bluuebunny/crossref_metadata_2025 huggingface dataset:
The immunologically high-risk kidney recipient in the early post-COVID-19 period. To do or not to do? A case report
Authors: Antal Oana , Daciana Elec Alina , Muntean Adriana , Moisoiu Tudor , Melinte Razvan Marian , Elec Florin Ioan
Published: March 2023

Kidney transplantation is nowadays the treatment of choice for end-stage kidney disease (ESKD), and it is the most performed organ transplantation. During the COVID-19 pandemic, kidney-transplant recipients appeared to be at higher risk of morbidity and mortality due to severe forms of illness. The result was a decrease in the number of solid organs transplants worldwide, with patients' reduced chance of receiving transplants. The best timing for surgery after COVID-19 infection is still controversial since most of the available data come from study periods with zero or low prevalence of vaccination and COVID-19 variants with high mortality rates. The American Society of Anesthesiologists (ASA) and the Anesthesia Patient Safety Foundation (APSF) Joint Statement on Elective Surgery/Procedures and Anesthesia for Patients after COVID-19 Infection states that elective surgery should be delayed for 7 weeks after a SARS-CoV-2 infection in unvaccinated patients while making no clear statement for vaccinated ones, or those which have already been infected with the virus. Kidney transplant, as opposed to tissue transplant, is not an elective surgery, so the question raised is whether to do it or not. We present the case of a hyper-immunized 47-year-old male patient with end-stage chronic kidney disease who received a second kidney transplant, despite having a mild SARS-COV 2 infection just 2 weeks before his transplantation surgery.
The case for considering volar skin in a “separate status” for wound healing
Authors: Tam Joshua
Published: March 2023

Foot ulcers, particularly in the diabetic setting, are a major medical and socioeconomic challenge. While the effects of diabetes and its various sequelae have been extensively studied, in the wound field it is commonly assumed that the wound healing process is essentially identical between different skin types, despite the many well-known specializations in palmoplantar skin, most of which are presumed to be evolutionary adaptations for weightbearing. This article will examine how these specializations could alter the wound healing trajectory and contribute to the pathology of foot ulcers.
Drug repositioning prediction for psoriasis using the adverse event reporting database
Authors: Ko Minoh , Oh Jung Mi , Kim In-Wha
Published: March 2023

Introduction

Inverse signals produced from disproportional analyses using spontaneous drug adverse event reports can be used for drug repositioning purposes. The purpose of this study is to predict drug candidates using a computational method that integrates reported drug adverse event data, disease-specific gene expression profiles, and drug-induced gene expression profiles.

Methods

Drug and adverse events from 2015 through 2020 were downloaded from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). The reporting odds ratio (ROR), information component (IC) and empirical Bayes geometric mean (EBGM) were used to calculate the inverse signals. Psoriasis was selected as the target disease. Disease specific gene expression profiles were obtained by the meta-analysis of the Gene Expression Omnibus (GEO). The reverse gene expression scores were calculated using the Library of Integrated Network-based Cellular Signatures (LINCS) and their correlations with the inverse signals were obtained.

Results

Reversal genes and the candidate compounds were identified. Additionally, these correlations were validated using the relationship between the reverse gene expression scores and the half-maximal inhibitory concentration (IC50) values from the Chemical European Molecular Biology Laboratory (ChEMBL).

Conclusion

Inverse signals produced from a disproportional analysis can be used for drug repositioning and to predict drug candidates against psoriasis.
An update on animal models of liver fibrosis
Authors: Wu ShuTing , Wang XinXin , Xing WenBo , Li FenYao , Liang Ming , Li KeShen , He Yan , Wang JianMing
Published: March 2023

The development of liver fibrosis primarily determines quality of life as well as prognosis. Animal models are often used to model and understand the underlying mechanisms of human disease. Although organoids can be used to simulate organ development and disease, the technology still faces significant challenges. Therefore animal models are still irreplaceable at this stage. Currently, in vivo models of liver fibrosis can be classified into five categories based on etiology: chemical, dietary, surgical, transgenic, and immune. There is a wide variety of animal models of liver fibrosis with varying efficacy, which have different implications for proper understanding of the disease and effective screening of therapeutic agents. There is no high-quality literature recommending the most appropriate animal models. In this paper, we will describe the progress of commonly used animal models of liver fibrosis in terms of their development mechanisms, applications, advantages and disadvantages, and recommend appropriate animal models for different research purposes.
Impact of oestrus synchronization devices on ewes vaginal microbiota and artificial insemination outcome
Authors: Reinoso-Peláez Edgar L. , Saura María , González-Recio Óscar , González Carmen , Fernández Almudena , Peiro-Pastor Ramón , López-García Adrián , Saborío-Montero Alejandro , Calvo Jorge H. , Ramón Manuel , Serrano Malena
Published: March 2023

Introduction

The low pregnancy rate by artificial insemination in sheep represents a fundamental challenge for breeding programs. In this species, oestrus synchronization is carried out by manipulating hormonal regimens through the insertion of progestogen intravaginal devices. This reproductive strategy may alter the vaginal microbiota affecting the artificial insemination outcome.

Methods

In this study, we analyzed the vaginal microbiome of 94 vaginal swabs collected from 47 ewes with alternative treatments applied to the progesterone-releasing intravaginal devices (probiotic, maltodextrin, antibiotic and control), in two sample periods (before placing and after removing the devices). To our knowledge, this is the first study using nanopore-based metagenome sequencing for vaginal microbiome characterization in livestock.

Results

Our results revealed a significant lower abundance of the genera Oenococcus (Firmicutes) and Neisseria (Proteobacteria) in pregnant compared to non-pregnant ewes. We also detected a significant lower abundance of Campylobacter in the group of samples treated with the probiotic.

Discussion

Although the use of probiotics represents a promising practice to improve insemination results, the election of the suitable species and concentration requires further investigation. In addition, the use of progestogen in the synchronization devices seemed to increase the alpha-diversity and decrease the abundance of harmful microorganisms belonging to Gammaproteobacteria and Fusobacteriia classes, suggesting a beneficial effect of their use.
Expanding the application of tryptophan: Industrial biomanufacturing of tryptophan derivatives
Authors: Xiao Shujian , Wang Zhen , Wang Bangxu , Hou Bo , Cheng Jie , Bai Ting , Zhang Yin , Wang Wei , Yan Lixiu , Zhang Jiamin
Published: March 2023

Tryptophan derivatives are various aromatic compounds produced in the tryptophan metabolic pathway, such as 5-hydroxytryptophan, 5-hydroxytryptamine, melatonin, 7-chloro-tryptophan, 7-bromo-tryptophan, indigo, indirubin, indole-3-acetic acid, violamycin, and dexoyviolacein. They have high added value, widely used in chemical, food, polymer and pharmaceutical industry and play an important role in treating diseases and improving life. At present, most tryptophan derivatives are synthesized by biosynthesis. The biosynthesis method is to combine metabolic engineering with synthetic biology and system biology, and use the tryptophan biosynthesis pathway of Escherichia coli, Corynebacterium glutamicum and other related microorganisms to reconstruct the artificial biosynthesis pathway, and then produce various tryptophan derivatives. In this paper, the characteristics, applications and specific biosynthetic pathways and methods of these derivatives were reviewed, and some strategies to increase the yield of derivatives and reduce the production cost on the basis of biosynthesis were introduced in order to make some contributions to the development of tryptophan derivatives biosynthesis industry.
Dominant plant species play an important role in regulating bacterial antagonism in terrestrial Antarctica
Authors: Naz Beenish , Liu Ziyang , Malard Lucie A. , Ali Izhar , Song Hongxian , Wang Yajun , Li Xin , Usman Muhammad , Ali Ikram , Liu Kun , An Lizhe , Xiao Sa , Chen Shuyan
Published: March 2023

In Antarctic terrestrial ecosystems, dominant plant species (grasses and mosses) and soil physicochemical properties have a significant influence on soil microbial communities. However, the effects of dominant plants on bacterial antagonistic interactions in Antarctica remain unclear. We hypothesized that dominant plant species can affect bacterial antagonistic interactions directly and indirectly by inducing alterations in soil physicochemical properties and bacterial abundance. We collected soil samples from two typical dominant plant species; the Antarctic grass Deschampsia antarctica and the Antarctic moss Sanionia uncinata, as well as bulk soil sample, devoid of vegetation. We evaluated bacterial antagonistic interactions, focusing on species from the genera Actinomyces, Bacillus, and Pseudomonas. We also measured soil physicochemical properties and evaluated bacterial abundance and diversity using high-throughput sequencing. Our results suggested that Antarctic dominant plants significantly influenced bacterial antagonistic interactions compared to bulk soils. Using structural equation modelling (SEM), we compared and analyzed the direct effect of grasses and mosses on bacterial antagonistic interactions and the indirect effects through changes in edaphic properties and bacterial abundance. SEMs showed that (1) grasses and mosses had a significant direct influence on bacterial antagonistic interactions; (2) grasses had a strong influence on soil water content, pH, and abundances of Actinomyces and Pseudomonas and (3) mosses influenced bacterial antagonistic interactions by impacting abundances of Actinomyces, Bacillus, and Pseudomonas. This study highlights the role of dominant plants in modulating bacterial antagonistic interactions in Antarctic terrestrial ecosystems.
Mitochondrial nanomotion measured by optical microscopy
Authors: Parmar Priyanka , Villalba Maria Ines , Horii Huber Alexandre Seiji , Kalauzi Aleksandar , Bartolić Dragana , Radotić Ksenija , Willaert Ronnie Guy , MacFabe Derrick F. , Kasas Sandor
Published: March 2023

Nanometric scale size oscillations seem to be a fundamental feature of all living organisms on Earth. Their detection usually requires complex and very sensitive devices. However, some recent studies demonstrated that very simple optical microscopes and dedicated image processing software can also fulfill this task. This novel technique, termed as optical nanomotion detection (ONMD), was recently successfully used on yeast cells to conduct rapid antifungal sensitivity tests. In this study, we demonstrate that the ONMD method can monitor motile sub-cellular organelles, such as mitochondria. Here, mitochondrial isolates (from HEK 293 T and Jurkat cells) undergo predictable motility when viewed by ONMD and triggered by mitochondrial toxins, citric acid intermediates, and dietary and bacterial fermentation products (short-chain fatty acids) at various doses and durations. The technique has superior advantages compared to classical methods since it is rapid, possesses a single organelle sensitivity, and is label- and attachment-free.
Highly active bacterial DMSP metabolism in the surface microlayer of the eastern China marginal seas
Authors: Liu Xiujie , Zhang Yunhui , Sun Hao , Tan Siyin , Zhang Xiao-Hua
Published: March 2023

The microbial cycling of dimethylsulfoniopropionate (DMSP) and the resulting gaseous catabolites dimethylsulfide (DMS) or methylmercaptan (MeSH) play key roles in the global sulfur cycle and potentially climate regulation. As the ocean–atmosphere boundary, the sea surface microlayer (SML) is important for the generation and emission of DMS and MeSH. However, understanding of the microbial DMSP metabolism remains limited in the SML. Here, we studied the spatiotemporal differences for DMS/DMSP, bacterial community structure and the key bacterial DMSP metabolic genes between SML and subsurface seawater (SSW) samples in the eastern China marginal seas (the East China Sea and Yellow Sea). In general, DMSPd and DMSPt concentrations, and the abundance of total, free-living and particle-associated bacteria were higher in SML than that in SSW. DMSP synthesis (~7.81-fold for dsyB, ~2.93-fold for mmtN) and degradation genes (~5.38-fold for dmdA, ~6.27-fold for dddP) detected in SML were more abundant compared with SSW samples. Free-living bacteria were the main DMSP producers and consumers in eastern Chinese marginal sea. Regionally, the bacterial community structure was distinct between the East China Sea and the Yellow Sea. The abundance of DMSP metabolic genes (dsyB, dmdA, and dddP) and genera in the East China Sea were higher than those of the Yellow Sea. Seasonally, DMSP/DMS level and DMSP metabolic genes and bacteria were more abundant in SML of the East China Sea in summer than in spring. Different from those in spring, Ruegeria was the dominant DMSP metabolic bacteria. In conclusion, the DMSP synthesis and degradation showed significant spatiotemporal differences in the SML of the eastern China marginal seas, and were consistently more active in the SML than in the SSW.
An ensemble method for prediction of phage-based therapy against bacterial infections
Authors: Aggarwal Suchet , Dhall Anjali , Patiyal Sumeet , Choudhury Shubham , Arora Akanksha , Raghava Gajendra P. S.
Published: March 2023

Phage therapy is a viable alternative to antibiotics for treating microbial infections, particularly managing drug-resistant strains of bacteria. One of the major challenges in designing phage-based therapy is to identify the most appropriate potential phage candidate to treat bacterial infections. In this study, an attempt has been made to predict phage-host interactions with high accuracy to identify the potential bacteriophage that can be used for treating a bacterial infection. The developed models have been created using a training dataset containing 826 phage- host interactions, and have been evaluated on a validation dataset comprising 1,201 phage-host interactions. Firstly, alignment-based models have been developed using similarity between phage-phage (BLASTPhage), host–host (BLASTHost) and phage-CRISPR (CRISPRPred), where we achieved accuracy between 42.4–66.2% for BLASTPhage, 55–78.4% for BLASTHost, and 43.7–80.2% for CRISPRPred across five taxonomic levels. Secondly, alignment free models have been developed using machine learning techniques. Thirdly, hybrid models have been developed by integrating the alignment-free models and the similarity-scores where we achieved maximum performance of (60.6–93.5%). Finally, an ensemble model has been developed that combines the hybrid and alignment-based models. Our ensemble model achieved highest accuracy of 67.9, 80.6, 85.5, 90, and 93.5% at Genus, Family, Order, Class, and Phylum levels on validation dataset. In order to serve the scientific community, we have also developed a webserver named PhageTB and provided a standalone software package (https://webs.iiitd.edu.in/raghava/phagetb/) for the same.
Limonene formulation exhibited potential application in the control of mycelial growth and deoxynivalenol production in Fusarium graminearum
Authors: Jian Yunqing , Chen Xia , Ma Haiqin , Zhang Changpeng , Luo Yuqin , Jiang Jinhua , Yin Yanni
Published: March 2023

Preventing grain from fungi and subsequent mycotoxins contamination has attracted notable attention. Present study demonstrated the limonene-formulated product Wetcit®, might be a biocontrol agent and potential alternative to synthetic fungicides to control Fusarium graminearum growth and deoxynivalenol (DON) production. The limonene formulation exhibited antifungal activity against F. graminearum with the EC50 at 1.40 μl/ml, electron microscopy and staining analysis showed limonene formulation could significantly decrease the quantity, length and septa of conidia, caused hyphal break and shrink, damaged the structures of cell membrane, cell wall, vacuoles and organelles in the hypha. Further study revealed the antifungal and antitoxic mechanism of limonene formulation against F. graminearum, limonene formulation significantly inhibited the toxisome and DON formation, was associated with the down-regulation of trichothecenes biosynthesis genes expression and many energy metabolism pathways as well as the inhibition of lipid droplets, the disturbed energy homeostasis and intracellular structures might ultimately inhibit fungal growth and DON production. In addition, limonene formulation enhanced the antifungal activity of triazole fungicides tebuconazole and mefentrifluconazole against F. graminearum, indicated limonene formulation has valuable potential as a bio-alternative fungicide and eco-friendly compound preparation for the effective management of F. graminearum and DON contamination in agriculture.
Studying pulmonary fibrosis due to microbial infection via automated microscopic image analysis
Authors: Chen Yajie , He Henghui , Luo Licheng , Liu Kangyi , Jiang Min , Li Shiqi , Zhang Xianqi , Yang Xin , Liu Qian
Published: March 2023

Introduction

Pulmonary fibrosis is a consequential complication of microbial infections, which has notably been observed in SARS-CoV-2 infections in recent times. Macrophage polarization, specifically the M2-type, is a significant mechanism that induces pulmonary fibrosis, and its role in the development of Post- COVID-19 Pulmonary Fibrosis is worth investigating. While pathological examination is the gold standard for studying pulmonary fibrosis, manual review is subject to limitations. In light of this, we have constructed a novel method that utilizes artificial intelligence techniques to analyze fibro-pathological images. This method involves image registration, cropping, fibrosis degree classification, cell counting and calibration, and it has been utilized to analyze microscopic images of COVID-19 lung tissue.

Methods

Our approach combines the Transformer network with ResNet for fibrosis degree classification, leading to a significant improvement over the use of ResNet or Transformer individually. Furthermore, we employ semi-supervised learning which utilize both labeled and unlabeled data to enhance the ability of the classification network in analyzing complex samples. To facilitate cell counting, we applied the Trimap method to localize target cells. To further improve the accuracy of the counting results, we utilized an effective area calibration method that better reflects the positive density of target cells.

Results

The image analysis method developed in this paper allows for standardization, precision, and staging of pulmonary fibrosis. Analysis of microscopic images of COVID-19 lung tissue revealed a significant number of macrophage aggregates, among which the number of M2-type macrophages was proportional to the degree of fibrosis.

Discussion

The image analysis method provids a more standardized approach and more accurate data for correlation studies on the degree of pulmonary fibrosis. This advancement can assist in the treatment and prevention of pulmonary fibrosis. And M2-type macrophage polarization is a critical mechanism that affects pulmonary fibrosis, and its specific molecular mechanism warrants further exploration.
Pain interference mediates the association between epigenetic aging and grip strength in middle to older aged males and females with chronic pain
Authors: Peterson Jessica A. , Crow Joshua A. , Johnson Alisa J. , Meng Lingsong , Rani Asha , Huo Zhiguang , Foster Thomas C. , Fillingim Roger B. , Cruz-Almeida Yenisel
Published: March 2023

Introduction

Chronic pain is one of the leading causes of disability that may accelerate biological aging and reduce physical function. Epigenetic clocks provide an estimate of how the system ages and can predict health outcomes such as physical function. Physical function declines may be attributed to decreases in muscle quality due to disuse that can be measured quickly and noninvasively using grip strength. The purpose of this study was to explore the associations among self-reported pain, grip strength, and epigenetic aging in those with chronic pain.

Methods

Participants (57.91 ± 8.04 years) completed pain questionnaires, a blood draw and hand grip strength task. We used an epigenetic clock previously associated with knee pain (DNAmGrimAge), and used the subsequent difference of predicted epigenetic age from chronological age (DNAmGrimAge-Difference).

Results

Exploratory pathway analyses revealed that pain intensity mediated the association between DNAmGrimAge-difference and handgrip strength in males only (β = −0.1115; CI [−0.2929, −0.0008]) and pain interference mediated the association between DNAmGrimAge-difference and handgrip strength in males β = −0.1401; CI [−0.3400, −0.0222]), and females (β = −0.024; CI [−0.2918, −0.0020]).

Discussion

Chronic knee pain may accelerate epigenetic aging processes that may influence handgrip strength in older age adults. Chronic pain could be a symptom of the aging body thus contributing to declines in musculoskeletal function in later life.
Foreign language learning can improve response inhibition in individuals with lower baseline cognition: Results from a randomized controlled superiority trial
Authors: Grossmann Judith Alina , Aschenbrenner Steffen , Teichmann Birgit , Meyer Patric
Published: March 2023

Introduction

The world’s population is aging, increasing the prevalence of dementia. Recently, foreign language learning in later life has been suggested to improve cognition and thus support healthy cognitive aging. To date, however, there are only a few studies with conflicting findings. Therefore, the purpose of this study was to examine whether learning a foreign language can improve executive attention and executive functions in healthy older adults. Additionally, we sought to identify factors affecting cognitive change in foreign language learners, such as cognitive reserve, previous foreign knowledge and usage, and global cognition at baseline.

Methods

In a randomized-controlled trial, we assigned 34 monolinguals between the ages of 65 and 80 to a language learning or a waiting list control group. The participants enrolled in a Spanish course for beginners that met five days a week for 1.5 h for a total of 3 weeks. The waiting list control group received no intervention but had the opportunity to join the language training at the end of the study. All participants underwent an assessment of executive attention (primary outcome), executive functions, verbal fluency, and attention (secondary outcomes) before, immediately after the course, or after a waiting period of 3 weeks for the control group and 3 months after the course or the waiting period.

Results

Foreign language learning did not significantly improve primary or secondary outcomes, neither immediately nor 3 months after the course. However, moderation analyses revealed that participants with lower global baseline cognition tended to improve more on response inhibition than individuals with higher baseline cognition. This relationship was not evident in the waiting list control group.

Discussion

Our results suggest that studying a foreign language does not generally improve executive attention or executive functioning. Nevertheless, individuals with poorer baseline cognition may benefit cognitively from foreign language learning in response inhibition, a domain particularly affected by cognitive aging. Our findings highlight the need of focusing dementia prevention efforts on groups that are more vulnerable to cognitive decline. Additionally, more individualized approaches, including utilizing technology-assisted learning, might enable participants to practice at their performance level, increasing the likelihood of discernible cognitive gains.

Clinical trial registration

https://drks.de/search/en, identifier DRKS00016552.
Activation of ventral tegmental area vesicular GABA transporter (Vgat) neurons alleviates social defeat stress-induced anxiety in APP/PS1 mice
Authors: Yao Di , Li Rong , Kora Musa , Huang Hongqing , Liu Xinghua , Gong Song
Published: March 2023

Introduction

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that results in cognitive impairment and is often accompanied by anxiety. In this study, we investigated whether the activation of VTAVgat neurons could reduce anxiety in APP/PS1 mice. We hypothesized that acute social defeat stress (SDS) would lead to anxiety in APP/PS1 mice, and that the activation of VTAVgat neurons would alleviate this anxiety.

Methods

We exposed APP/PS1 mice to acute SDS and assessed anxiety using the open field test and elevated plus-arm test. Activated VTAVgat neurons was tested by cfos staining. Sleep quality was detected using electroencephalogram after SDS or non-SDS procedure. Sleep duration, sleep latency, and non-rapid eye movement (NREM) percentage were analyzed. VTAVgat neurons were chemogenetically activated by deschloroclozapine.

Results

Our results showed that acute SDS led to anxiety in APP/PS1 mice, as evidenced by increased anxiety-related behaviors in the open field and elevated plus-arm tests. Activation of VTAVgat neurons by SDS led to an increase in sleep duration, primarily due to a decrease in sleep latency and an increase in NREMs. However, the quality of sleep was poor. Chemogenetical activation of VTAVgat neurons improved sleep quality and relieved SDS-induced anxiety. Furthermore, the anxiety state correlated negatively with sleep duration and NREM percentage and correlated positively with theta power density in APP/PS1 mice.

Discussion

Our study provides evidence that the activation of VTAVgat neurons alleviates SDS-induced anxiety in APP/PS1 mice, suggesting that poor sleep quality may exacerbate anxiety in AD. These findings may have important implications for the treatment of anxiety in AD, as targeting VTAVgat neurons could be a potential therapeutic approach.
Endovascular intervention vs. microsurgery on the prognosis of anterior circulation blood blister-like aneurysm: A cohort study
Authors: Tan Haibin , Zhang Tian , Huang Guangfu , Li Zhili , Wang Zhenyu , Cheng Meixong , Liu Ling , Liu Lingtong
Published: March 2023

Background

There are no universally acknowledged standardized treatment strategies for blood blister-like aneurysms (BBAs). This study compared the prognosis of patients with BBA who underwent craniotomy microsurgery vs. endovascular intervention.

Methods

This retrospective cohort study included patients with BBA treated between September 2009 and August 2020 at Sichuan Provincial People's Hospital affiliated to the Sichuan Academy of Medical Science. Patients were divided into the microsurgery and endovascular groups. The preoperative Hunt-Hess grade and modified Fisher grade were collected. The intraoperative and postoperative complications (including intraoperative aneurysm rupture and hemorrhage, postoperative cerebral hemorrhage, and BBA recurrence) were recorded.

Results

Seventy-two patients were included: 28 and 44 in the microsurgery and endovascular groups, respectively. Only the preoperative Fisher grade was different between the two groups (P = 0.041). The proportion of patients with good outcomes was lower in the microsurgery group (28.6%) than in the endovascular group (72.7%), and the mortality rate was higher in the microsurgery group (32.1%) than in the endovascular group (11.4%) (P < 0.05). After adjustment for the modified Fisher grade, the multivariable analysis showed that compared with craniotomy microsurgery, an endovascular intervention was associated with the prognosis of patients with BBA (OR = 0.128, 95%CI: 0.040–0.415, P < 0.001). The rate of complications (intraoperative hemorrhage, cerebral infarction, and recurrence) was higher in the microsurgery group than in the endovascular group.

Conclusion

In patients with BBA, an endovascular intervention appears to be associated with a better prognosis compared with craniotomy microsurgery.
Segmentation of incident lacunes during the course of ischemic cerebral small vessel diseases
Authors: Lebenberg Jessica , Zhang Ruiting , Grosset Lina , Guichard Jean Pierre , Fernandes Fanny , Jouvent Eric , Chabriat Hugues
Published: March 2023

Background

Lacunes represent key imaging markers of cerebral small vessel diseases (cSVDs). During their progression, incident lacunes are related to stroke manifestations and contribute to progressive cognitive and/or motor decline. Assessing new lesions has become crucial but remains time-consuming and error-prone, even for an expert. We, thus, sought to develop and validate an automatic segmentation method of incident lacunes in CADASIL caused by cysteine mutation in the EGFr domains of the NOTCH3 gene, a severe and progressive monogenic form of cSVD.

Methods

Incident lacunes were identified based on difference maps of 3D T1-weighted MRIs obtained at the baseline and 2 years later. These maps were thresholded using clustering analysis and compared with results obtained by expert visual analysis, which is considered the gold standard approach.

Results

The median number of lacunes at the baseline in 30 randomly selected patients was 7 (IQR = [2, 11]). The median number of incident lacunes was 2 (IQR = [0, 3]) using the automatic method (mean time-processing: 25 s/patient) and 0.5 (IQR = [0, 2]) using the standard visual approach (mean time-processing: 8 min/patient). The complementary analysis of segmentation results is enabled to quickly remove false positives detected in specific locations and to identify true incident lesions not previously detected by the standard analysis (2 min/case). A combined approach based on automatic segmentation of incident lacunes followed by quick corrections of false positives allowed to reach high individual sensitivity (median at 0.66, IQR = [0.21, 1.00]) and global specificity scores (0.80).

Conclusion

The automatic segmentation of incident lacunes followed by quick corrections of false positives appears promising for properly and rapidly quantifying incident lacunes in large cohorts of cSVDs.
Echocardiographic correlates of MRI imaging markers of cerebral small-vessel disease in patients with atrial-fibrillation-related ischemic stroke
Authors: Ye Kaili , Tao Wendan , Wang Zhetao , Li Dayan , Xu Mangmang , Liu Junfeng , Liu Ming
Published: March 2023

Background and objectives

Atrial fibrillation (AF) has been linked to dementia risk, partly explained by cerebral small vessel disease (CSVD). Since AF and cardiovascular comorbidities were associated with cardiac dysfunction, we aimed to determine the association between echocardiographic parameters and neuroimaging markers of CSVD in patients with AF-related ischemic stroke.

Methods

This cross-sectional study enrolled patients with AF-related ischemic stroke from March 2013 to December 2019 who underwent transthoracic echocardiography and brain 3T MRI, including T1, T2, Flair, and SWI imaging sequences. We assessed the presence of lacunes and cerebellar microbleeds (CMBs), the severity of white matter hyperintensity (WMH) scored by the Fazekas scale (0-6), and the severity of enlarged perivascular spaces (EPVS) in basal ganglia (BG) and centrum semiovale (CSO) classified into three categories (0–10, 10–25, and >25). CSVD burden was rated on a 0-to-4 ordinal scale. Generalized linear regression analysis and post hoc comparisons with Bonferroni correction were performed to assess the association between various echocardiographic parameters and these lesions, adjusted for demographics and potential confounders.

Results

119 patients (68.38 ± 12.692 years; male 45.4 %) were included for analysis, of whom 55 (46.2%) had lacunes, 40 (33.6%) had CMBs, and median severity for WMH, BG-EPVS, CSO-EPVS, and CSVD burden were 2 (IQR: 1–3), 1 (IQR: 1–2), 1 (IQR: 0–1), and 1 (IQR: 1–2) respectively. In multivariable, fully adjusted models, left ventricular posterior wall thickness (LVPW) was associated with a higher risk of lacunes (RR 1.899, 95% CI: 1.342–2.686) and CSVD burden (RR = 2.081, 95%CI: 1.562–2.070). Right atrial diameter (RAD) was associated with greater CSO-EPVS (RR = 2.243, 95%CI: 1.234–4.075). No echocardiographic parameters were revealed to be associated with CMBs and WMH.

Conclusion

In patients with AF-related ischemic stroke, LVPW is associated with a higher risk of lacunes and CSVD burden, while RAD was associated with greater CSO-EPVS. Larger studies are required to determine these associations and to elucidate if these associations can help facilitate cognitive evaluation and brain MRI screening.
Structural connectivity and brain network analyses in Parkinson's disease: A cross-sectional and longitudinal study
Authors: Bergamino Maurizio , Keeling Elizabeth G. , Ray Nicola J. , Macerollo Antonella , Silverdale Monty , Stokes Ashley M.
Published: March 2023

Introduction

Parkinson's disease (PD) is an idiopathic disease of the central nervous system characterized by both motor and non-motor symptoms. It is the second most common neurodegenerative disease. Magnetic resonance imaging (MRI) can reveal underlying brain changes associated with PD.

Objective

In this study, structural connectivity and white matter networks were analyzed by diffusion MRI and graph theory in a cohort of patients with PD and a cohort of healthy controls (HC) obtained from the Parkinson's Progression Markers Initiative (PPMI) database in a cross-sectional analysis. Furthermore, we investigated longitudinal changes in the PD cohort over 36 months.

Result

Compared with the control group, participants with PD showed lower structural connectivity in several brain areas, including the corpus callosum, fornix, and uncinate fasciculus, which were also confirmed by a large effect-size. Additionally, altered connectivity between baseline and after 36 months was found in different network paths inside the white matter with a medium effect-size. Network analysis showed trends toward lower network density in PD compared with HC at baseline and after 36 months, though not significant after correction. Significant differences were observed in nodal degree and strength in several nodes.

Conclusion

In conclusion, altered structural and network metrics in several brain regions, such as corpus callosum, fornix, and cingulum were found in PD, compared to HC. We also report altered connectivity in the PD group after 36 months, reflecting the impact of both PD pathology and aging processes. These results indicate that structural and network metrics might yield insight into network reorganization that occurs in PD.
Functional connectivity MRI quality control procedures in CONN
Authors: Morfini Francesca , Whitfield-Gabrieli Susan , Nieto-Castañón Alfonso
Published: March 2023

Quality control (QC) for functional connectivity magnetic resonance imaging (FC-MRI) is critical to ensure the validity of neuroimaging studies. Noise confounds are common in MRI data and, if not accounted for, may introduce biases in functional measures affecting the validity, replicability, and interpretation of FC-MRI study results. Although FC-MRI analysis rests on the assumption of adequate data processing, QC is underutilized and not systematically reported. Here, we describe a quality control pipeline for the visual and automated evaluation of MRI data implemented as part of the CONN toolbox. We analyzed publicly available resting state MRI data (N = 139 from 7 MRI sites) from the FMRI Open QC Project. Preprocessing steps included realignment, unwarp, normalization, segmentation, outlier identification, and smoothing. Data denoising was performed based on the combination of scrubbing, motion regression, and aCompCor – a principal component characterization of noise from minimally eroded masks of white matter and of cerebrospinal fluid tissues. Participant-level QC procedures included visual inspection of raw-level data and of representative images after each preprocessing step for each run, as well as the computation of automated descriptive QC measures such as average framewise displacement, average global signal change, prevalence of outlier scans, MNI to anatomical and functional overlap, anatomical to functional overlap, residual BOLD timeseries variability, effective degrees of freedom, and global correlation strength. Dataset-level QC procedures included the evaluation of inter-subject variability in the distributions of edge connectivity in a 1,000-node graph (FC distribution displays), and the estimation of residual associations across participants between functional connectivity strength and potential noise indicators such as participant’s head motion and prevalence of outlier scans (QC-FC analyses). QC procedures are demonstrated on the reference dataset with an emphasis on visualization, and general recommendations for best practices are discussed in the context of functional connectivity and other fMRI analysis. We hope this work contributes toward the dissemination and standardization of QC testing performance reporting among peers and in scientific journals.
The effect of single-cell knockout of Fragile X Messenger Ribonucleoprotein on synaptic structural plasticity
Authors: Gredell Marie , Lu Ju , Zuo Yi
Published: March 2023

Fragile X Syndrome (FXS) is the best-known form of inherited intellectual disability caused by the loss-of-function mutation in a single gene. The FMR1 gene mutation abolishes the expression of Fragile X Messenger Ribonucleoprotein (FMRP), which regulates the expression of many synaptic proteins. Cortical pyramidal neurons in postmortem FXS patient brains show abnormally high density and immature morphology of dendritic spines; this phenotype is replicated in the Fmr1 knockout (KO) mouse. While FMRP is well-positioned in the dendrite to regulate synaptic plasticity, intriguing in vitro and in vivo data show that wild type neurons embedded in a network of Fmr1 KO neurons or glia exhibit spine abnormalities just as neurons in Fmr1 global KO mice. This raises the question: does FMRP regulate synaptic morphology and dynamics in a cell-autonomous manner, or do the synaptic phenotypes arise from abnormal pre-synaptic inputs? To address this question, we combined viral and mouse genetic approaches to delete FMRP from a very sparse subset of cortical layer 5 pyramidal neurons (L5 PyrNs) either during early postnatal development or in adulthood. We then followed the structural dynamics of dendritic spines on these Fmr1 KO neurons by in vivo two-photon microscopy. We found that, while L5 PyrNs in adult Fmr1 global KO mice have abnormally high density of thin spines, single-cell Fmr1 KO in adulthood does not affect spine density, morphology, or dynamics. On the contrary, neurons with neonatal FMRP deletion have normal spine density but elevated spine formation at 1 month of age, replicating the phenotype in Fmr1 global KO mice. Interestingly, these neurons exhibit elevated thin spine density, but normal total spine density, by adulthood. Together, our data reveal cell-autonomous FMRP regulation of cortical synaptic dynamics during adolescence, but spine defects in adulthood also implicate non-cell-autonomous factors.
Glucocorticoid mediated inhibition of LKB1 mutant non-small cell lung cancers
Authors: Huffman Kenneth E. , Li Long Shan , Carstens Ryan , Park Hyunsil , Girard Luc , Avila Kimberley , Wei Shuguang , Kollipara Rahul , Timmons Brenda , Sudderth Jessica , Bendris Nawal , Kim Jiyeon , Villalobos Pamela , Fujimoto Junya , Schmid Sandra , Deberardinis Ralph J. , Wistuba Ignacio , Heymach John , Kittler Ralf , Akbay Esra A. , Posner Bruce , Wang Yuzhuo , Lam Stephen , Kliewer Steven A. , Mangelsdorf David J. , Minna John D.
Published: March 2023

The glucocorticoid receptor (GR) is an important anti-cancer target in lymphoid cancers but has been understudied in solid tumors like lung cancer, although glucocorticoids are often given with chemotherapy regimens to mitigate side effects. Here, we identify a dexamethasone-GR mediated anti-cancer response in a subset of aggressive non-small cell lung cancers (NSCLCs) that harbor Serine/Threonine Kinase 11 (STK11/LKB1) mutations. High tumor expression of carbamoyl phosphate synthase 1 (CPS1) was strongly linked to the presence of LKB1 mutations, was the best predictor of NSCLC dexamethasone (DEX) sensitivity (p < 10-16) but was not mechanistically involved in DEX sensitivity. Subcutaneous, orthotopic and metastatic NSCLC xenografts, biomarker-selected, STK11/LKB1 mutant patient derived xenografts, and genetically engineered mouse models with KRAS/LKB1 mutant lung adenocarcinomas all showed marked in vivo anti-tumor responses with the glucocorticoid dexamethasone as a single agent or in combination with cisplatin. Mechanistically, GR activation triggers G1/S cell cycle arrest in LKB1 mutant NSCLCs by inducing the expression of the cyclin-dependent kinase inhibitor, CDKN1C/p57(Kip2). All findings were confirmed with functional genomic experiments including CRISPR knockouts and exogenous expression. Importantly, DEX-GR mediated cell cycle arrest did not interfere with NSCLC radiotherapy, or platinum response in vitro or with platinum response in vivo. While DEX induced LKB1 mutant NSCLCs in vitro exhibit markers of cellular senescence and demonstrate impaired migration, in vivo DEX treatment of a patient derived xenograft (PDX) STK11/LKB1 mutant model resulted in expression of apoptosis markers. These findings identify a previously unknown GR mediated therapeutic vulnerability in STK11/LKB1 mutant NSCLCs caused by induction of p57(Kip2) expression with both STK11 mutation and high expression of CPS1 as precision medicine biomarkers of this vulnerability.
Case Report: Intramural colonic signet ring cell carcinoma presenting as intestinal pseudo-obstruction: A case presentation and review of the literature
Authors: Li Yuxia , He Genmei , Zhong Ruqin , Li Xuejuan , Li Huamei , Dong Huaqiong , Zhang Yun , Zhao Guohong , Fang Leilei
Published: March 2023

Colorectal cancer (CRC) is the third most common cancer in the world. Other than adenocarcinomas, exceptional tumors of the colon and rectum represent a neglected clinical issue due to their rarity. Signet ring cell carcinoma (SRCC) is a rare subtype of CRC and has an extremely poor prognosis due to its advanced stage at diagnosis. Here we report a rare case of colorectal SRCC manifested as recurrent intestinal obstruction with a negative colonoscopy. Finally, he was diagnosed with signet ring cell carcinoma of the colon by postoperative pathology. It emphasized the special feature of intramural tumor growth without penetrating the mucosa in SRCC, which requires timely surgical intervention to avoid delay in diagnosis and treatment.
Neoadjuvant radiotherapy plus single-incision thoracoscopic surgery in the treatment of type B3 thymomas
Authors: Li Wenshan , Wu Yimin , Huang Lijian , Chai Ying
Published: March 2023

Background

Although minimally invasive surgery is the standard treatment for thymomas, minimally invasive thymectomy is difficult for patients with type B3 thymomas, especially for giant or aggressive lesions. These tumors are frequently treated with radical radiation therapy or surgery plus adjuvant radiotherapy. Few studies, however, have tested the efficacy of neoadjuvant radiotherapy prior to thoracoscopic surgery.

Methods

Patients with type B3 thymomas >5 cm or with infiltrates into vital organs on CT-guided puncture biopsy who underwent neoadjuvant radiotherapy followed by single-incision minimally invasive thymectomy from March 2016 to July 2020 were retrospectively evaluated. Reduction ratios, TNM stage changes according to WHO stage criteria, resectability, long-term survival, and the response in terms of RECIST v1.1 criteria achieved by preoperative RT were analyzed.

Results

The 11 patients who underwent neoadjuvant radiotherapy plus minimally invasive thymectomy included five men and six women, of mean age 49.5 years. Four patients had myasthenia gravis. Neoadjuvant radiotherapy consisted of 50 Gy in 25 fractions, with all patients showing varying degrees of lesion reduction after radiotherapy. Surgery was performed about 1 month after neoadjuvant radiotherapy, with none of these patients having severe radiation pneumonitis. All patients underwent radical resection of the tumor and adjacent tissue, with none experiencing tumor seeding or rupture during surgery. The median postoperative hospital stay was 3 days (range: 2–6 days) and the frequency of additional regular analgesics (including those for wound pain and neuralgia) was 2.5 times per person. On follow-up, one patient experienced pleural metastasis and one experienced pulmonary metastasis, with the other nine patients showing no evidence of tumor recurrence.

Conclusion

Neoadjuvant radiotherapy followed by minimally invasive surgery was a safe and efficacious procedure for the treatment of type B3 thymomas, with less postoperative pain and faster recovery. This strategy, of tumor shrinkage prior to surgery, may make possible the easier removal of type B3 thymomas by single-incision thoracoscopy.
Case report: First report of isolated central nervous system lymphoblastic crisis in a child with chronic myeloid leukemia on dasatinib therapy
Authors: Jo Suejung , Yoo Jae Won , Kim Seongkoo , Lee Jae Wook , Im Soo-Ah , Cho Bin , Chung Nack-Gyun
Published: March 2023

Most children with chronic myeloid leukemia (CML) present with the chronic phase (CML-CP) at diagnosis, exhibiting an excellent treatment response to contemporary tyrosine kinase inhibitors (TKIs). However, despite TKI therapy, patients with CML-CP may progress to blastic crisis (BC). CML-BC rarely occurs in extramedullary sites, and isolated central nervous system (CNS) BC is an extremely rare condition. It may with present various neurologic symptoms that necessitates differential diagnosis from other causes such as TKI toxicity. Information on the diagnosis and treatment of this condition is lacking, as are well-established diagnostic criteria. Here, we report a case of isolated CNS lymphoblastic crisis in a child with CML-CP who was treated with dasatinib. The patient, an 8-year-old girl, was admitted owing to visual disturbance and severe headache. We highlight the importance of a CSF study for the differential diagnosis of CNS BC in patients with CML-CP who present with common neurologic symptoms during TKI therapy.