bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of retinal and choroidal characteristics in patients with early diabetic retinopathy using WSS-OCTA
Authors: Qi Zhihao , Si Yuanyuan , Feng Feng , Zhu Jing , Yang Xuepeng , Wang Wenjuan , Zhang Yuting , Cui Yan
Published: May 2023

Introduction

Diabetic retinopathy (DR) is one of the most common and destructive microvascular complications of DM, and has become a major cause of irreversible visual impairment. The purpose of this study was to evaluate the changes in fundus microcirculation in non-diabetic retinopathy (NDR) and mild non-proliferative diabetic retinopathy (NPDR) in patients with type 2 diabetic mellitus (T2DM) using widefield swept-source optical coherence tomography angiography (WSSOCTA), and to investigate the correlation with laboratory indices of T2DM.

Methods

Eighty nine, 58 and 28 eyes were included in the NDR, NPDR and Control groups, respectively, were enrolled in this study. The 12mm×12mm fundus images obtained by WSS-OCTA were divided into 9 regions (supratemporal, ST; temporal, T; inferotemporal, IT; superior, S; central macular area, C; inferior, I; supranasal, SN; nasal, N; inferonasal, IN) to evaluate changes in vessel density (VD) of the superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris, and mid-large choroidal vessel (MLCV), as well as changes in inner retinal thickness (IRT), outer retinal thickness (ORT), and choroidal thickness (CT). Results: Compared with control group, MLCV VD (I, N, IN) was significantly decreased in NDR group, SCP VD (IT, C, I) and DCP VD (T, IT, I) were significantly decreased in NPDR group. In NPDR group, DCP VD (IT) was significantly decreased compared with that in NDR group. Compared with control group, CT (ST, T, IT, S, SN, IN) was significantly declined in NDR group, and IRT (ST, IT) and ORT (ST, N) were significantly increased in NPDR group. In NPDR group, IRT (ST) and ORT (T, S) were significantly increased compared with NDR group. Correlation analysis showed that age, body mass index, fasting blood glucose, fasting insulin, fasting C-peptide, and estimated glomerular filtration rate in T2DM patients were statistically correlated with retinal and choroidal thickness/VD.

Discussion

Structural and blood flow changes in the choroid occur before the onset of DR and precede changes in the retinal microcirculation, and MLCV thickness/VD is a more sensitive imaging biomarker for the clinical detection of DR. WSS-OCTA enables large-scale non-invasive visual screening and follow-up of the retinal and choroidal vasculature in DR patients, providing a new strategy for the prevention and monitoring of DR in patients with T2DM.
The effects and underlying mechanism of extracorporeal shockwave therapy on fracture healing
Authors: Lv Fuxian , Li Zhenlan , Jing Yuling , Sun Liyuan , Li Zhiwei , Duan Haoyang
Published: May 2023

The clinical efficacy of ESWT in treating bone non union has been widely recognized, but the biological mechanism of ESWT promoting bone non union healing is still unclear. ESWT can make old callus micro fracture through mechanical conduction, form subperiosteal hematoma, promote the release of bioactive factors, reactivate the fracture healing mechanism, rebalance the activities of osteoblasts and osteoclast, promote the angiogenesis of fracture site, and accelerate the healing of bone nonunion.Over recent years, great efforts have been made by both scientists and clinicians to explore the underlying mechanism behind the healing effect of ESWT on bone fractures. In this review, we introduced the growth factors during osteogenesis induced by ESWT hoping to provide new insights in the clinical use of ESWT.
The oxidative aging model integrated various risk factors in type 2 diabetes mellitus at system level
Authors: Chen Yao , Yao Lilin , Zhao Shuheng , Xu Mengchu , Ren Siwei , Xie Lu , Liu Lei , Wang Yin
Published: May 2023

Background

Type 2 diabetes mellitus (T2DM) is a chronic endocrine metabolic disease caused by insulin dysregulation. Studies have shown that aging-related oxidative stress (as “oxidative aging”) play a critical role in the onset and progression of T2DM, by leading to an energy metabolism imbalance. However, the precise mechanisms through which oxidative aging lead to T2DM are yet to be fully comprehended. Thus, it is urgent to integrate the underlying mechanisms between oxidative aging and T2DM, where meaningful prediction models based on relative profiles are needed.

Methods

First, machine learning was used to build the aging model and disease model. Next, an integrated oxidative aging model was employed to identify crucial oxidative aging risk factors. Finally, a series of bioinformatic analyses (including network, enrichment, sensitivity, and pan-cancer analyses) were used to explore potential mechanisms underlying oxidative aging and T2DM.

Results

The study revealed a close relationship between oxidative aging and T2DM. Our results indicate that nutritional metabolism, inflammation response, mitochondrial function, and protein homeostasis are key factors involved in the interplay between oxidative aging and T2DM, even indicating key indices across different cancer types. Therefore, various risk factors in T2DM were integrated, and the theories of oxi-inflamm-aging and cellular senescence were also confirmed.

Conclusion

In sum, our study successfully integrated the underlying mechanisms linking oxidative aging and T2DM through a series of computational methodologies.
Fine mapping and multidimensional analysis of carbon emission reduction in China
Authors: Xu Feng , Zheng Xinqi , Zheng Minrui , Liu Dongya , Ma Yin , Wang Tingting , Han Xu
Published: May 2023

With the escalating impacts of global climate change, carbon peaking and carbon neutrality have become pressing issues of mutual concern for nations worldwide. Accurately measuring carbon emissions at regional and municipal levels in order to design differentiated reduction policies and promote carbon neutrality has become a challenging problem. To tackle this challenge, we developed a 250 m resolution grid map of carbon footprint data and constructed a national-level database (comprised of 2,800 county-level units) to analyze China’s carbon footprint from multiple angles such as overall characteristics, urban agglomerations, county-level units, population density, per capita disposable income, and more. This research provides fresh insights for studying multi-scale footprint spatial pattern dynamics. Our findings indicate that (1) The 250 m resolution Carbon Footprint Database developed in this study covers the national, provincial, county, urban, and rural areas, enabling dynamic research on multi-scale footprint spatial patterns; (2) The top 5% of areas with the highest carbon footprints account for approximately 1/5 of total carbon footprints in China, and approximately 1/4 of areas account for more than 50% of total carbon footprints; (3) The potential for reducing carbon emissions in China’s rural areas has been underestimated by over 10%, while those in the western regions are growing rapidly due to poverty alleviation efforts; (4) An inverted U-shaped “environmental Kuznets curve” emerges between disposable income and emissions intensity, with different regions exhibiting different consumption patterns. This study offers a novel approach for formulating reduction policies at different levels throughout the country.
An exceptional finding in an explanted liver: a case report of cirrhotomimetic hepatocellular carcinoma
Authors: Aby Elizabeth S. , Lou Susan M. , Amin Khalid , Leventhal Thomas M.
Published: May 2023

We present a case of cirrhotomimetic hepatocellular carcinoma (HCC) diagnosed on an explant following a liver transplantation (LT). The pre-LT computerized tomography (CT) scan demonstrated a nodular, cirrhotic-appearing liver; there was no evidence of lesions consistent with HCC. The level of serum alpha fetoprotein (AFP) 1 month pre LT was 4 ng/dL. Following LT, the patient underwent surveillance for HCC. Eight months post LT, he was noted to have lytic osseous lesions in his sternum and T10 vertebral body. Biopsies of these lesions demonstrated metastatic poorly differentiated carcinoma, which was concerning for progression to metastatic HCC. It is important to spread awareness of cirrhotomimetic HCC as it often evades detection by current screening methods, and if patients are inadvertently transplanted with a liver with cirrhotomimetic HCC, this can have significant consequences downstream. A multidisciplinary team approach is critical to ensure early detection of any recurrence and timely treatment.
Activation of cytosolic RNA sensors by endogenous ligands: roles in disease pathogenesis
Authors: Straub Sarah , Sampaio Natalia G.
Published: May 2023

Early detection of infection is a central and critical component of our innate immune system. Mammalian cells have developed specialized receptors that detect RNA with unusual structures or of foreign origin – a hallmark of many virus infections. Activation of these receptors induces inflammatory responses and an antiviral state. However, it is increasingly appreciated that these RNA sensors can also be activated in the absence of infection, and that this ‘self-activation’ can be pathogenic and promote disease. Here, we review recent discoveries in sterile activation of the cytosolic innate immune receptors that bind RNA. We focus on new aspects of endogenous ligand recognition uncovered in these studies, and their roles in disease pathogenesis.
Cardiovascular toxicity profiles of immune checkpoint inhibitors with or without angiogenesis inhibitors: a real-world pharmacovigilance analysis based on the FAERS database from 2014 to 2022
Authors: Wang Yanfeng , Cui Chanjuan , Deng Lei , Wang Lin , Ren Xiayang
Published: May 2023

Background

Immune checkpoint inhibitors (ICIs) combined with angiogenesis inhibitors (AGIs) have become increasingly available for multiple types of cancers, although the cardiovascular safety profiles of this combination therapy in real-world settings have not been elucidated to date. Therefore, we aimed to comprehensively investigate the cardiovascular toxicity profiles of ICIs combined with AGIs in comparison with ICIs alone.

Methods

The Food and Drug Administration Adverse Event Reporting System (FAERS) database from the 1st quarter of 2014 to the 1st quarter of 2022 was retrospectively queried to extract reports of cardiovascular adverse events (AEs) associated with ICIs alone, AGIs alone and combination therapy. To perform disproportionality analysis, the reporting odds ratios (RORs) and information components (ICs) were calculated with statistical shrinkage transformation formulas and a lower limit of the 95% confidence interval (CI) for ROR (ROR025) > 1 or IC (IC025) > 0 with at least 3 reports was considered statistically significant.

Results

A total of 18 854 cardiovascular AE cases/26 059 reports for ICIs alone, 47 168 cases/67 595 reports for AGIs alone, and 3 978 cases/5 263 reports for combination therapy were extracted. Compared to the entire database of patients without AGIs or ICIs, cardiovascular AEs were overreported in patients with combination therapy (IC025/ROR025 = 0.559/1.478), showing stronger signal strength than those taking ICIs alone (IC025/ROR025 = 0.118/1.086) or AGIs alone (IC025/ROR025 = 0.323/1.252). Importantly, compared with ICIs alone, combination therapy showed a decrease in signal strength for noninfectious myocarditis/pericarditis (IC025/ROR025 = 1.142/2.216 vs. IC025/ROR025 = 0.673/1.614), while an increase in signal value for embolic and thrombotic events (IC025/ROR025 = 0.147/1.111 vs. IC025/ROR025 = 0.591/1.519). For outcomes of cardiovascular AEs, the frequency of death and life-threatening AEs was lower for combination therapy than ICIs alone in noninfectious myocarditis/pericarditis (37.7% vs. 49.2%) as well as in embolic and thrombotic events (29.9% vs. 39.6%). Analysis among indications of cancer showed similar findings.

Conclusion

Overall, ICIs combined with AGIs showed a greater risk of cardiovascular AEs than ICIs alone, mainly due to an increase in embolic and thrombotic events while a decrease in noninfectious myocarditis/pericarditis. In addition, compared with ICIs alone, combination therapy presented a lower frequency of death and life-threatening in noninfectious myocarditis/pericarditis and embolic and thrombotic events.
Impact of aging on immunity in the context of COVID-19, HIV, and tuberculosis
Authors: Grifoni Alba , Alonzi Tonino , Alter Galit , Noonan Douglas McClain , Landay Alan L. , Albini Adriana , Goletti Delia
Published: May 2023

Knowledge of aging biology needs to be expanded due to the continuously growing number of elderly people worldwide. Aging induces changes that affect all systems of the body. The risk of cardiovascular disease and cancer increases with age. In particular, the age-induced adaptation of the immune system causes a greater susceptibility to infections and contributes to the inability to control pathogen growth and immune-mediated tissue damage. Since the impact of aging on immune function, is still to be fully elucidated, this review addresses some of the recent understanding of age-related changes affecting key components of immunity. The emphasis is on immunosenescence and inflammaging that are impacted by common infectious diseases that are characterized by a high mortality, and includes COVID-19, HIV and tuberculosis.
Circulating sepsis-related metabolite sphinganine could protect against intestinal damage during sepsis
Authors: Wang Zetian , Qi Yue , Wang Fei , Zhang Baiyin , Jianguo Tang
Published: May 2023

Introduction

Sepsis is intricately linked to intestinal damage and barrier dysfunction. At present times, there is a growing interest in a metabolite-based therapy for multiple diseases.

Methods

Serum samples from septic patients and healthy individuals were collected and their metabonomics profiling assessed using Ultra-Performance Liquid Chromatography-Time of Flight Mass Spectrometry (UPLC-TOFMS). The eXtreme Gradient Boosting algorithms (XGBOOST) method was used to screen essential metabolites associated with sepsis, and five machine learning models, including Logistic Regression, XGBoost, GaussianNB(GNB), upport vector machines(SVM) and RandomForest were constructed to distinguish sepsis including a training set (75%) and validation set(25%). The area under the receiver-operating characteristic curve (AUROC) and Brier scores were used to compare the prediction performances of different models. Pearson analysis was used to analysis the relationship between the metabolites and the severity of sepsis. Both cellular and animal models were used to HYPERLINK "javascript:;" assess the function of the metabolites.

Results

The occurrence of sepsis involve metabolite dysregulation. The metabolites mannose-6-phosphate and sphinganine as the optimal sepsis-related variables screened by XGBOOST algorithm. The XGBoost model (AUROC=0.956) has the most stable performance to establish diagnostic model among the five machine learning methods. The SHapley Additive exPlanations (SHAP) package was used to interpret the XGBOOST model. Pearson analysis reinforced the expression of Sphinganine, Mannose 6-phosphate were positively associated with the APACHE-II, PCT, WBC, CRP, and IL-6. We also demonstrated that sphinganine strongly diminished the LDH content in LPS-treated Caco-2 cells. In addition, using both in vitro and in vivo examination, we revealed that sphinganine strongly protects against sepsis-induced intestinal barrier injury.

Discussion

These findings highlighted the potential diagnostic value of the ML, and also provided new insight into enhanced therapy and/or preventative measures against sepsis.
A case report of pulmonary hepatoid adenocarcinoma: promoting standardized diagnosis and treatment of the rare disease
Authors: Xu Kun , Gao Jin , Feng Lili , Fang Ying , Tang Xiuliang
Published: May 2023

Objective

To investigate the clinical features, pathological characteristics, immunophenotype, differential diagnosis and prognosis of pulmonary hepatoid adenocarcinoma using a clinical case and literature report.

Methods

We analyzed the clinical presentation, histological pattern and immunohistochemistry of a case of primary hepatoid adenocarcinoma of the lung in April 2022. We also reviewed literature on hepatoid adenocarcinoma of the lung from PubMed database.

Results

The patient was a 65-year-old male with smoking history, who was admitted to hospital with an enlarged axillary lymph node. The mass was round, hard, and grayish-white and grayish-yellow in color. Microscopically, it presented hepatocellular carcinoma-like and adenocarcinoma differentiation features, with abundant blood sinuses visible in the interstitium. Immunohistochemistry showed that the tumor cells were positive for hepatocyte markers, including AFP, TTF-1, CK7 and villin, and negative for CK5/6, CD56, GATA3, CEA and vimentin.

Conclusion

Pulmonary hepatoid adenocarcinoma is a rare epithelial malignancy of primary origin in the lung with poor prognosis. Establishing the diagnosis relies mainly on the detection of hepatocellular structural morphology resembling hepatocellular carcinoma, and on clinicopathological and immunohistochemical testing to exclude diseases such as hepatocellular carcinoma. Combination treatment, mainly surgery, can prolong the survival of early-stage cases of the disease, whereas radiotherapy is mostly used for intermediate and advanced cases. Individualized treatment with molecular-targeted drugs and immunotherapy has shown different therapeutic effects for different patients. Further research is needed to better understand this rare clinical condition for the development and optimization of treatment strategies.
Impact of metal salts on the survival, development, and oviposition behavior of coconut rhinoceros beetle (Coleoptera: Scarabaeidae)
Authors: Vowell Tomie , Manley Megan E. , Ho Jordie R. , Watanabe Shizu , Melzer Michael J.
Published: May 2023

Oryctes rhinoceros (Coleoptera: Scarabaeidae) is an invasive pest of palms in the Pacific Region, including Hawaii, for which limited management options are available. O. rhinoceros larvae develop in materials rich in organic materials such as green waste and animal manure. Biosolid waste within Hawaii’s infestation zone, however, was determined to inhospitable to O. rhinoceros. To determine if the elevated metal salts present in the biosolid waste was responsible for this observation, O. rhinoceros life stages were acutely and chronically exposed to several metal salts at increasing concentrations to determine the impact of these salts on survival, development, and oviposition behavior. Acute (7 days) exposure to mulch rehydrated in solutions of CaCl2, KCl, MgCl2, or NaCl increasing in concentration from 0 to 0.7 M resulted in increased mortality, with concentrations > 0.5 M generally being 100% lethal to both first and second-instar larvae. A similar trend in survival was observed in subsequent experiments using a horticultural grade of Epsom salt (MgSO4) at 1×, 2×, and 5× the recommended application rate. Chronic exposure (eggs reared on mulch through pupation) to Epsom salt at these same rates resulted in significantly delayed instar development and reduced adult biometrics at both 1× and 2× levels. Similar to the acute exposure, eggs exposed to 5× levels did not hatch, or the first instar died soon after emergence. In choice experiments, gravid females showed no oviposition preference for media hydrated with water or 2× Epsom salt but did avoid ovipositing in mulch rehydrated in 5× Epsom salt. These trials demonstrate a potentially novel approach to managing pest populations of O. rhinoceros.
SSR and 18S rDNA based molecular profiling of Neopyropia yezoensis (Rhodophyta) in China: insight into genetic impact of laver aquaculture on wild resource
Authors: Xu Hui , Jia Rujie , Liang Zhourui , Lu Xiaoping , Wang Wenjun
Published: May 2023

Neopyropia yezoensis is a typical intertidal seaweed and an indispensable species for conservation of seaweed resources. As one of the most important marine vegetables, the cultivation area of N. yezoensis has been largely increasing in the past decade and ranked the second highest among all the farmed seaweeds in China. It remains unknown whether large-scale cultivation of N. yezoensis has a genetic impact on wild populations. In this study, SSR markers and 18S rDNA were applied for diversity and genetic structure analysis of 22 N. yezoensis populations from North China. Twenty-two haplotypes were generated from 352 18S rDNA sequences and only three haplotypes were shared by both cultivated and wild populations. Based on 11 polymorphic SSR markers developed, the average polymorphism of the cultivated N. yezoensis populations was higher than that of the wild populations, with the percentage of polymorphic loci being 90.91% in most cultivated populations. The cultivated populations were clustered separately from the wild ones based on the population phylogenetic tree. This indicates that cultivated N. yezoensis populations are diverse and divergent from wild populations in China. However, there were cultivated individuals mixed with the wild ones based on the individual phylogenetic tree and STRUCTURE analysis. The genetic differentiation between cultivated and wild populations decreased with increasing cultivation time, suggesting a possible long-term and slow process of genetic introgression between cultivated N. yezoensis and the wild resource. The wild populations were grouped into two distinct clades by SSRs, with one distributed around the intersection between the Yellow Sea and the Bohai Sea, where the populations were characterized by a specific 18S rDNA haplotype. These findings provide useful insights into germplasm conservation, genetic breeding and improvement of N. yezoensis farming practices.
Serum protein coating enhances the antisepsis efficacy of silver nanoparticles against multidrug-resistant Escherichia coli infections in mice
Authors: Du Huamao , Wang Xiaoling , Zhang Hongying , Chen Heming , Deng Xiaoyu , He Yujing , Tang Huaze , Deng Fuchang , Ren Zhihong
Published: May 2023

Antimicrobial resistance poses a significant threat to public health and social development worldwide. This study aimed to investigate the effectiveness of silver nanoparticles (AgNPs) in treating multidrug-resistant bacterial infections. Eco-friendly spherical AgNPs were synthesized using rutin at room temperature. The biocompatibility of both polyvinyl pyrrolidone (PVP) and mouse serum (MS)-stabilized AgNPs was evaluated at 20 μg/mL and showed a similar distribution in mice. However, only MS-AgNPs significantly protected mice from sepsis caused by the multidrug-resistant Escherichia coli (E. coli) CQ10 strain (p = 0.039). The data revealed that MS-AgNPs facilitated the elimination of Escherichia coli (E. coli) in the blood and the spleen, and the mice experienced only a mild inflammatory response, as interleukin-6, tumor necrosis factor-α, chemokine KC, and C-reactive protein levels were significantly lower than those in the control group. The results suggest that the plasma protein corona strengthens the antibacterial effect of AgNPs in vivo and may be a potential strategy for combating antimicrobial resistance.
Runoff and soil loss in biocrusts and physical crusts from the Tabernas Desert (southeast Spain) according to rainfall intensity
Authors: Lázaro Roberto , Gascón Cayetana , Rubio Consuelo
Published: May 2023

Biological soil crusts (biocrusts) influence hydrological and erosive processes in drylands, and their effects increase with hypothetic successional development. Runoff and raindrops, both dependent on rain intensity, are among the main causes of erosion in these areas. However, little is known about the existence of soil loss nonlinearity in relation to rain intensity and crust types; this nonlinearity could control biocrust succession and dynamics. The assumption of biocrust types as successional stages, which allow space-for-time sampling, makes it advisable to include all the successional stages when exploring possible nonlinearity. We considered seven types of crusts, three physical and four biological. We created four rainfall intensity levels in controlled laboratory conditions: 18, 60, 120, and 240 mm/h. In all but the last, we conducted the experiments at two levels of antecedent soil moisture. Generalized Lineal Models enabled us to test for differences. These analyses confirmed previous knowledge regarding the significant effect of rainfall intensity, crust type and antecedent soil moisture and their interactions on runoff and soil loss, despite the small sample size of the sample units. For example, runoff, and particularly soil loss, decreased along succession. Moreover, some results were novel: the runoff coefficient increased only up to 120 mm/h of rain intensity. A decoupling between runoff and soil loss occurred at high intensities. Soil loss increased as rainfall intensity increased only up to 60 mm/h, and then it decreased, mainly due to physical crusts, because of the formation of a water sheet on the surface due to the incoming rainwater exceeding the drainage capacity. Although soil loss was greater in the incipient cyanobacteria than in the most developed lichen biocrust (Lepraria community), the protection provided by any biocrust against soil loss was great compared to the physical crust, and almost as strong at all rain intensities. Soil loss increased with antecedent soil moisture only in physical crusts. Biocrusts resisted the rain splash even at a rainfall intensity of 240 mm/h.
Implications of viral infections and oncogenesis in uterine cervical carcinoma etiology and pathogenesis
Authors: Chu Daming , Liu Tengteng , Yao Yuan
Published: May 2023

Background

Uterine Cervical Carcinoma (UCC) is the most prevalent gynecological malignancy globally, with a rising incidence in recent years. Accumulating evidence indicates that specific viral infections, including human papillomavirus (HPV), Epstein-Barr virus (EBV), Hepatitis B and C viruses (HBV and HCV), and human herpesvirus (HHV), may contribute to UCC development and progression. Understanding the complex interplay between viral infections and UCC risk is crucial for developing novel preventative and therapeutic interventions.

Methods

This comprehensive review investigates the association between viral infections and UCC risk by examining the roles of various viral pathogens in UCC etiology and pathogenesis, and possible molecular mechanisms. Additionally, we evaluate current diagnostic methods and potential therapeutic strategies targeting viral infections for UCC prevention or treatment.

Results

The prevention of UCC has been significantly advanced by the emergence of self-sampling for HPV testing as a crucial tool, allowing for early detection and intervention. However, an essential challenge in UCC prevention lies in understanding how HPV and other viral coinfections, including EBV, HBV, HCV, HHV, HIV, or their concurrent presence, may potentially contribute to UCC development. The molecular mechanisms implicated in the association between viral infections and cervical cancer development include: (1) interference of viral oncogenes with cellular regulatory proteins, resulting in uncontrolled cell proliferation and malignant transformation; (2) inactivation of tumor suppressor genes by viral proteins; (3) evasion of host immune responses by viruses; (4) induction of a persistent inflammatory response, contributing to a tumor-promoting microenvironment; (5) epigenetic modifications that lead to aberrant gene expression; (6) stimulation of angiogenesis by viruses; and (7) activation of telomerase by viral proteins, leading to cellular immortalization. Additionally, viral coinfections can also enhance oncogenic potential through synergistic interactions between viral oncoproteins, employ immune evasion strategies, contribute to chronic inflammation, modulate host cellular signaling pathways, and induce epigenetic alterations, ultimately leading to cervical carcinogenesis.

Conclusion

Recognizing the implications of viral oncogenes in UCC etiology and pathogenesis is vital for addressing the escalating burden of UCC. Developing innovative preventative and therapeutic interventions requires a thorough understanding of the intricate relationship between viral infections and UCC risk.
Ubiquitin E3 ligase activity of Ralstonia solanacearum effector RipAW is not essential for induction of plant defense in Nicotiana benthamiana
Authors: Ouyang Xue , Chen Jialan , Sun Zhimao , Wang Rongbo , Wu Xuan , Li Benjin , Song Congfeng , Liu Peiqing , Zhang Meixiang
Published: May 2023

As one of the most destructive bacterial phytopathogens, Ralstonia solanacearum causes substantial annual yield losses of many important crops. Deciphering the functional mechanisms of type III effectors, the crucial factors mediating R. solanacearum-plant interactions, will provide a valuable basis for protecting crop plants from R. solanacearum. Recently, the NEL (novel E3 ligase) effector RipAW was found to induce cell death on Nicotiana benthamiana in a E3 ligase activity-dependent manner. Here, we further deciphered the role of the E3 ligase activity in RipAW-triggered plant immunity. We found that RipAWC177A, the E3 ligase mutant of RipAW, could not induce cell death but retained the ability of triggering plant immunity in N. benthamiana, indicating that the E3 ligase activity is not essential for RipAW-triggered immunity. By generating truncated mutants of RipAW, we further showed that the N-terminus, NEL domain and C-terminus are all required but not sufficient for RipAW-induced cell death. Furthermore, all truncated mutants of RipAW triggered ETI immune responses in N. benthamiana, confirming that the E3 ligase activity is not essential for RipAW-triggered plant immunity. Finally, we demonstrated that RipAW- and RipAWC177A-triggered immunity in N. benthamiana requires SGT1 (suppressor of G2 allele of skp1), but not EDS1 (enhanced disease susceptibility), NRG1 (N requirement gene 1), NRC (NLR required for cell death) proteins or SA (salicylic acid) pathway. Our findings provide a typical case in which the effector-induced cell death can be uncoupled with immune responses, shedding new light on effector-triggered plant immunity. Our data also provide clues for further in-depth study of mechanism underlying RipAW-induced plant immunity.
Learning cortical hierarchies with temporal Hebbian updates
Authors: Aceituno Pau Vilimelis , Farinha Matilde Tristany , Loidl Reinhard , Grewe Benjamin F.
Published: May 2023

A key driver of mammalian intelligence is the ability to represent incoming sensory information across multiple abstraction levels. For example, in the visual ventral stream, incoming signals are first represented as low-level edge filters and then transformed into high-level object representations. Similar hierarchical structures routinely emerge in artificial neural networks (ANNs) trained for object recognition tasks, suggesting that similar structures may underlie biological neural networks. However, the classical ANN training algorithm, backpropagation, is considered biologically implausible, and thus alternative biologically plausible training methods have been developed such as Equilibrium Propagation, Deep Feedback Control, Supervised Predictive Coding, and Dendritic Error Backpropagation. Several of those models propose that local errors are calculated for each neuron by comparing apical and somatic activities. Notwithstanding, from a neuroscience perspective, it is not clear how a neuron could compare compartmental signals. Here, we propose a solution to this problem in that we let the apical feedback signal change the postsynaptic firing rate and combine this with a differential Hebbian update, a rate-based version of classical spiking time-dependent plasticity (STDP). We prove that weight updates of this form minimize two alternative loss functions that we prove to be equivalent to the error-based losses used in machine learning: the inference latency and the amount of top-down feedback necessary. Moreover, we show that the use of differential Hebbian updates works similarly well in other feedback-based deep learning frameworks such as Predictive Coding or Equilibrium Propagation. Finally, our work removes a key requirement of biologically plausible models for deep learning and proposes a learning mechanism that would explain how temporal Hebbian learning rules can implement supervised hierarchical learning.
The fibrinogen-to-albumin ratio is associated with intracranial atherosclerosis plaque enhancement on contrast-enhanced high-resolution magnetic resonance imaging
Authors: Li Ye , Feng Yuxuan , Liu Rui , Dang Meijuan , Li Tao , Zhao Lili , Lu Jialiang , Lu Ziwei , Yang Yang , Wang Xiaoya , Jian Yating , Wang Heying , Huang Wei , Zhang Lei , Zhang Guilian
Published: May 2023

Background

Contrast-enhanced high-resolution magnetic resonance imaging (CE-HR-MRI) is a useful imaging modality to assess vulnerable plaques in intracranial atherosclerotic stenosis (ICAS) patients. We studied the relationship between the fibrinogen-to-albumin ratio (FAR) and plaque enhancement in patients with ICAS.

Methods

We retrospectively enrolled consecutive ICAS patients who had undergone CE-HR-MRI. The degree of plaque enhancement on CE-HR-MRI was evaluated both qualitatively and quantitatively. Enrolled patients were classified into no enhancement, mild enhancement, and obvious enhancement groups. An independent association of the FAR with plaque enhancement was identified by multivariate logistic regression and receiver operating characteristic (ROC) curve analyses.

Results

Of the 69 enrolled patients, 40 (58%) were classified into the no/mild enhancement group, and 29 (42%) into the obvious enhancement group. The obvious enhancement group had a significantly higher FAR than the no/mild enhancement group (7.36 vs. 6.05, p = 0.001). After adjusting for potential confounders, the FAR was still significantly independently associated with obvious plaque enhancement in multiple regression analysis (odds ratio: 1.399, 95% confidence interval [CI]: 1.080–1.813; p = 0.011). ROC curve analysis revealed that FAR >6.37 predicted obvious plaque enhancement with 75.86% sensitivity and 67.50% specificity (area under the ROC curve = 0.726, 95% CI: 0.606–0.827, p < 0.001).

Conclusion

The FAR can serve as an independent predictor of the degree of plaque enhancement on CE-HR-MRI in patients with ICAS. Also, as an inflammatory marker, the FAR has potential as a serological biomarker of intracranial atherosclerotic plaque vulnerability.
Urinary incontinence as a main clinical manifestation of early stage Wernicke’s encephalopathy: a case report
Authors: He Haitian , Wang Kebing , Wang Yang , Luo Jinbin
Published: May 2023

Wernicke’s encephalopathy (WE) is a condition caused by a deficiency of vitamin B1. While there have been many reported cases of WE in the literature, there are few reports on the early stages of the disorder. In this report, we present a case of WE with urinary incontinence as the main clinical manifestation. A 62-year-old female patient was admitted to the hospital due to intestinal obstruction and did not receive vitamin B1 supplements for 10 days. Three days after her operation, she developed urinary incontinence. She also had mild mental symptoms, such as a little indifference. After consultation with a urologist and neurologist, the patient was immediately given intramuscular vitamin B1 at a dosage of 200 mg/day. After 3 days of supplementing with vitamin B1, her urinary incontinence and mental symptoms improved and were completely resolved after 7 days of treatment. Surgeons should be aware that when long-term fasting patients have urinary incontinence, it may be a symptom of WE, and they should be supplied with vitamin B1 in a timely manner without extensive examination.
Variants in genes related to inflammation and endothelial function can increase the risk for carotid atherosclerosis in southwestern China
Authors: Xie Yong , Yu Ming , Qing Ting , Luo Hua , Shao Minjie , Wei Wei , Yi Xingyang
Published: May 2023

Aim

To investigate the potential association between polymorphisms in genes involved in endothelial function, inflammation and carotid atherosclerosis.

Methods

This was a three-center, population-based sectional survey conducted in Sichuan province of southwestern China. We randomly selected 8 different communities in Sichuan, and the residents in each community volunteered to participate in the survey by face-to-face questionnaire. A total of 2,377 residents with high stroke risk population in the 8 communities were included. Carotid atherosclerosis was evaluated by carotid ultrasound, and the 19 single nucleotide polymorphisms (SNPs) in 10 endothelial function as well as inflammation relevant genes were measured in the high stroke risk population. Carotid atherosclerosis was defined by the presence of carotid plaque or any carotid stenosis ≥15% or mean intima-media thickness (IMT) > 0.9 mm. Generalized multifactor dimensionality reduction (GMDR) approach was used to analyze gene–gene interactions among the 19 SNPs.

Results

Among the 2,377 subjects with high stroke risk, 1,028 subjects had carotid atherosclerosis (43.2%), of which 852 (35.8%) cases had carotid plaque, 295 (12.4%) cases had ≥15% carotid stenosis, whereas 445 (18.7%) had mean IMT > 0.9 mm. Multivariate logistic regression revealed that IL1A rs1609682 TT and HABP2 rs7923349 TT served as independent risk factors for carotid atherosclerosis (OR, 1.45, 95% CI: 1.034–2.032, p = 0.031, and OR, 1.829, 95% CI: 1.228–2.723, p = 0.003). GMDR analysis indicated that there was a significant gene–gene interaction found among IL1A rs1609682, ITGA2 rs1991013, and HABP2 rs7923349. After adjusting the covariates, the high-risk interactive genotypes in the 3 variants were significantly associated with a significantly higher risk for carotid atherosclerosis (OR, 2.08, 95% CI: 1.257–5.98, p < 0.001).

Conclusion

The prevalence of carotid atherosclerosis was observed to be extremely high in the high-risk stroke population in southwestern China. There were associations observed between the specific variants in inflammation and endothelial function relevant genes and carotid atherosclerosis. The high-risk interactive genotypes among IL1A rs1609682, ITGA2 rs1991013, and HABP2 rs7923349 significantly increased the risk of carotid atherosclerosis. These results are expected to provide novel strategies for the prevention of carotid atherosclerosis. The gene–gene interactive analysis used in this study may be very helpful to elucidate complex genetic risk factors for carotid atherosclerosis.
Effectiveness on level of consciousness of non-invasive neuromodulation therapy in patients with disorders of consciousness: a systematic review and meta-analysis
Authors: Liu Zhenyu , Zhang Xintong , Yu Binbin , Wang Jiayue , Lu Xiao
Published: May 2023

Background

Disorders of consciousness (DoC) commonly occurs secondary to severe neurological injury. A considerable volume of research has explored the effectiveness of different non-invasive neuromodulation therapy (NINT) on awaking therapy, however, equivocal findings were reported.

Objective

The aim of this study was to systematically investigate the effectiveness on level of consciousness of different NINT in patients with DoC and explore optimal stimulation parameters and characteristics of patients.

Methods

PubMed, Embase, Web of Science, Scopus, and Cochrane central register of controlled trials were searched from their inception through November 2022. Randomized controlled trials, that investigated effectiveness on level of consciousness of NINT, were included. Mean difference (MD) with 95% confidence interval (CI) was evaluated as effect size. Risk of bias was assessed with revised Cochrane risk-of-bias tool.

Results

A total of 15 randomized controlled trials with 345 patients were included. Meta-analysis was performed on 13 out of 15 reviewed trials indicating that transcranial Direct Current Stimulation (tDCS), Transcranial Magnetic Stimulation (TMS), and median nerve stimulation (MNS) all had a small but significant effect (MD 0.71 [95% CI 0.28, 1.13]; MD 1.51 [95% CI 0.87, 2.15]; MD 3.20 [95%CI: 1.45, 4.96]) on level of consciousness. Subgroup analyses revealed that patients with traumatic brain injury, higher initial level of consciousness (minimally conscious state), and shorter duration of prolonged DoC (subacute phase of DoC) reserved better awaking ability after tDCS. TMS also showed encouraging awaking effect when stimulation was applied on dorsolateral prefrontal cortex in patients with prolonged DoC.

Conclusion

tDCS and TMS appear to be effective interventions for improving level of consciousness of patients with prolonged DoC. Subgroup analyses identified the key parameters required to enhance the effects of tDCS and TMS on level of consciousness. Etiology of DoC, initial level of consciousness, and phase of DoC could act as significant characteristics of patients related to the effectiveness of tDCS. Stimulation site could act as significant stimulation parameter related to the effectiveness of TMS. There is insufficient evidence to support the use of MNS in clinical practice to improve level of consciousness in patients with coma.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=337780, identifier: CRD42022337780.
In vivo18F-DOPA PET imaging identifies a dopaminergic deficit in a rat model with a G51D α-synuclein mutation
Authors: Morley Victoria , Dolt Karamjit Singh , Alcaide-Corral Carlos J. , Walton Tashfeen , Lucatelli Christophe , Mashimo Tomoji , Tavares Adriana A. S. , Kunath Tilo
Published: May 2023

Parkinson’s disease (PD) is a neurodegenerative condition with several major hallmarks, including loss of substantia nigra neurons, reduction in striatal dopaminergic function, and formation of α-synuclein-rich Lewy bodies. Mutations in SNCA, encoding for α-synuclein, are a known cause of familial PD, and the G51D mutation causes a particularly aggressive form of the condition. CRISPR/Cas9 technology was used to introduce the G51D mutation into the endogenous rat SNCA gene. SNCAG51D/+ and SNCAG51D/G51D rats were born in Mendelian ratios and did not exhibit any severe behavourial defects. L-3,4-dihydroxy-6-18F-fluorophenylalanine (18F-DOPA) positron emission tomography (PET) imaging was used to investigate this novel rat model. Wild-type (WT), SNCAG51D/+ and SNCAG51D/G51D rats were characterized over the course of ageing (5, 11, and 16 months old) using 18F-DOPA PET imaging and kinetic modelling. We measured the influx rate constant (Ki) and effective distribution volume ratio (EDVR) of 18F-DOPA in the striatum relative to the cerebellum in WT, SNCAG51D/+ and SNCAG51D/G51D rats. A significant reduction in EDVR was observed in SNCAG51D/G51D rats at 16 months of age indicative of increased dopamine turnover. Furthermore, we observed a significant asymmetry in EDVR between the left and right striatum in aged SNCAG51D/G51D rats. The increased and asymmetric dopamine turnover observed in the striatum of aged SNCAG51D/G51D rats reflects one aspect of prodromal PD, and suggests the presence of compensatory mechanisms. SNCAG51D rats represent a novel genetic model of PD, and kinetic modelling of 18F-DOPA PET data has identified a highly relevant early disease phenotype.
A facial depression recognition method based on hybrid multi-head cross attention network
Authors: Li Yutong , Liu Zhenyu , Zhou Li , Yuan Xiaoyan , Shangguan Zixuan , Hu Xiping , Hu Bin
Published: May 2023

Introduction

Deep-learn methods based on convolutional neural networks (CNNs) have demonstrated impressive performance in depression analysis. Nevertheless, some critical challenges need to be resolved in these methods: (1) It is still difficult for CNNs to learn long-range inductive biases in the low-level feature extraction of different facial regions because of the spatial locality. (2) It is difficult for a model with only a single attention head to concentrate on various parts of the face simultaneously, leading to less sensitivity to other important facial regions associated with depression. In the case of facial depression recognition, many of the clues come from a few areas of the face simultaneously, e.g., the mouth and eyes.

Methods

To address these issues, we present an end-to-end integrated framework called Hybrid Multi-head Cross Attention Network (HMHN), which includes two stages. The first stage consists of the Grid-Wise Attention block (GWA) and Deep Feature Fusion block (DFF) for the low-level visual depression feature learning. In the second stage, we obtain the global representation by encoding high-order interactions among local features with Multi-head Cross Attention block (MAB) and Attention Fusion block (AFB).

Results

We experimented on AVEC2013 and AVEC2014 depression datasets. The results of AVEC 2013 (RMSE = 7.38, MAE = 6.05) and AVEC 2014 (RMSE = 7.60, MAE = 6.01) demonstrated the efficacy of our method and outperformed most of the state-of-the-art video-based depression recognition approaches.

Discussion

We proposed a deep learning hybrid model for depression recognition by capturing the higher-order interactions between the depression features of multiple facial regions, which can effectively reduce the error in depression recognition and gives great potential for clinical experiments.
The impact of environmental factors during maternal separation on the behaviors of adolescent C57BL/6 mice
Authors: Shin Sangyep , Lee Sukwon
Published: May 2023

Neonatal maternal separation is a widely used method to construct an early-life stress model in rodents. In this method, pups are separated from their mothers for several hours every day during the first 2 weeks of life, which results in adverse early-life events. It is a known fact that maternal separation can exert a significant impact on the behavior and psychological health, such as anxiety and depression, in adolescent offspring. However, environmental conditions during maternal separation can differ such as the presence of other animals or by placing pups in a different dam. To investigate the differential effects of various conditions of maternal separation on the behavior of adolescent mice, we created the following groups: (1) iMS group: pups were moved to an isolated room with no other adult mice in a nearby cage, (2) eDam group: the pups randomly exchanged their dams, (3) OF group: pups were shifted to another cage with the bedding material containing maternal odor (olfactory stimulation), and (4) MS group: pups were shifted to another vivarium. From postnatal day (PND) 2–20 (i.e., 19 consecutive days), pups were separated from the dam daily for 4 h and exposed to various environments (MS, iMS, eDam, and OF) or were left undisturbed [control (CON) group]. A series of behavioral assessments were conducted to evaluate locomotion, anxiety, recognition, learning, and memory in adolescent offspring. The results showed that neonatal maternal separation led to impaired recognition memory, motor coordination, and motor skill learning across all groups. However, the iMS group exhibited anxiety-like behavior in the elevated plus maze test and enhanced the extinction of fear memory in the auditory fear conditioning test. The OF and eDam groups displayed partially recovered short-term working memory in the Y-maze test but exhibited opposite exploratory behaviors. The OF group spent more time in the center, while the eDam group spent less time. These findings demonstrated that exposure to different environmental conditions during maternal separation causes behavioral alterations in adolescent offspring, providing a potential explanation for the variation in behavioral phenotypes observed in the early-life stress models.