bluuebunny/crossref_metadata_2025 huggingface dataset:
Early atrial remodeling predicts the risk of cardiovascular events in patients with metabolic syndrome: a retrospective cohort study
Authors: Wali Rohbaiz , Wang Xinying , Li Chenglin , Yang Heng , Liu Fei , Sama Salah D. , Bai Lan , Lee Sharen , Hidru Tesfaldet H. , Yang Xiaolei , Xia Yunlong
Published: May 2023

Background

This study aims to assess the prevalence of atrial cardiomyopathy (ACM) in patients with new-onset metabolic syndrome (MetS) and investigate whether ACM could be a predictor of hospital admission for cardiovascular (CV) events.

Methods

Patients with MetS who were free of clinically proven atrial fibrillation and other CV diseases (CVDs) at baseline were included in the present study. The prevalence of ACM was compared between MetS patients with and without left ventricular hypertrophy (LVH). The time to first hospital admission for a CV event between subgroups was assessed using the Cox proportional hazard model.

Results

A total of 15,528 MetS patients were included in the final analysis. Overall, LVH patients accounted for 25.6% of all newly diagnosed MetS patients. ACM occurred in 52.9% of the cohort and involved 74.8% of LVH patients. Interestingly, a significant percentage of ACM patients (45.4%) experienced MetS without LVH. After 33.2 ± 20.6 months of follow-up, 7,468 (48.1%) patients had a history of readmission due to CV events. Multivariable Cox regression analysis revealed that ACM was associated with an increased risk of admission for CVDs in the MetS patients with LVH [hazard ratio (HR), 1.29; 95% confidence interval (CI), 1.142–1.458; P < 0.001]. Likewise, ACM was found to be independently associated with hospital readmission due to CVD-related events in MetS patients without LVH (HR, 1.175; 95% CI, 1.105–1.250; P < 0.001).

Conclusion

ACM is a marker of early myocardial remodeling and predicts hospitalization for CV events in patients with MetS.
Cardiogenic shock due to reverse takotsubo syndrome triggered by multiple sclerosis brainstem lesions: a case report and mini review
Authors: Brandner Joas , Lu Henri , Muller Olivier , Eskioglou Elissavet , Chiche Jean-Daniel , Antiochos Panagiotis , Chocron Yaniv
Published: May 2023

Background

Takotsubo syndrome (TTS) is mainly characterized by chest pain, left ventricular dysfunction, ST-segment deviation on electrocardiogram (ECG) and elevated troponins in the absence of obstructive coronary artery disease. Diagnostic features include left ventricular systolic dysfunction shown on transthoracic echocardiography (TTE) with wall motion abnormalities, generally with the typical “apical ballooning” pattern. In very rare cases, it involves a reverse form which is characterized by basal and mid-ventricular severe hypokinesia or akinesia, and sparing of the apex. TTS is known to be triggered by emotional or physical stressors. Recently, multiple sclerosis (MS) has been described as a potential trigger of TTS, especially when lesions are located in the brainstem.

Case summary

We herein report the case of a 26-year-old woman who developed cardiogenic shock due to reverse TTS in the setting of MS. After being admitted for suspected MS, the patient presented with rapidly deteriorating clinical condition, with acute pulmonary oedema and hemodynamic collapse, requiring mechanical ventilation and aminergic support. TTE found a severely reduced left ventricular ejection fraction (LVEF) of 20%, consistent with reverse TTS (basal and mid ventricular akinesia, apical hyperkinesia). Cardiac magnetic resonance imaging (MRI) performed 4 days later showed myocardial oedema in the mid and basal segments on T2-weighted imaging, with partial recovery of LVEF (46%), confirmed the diagnosis of TTS. In the meantime, the suspicion of MS was also confirmed, based on cerebral MRI and cerebral spinal fluid analyses, with a final diagnosis of reverse TTS induced by MS. High-dose intravenous corticotherapy was initiated. Subsequent evolution was marked by rapid clinical improvement, as well as normalization of LVEF and segmental wall-motion abnormalities.

Conclusion

Our case is an example of the brain-heart relationship: it shows how neurologic inflammatory diseases can trigger a cardiogenic shock due to TTS, with potentially serious outcomes. It sheds light on the reverse form, which, although rare, has already been described in the setting of acute neurologic disorders. Only a handful of case reports have highlighted MS as a trigger of reverse TTS. Finally, through an updated systematic review, we highlight the unique features of patients with reversed TTS triggered by MS.
Risk of diabetic retinopathy and retinal neurodegeneration in individuals with type 2 diabetes: Beichen Eye Study
Authors: Yang Zhengwei , Liu Qingyan , Wen Dejia , Yu Zihao , Zheng Chuanzhen , Gao Fei , Chen Chen , Hu Liying , Shi Yu , Zhu Xiuqing , Liu Juping , Shao Yan , Li Xiaorong
Published: May 2023

Objective

Our aim was to evaluate associations of different risk factors with odds of diabetic retinopathy (DR) diagnosis and retinal neurodegeneration represented by macular ganglion cell-inner plexiform layer (mGCIPL).

Methods

This cross-sectional study analyzed data from individuals aged over 50 years examined between June 2020 and February 2022 in the community-based Beichen Eye Study on ocular diseases. Baseline characteristics included demographic data, cardiometabolic risk factors, laboratory findings, and medications at enrollment. Retinal thickness in both eyes of all participants was measured automatically via optical coherence tomography. Risk factors associated with DR status were investigated using multivariable logistic regression. Multivariable linear regression analysis was performed to explore associations of potential risk factors with mGCIPL thickness.

Results

Among the 5037 included participants with a mean (standard deviation, SD) age of 62.6 (6.7) years (3258 women [64.6%]), 4018 (79.8%) were control individuals, 835 (16.6%) were diabetic individuals with no DR, and 184 (3.7%) were diabetic individuals with DR. The risk factors significantly associated with DR status were family history of diabetes (odds ratio [OR], 4.09 [95% CI, 2.44-6.85]), fasting plasma glucose (OR, 5.88 [95% CI, 4.66-7.43]), and statins (OR, 2.13 [95% CI, 1.03-4.43]) relative to the control individuals. Compared with the no DR, diabetes duration (OR, 1.17 [95% CI, 1.13-1.22]), hypertension (OR, 1.60 [95% CI, 1.26-2.45]), and glycated hemoglobin A1C (HbA1c) (OR, 1.27 [95% CI, 1.00-1.59]) were significantly correlated with DR status. Furthermore, age (adjusted β = -0.19 [95% CI, -0.25 to -0.13] μm; P < 0.001), cardiovascular events (adjusted β = -0.95 [95% CI, -1.78 to -0.12] μm; P = 0.03), and axial length (adjusted β = -0.82 [95% CI, -1.29 to -0.35] μm; P = 0.001) were associated with mGCIPL thinning in diabetic individuals with no DR.

Conclusion

Multiple risk factors were associated with higher odds of DR development and lower mGCIPL thickness in our study. Risk factors affecting DR status varied among the different study populations. Age, cardiovascular events, and axial length were identified as potential risk factors for consideration in relation to retinal neurodegeneration in diabetic patients.
The cuproptosis-associated 11 gene signature as a predictor for outcomes and response to Bacillus Calmette-Guerin and immune checkpoint inhibitor therapies in bladder carcinoma
Authors: Yuan Huiyang , Xiu Yuchen , Liu Tiantian , Fan Yidong , Xu Dawei
Published: May 2023

Bladder cancer (BC) or carcinoma (BLCA) is predominantly derived from urothelium and includes non-muscle invasive BC (NMIBC) and muscle invasive BC (MIBC). Bacillus Calmette-Guerin (BCG) has long been applied for NMIBC to effectively reduce disease recurrence or progression, whereas immune checkpoint inhibitors (ICIs) were recently introduced to treat advanced BLCA with good efficacy. For BCG and ICI applications, reliable biomarkers are required to stratify potential responders for better personalized interventions, and ideally, they can replace or reduce invasive examinations such as cystoscopy in monitoring treatment efficacy. Here we developed the cuproptosis-associated 11 gene signature (CuAGS-11) model to accurately predict survival and response to BCG and ICI regimens in BLCA patients. In both discovery and validation cohorts where BLCA patients were divided into high- and low-risk groups based on a median CuAGS-11 score as the cutoff, the high-risk group was associated with significantly shortened overall survival (OS) and progression-free survival (PFS) independently. The survival predictive accuracy was comparable between CuAGS-11 and stage, and their combination-based nomograms showed high consistence between predicted and observed OS/PFS. The analysis of 3 BLCA cohorts treated with BCG unveiled lower response rates and higher frequencies of recurrence or progression coupled with shorter survival in CuAGS-11 high-risk groups. In contrast, almost none of patients underwent progression in low-risk groups. In IMvigor210 cohort of 298 BLCA patients treated with ICI Atezolizumab, complete/partial remissions were 3-fold higher accompanied by significantly longer OS in the CuAGS-11 low- than high-risk groups (P = 7.018E-06). Very similar results were obtained from the validation cohort (P = 8.65E-05). Further analyses of Tumor Immune Dysfunction and Exclusion (TIDE) scores revealed that CuAGS-11 high-risk groups displayed robustly higher T cell exclusion scores in both discovery (P = 1.96E-05) and validation (P = 0.008) cohorts. Collectively, the CuAGS-11 score model is a useful predictor for OS/PFS and BCG/ICI efficacy in BLCA patients. For BCG-treated patients, reduced invasive examinations are suggested for monitoring the CuAGS-11 low-risk patients. The present findings thus provide a framework to improve BLCA patient stratification for personalized interventions and to reduce invasive monitoring inspections.
Macrophage polarization states in atherosclerosis
Authors: Wu Jiayong , He Shengping , Song Zhengkun , Chen Sikai , Lin Xuefeng , Sun Huimei , Zhou Pengyu , Peng Qinbao , Du Songlin , Zheng Shaoyi , Liu Xiu
Published: May 2023

Atherosclerosis, a chronic inflammatory condition primarily affecting large and medium arteries, is the main cause of cardiovascular diseases. Macrophages are key mediators of inflammatory responses. They are involved in all stages of atherosclerosis development and progression, from plaque formation to transition into vulnerable plaques, and are considered important therapeutic targets. Increasing evidence suggests that the modulation of macrophage polarization can effectively control the progression of atherosclerosis. Herein, we explore the role of macrophage polarization in the progression of atherosclerosis and summarize emerging therapies for the regulation of macrophage polarization. Thus, the aim is to inspire new avenues of research in disease mechanisms and clinical prevention and treatment of atherosclerosis.
Case report: A novel 5'-UTR-exon1-intron1 deletion in MLYCD in an IVF child with malonyl coenzyme A decarboxylase deficiency and literature review
Authors: Xu Fang , Wu Yangyang , Huang Jiyi , Zhou Yunguo , Xu Fei , Duan Junkai , Li Hong
Published: May 2023

The subject of the study is an 11-month old IVF baby girl with the typical clinical manifestation of malonyl coenzyme A decarboxylase deficiency, including developmental delay, limb weakness, cardiomyopathy, and excessive excretion of malonic acid and methylmalonic acid. Whole genome sequencing (WGS) revealed a novel heterozygous nonsense mutation (c.672delG, p.Trp224Ter) in the MLYCD gene of the proband and her father and a novel heterozygous deletion in 5'-UTR-exon1-intron1 of the MLYCD gene of the proband and her mother. The patient's cardiac function and limb weakness improved considerably after 3 months of a low-fat diet supplemented with L-carnitine. Furthermore, mapping of gene mutations and clinical manifestations was done by case collection.
Characteristics and a comparison of the gut microbiota in two frog species at the beginning and end of hibernation
Authors: Tong Qing , Dong Wen-jing , Xu Ming-da , Hu Zong-fu , Guo Peng , Han Xiao-yun , Cui Li-yong
Published: May 2023

Season has been suggested to contribute to variation in the gut microbiota of animals. The complicated relationships between amphibians and their gut microbiota and how they change throughout the year require more research. Short-term and long-term hypothermic fasting of amphibians may affect gut microbiota differently; however, these changes have not been explored. In this study, the composition and characteristics of the gut microbiota of Rana amurensis and Rana dybowskii during summer, autumn (short-term fasting) and winter (long-term fasting) were studied by high-throughput Illumina sequencing. Both frog species had higher gut microbiota alpha diversity in summer than autumn and winter, but no significant variations between autumn and spring. The summer, autumn, and spring gut microbiotas of both species differed, as did the autumn and winter microbiomes. In summer, autumn and winter, the dominant phyla in the gut microbiota of both species were Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. All animals have 10 OTUs (>90% of all 52 frogs). Both species had 23 OTUs (>90% of all 28 frogs) in winter, accounting for 47.49 ± 3.84% and 63.17 ± 3.69% of their relative abundance, respectively. PICRUSt2 analysis showed that the predominant functions of the gut microbiota in these two Rana were focused on carbohydrate metabolism, Global and overview maps, Glycan biosynthesis metabolism, membrane transport, and replication and repair, translation. The BugBase analysis estimated that among the seasons in the R. amurensis group, Facultatively_Anaerobic, Forms_Biofilms, Gram_Negative, Gram_Positive, Potentially_Pathogenic were significantly different. However, there was no difference for R. dybowskii. The research will reveal how the gut microbiota of amphibians adapts to environmental changes during hibernation, aid in the conservation of endangered amphibians, particularly those that hibernate, and advance microbiota research by elucidating the role of microbiota under various physiological states and environmental conditions.
Seasonal fluctuations attenuate stimulatory or inhibitory impacts of colonial birds on abundance, structure and diversity of soil biota
Authors: Pen-Mouratov Stanislav , Dayan Tamar
Published: May 2023

Soil microorganisms and free-living nematodes were investigated in association with the nesting and roosting habitats of the following piscivorous and omnivorous colonial birds: black kite (Milvus migrans), great cormorant (Phalacrocorax carbo), black-crowned night heron (Nycticorax nycticorax) and little egret (Egretta garzetta), in Israel’s Mediterranean region. Abiotic variables, abundance, trophic structure, sex ratio and genus diversity of soil free-living nematodes, and total abundance of bacteria and fungi, were measured during the wet season, following our previous study conducted during the dry season. The observed soil properties were important drivers of soil biota structure. Presence of the most efficient elements for soil organisms, such as phosphorus and nitrogen, was strongly dependent on the diet of the compared piscivorous and omnivorous bird colonies; levels of these nutrients were notably higher in the bird habitats than in their respective control sites during the study period. Ecological indices showed that the different species of colonial birds can have different (stimulatory or inhibitory) impacts on abundance and diversity of the soil biota, affecting the structure of the soil free-living nematode population at the generic, trophic and sexual levels during the wet season. A comparison with results from the dry season illustrated that seasonal fluctuations can change, and even attenuate the effect of bird activity on the abundance, structure and diversity of the soil communities.
Synergistic impact of nanomaterials and plant probiotics in agriculture: A tale of two-way strategy for long-term sustainability
Authors: Upadhayay Viabhav Kumar , Chitara Manoj Kumar , Mishra Dhruv , Jha Manindra Nath , Jaiswal Aman , Kumari Geeta , Ghosh Saipayan , Patel Vivek Kumar , Naitam Mayur G. , Singh Ashish Kumar , Pareek Navneet , Taj Gohar , Maithani Damini , Kumar Ankit , Dasila Hemant , Sharma Adita
Published: May 2023

Modern agriculture is primarily focused on the massive production of cereals and other food-based crops in a sustainable manner in order to fulfill the food demands of an ever-increasing global population. However, intensive agricultural practices, rampant use of agrochemicals, and other environmental factors result in soil fertility degradation, environmental pollution, disruption of soil biodiversity, pest resistance, and a decline in crop yields. Thus, experts are shifting their focus to other eco-friendly and safer methods of fertilization in order to ensure agricultural sustainability. Indeed, the importance of plant growth-promoting microorganisms, also determined as “plant probiotics (PPs),” has gained widespread recognition, and their usage as biofertilizers is being actively promoted as a means of mitigating the harmful effects of agrochemicals. As bio-elicitors, PPs promote plant growth and colonize soil or plant tissues when administered in soil, seeds, or plant surface and are used as an alternative means to avoid heavy use of agrochemicals. In the past few years, the use of nanotechnology has also brought a revolution in agriculture due to the application of various nanomaterials (NMs) or nano-based fertilizers to increase crop productivity. Given the beneficial properties of PPs and NMs, these two can be used in tandem to maximize benefits. However, the use of combinations of NMs and PPs, or their synergistic use, is in its infancy but has exhibited better crop-modulating effects in terms of improvement in crop productivity, mitigation of environmental stress (drought, salinity, etc.), restoration of soil fertility, and strengthening of the bioeconomy. In addition, a proper assessment of nanomaterials is necessary before their application, and a safer dose of NMs should be applicable without showing any toxic impact on the environment and soil microbial communities. The combo of NMs and PPs can also be encapsulated within a suitable carrier, and this method aids in the controlled and targeted delivery of entrapped components and also increases the shelf life of PPs. However, this review highlights the functional annotation of the combined impact of NMs and PPs on sustainable agricultural production in an eco-friendly manner.
The screening for marine fungal strains with high potential in alkaloids production by in situ colony assay and LC-MS/MS based secondary metabolic profiling
Authors: Lu Tiantian , Liu Yayue , Zhou Longjian , Liao Qingnan , Nie Yingying , Wang Xingyuan , Lei Xiaoling , Hong Pengzhi , Feng Yan , Hu Xueqiong , Zhang Yi
Published: May 2023

Background

Alkaloids are the second primary class of secondary metabolites (SMs) from marine organisms, most of which have antioxidant, antitumor, antibacterial, anti-inflammatory, and other activities. However, the SMs obtained by traditional isolation strategies have drawbacks such as highly reduplication and weak bioactivity. Therefore, it is significantly important to establish an efficient strategy for screening strains and mining novel compounds.

Methods

In this study, we utilized in situ colony assay combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify the strain with high potential in alkaloids production. The strain was identified by genetic marker genes and morphological analysis. The secondary metabolites from the strain were isolated by the combine use of vacuum liquid chromatography (VLC), ODS column chromatography, and Sephadex LH-20. Their structures were elucidated by 1D/2D NMR, HR-ESI-MS, and other spectroscopic technologies. Finally, these compounds bioactivity were assay, including anti-inflammatory and anti-β aggregation.

Results

Eighteen marine fungi were preliminarily screened for alkaloids production by in situ colony assay using Dragendorff reagent as dye, and nine of them turned orange, which indicated abundant alkaloids. By thin-layer chromatography (TLC), LC-MS/MS, and multiple approaches assisted Feature-Based Molecular Networking (FBMN) analysis of fermentation extracts, a strain ACD-5 (Penicillium mallochii with GenBank accession number OM368350) from sea cucumber gut was selected for its diverse alkaloids profiles especially azaphilones. In bioassays, the crude extracts of ACD-5 in Czapek–dox broth and brown rice medium showed moderate antioxidant, acetylcholinesterase inhibitory, anti-neuroinflammatory, and anti-β aggregation activities. Three chlorinated azaphilone alkaloids, compounds 1–3 (sclerotioramine, isochromophilone VI, and isochromophilone IX, respectively), were isolated from the fermentation products of ACD-5 in brown rice medium guided by bioactivities and mass spectrometry analysis. Compound 1 had shown remarkable anti-neuroinflammatory activity in liposaccharide induced BV-2 cells.

Conclusion

In summary, in situ colony screening together with LC-MS/MS, multi-approach assisted FBMN can act as an efficient screening method for strains with potential in alkaloids production.
Histological and MRI brain atlas of the common shrew, Sorex araneus, with brain region-specific gene expression profiles
Authors: Baldoni Cecilia , Thomas William R. , von Elverfeldt Dominik , Reisert Marco , Làzaro Javier , Muturi Marion , Dávalos Liliana M. , Nieland John D. , Dechmann Dina K. N.
Published: May 2023

The common shrew, Sorex araneus, is a small mammal of growing interest in neuroscience research, as it exhibits dramatic and reversible seasonal changes in individual brain size and organization (a process known as Dehnel’s phenomenon). Despite decades of studies on this system, the mechanisms behind the structural changes during Dehnel’s phenomenon are not yet understood. To resolve these questions and foster research on this unique species, we present the first combined histological, magnetic resonance imaging (MRI), and transcriptomic atlas of the common shrew brain. Our integrated morphometric brain atlas provides easily obtainable and comparable anatomic structures, while transcriptomic mapping identified distinct expression profiles across most brain regions. These results suggest that high-resolution morphological and genetic research is pivotal for elucidating the mechanisms underlying Dehnel’s phenomenon while providing a communal resource for continued research on a model of natural mammalian regeneration. Morphometric and NCBI Sequencing Read Archive are available at https://doi.org/10.17617/3.HVW8ZN.
Glial cells: an important switch for the vascular function of the central nervous system
Authors: Gao Ling , Pan Xuezhen , Zhang John H. , Xia Ying
Published: May 2023

In this review, we first describe the current understanding of glial-mediated vascular function affecting the role of the blood-brain barrier (BBB) in central nervous system (CNS) disorders. BBB, mainly composed of glial and endothelial cells (ECs), is the protective structure that orchestrates the transport of substances, including ions, molecules, and cells from brain vessels into or out of the CNS. Then, we display the multiple communication between glial and vascular function based on angiogenesis, vascular wrapping, and blood perfusion in the brain. Glial can support microvascular ECs to form a blood network connecting to neurons. Astrocytes, microglia, and oligodendrocytes are the common types of glial surrounding the brain vessel. Glial-vessel interaction is required for the permeability and integrity of BBB. Glial cells surrounding the cerebral blood vessels can transmit communication signals to ECs and regulate the activity of vascular endothelial growth factor (VEGF) or Wnt-dependent endothelial angiogenesis mechanism. In addition, these glial cells monitor the blood flow in the brain via Ca2+/K+-dependent pathways. Finally, we provide a potential research direction for the glial-vessel axis in CNS disorders. Microglial activation can trigger astrocyte activation, which suggests that microglia-astrocyte interaction may play a key role in monitoring cerebral blood flow. Thus, microglia-astrocyte interaction can be the key point of follow-up studies focusing on the microglia-blood mechanism. More investigations focus on the mechanism of how oligodendrocyte progenitor cells communicate and interact with ECs. The direct role of oligodendrocytes in modulating vascular function needs to be explored in the future.
Modeling the innate inflammatory cGAS/STING pathway: sexually dimorphic effects on microglia and cognition in obesity and prediabetes
Authors: Elzinga Sarah E. , Koubek Emily J. , Hayes John M. , Carter A. , Mendelson Faye E. , Webber-Davis Ian , Lentz Stephen I. , Feldman Eva L.
Published: May 2023

Introduction

The prevalence of obesity, prediabetes, and diabetes continues to grow worldwide. These metabolic dysfunctions predispose individuals to neurodegenerative diseases and cognitive impairment, including dementias such as Alzheimer’s disease and Alzheimer’s disease related dementias (AD/ADRD). The innate inflammatory cGAS/STING pathway plays a pivotal role in metabolic dysfunction and is an emerging target of interest in multiple neurodegenerative diseases, including AD/ADRD. Therefore, our goal was to establish a murine model to specifically target the cGAS/STING pathway to study obesity- and prediabetes-induced cognitive impairment.

Methods

We performed two pilot studies in cGAS knockout (cGAS-/-) male and female mice designed to characterize basic metabolic and inflammatory phenotypes and examine the impact of high-fat diet (HFD) on metabolic, inflammatory, and cognitive parameters.

Results

cGAS-/- mice displayed normal metabolic profiles and retained the ability to respond to inflammatory stimuli, as indicated by an increase in plasma inflammatory cytokine production in response to lipopolysaccharide injection. HFD feeding caused expected increases in body weight and decreases in glucose tolerance, although onset was accelerated in females versus males. While HFD did not increase plasma or hippocampal inflammatory cytokine production, it did alter microglial morphology to a state indicative of activation, particularly in female cGAS-/- mice. However, HFD negatively impacted cognitive outcomes in male, but not female animals.

Discussion

Collectively, these results suggest that cGAS-/- mice display sexually dimorphic responses to HFD, possibly based on differences in microglial morphology and cognition.
The contribution of gamma bursting to spontaneous gamma activity in schizophrenia
Authors: Spencer Kevin M. , Nakhnikian Alexander , Hirano Yoji , Levin Margaret
Published: May 2023

Increased spontaneous gamma (30–100 Hz) activity (SGA) has been reported in the auditory cortex in schizophrenia. This phenomenon has been correlated with psychotic symptoms such as auditory hallucinations and could reflect the dysfunction of NMDA receptors on parvalbumin-expressing inhibitory interneurons. Previous findings are from time-averaged spectra, so it is unknown whether increased spontaneous gamma occurs at a constant level, or rather in bursts. To better understand the dynamical nature of spontaneous gamma activity in schizophrenia, here we examined the contribution of gamma bursting and the slope of the EEG spectrum to this phenomenon. The main results from this data set were previously reported. Participants were 24 healthy control participants (HC) and 24 matched participants with schizophrenia (SZ). The data were from EEG recordings during auditory steady-state stimulation, which were localized to bilateral pairs of dipoles in auditory cortex. Time-frequency analysis was performed using Morlet wavelets. Oscillation bursts in the gamma range were defined as periods during which power exceeded 2 standard deviations above the trial-wide average value for at least one cycle. We extracted the burst parameters power, count, and area, as well as non-burst trial power and spectral slope. Gamma burst power and non-burst trial power were greater in SZ than HC, but burst count and area did not differ. Spectral slope was less negative in SZ than HC. Regression modeling found that gamma burst power alone best predicted SGA for both HC and SZ (> = 90% of variance), while spectral slope made a small contribution and non-burst trial power did not influence SGA. Increased SGA in the auditory cortex in schizophrenia is accounted for by increased power within gamma bursts, rather than a tonic increase in gamma-range activity, or a shift in spectral slope. Further research will be necessary to determine if these measures reflect different network mechanisms. We propose that increased gamma burst power is the main component of increased SGA in SZ and could reflect abnormally increased plasticity in cortical circuits due to enhanced plasticity of synapses on parvalbumin-expressing inhibitory interneurons. Thus, increased gamma burst power may be involved in producing psychotic symptoms and cognitive dysfunction.
Altered coupling of resting-state cerebral blood flow and functional connectivity in Meige syndrome
Authors: Yang Aocai , Liu Bing , Lv Kuan , Luan Jixin , Hu Pianpian , Yu Hongwei , Shmuel Amir , Li Shijun , Tian Hong , Ma Guolin , Zhang Bing
Published: May 2023

Introduction

Meige syndrome (MS) is an adult-onset segmental dystonia disease, mainly manifested as blepharospasm and involuntary movement caused by dystonic dysfunction of the oromandibular muscles. The changes of brain activity, perfusion and neurovascular coupling in patients with Meige syndrome are hitherto unknown.

Methods

Twenty-five MS patients and thirty age- and sex-matched healthy controls (HC) were prospectively recruited in this study. All the participants underwent resting-state arterial spin labeling and blood oxygen level-dependent examinations on a 3.0 T MR scanner. The measurement of neurovascular coupling was calculated using cerebral blood flow (CBF)-functional connectivity strength (FCS) correlations across the voxels of whole gray matter. Also, voxel-wised analyses of CBF, FCS, and CBF/FCS ratio images between MS and HC were conducted. Additionally, CBF and FCS values were compared between these two groups in selected motion-related brain regions.

Results

MS patients showed increased whole gray matter CBF-FCS coupling relative to HC (t = 2.262, p = 0.028). In addition, MS patients showed significantly increased CBF value in middle frontal gyrus and bilateral precentral gyrus.

Conclusion

The abnormal elevated neurovascular coupling of MS may indicate a compensated blood perfusion in motor-related brain regions and reorganized the balance between neuronal activity and brain blood supply. Our results provide a new insight into the neural mechanism underlying MS from the perspective of neurovascular coupling and cerebral perfusion.
Multiparametric MRI radiomics fusion for predicting the response and shrinkage pattern to neoadjuvant chemotherapy in breast cancer
Authors: Fan Ming , Wu Xilin , Yu Jiadong , Liu Yueyue , Wang Kailang , Xue Tailong , Zeng Tieyong , Chen Shujun , Li Lihua
Published: May 2023

Purpose

During neoadjuvant chemotherapy (NACT), breast tumor morphological and vascular characteristics are usually changed. This study aimed to evaluate the tumor shrinkage pattern and response to NACT by preoperative multiparametric magnetic resonance imaging (MRI), including dynamic contrast-enhanced MRI (DCE-MRI), diffuse weighted imaging (DWI) and T2 weighted imaging (T2WI).

Method

In this retrospective analysis, female patients with unilateral unifocal primary breast cancer were included for predicting tumor pathologic/clinical response to NACT (n=216, development set, n=151 and validation set, n=65) and for discriminating the tumor concentric shrinkage (CS) pattern from the others (n=193; development set, n=135 and validation set, n=58). Radiomic features (n=102) of first-order statistical, morphological and textural features were calculated on tumors from the multiparametric MRI. Single- and multiparametric image-based features were assessed separately and were further combined to feed into a random forest-based predictive model. The predictive model was trained in the testing set and assessed on the testing dataset with an area under the curve (AUC). Molecular subtype information and radiomic features were fused to enhance the predictive performance.

Results

The DCE-MRI-based model showed higher performance (AUCs of 0.919, 0.830 and 0.825 for tumor pathologic response, clinical response and tumor shrinkage patterns, respectively) than either the T2WI or the ADC image-based model. An increased prediction performance was achieved by a model with multiparametric MRI radiomic feature fusion.

Conclusions

All these results demonstrated that multiparametric MRI features and their information fusion could be of important clinical value for the preoperative prediction of treatment response and shrinkage pattern.
The prognostic value of multiparametric cardiac magnetic resonance in patients with systemic light chain amyloidosis
Authors: Miao Fujia , Tang Chunxiang , Ren Guisheng , Guo Jinzhou , Zhao Liang , Xu Weiwei , Zhou Xiyang , Zhang Longjiang , Huang Xianghua
Published: May 2023

Background

Late gadolinium enhancement (LGE) is a classic imaging modality derived from cardiac magnetic resonance (CMR), which is commonly used to describe cardiac tissue characterization. T1 mapping with extracellular volume (ECV) and native T1 are novel quantitative parameters. The prognostic value of multiparametric CMR in patients with light chain (AL) amyloidosis remains to be thoroughly investigated.

Methods

A total of 89 subjects with AL amyloidosis were enrolled from April 2016 to January 2021, and all of them underwent CMR on a 3.0 T scanner. The clinical outcome and therapeutic effect were observed. Cox regression was used to investigate the effect of multiple CMR parameters on outcomes in this population.

Results

LGE extent, native T1 and ECV correlated well with cardiac biomarkers. During a median follow-up of 40 months, 21 patients died. ECV (hazard ratio [HR]: 2.087 for per 10% increase, 95% confidence interval [CI]: 1.379-3.157, P < 0.001) and native T1 (HR: 2.443 for per 100 ms increase, 95% CI: 1.381-4.321, P=0.002) were independently predictive of mortality. A novel prognostic staging system based on median native T1 (1344 ms) and ECV (40%) was similar to Mayo 2004 Stage, and the 5-year estimated overall survival rates in Stage I, II, and III were 95%, 80%, and 53%, respectively. In patients with ECV > 40%, receiving autologous stem cell transplantation had higher cardiac and renal response rates than conventional chemotherapy.

Conclusion

Both native T1 and ECV independently predict mortality in patients with AL amyloidosis. Receiving autologous stem cell transplantation is effective and significantly improves the clinical outcomes in patients with ECV > 40%.
Isolated splenic metastasis from primary fallopian tube carcinoma and the application of laparoscopic splenectomy: a case report and literature review
Authors: Kang Dongxue , Zhao Danyang , Jiang Xiaodi , Li Deming
Published: May 2023

Metastases to the spleen from various non-hematologic malignancies are generally not a common clinical event and usually indicate the late dissemination of disease. Solitary splenic metastases from solid neoplasm are extremely uncommon. Furthermore, solitary metastasis to the spleen from primary fallopian tube carcinoma (PFTC) is extremely rare and has not been reported previously. We report a case of isolated splenic metastasis in a 60-year-old woman, occurring 13 months after a total hysterectomy, a bilateral salpingo-oophorectomy, a pelvic lymphadenectomy, a para-aortic lymphadenectomy, an omentectomy, and an appendectomy were performed for PFTC. The patient’s serum tumor marker CA125 was elevated to 49.25 U/ml (N < 35.0 U/ml). An abdominal computed tomography (CT) scan revealed a 4.0 × 3.0 cm low-density lesion in the spleen that was potentially malignant, with no lymphadenectasis or distant metastasis. The patient underwent a laparoscopic exploration, and one lesion was found in the spleen. Then, a laparoscopic splenectomy (LS) confirmed a splenic metastasis from PFTC. The histopathological diagnosis showed that the splenic lesion was a high-differentiated serous carcinoma from PFTC metastasis. The patient recovered for over 1 year, with no tumor recurrence. This is the first reported case of an isolated splenic metastasis from PFTC. This case underlines the importance of serum tumor marker assessment, medical imaging examination, and history of malignancy during follow-up, and LS seems to be the optimal approach for isolated splenic metastasis from PFTC.
The metastatic niche formation: focus on extracellular vesicle-mediated dialogue between lung cancer cells and the microenvironment
Authors: Pontis Francesca , Roz Luca , Fortunato Orazio , Bertolini Giulia
Published: May 2023

Lung cancer is the deadliest cancer in the world, with the majority of patients presenting with advanced or metastatic disease at first diagnosis. The lungs are also one of the most common sites of metastasis from lung cancer and other tumors. Understanding the mechanisms that regulate metastasis formation from primary lung cancer and in the lungs is therefore fundamental unmet clinical need. One of the first steps during the establishment of lung cancer metastases includes the formation of the pre-metastatic niche (PMN) at distant organs, which may occur even during the early phases of cancer development. The PMN is established through intricate cross-talk between primary tumor-secreted factors and stromal components at distant sites. Mechanisms controlling primary tumor escape and seeding of distant organs rely on specific properties of tumor cells but are also tightly regulated by interactions with stromal cells at the metastatic niche that finally dictate the success of metastasis establishment. Here, we summarize the mechanisms underlying pre-metastatic niche formation starting from how lung primary tumor cells modulate distant sites through the release of several factors, focusing on Extracellular Vesicles (EVs). In this context, we highlight the role of lung cancer-derived EVs in the modulation of tumor immune escape. Then, we illustrate the complexity of Circulating Tumor Cells (CTCs) that represent the seeds of metastasis and how interactions with stromal and immune cells can help their metastatic dissemination. Finally, we evaluate the contribution of EVs in dictating metastasis development at the PMN through stimulation of proliferation and control of disseminated tumor cell dormancy. Overall, we present an overview of different steps in the lung cancer metastatic cascade, focusing on the EV-mediated interactions between tumor cells and stromal/immune cells.
Lipid metabolism marker CD36 is associated with 18FDG-PET/CT false negative lymph nodes in head and neck squamous cell carcinoma
Authors: Meng Xiaoyan , Sun Jingjing , Xu Feng , Liu Zhonglong , He Yue
Published: May 2023

Background

Lymph node metastasis frequently occurs in head and neck squamous cell carcinoma (HNSCC) patients, and [18F] fluorodeoxyglucose positron emission tomography with computed tomography (18FDG-PET/CT) examination for lymph node metastasis could result in false negativity and delay following treatment. However, the mechanism and resolution for 18FDG-PET/CT false negatives remain unclear. Our study was aim to found biomarkers for false negativity and true positivity from a metabolic perspective.

Methods

Ninety-two patients diagnosed with HNSCC who underwent preoperative 18FDG-PET/CT and subsequent surgery in our institution were reviewed. Immunohistochemistry (IHC) examinations of glucose metabolism (GLUT1 and GLUT5), amino acid metabolism4 (GLS and SLC1A5), and lipid metabolism (CPT1A and CD36) markers were conducted on their primary lesion and lymph node sections.

Results

We identified specific metabolic patterns of the false-negative group. Significantly, CD36 IHC score of primary lesions was higher in false-negative group than true-positive group. Moreover, we validated pro-invasive biological effects of CD36 by bioinformatics analysis as well as experiments. Conclusion: IHC examination of CD36 expression, which is a lipid metabolism marker, in primary lesions could distinguish HNSCC patients’ lymph nodes false negatives in 18FDG-PET/CT.
The role of immunotherapy in microsatellites stable metastatic colorectal cancer: state of the art and future perspectives
Authors: Gandini Annalice , Puglisi Silvia , Pirrone Chiara , Martelli Valentino , Catalano Fabio , Nardin Simone , Seeber Andreas , Puccini Alberto , Sciallero Stefania
Published: May 2023

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide, despite several advances has been achieved in last decades. Few prognostic and predictive biomarkers guide therapeutic choice in metastatic CRC (mCRC), among which DNA mismatch repair deficiency and/or microsatellite instability (dMMR/MSI) holds a crucial role. Tumors characterized by dMMR/MSI benefit from immune checkpoint inhibitors. However, most of the mCRC patients (around 95%) are microsatellite stable (MSS), thereby intrinsically resistant to immunotherapy. This represents a clear unmet need for more effective treatments in this population of patients. In this review, we aim to analyze immune-resistance mechanisms and therapeutic strategies to overcome them, such as combinations of immunotherapy and chemotherapy, radiotherapy or target therapies specifically in MSS mCRC. We also explored both available and potential biomarkers that may better select MSS mCRC patients for immunotherapy. Lastly, we provide a brief overview on future perspectives in this field, such as the gut microbiome and its potential role as immunomodulator.
Efficacy and safety of hepatic artery infusion chemotherapy combined with tyrosine kinase inhibitors plus programmed death-1 inhibitors for hepatocellular carcinoma refractory to transarterial chemoembolization
Authors: Lin Long-Wang , Ke Kun , Yan Le-Ye , Chen Rong , Huang Jing-Yao
Published: May 2023

Background

The subsequent therapy for hepatocellular carcinoma (HCC) patients with refractory to transarterial chemoembolization (TACE) is still controversial. This study was performed to evaluate the efficacy and safety of combination therapy comprising hepatic artery infusion chemotherapy (HAIC), lenvatinib, and programmed death-1 inhibitors relative to HAIC combined with lenvatinib.

Methods

In this single-center retrospective study, we analyzed data from HCC patients with refractory to TACE from June 2017 to July 2022. Primary study outcomes were overall survival (OS) and progression-free survival (PFS), while the secondary outcomes were the objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events.

Results

We enrolled 149 patients finally, including 75 patients who received HAIC combined with lenvatinib plus PD-1 inhibitors therapy (HAIC+L+P group) and 74 patients who received HAIC combined with lenvatinib therapy (HAIC+L group). The median OS in the HAIC+L+P group (16.0; 95% CI: 13.6~18.3 months) was significantly higher compared to the HAIC+L group (9.0; 95% CI: 6.5~11.4 months) (p = 0.002), while the median PFS in the HAIC+L+P group (11.0; 95% CI: 8.6~13.3 months) was significantly higher compared to the HAIC+L group (6.0; 95% CI: 5.0~6.9 months) (p < 0.001). Significant between-group differences in DCR (p = 0.027) were found. Additionally, 48 pairs of patients were matched after propensity matching analysis. The survival prognosis between two groups before propensity matching is similar to that after propensity matching. Moreover, the percentage of patients with hypertension in the HAIC+L+P group was significantly higher compared to the HAIC+L group (28.00% vs. 13.51%; p = 0.029).

Conclusions

A combination therapy of HAIC, lenvatinib, and programmed death-1 inhibitors significantly improved oncologic response and prolonged survival duration, showing a better survival prognosis for HCC patients with refractory toTACE.
Identification of prognostic cancer-associated fibroblast markers in luminal breast cancer using weighted gene co-expression network analysis
Authors: Xu An , Xu Xiang-Nan , Luo Zhou , Huang Xiao , Gong Rong-Quan , Fu De-Yuan
Published: May 2023

Background

Cancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression and are known to mediate endocrine and chemotherapy resistance through paracrine signaling. Additionally, they directly influence the expression and growth dependence of ER in Luminal breast cancer (LBC). This study aims to investigate stromal CAF-related factors and develop a CAF-related classifier to predict the prognosis and therapeutic outcomes in LBC.

Methods

The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were utilized to obtain mRNA expression and clinical information from 694 and 101 LBC samples, respectively. CAF infiltrations were determined by estimating the proportion of immune and cancer cells (EPIC) method, while stromal scores were calculated using the Estimation of STromal and Immune cells in MAlignant Tumors using Expression data (ESTIMATE) algorithm. Weighted gene co-expression network analysis (WGCNA) was used to identify stromal CAF-related genes. A CAF risk signature was developed through univariate and least absolute shrinkage and selection operator method (LASSO) Cox regression model. The Spearman test was used to evaluate the correlation between CAF risk score, CAF markers, and CAF infiltrations estimated through EPIC, xCell, microenvironment cell populations-counter (MCP-counter), and Tumor Immune Dysfunction and Exclusion (TIDE) algorithms. The TIDE algorithm was further utilized to assess the response to immunotherapy. Additionally, Gene set enrichment analysis (GSEA) was applied to elucidate the molecular mechanisms underlying the findings.

Results

We constructed a 5-gene prognostic model consisting of RIN2, THBS1, IL1R1, RAB31, and COL11A1 for CAF. Using the median CAF risk score as the cutoff, we classified LBC patients into high- and low-CAF-risk groups and found that those in the high-risk group had a significantly worse prognosis. Spearman correlation analyses demonstrated a strong positive correlation between the CAF risk score and stromal and CAF infiltrations, with the five model genes showing positive correlations with CAF markers. In addition, the TIDE analysis revealed that high-CAF-risk patients were less likely to respond to immunotherapy. Gene set enrichment analysis (GSEA) identified significant enrichment of ECM receptor interaction, regulation of actin cytoskeleton, epithelial-mesenchymal transition (EMT), and TGF-β signaling pathway gene sets in the high-CAF-risk group patients.

Conclusion

The five-gene prognostic CAF signature presented in this study was not only reliable for predicting prognosis in LBC patients, but it was also effective in estimating clinical immunotherapy response. These findings have significant clinical implications, as the signature may guide tailored anti-CAF therapy in combination with immunotherapy for LBC patients.