during child monitoring, systematic distribution of information on fetal alcohol exposure during pre-conception or early pregnancy, and the publication of a leaflet for general practitioners on the identification of children with FAS or FASD and the contact details of relevant associations.

Conclusion

Prevention and identification of FASD can be improved through short and general training supports for general practitioners. Early screening of FASD is crucial for children, and should be maintained throughout their monitoring. This study could be used for communication and dissemination of information based on the consensus obtained.
Case report: Successful treatment with biologics in a pediatric patient with a severe inflammatory skin disease and novel CARD14 mutation
Authors: Niedźwiedź Michał , Narbutt Joanna , Siekierko Aleksandra , Skibińska Małgorzata , Kwiek Bartłomiej , Sobolewska-Sztychny Dorota , Ciążyńska Magdalena , Poznańska-Kurowska Katarzyna , Gostyński Antoni , Lesiak Aleksandra
Published: February 2024

CARD14 (caspase activation and recruitment domain) mutations have been associated with psoriasis vulgaris, psoriatic arthritis, generalized and palmoplantar pustular psoriasis, pityriasis rubra pilaris, and atopic dermatitis. We present a pediatric patient with a novel CARD14: c.394A > T/− (Ile123Phe) mutation, diagnosed with CARD14-associated papulosquamous eruption (CAPE), who was successfully treated with biological treatment.
Secretory CAZymes profile and GH19 enzymes analysis of Corallococcus silvisoli c25j21
Authors: Zhou Xiaoli , Zhou Xianmin , Zhang Xianjiao , Dong Honghong , Dong Yijie , Zhu Honghui
Published: February 2024

Extracellular enzymes play important roles in myxobacteria degrading macromolecules and preying on other microorganisms. Glycoside hydrolases 19 (GH19) are widely present in myxobacteria, but their evolution and biological functions have not been fully elucidated. Here we investigated the comparative secretory proteome of Corallococcus silvisoli c25j21 in the presence of cellulose and chitin. A total of 313 proteins were detected, including 16 carbohydrate-active enzymes (CAZymes), 7 of which were induced by cellulose or chitin, such as GH6, GH13, GH19, AA4, and CBM56. We further analyzed the sequence and structural characteristics of its three GH19 enzymes to understand their potential functions. The results revealed that myxobacterial GH19 enzymes are evolutionarily divided into two clades with different appended modules, and their different amino acid compositions in the substrate binding pockets lead to the differences in molecular surface electrostatic potentials, which may, in turn, affect their substrate selectivity and biological functions. Our study is helpful for further understanding the biological functions and catalytic mechanisms of myxobacterial CAZymes.
Pseudorabies virus uses clathrin mediated endocytosis to enter PK15 swine cell line
Authors: Andreu Sabina , Agúndez Carmen , Ripa Inés , López-Guerrero José Antonio , Bello-Morales Raquel
Published: February 2024

Pseudorabies virus (PRV), a herpesvirus responsible for Aujeszky’s disease, causes high mortality in swine populations. To develop effective and novel antiviral strategies, it is essential to understand the mechanism of entry used by PRV to infect its host. Viruses have different ways of entering host cells. Among others, they can use endocytosis, a fundamental cellular process by which substances from the external environment are internalized into the cell. This process is classified into clathrin-mediated endocytosis (CME) and clathrin-independent endocytosis (CIE), depending on the role of clathrin. Although the involvement of cholesterol-rich lipid rafts in the entry of PRV has already been described, the importance of other endocytic pathways involving clathrin remains unexplored to date. Here, we characterize the role of CME in PRV entry into the PK15 swine cell line. By using CME inhibitory drugs, we report a decrease in PRV infection when the CME pathway is blocked. We also perform the shRNA knockdown of the μ-subunit of the adaptor protein AP-2 (AP2M1), which plays an important role in the maturation of clathrin-coated vesicles, and the infection is greatly reduced when this subunit is knocked down. Furthermore, transmission electron microscopy images report PRV virions inside clathrin-coated vesicles. Overall, this study suggests for the first time that CME is a mechanism used by PRV to enter PK15 cells and provides valuable insights into its possible routes of entry.
Virus sequencing performance during the SARS-CoV-2 pandemic: a retrospective analysis of data from multiple rounds of external quality assessment in Austria
Authors: Camp Jeremy V. , Puchhammer-Stöckl Elisabeth , Aberle Stephan W. , Buchta Christoph
Published: February 2024

Introduction: A notable feature of the 2019 coronavirus disease (COVID-19) pandemic was the widespread use of whole genome sequencing (WGS) to monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Countries around the world relied on sequencing and other forms of variant detection to perform contact tracing and monitor changes in the virus genome, in the hopes that epidemic waves caused by variants would be detected and managed earlier. As sequencing was encouraged and rewarded by the government in Austria, but represented a new technicque for many laboratories, we designed an external quality assessment (EQA) scheme to monitor the accuracy of WGS and assist laboratories in validating their methods.

Methods: We implemented SARS-CoV-2 WGS EQAs in Austria and report the results from 7 participants over 5 rounds from February 2021 until June 2023. The participants received sample material, sequenced genomes with routine methods, and provided the sequences as well as information about mutations and lineages. Participants were evaluated on the completeness and accuracy of the submitted sequence and the ability to analyze and interpret sequencing data.

Results: The results indicate that performance was excellent with few exceptions, and these exceptions showed improvement over time. We extend our findings to infer that most publicly available sequences are accurate within ≤1 nucleotide, somewhat randomly distributed through the genome.

Conclusion: WGS continues to be used for SARS-CoV-2 surveillance, and will likely be instrumental in future outbreak scenarios. We identified hurdles in building next-generation sequencing capacity in diagnostic laboratories. EQAs will help individual laboratories maintain high quality next-generation sequencing output, and strengthen variant monitoring and molecular epidemiology efforts.
CCN3, POSTN, and PTHLH as potential key regulators of genomic integrity and cellular survival in iPSCs
Authors: Swaidan Nuha T. , Soliman Nada H. , Aboughalia Ahmed T. , Darwish Toqa , Almeshal Ruba O. , Al-Khulaifi Azhar A. , Taha Rowaida Z. , Alanany Rania , Hussein Ahmed Y. , Salloum-Asfar Salam , Abdulla Sara A. , Abdallah Abdallah M. , Emara Mohamed M.
Published: February 2024

Reprogramming human somatic cells into a pluripotent state, achieved through the activation of well-defined transcriptional factors known as OSKM factors, offers significant potential for regenerative medicine. While OSKM factors are a robust reprogramming method, efficiency remains a challenge, with only a fraction of cells undergoing successful reprogramming. To address this, we explored genes related to genomic integrity and cellular survival, focusing on iPSCs (A53T-PD1) that displayed enhanced colony stability. Our investigation had revealed three candidate genes CCN3, POSTN, and PTHLH that exhibited differential expression levels and potential roles in iPSC stability. Subsequent analyses identified various protein interactions for these candidate genes. POSTN, significantly upregulated in A53T-PD1 iPSC line, showed interactions with extracellular matrix components and potential involvement in Wnt signaling. CCN3, also highly upregulated, demonstrated interactions with TP53, CDKN1A, and factors related to apoptosis and proliferation. PTHLH, while upregulated, exhibited interactions with CDK2 and genes involved in cell cycle regulation. RT-qPCR validation confirmed elevated CCN3 and PTHLH expression in A53T-PD1 iPSCs, aligning with RNA-seq findings. These genes’ roles in preserving pluripotency and cellular stability require further exploration. In conclusion, we identified CCN3, POSTN, and PTHLH as potential contributors to genomic integrity and pluripotency maintenance in iPSCs. Their roles in DNA repair, apoptosis evasion, and signaling pathways could offer valuable insights for enhancing reprogramming efficiency and sustaining pluripotency. Further investigations are essential to unravel the mechanisms underlying their actions.
Potential role of APOE ɛ4 allele as a modifier for the association of BDNF Val66Met polymorphisms and cognitive impairment in community-dwelling older adults
Authors: Ji Shaozhen , Kang Jia , Han Chao , Xu Xitong , Chen Meijie , Chen Jie , Chhetri Jagadish K , Pan Jing , Chan Piu
Published: February 2024

Objective

To determine whether the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with cognitive impairment (CI) in community-dwelling Chinese older adults, and to investigate whether this relationship is modified by the Apolipoprotein E (APOE) ɛ4 allele.

Methods

The study is a secondary analysis of 703 participants aged ≥60 years randomly enrolled from the Beijing Longitudinal Study of Aging II prospective cohort. The education-adjusted Mini-Mental State Examination and the Clinical Dementia Rating Scale were used to measure the cognitive performance of the subjects. The main effects and interactions (additive and multiplicative) of the BDNF Met and the APOE ε4 alleles on CI were estimated by logistic regression models.

Results

In total, 84 out of 703 older adults aged ≥60 years old had CI. No significant difference was observed in the risk of CI between participants with the BDNF Met allele and that of subjects without the BDNF Met allele (p = 0.213; p = 0.164). Individuals carrying both the BDNF Met and APOE ε4 alleles had an almost 1.5-fold increased odds of CI compared with carriers of the BDNF Met allele but without the APOE ε4 allele. The additive association indicated a positive interaction of both BDNF Met and APOE ε4 alleles with wide CIs (p = 0.021; p = 0.018).

Conclusion

The results suggest that the APOE ε4 allele may be a potential modifier for the association of the BDNF Val66Met polymorphism with CI in community-dwelling older adults.
Quasi-freestanding AA-stacked bilayer graphene induced by calcium intercalation of the graphene-silicon carbide interface
Authors: Grubišić-Čabo Antonija , Kotsakidis Jimmy C. , Yin Yuefeng , Tadich Anton , Haldon Matthew , Solari Sean , Riley John , Huwald Eric , Daniels Kevin M. , Myers-Ward Rachael L. , Edmonds Mark T. , Medhekar Nikhil V. , Gaskill D. Kurt , Fuhrer Michael S.
Published: February 2024

We study quasi-freestanding bilayer graphene on silicon carbide intercalated by calcium. The intercalation, and subsequent changes to the system, were investigated by low-energy electron diffraction, angle-resolved photoemission spectroscopy (ARPES) and density-functional theory (DFT). Calcium is found to intercalate only at the graphene-SiC interface, completely displacing the hydrogen terminating SiC. As a consequence, the system becomes highly n-doped. Comparison to DFT calculations shows that the band dispersion, as determined by ARPES, deviates from the band structure expected for Bernal-stacked bilayer graphene. Instead, the electronic structure closely matches AA-stacked bilayer graphene on calcium-terminated SiC, indicating a spontaneous transition from AB- to AA-stacked bilayer graphene following calcium intercalation of the underlying graphene-SiC interface.
Advances in balance training to prevent falls in stroke patients: a scoping review
Authors: Chen Kehan , Zhu Siyi , Tang Yidan , Lan Fuxia , Liu Zuoyan
Published: February 2024

Objective

To summarize the status and characteristics of the available evidence, research gaps, and future research priorities for preventing falls in stroke patients through balance training.

Methods

We used a scoping review framework. A systematic search of PUBMED, Embase, and Cochrane databases for main articles was conducted. Our study only included articles that on balance training and fall-related indicators in stroke patients. Two researchers independently screened the literature according to the inclusion and exclusion criteria. The data of demographic, clinical characteristics, intervention, sample, and outcome indicators were extracted. The characteristics and limitations of the included literature were comprehensively analyzed.

Results

Of the 1,058 studies, 31 were included. The methods of balance training include regular balance training, Tai Chi, Yoga, task balance training, visual balance training, multisensory training, aquatic balance training, perturbation-based balance training, cognitive balance training, system-based balance training, and robot-assisted balance training. The commonly used outcome measures include clinical balance test, such as Berg balance scale (BBS), Timed Up-and-Go Test (TUG), Fall Risk Index assessment (FRI), Fall Efficacy Scale score (FES), and instrumented balance tests.

Conclusion

This scoping review summarizes the existing primary research on preventing falls in stroke patients by balance training. Based on the summary of the existing evidence, the characteristics of balance training and their relation to falls in stroke patients were found. The future researches should explore how to develop personalized training program, the sound combination of various balance training, to more effectively prevent falls.
Unlocking the neural mechanisms of consumer loan evaluations: an fNIRS and ML-based consumer neuroscience study
Authors: Çakar Tuna , Son-Turan Semen , Girişken Yener , Sayar Alperen , Ertuğrul Seyit , Filiz Gözde , Tuna Esin
Published: February 2024

Introduction

This study conducts a comprehensive exploration of the neurocognitive processes underlying consumer credit decision-making using cutting-edge techniques from neuroscience and machine learning (ML). Employing functional Near-Infrared Spectroscopy (fNIRS), the research examines the hemodynamic responses of participants while evaluating diverse credit offers.

Methods

The experimental phase of this study investigates the hemodynamic responses collected from 39 healthy participants with respect to different loan offers. This study integrates fNIRS data with advanced ML algorithms, specifically Extreme Gradient Boosting, CatBoost, Extra Tree Classifier, and Light Gradient Boosted Machine, to predict participants’ credit decisions based on prefrontal cortex (PFC) activation patterns.

Results

Findings reveal distinctive PFC regions correlating with credit behaviors, including the dorsolateral prefrontal cortex (dlPFC) associated with strategic decision-making, the orbitofrontal cortex (OFC) linked to emotional valuations, and the ventromedial prefrontal cortex (vmPFC) reflecting brand integration and reward processing. Notably, the right dorsomedial prefrontal cortex (dmPFC) and the right vmPFC contribute to positive credit preferences.

Discussion

This interdisciplinary approach bridges neuroscience, machine learning and finance, offering unprecedented insights into the neural mechanisms guiding financial choices regarding different loan offers. The study’s predictive model holds promise for refining financial services and illuminating human financial behavior within the burgeoning field of neurofinance. The work exemplifies the potential of interdisciplinary research to enhance our understanding of human financial decision-making.
Examining resting state functional connectivity and frequency power analysis in adults who stutter compared to adults who do not stutter
Authors: Valaei Atefeh , Bamdad Sobhan , Golfam Arsalan , Golmohammadi Golnoosh , Ameri Hayat , Raoufy Mohammad Reza
Published: February 2024

Introduction

Stuttering is a speech disorder characterized by impaired connections between brain regions involved in speech production. This study aimed to investigate functional connectivity and frequency power during rest in adults who stutter (AWS) compared to fluent adults (AWNS) in the dorsolateral prefrontal cortex (DLPFC), dorsolateral frontal cortex (DLFC), supplementary motor area (SMA), motor speech, angular gyrus (AG), and inferior temporal gyrus (ITG).

Materials and methods

Fifteen AWS (3 females, 12 males) and fifteen age- and sex-matched AWNS (3 females, 12 males) participated in this study. All participants were native Persian speakers. Stuttering severity in the AWS group was assessed using the Persian version of the Stuttering Severity Instrument Fourth Edition (SSI-4). Resting-state electroencephalography (EEG) was recorded for 5 min while participants sat comfortably with their eyes open. We analyzed frequency band power across various frequency bands and investigated functional connectivity within the specified speech region.

Results

Significant between-group differences were found in band powers including alpha, beta, delta, theta, and gamma, specifically in the premotor, SMA, motor speech, and frontal regions. AWS also showed increased coherence between the right motor speech region compared to controls. We demonstrate that the proposed hierarchical false discovery rate (FDR) method is the most effective for both simulations and experimental data. In the expected regions, this method revealed significant synchrony effects at an acceptable error rate of 5%.

Conclusion

The results highlight disrupted functional connectivity in AWS at resting state, particularly in speech-related and associated areas. Given the complex neurological basis of developmental stuttering, robust neural markers are closely linked to this phenomenon. These markers include imbalanced activity within brain regions associated with speech and motor functions, coupled with impaired functional connectivity between these regions. The cortico-basal ganglia-thalamo-cortical system governs the dynamic interplay between cortical regions, with SMA as a key cortical site. It is hypothesized that the aberrant resting state functional connectivity will impact the language planning and motor execution necessary for fluent speech. Examining resting-state metrics as biomarkers could further elucidate the neural underpinnings of stuttering and guide intervention.
Case Report: Radiopharmaceutical extravasation, radiation paranoia, and chilling effect
Authors: Mace Jason , Kiser Jackson W.
Published: February 2024

The Society of Nuclear Medicine and Molecular Imaging (SNMMI) has publicly commented that they do not support the reporting of large extravasations to patients or regulatory bodies. The comment cites recently published articles suggesting that extravasations are infrequent and not severe. The comment stresses the importance of ensuring patients are not apprehensive or resistant to nuclear medicine procedures because of “radiation paranoia” and a “chilling effect” that can result from misinformation. Radiation paranoia and chilling effect are not defined, and there are no references to specific misinformation. Our experiences and this case suggest the comment may be incongruent with real-world clinical experiences. Our severe case, at a center with a long-standing focus on reducing radiopharmaceutical extravasation, suggests these events can still happen, can be significant, and should be shared with our patients. Our experiences also suggest that being transparent with patients builds trust. We are concerned that a reluctance to recognize the true frequency of extravasations and their severity may create distrust in the relationship between the nuclear medicine community and patients.
Optimization of treatment strategies based on preoperative imaging features and local recurrence areas for locally advanced lower rectal cancer after lateral pelvic lymph node dissection
Authors: Xu Zhao , Bao Mandula , Cai Qiang , Wang Qian , Xing Wei , Liu Qian
Published: February 2024

Purpose

Local recurrence (LR) is the main cause of treatment failure in locally advanced lower rectal cancer (LALRC). This study evaluated the preoperative risk factors for LR in patients with LALRC to improve the therapeutic strategies.

Patients and Methods

LALRC patients who underwent total mesorectal excision (TME) with lateral pelvic lymph node (LPN) dissection (LPND) from January 2012 to December 2019 were reviewed. The log-rank test was used to assess local recurrence-free survival (LRFS), and multivariate Cox regression was used to identify the prognostic risk factors for LRFS. Follow-up imaging data were used to classify LR according to the location.

Results

Overall, 376 patients were enrolled, and 8.8% (n=33) of these patients developed LR after surgery. Multivariate analysis identified positive clinical circumferential resection margin (cCRM) as an independent prognostic factor for LRFS (HR: 4.94; 95% CI, 1.75-13.94; P=0.003). The most common sites for LR were the pelvic plexus and internal iliac area (PIA) (54.5%), followed by the central pelvic area (CPA) (39.4%) and obturator area (OA) (6.1%). Following a subgroup analysis, LR in the OA was not associated with positive cCRM. Patients treated with upfront surgery (n=35, 14.1%) had a lower cCRM positive rate when compared with patients treated with neoadjuvant chemoradiotherapy (nCRT) (n=12, 23.5%). However, the LR rate in the nCRT group was still lower (n=28, 36.4%) than that in the upfront surgery group (n=35, 14.%). Among patients with positive cCRM, the LR rate in patients with nCRT remained low (n=3, 10.7%).

Conclusion

Positive cCRM is an independent risk factor for LR after TME plus LPND in LALRC patients. LPND is effective and adequate for local control within the OA regardless of cCRM status. However, for LALRC patients with positive cCRM, nCRT should be considered before LPND to further reduce LR in the PIA and CPA.