bluuebunny/crossref_metadata_2025 huggingface dataset:
The severity of depression is associated with pelvic inflammatory diseases: A cross-sectional study of the United States National Health and Nutrition Examinations from 2013 to 2018
Authors: Huang TianJiao , Cao RenShuang , Liu PengFei , Liu JinXing , Yu Xiao
Published: October 2022

Purpose

As depression in patients with pelvic inflammatory diseases (PID) has received increasing attention in recent years, this study aims to investigate the relationship between depression severity and risk factors for pelvic inflammatory disease, and to provide new perspectives in the treatment of PID.

Patients and methods

Multivariate regression was used to evaluate the association between pelvic inflammatory disease and the severity of depression. Females who participated in the United States National Health and Nutrition Examination Survey (NHANES) from 2013 to 2018 were included. In addition, risk factors for PID and depression were also included in the analysis as adjustment factors.

Results

The risk of developing PID was associated with depressive status (odds ratio, OR 1.10, 95% confidence interval, CI 1.08–1.12), especially in people with severe depression (odds ratio, OR 6.34, 95% confidence interval, CI 3.72–10.79). Subgroup analysis showed differences in the risk of PID among people with different characteristics.

Conclusion

This study showed that there may be a potential positive association between depressive status and the prevalence of PID in the United States adult female population. Depression should be actively looked for in all patients with PID and treated appropriately
Comparison of six risk scores for stroke-associated pneumonia in patients with acute ischemic stroke: A systematic review and Bayesian network meta-analysis
Authors: Zhang Xuemin , Xiao Lu , Niu Liqing , Tian Yongchao , Chen Kuang
Published: October 2022

Background

Stroke-associated pneumonia (SAP) is one of the major causes of death after suffering a stroke. Several scoring systems have been developed for the early prediction of SAP. However, it is unclear which scoring system is more suitable as a risk prediction tool. We performed this Bayesian network meta-analysis to compare the prediction accuracy of these scoring systems.

Methods

Seven databases were searched from their inception up to April 8, 2022. The risk of bias assessment of included study was evaluated by the QUADAS-C tool. Then, a Bayesian network meta-analysis (NMA) was performed by R 4.1.3 and STATA 17.0 software. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined scoring systems.

Results

A total of 20 cohort studies involving 42,236 participants were included in this analysis. The results of the NMA showed that AIS-APS had excellent performance in prediction accuracy for SAP than Chumbler (MD = 0.030, 95%CI: 0.004, 0.054), A2DS2 (MD = 0.041, 95% CI: 0.023, 0.059), ISAN (MD = 0.045, 95% CI: 0.022, 0.069), Kwon (MD = 0.077, 95% CI: 0.055, 0.099) and PANTHERIS (MD = 0.082, 95% CI: 0.049, 0.114). Based on SUCRA values, AIS-APS (SUCRA: 99.8%) ranked the highest.

Conclusion

In conclusion, the study found that the AIS-APS is a validated clinical tool for predicting SAP after the onset of acute ischemic stroke.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=292375, identifier: CRD42021292375.
The role of microRNAs in ferroptosis
Authors: Guo Liqing , Zhang Qingkun , Liu Yuehui
Published: October 2022

Ferroptosis is a newly discovered type of programmed cell death, which is closely related to the imbalance of iron metabolism and oxidative stress. Ferroptosis has become an important research topic in the fields of cardiomyopathy, tumors, neuronal injury disorders, and ischemia perfusion disorders. As an important part of non-coding RNA, microRNAs regulate various metabolic pathways in the human body at the post-transcriptional level and play a crucial role in the occurrence and development of many diseases. The present review introduces the mechanisms of ferroptosis and describes the relevant pathways by which microRNAs affect cardiomyopathy, tumors, neuronal injury disorders and ischemia perfusion disorders through regulating ferroptosis. In addition, it provides important insights into ferroptosis-related microRNAs, aiming to uncover new methods for treatment of the above diseases, and discusses new ideas for the implementation of possible microRNA-based ferroptosis-targeted therapies in the future.
Interaction of client—the scaffold on which FeS clusters are build—with J-domain protein Hsc20 and its evolving Hsp70 partners
Authors: Marszalek Jaroslaw , Craig Elizabeth A.
Published: October 2022

In cells molecular chaperone systems consisting of Hsp70 and its obligatory J-domain protein (JDP) co-chaperones transiently interact with a myriad of client proteins—with JDPs typically recruiting their partner Hsp70 to interact with particular clients. The fundamentals of this cyclical interactions between JDP/Hsp70 systems and clients are well established. Much less is known about other aspects of JDP/Hsp70 system function, including how such systems evolved over time. Here we discuss the JDP/Hsp70 system involved in the biogenesis of iron-sulfur (FeS) clusters. Interaction between the client protein, the scaffold on which clusters are built, and its specialized JDP Hsc20 has stayed constant. However, the system’s Hsp70 has changed at least twice. In some species Hsc20’s Hsp70 partner interacts only with the scaffold, in others it has many JDP partners in addition to Hsc20 and interacts with many client proteins. Analysis of this switching of Hsp70 partners has provided insight into the insulation of JDP/Hsp70 systems from one another that can occur when more than one Hsp70 is present in a cellular compartment, as well as how competition among JDPs is balanced when an Hsp70 partner is shared amongst a number of JDPs. Of particularly broad relevance, even though the scaffold’s interactions with Hsc20 and Hsp70 are functionally critical for the biogenesis of FeS cluster-containing proteins, it is the modulation of the Hsc20-Hsp70 interaction per se that allows Hsc20 to function with such different Hsp70 partners.
Impact of normative brain volume reports on the diagnosis of neurodegenerative dementia disorders in neuroradiology: A real-world, clinical practice study
Authors: Hedderich Dennis M. , Schmitz-Koep Benita , Schuberth Madeleine , Schultz Vivian , Schlaeger Sarah J. , Schinz David , Rubbert Christian , Caspers Julian , Zimmer Claus , Grimmer Timo , Yakushev Igor
Published: October 2022

Background: Normative brain volume reports (NBVR) are becoming more available in the work-up of patients with suspected dementia disorders, potentially leveraging the value of structural MRI in clinical settings. The present study aims to investigate the impact of NBVRs on the diagnosis of neurodegenerative dementia disorders in real-world clinical practice.

Methods: We retrospectively analyzed data of 112 memory clinic patients, who were consecutively referred for MRI and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) during a 12-month period. Structural MRI was assessed by two residents with 2 and 3 years of neuroimaging experience. Statements and diagnostic confidence regarding the presence of a neurodegenerative disorder in general (first level) and Alzheimer’s disease (AD) pattern in particular (second level) were recorded without and with NBVR information. FDG-PET served as the reference standard.

Results: Overall, despite a trend towards increased accuracy, the impact of NBVRs on diagnostic accuracy was low and non-significant. We found a significant drop of sensitivity (0.75–0.58; p < 0.001) and increase of specificity (0.62–0.85; p < 0.001) for rater 1 at identifying patients with neurodegenerative dementia disorders. Diagnostic confidence increased for rater 2 (p < 0.001).

Conclusions: Overall, NBVRs had a limited impact on diagnostic accuracy in real-world clinical practice. Potentially, NBVR might increase diagnostic specificity and confidence of neuroradiology residents. To this end, a well-defined framework for integration of NBVR in the diagnostic process and improved algorithms of NBVR generation are essential.
β2* nicotinic acetylcholine receptor subtypes mediate nicotine-induced enhancement of Pavlovian conditioned responding to an alcohol cue
Authors: Maddux Jean-Marie , Gonzales Leslie , Kregar Nathaniel P.
Published: October 2022

Nicotine enhances Pavlovian conditioned responses to reward-associated cues. We investigated through which nicotinic acetylcholine receptor (nAChR) subtypes nicotine acts to produce this behavioral effect to an alcohol-associated cue. Male Long-Evans rats with freely available food and water were first accustomed to drinking 15% ethanol in their home cages using an intermittent access, two-bottle choice procedure. Then the rats were given 15 Pavlovian conditioning sessions in which a 15-s audiovisual conditioned stimulus (CS) predicted the delivery of 0.2 ml of ethanol, the unconditioned stimulus (US). Each session contained 12 CS-US trials. A control group received explicitly unpaired presentations of the CS and US. We measured Pavlovian conditioned approach to the site of US delivery during presentations of the CS, accounting for pre-CS baseline activity. Before each conditioning session, rats were injected subcutaneously with nicotine (0.4 mg/kg) or saline (1 ml/kg). During nAChR antagonist test sessions, rats were first injected systemically with the β2*-selective nAChR antagonist dihydro-beta-erythroidine (DHβE; 3 mg/kg) or the α7-selective nAChR antagonist methyllycaconitine (MLA; 6 mg/kg), followed by their assigned nicotine or saline injection before assessing their conditioned response to the alcohol-associated cue. Consistent with previous reports, nicotine enhanced the Pavlovian conditioned response to the alcohol-paired cue. DHβE attenuated this enhancement, whereas MLA did not. These results suggest that nicotine acts via β2*, but not α7, nAChRs to amplify Pavlovian conditioned responding to an alcohol cue. These findings contribute to a growing literature that identifies nAChRs as potential targets for pharmacological treatment of co-morbid alcohol and tobacco use disorders.
Impaired Morris water task retention following T21 light dark cycle exposure is not due to reduced hippocampal c-FOS expression
Authors: Deibel Scott H. , Higdon S. , Cassell T. T. S. , House-Denine M. L. , Giberson E. , Webb I. C. , Thorpe C. M.
Published: October 2022

Circadian rhythms influence virtually all aspects of physiology and behavior. This is problematic when circadian rhythms no longer reliably predict time. Circadian rhythm disruption can impair memory, yet we don’t know how this fully works at the systems and molecular level. When trying to determine the root of a memory impairment, assessing neuronal activation with c-FOS is useful. This has yet to be assessed in the hippocampi of circadian rhythm disrupted rats in a hippocampal gold standard task. Rats were trained on the Morris water task (MWT), then received 6 days of a 21-h day (T21), 13 days of a normal light dark cycle, probe trial, and tissue extraction an hour later. Despite having impaired memory in the probe trial, compared to controls there were no differences in c-FOS expression in hippocampal sub regions: CA1; CA3; Dentate gyrus. These data confirm others in hamsters demonstrating that arrhythmicity which produces an impairment in spontaneous alternation does not affect c-FOS in the dentate gyrus. The current study indicates that the memory impairment induced by a lighting manipulation is likely not due to attenuated neuronal activation. Determining how the master clock in the brain communicates with the hippocampus is needed to untangle the relationship between circadian rhythms and memory.
Contribution of CD4+ cells in the emotional alterations induced by endometriosis in mice
Authors: Escudero-Lara Alejandra , Cabañero David , Maldonado Rafael
Published: October 2022

Endometriosis is a disease defined by the presence of endometrial tissue in extrauterine locations. This chronic condition is frequently associated with pain and emotional disorders and has been related with altered immune function. However, the specific involvement of immune cells in pain and behavioral symptoms of endometriosis has not been yet elucidated. Here, we implement a mouse model of non-surgical endometriosis in which immunocompetent mice develop abdomino-pelvic hypersensitivity, cognitive deficits, anxiety and depressive-like behaviors. This behavioral phenotype correlates with expression of inflammatory markers in the brain, including the immune cell marker CD4. Depletion of CD4 + cells decreases the anxiety-like behavior of mice subjected to the endometriosis model, whereas abdomino-pelvic hypersensitivity, depressive-like behavior and cognitive deficits remain unaltered. The present data reveal the involvement of the immune response characterized by CD4 + white blood cells in the anxiety-like behavior induced by endometriosis in mice. This model, which recapitulates the symptoms of human endometriosis, may be a useful tool to study the immune mechanisms involved in pain and behavioral alterations associated to endometriosis.
Prevalence and risk factors of MRI-defined brain infarcts among Chinese adults
Authors: Wu Jing , Gao Yongxiang , Malik Vasanti , Gao Xiang , Shan Ruiqi , Lv Jun , Ning Yi , Wang Bo , Li Liming
Published: October 2022

Background

Few studies have explored the prevalence and risk factors of brain infarcts (BI) detected by magnetic resonance imaging (MRI) in China. The purpose was to evaluate the prevalence and risk factors of brain infarcts (BI) detected by magnetic resonance imaging (MRI) in 1.4 million Chinese adults.

Methods

This was a multicenter cross-sectional study conducted on 1,431,527 participants aged ≥18 years (mean age: 46.4 years) who underwent MRI scans in health examinations from 28 provinces of China in 2018. MRI-defined BI was defined as focal parenchymal lesions ≥3 mm. Multivariable logistic regression analyses were performed to evaluate risk factors associated with MRI-defined BI.

Results

The age- and sex-standardized prevalence of MRI-defined BI, lacunar and non-lacunar infarcts were 5.79% (5.75–5.83%), 4.56% (4.52–4.60%), and 1.23% (1.21–1.25%), respectively. The sex-standardized prevalence of MRI-defined BI ranged from 0.46% among those aged 18–29 years to 37.33% among those aged ≥80 years. Men (6.30%) had a higher age-standardized prevalence of MRI-defined BI than women (5.28%). The highest age- and sex-standardized prevalence of MRI-defined BI was observed in the Northwest (8.34%) and Northeast (8.02%) regions, while the lowest prevalence was observed in the Southwest (4.02%). A higher risk of MRI-defined BI was associated with being male [odd ratio (OR) 1.17, 95% CI 1.15–1.19], older age (OR per 10-year increments 2.33, 2.31–2.35), overweight (1.12, 1.10–1.14) or obesity (1.18, 1.16–1.21), hypertension (1.80, 1.77–1.83), diabetes (1.24, 1.21–1.26), and dyslipidemia (1.07, 1.05–1.08).

Conclusion

MRI-defined BI is highly prevalent in China, even among young adults. MRI-defined BI was associated with being male, older age, living in the northern region, and metabolic conditions.
Using gene panels in the diagnosis of neuromuscular disorders: A mini-review
Authors: Ng Kay W. P. , Chin Hui-Lin , Chin Amanda X. Y. , Goh Denise Li-Meng
Published: October 2022

The diagnosis of inherited neuromuscular disorders is challenging due to their genetic and phenotypic variability. Traditionally, neurophysiology and histopathology were primarily used in the initial diagnostic approach to these conditions. Sanger sequencing for molecular diagnosis was less frequently utilized as its application was a time-consuming and cost-intensive process. The advent and accessibility of next-generation sequencing (NGS) has revolutionized the evaluation process of genetically heterogenous neuromuscular disorders. Current NGS diagnostic testing approaches include gene panels, whole exome sequencing (WES), and whole genome sequencing (WGS). Gene panels are often the most widely used, being more accessible due to availability and affordability. In this mini-review, we describe the benefits and risks of clinical genetic testing. We also discuss the utility, benefits, challenges, and limitations of using gene panels in the evaluation of neuromuscular disorders.
Connecting phenotype to genotype: PheWAS-inspired analysis of autism spectrum disorder
Authors: Matta John , Dobrino Daniel , Yeboah Dacosta , Howard Swade , EL-Manzalawy Yasser , Obafemi-Ajayi Tayo
Published: October 2022

Autism Spectrum Disorder (ASD) is extremely heterogeneous clinically and genetically. There is a pressing need for a better understanding of the heterogeneity of ASD based on scientifically rigorous approaches centered on systematic evaluation of the clinical and research utility of both phenotype and genotype markers. This paper presents a holistic PheWAS-inspired method to identify meaningful associations between ASD phenotypes and genotypes. We generate two types of phenotype-phenotype (p-p) graphs: a direct graph that utilizes only phenotype data, and an indirect graph that incorporates genotype as well as phenotype data. We introduce a novel methodology for fusing the direct and indirect p-p networks in which the genotype data is incorporated into the phenotype data in varying degrees. The hypothesis is that the heterogeneity of ASD can be distinguished by clustering the p-p graph. The obtained graphs are clustered using network-oriented clustering techniques, and results are evaluated. The most promising clusterings are subsequently analyzed for biological and domain-based relevance. Clusters obtained delineated different aspects of ASD, including differentiating ASD-specific symptoms, cognitive, adaptive, language and communication functions, and behavioral problems. Some of the important genes associated with the clusters have previous known associations to ASD. We found that clusters based on integrated genetic and phenotype data were more effective at identifying relevant genes than clusters constructed from phenotype information alone. These genes included five with suggestive evidence of ASD association and one known to be a strong candidate.
Aberrant brain functional networks in type 2 diabetes mellitus: A graph theoretical and support-vector machine approach
Authors: Lin Lin , Zhang Jindi , Liu Yutong , Hao Xinyu , Shen Jing , Yu Yang , Xu Huashuai , Cong Fengyu , Li Huanjie , Wu Jianlin
Published: October 2022

Objective

Type 2 diabetes mellitus (T2DM) is a high risk of cognitive decline and dementia, but the underlying mechanisms are not yet clearly understood. This study aimed to explore the functional connectivity (FC) and topological properties among whole brain networks and correlations with impaired cognition and distinguish T2DM from healthy controls (HC) to identify potential biomarkers for cognition abnormalities.

Methods

A total of 80 T2DM and 55 well-matched HC were recruited in this study. Subjects’ clinical data, neuropsychological tests and resting-state functional magnetic resonance imaging data were acquired. Whole-brain network FC were mapped, the topological characteristics were analyzed using a graph-theoretic approach, the FC and topological characteristics of the network were compared between T2DM and HC using a general linear model, and correlations between networks and clinical and cognitive characteristics were identified. The support vector machine (SVM) model was used to identify differences between T2DM and HC.

Results

In patients with T2DM, FC was higher in two core regions [precuneus/posterior cingulated cortex (PCC)_1 and later prefrontal cortex_1] in the default mode network and lower in bilateral superior parietal lobes (within dorsal attention network), and decreased between the right medial frontal cortex and left auditory cortex. The FC of the right frontal medial-left auditory cortex was positively correlated with the Montreal Cognitive Assessment scales and negatively correlated with the blood glucose levels. Long-range connectivity between bilateral auditory cortex was missing in the T2DM. The nodal degree centrality and efficiency of PCC were higher in T2DM than in HC (P < 0.005). The nodal degree centrality in the PCC in the SVM model was 97.56% accurate in distinguishing T2DM patients from HC, demonstrating the reliability of the prediction model.

Conclusion

Functional abnormalities in the auditory cortex in T2DM may be related to cognitive impairment, such as memory and attention, and nodal degree centrality in the PCC might serve as a potential neuroimaging biomarker to predict and identify T2DM.
Chloride imbalance in Fragile X syndrome
Authors: Miles Kaleb Dee , Doll Caleb Andrew
Published: October 2022

Developmental changes in ionic balance are associated with crucial hallmarks in neural circuit formation, including changes in excitation and inhibition, neurogenesis, and synaptogenesis. Neuronal excitability is largely mediated by ionic concentrations inside and outside of the cell, and chloride (Cl–) ions are highly influential in early neurodevelopmental events. For example, γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter of the mature central nervous system (CNS). However, during early development GABA can depolarize target neurons, and GABAergic depolarization is implicated in crucial neurodevelopmental processes. This developmental shift of GABAergic neurotransmission from depolarizing to hyperpolarizing output is induced by changes in Cl– gradients, which are generated by the relative expression of Cl– transporters Nkcc1 and Kcc2. Interestingly, the GABA polarity shift is delayed in Fragile X syndrome (FXS) models; FXS is one of the most common heritable neurodevelopmental disorders. The RNA binding protein FMRP, encoded by the gene Fragile X Messenger Ribonucleoprotein-1 (Fmr1) and absent in FXS, appears to regulate chloride transporter expression. This could dramatically influence FXS phenotypes, as the syndrome is hypothesized to be rooted in defects in neural circuit development and imbalanced excitatory/inhibitory (E/I) neurotransmission. In this perspective, we summarize canonical Cl– transporter expression and investigate altered gene and protein expression of Nkcc1 and Kcc2 in FXS models. We then discuss interactions between Cl– transporters and neurotransmission complexes, and how these links could cause imbalances in inhibitory neurotransmission that may alter mature circuits. Finally, we highlight current therapeutic strategies and promising new directions in targeting Cl– transporter expression in FXS patients.
Neural activity changes in first-episode, drug-naïve patients with major depressive disorder after transcutaneous auricular vagus nerve stimulation treatment: A resting-state fMRI study
Authors: Yi Sijie , Wang Zhi , Yang Wenhan , Huang Chuxin , Liu Ping , Chen Yanjing , Zhang Huiting , Zhao Guangju , Li Weihui , Fang Jiliang , Liu Jun
Published: October 2022

Introduction

Major depressive disorder (MDD) is a disease with prominent individual, medical, and economic impacts. Drug therapy and other treatment methods (such as Electroconvulsive therapy) may induce treatment-resistance and have associated side effects including loss of memory, decrease of reaction time, and residual symptoms. Transcutaneous auricular vagus nerve stimulation (taVNS) is a novel and non-invasive treatment approach which stimulates brain structures with no side-effects. However, it remains little understood whether and how the neural activation is modulated by taVNS in MDD patients. Herein, we used the regional homogeneity (ReHo) to investigate the brain activity in first-episode, drug-naïve MDD patients after taVNS treatment.

Materials and methods

Twenty-two first-episode, drug-naïve MDD patients were enrolled in the study. These patients received the first taVNS treatment at the baseline time, and underwent resting-state MRI scanning twice, before and after taVNS. All the patients then received taVNS treatments for 4 weeks. The severity of depression was assessed by the 17-item Hamilton Depression Rating Scale (HAMD) at the baseline time and after 4-week’s treatment. Pearson analysis was used to assess the correlation between alterations of ReHo and changes of the HAMD scores. Two patients were excluded due to excessive head movement, two patients lack clinical data in the fourth week, thus, imaging analysis was performed in 20 patients, while correlation analysis between clinical and imaging data was performed in only 18 patients.

Results

There were significant differences in the ReHo values in first-episode, drug-naïve MDD patients between pre- or post- taVNS. The primary finding is that the patients exhibited a significantly lower ReHo in the left/right median cingulate cortex, the left precentral gyrus, the left postcentral gyrus, the right calcarine cortex, the left supplementary motor area, the left paracentral lobule, and the right lingual gyrus. Pearson analysis revealed a positive correlation between changes of ReHo in the right median cingulate cortex/the left supplementary motor area and changes of HAMD scores after taVNS.

Conclusion

The decreased ReHo were found after taVNS. The sensorimotor, limbic and visual-related brain regions may play an important role in understanding the underlying neural mechanisms and be the target brain regions in the further therapy.
Artifact propagation in subdural cortical electrostimulation: Characterization and modeling
Authors: Lim Jeffrey , Wang Po T. , Shaw Susan J. , Gong Hui , Armacost Michelle , Liu Charles Y. , Do An H. , Heydari Payam , Nenadic Zoran
Published: October 2022

Cortical stimulation via electrocorticography (ECoG) may be an effective method for inducing artificial sensation in bi-directional brain-computer interfaces (BD-BCIs). However, strong electrical artifacts caused by electrostimulation may significantly degrade or obscure neural information. A detailed understanding of stimulation artifact propagation through relevant tissues may improve existing artifact suppression techniques or inspire the development of novel artifact mitigation strategies. Our work thus seeks to comprehensively characterize and model the propagation of artifacts in subdural ECoG stimulation. To this end, we collected and analyzed data from eloquent cortex mapping procedures of four subjects with epilepsy who were implanted with subdural ECoG electrodes. From this data, we observed that artifacts exhibited phase-locking and ratcheting characteristics in the time domain across all subjects. In the frequency domain, stimulation caused broadband power increases, as well as power bursts at the fundamental stimulation frequency and its super-harmonics. The spatial distribution of artifacts followed the potential distribution of an electric dipole with a median goodness-of-fit of R2 = 0.80 across all subjects and stimulation channels. Artifacts as large as ±1,100 μV appeared anywhere from 4.43 to 38.34 mm from the stimulation channel. These temporal, spectral and spatial characteristics can be utilized to improve existing artifact suppression techniques, inspire new strategies for artifact mitigation, and aid in the development of novel cortical stimulation protocols. Taken together, these findings deepen our understanding of cortical electrostimulation and provide critical design specifications for future BD-BCI systems.
Susceptibility-weighted imaging at high-performance 0.5T magnetic resonance imaging system: Protocol considerations and experimental results
Authors: Qiu Yueqi , Bai Haoran , Chen Hao , Zhao Yue , Luo Hai , Wu Ziyue , Zhang Zhiyong
Published: October 2022

The high-performance low-field magnetic resonance imaging (MRI) system, equipped with modern hardware and contemporary imaging capabilities, has garnered interest within the MRI community in recent years. It has also been proven to have unique advantages over high-field MRI in both physical and cost aspects. However, for susceptibility weighted imaging (SWI), the low signal-to-noise ratio and the long echo time inherent at low field hinder the SWI from being applied to clinical applications. This work optimized the imaging protocol to select suitable parameters such as the values of time of echo (TE), repetition time (TR), and the flip angle (FA) of the RF pulse according to the signal simulations for low-field SWI. To improve the signal-to-noise ratio (SNR) performance, averaging multi-echo magnitude images and BM4D phase denoising were proposed. A comparison of the SWI in 0.5T and 1.5T was carried out, demonstrating the capability to identify magnetic susceptibility differences between variable tissues, especially, the blood veins. This would open the possibility to extend SWI applications in the high-performance low field MRI.
Clinical and biochemical characterization of hereditary transthyretin amyloidosis caused by E61K mutation
Authors: Chu Xujun , Wang Mengdie , Tang Ran , Huang Yanan , Yu Jiaxi , Cao Yunfeng , Zheng Yilei , Xie Zhiying , Deng Jianwen , Wang Zhi , Ma Wei , Song Wenjing , Wu Yuan , Lv He , Zhang Wei , Wang Zhaoxia , Yuan Yun , Liu Yu , Meng Lingchao
Published: October 2022

Objects: This study was intended to find out more about the clinical characterizations of patients carrying transthyretin (TTR) E61K (p.Glu81Lys) gene mutation and the biochemical characterization of this mutant protein.

Materials and methods: Five patients who had been diagnosed with hereditary transthyretin amyloidosis and two asymptomatic carriers carrying TTR E61K gene mutation were reported. Biochemical and biophysical tests were conducted to observe the thermodynamic and kinetic stability. Fibril formation tests measured by turbidity assay were performed to explore the pathogenicity of this mutation. Kinetic stabilizer responsiveness was measured to determine the inhibitory effect on protein aggregation.

Results: The average age of onset for the five patients was 62 years, and the course of the disease ranged from 2 to 10 years. Cardiac disease was prominent in this group of patients. Nerve pathology revealed a mildly to moderately reduced myelinated fiber density and muscle pathology showed predominant neurogenic impairment accompanied by possible myogenic impairment. E61K-TTR was characterized as a kinetically destabilized protein compared to WT-TTR but its thermodynamic stability was not compromised. In addition, the subunit exchange of E61K with WT-TTR further destabilized the heterozygous tetramer. Meanwhile, the E61K:WT heterozygous tetramer exhibited a poor response to kinetic stabilizers in the fibril formation assay. Finally, the serum TTR tetramer concentration was low in E61K-TTR symptomatic patients and in one asymptomatic gene carrier. Vyndamax (Tafamidis) could increase the TTR tetramer concentration.

Conclusions: Patients with E61K mutation tended to be late-onset. The concentration of TTR tetramer in the serum might serve as a biomarker to monitor disease progress, therapeutic window time, and therapeutic response to TTR kinetic stabilizer drugs.
Age, brain region, and gene dosage-differential transcriptomic changes in Shank3-mutant mice
Authors: Yoo Taesun , Yoo Ye-Eun , Kang Hyojin , Kim Eunjoon
Published: October 2022

Shank3 is an abundant excitatory postsynaptic scaffolding protein implicated in various neurodevelopmental disorders, including autism spectrum disorder (ASD), Phelan-McDermid syndrome, intellectual disability, and schizophrenia. Shank3-mutant mice show various molecular, synaptic, and behavioral deficits, but little is known about how transcriptomic phenotypes vary across different ages, brain regions, and gene dosages. Here, we report transcriptomic patterns in the forebrains of juvenile and adult homozygous Shank3-mutant mice that lack exons 14–16 and also the prefrontal, hippocampal, and striatal transcriptomes in adult heterozygous and homozygous Shank3-mutant mice. The juvenile and adult mutant transcriptomes show patterns opposite from and similar to those observed in ASD (termed reverse-ASD and ASD-like patterns), respectively. The juvenile transcriptomic changes accompany synaptic upregulations and ribosomal and mitochondrial downregulations, whereas the adult transcriptome show opposite changes. The prefrontal, hippocampal, and striatal transcriptomes show differential changes in ASD-related gene expressions and biological functions associated with synapse, ribosome, mitochondria, and spliceosome. These patterns also differ across heterozygous and homozygous Shank3-mutant mice. These results suggest age, brain region, and gene dosage-differential transcriptomic changes in Shank3-mutant mice.
G protein-coupled receptors in cochlea: Potential therapeutic targets for hearing loss
Authors: Ma Xiangyu , Guo Jiamin , Fu Yaoyang , Shen Cangsong , Jiang Pei , Zhang Yuan , Zhang Lei , Yu Yafeng , Fan Jiangang , Chai Renjie
Published: October 2022

The prevalence of hearing loss-related diseases caused by different factors is increasing worldwide year by year. Currently, however, the patient’s hearing loss has not been effectively improved. Therefore, there is an urgent need to adopt new treatment measures and treatment techniques to help improve the therapeutic effect of hearing loss. G protein-coupled receptors (GPCRs), as crucial cell surface receptors, can widely participate in different physiological and pathological processes, particularly play an essential role in many disease occurrences and be served as promising therapeutic targets. However, no specific drugs on the market have been found to target the GPCRs of the cochlea. Interestingly, many recent studies have demonstrated that GPCRs can participate in various pathogenic process related to hearing loss in the cochlea including heredity, noise, ototoxic drugs, cochlear structure, and so on. In this review, we comprehensively summarize the functions of 53 GPCRs known in the cochlea and their relationships with hearing loss, and highlight the recent advances of new techniques used in cochlear study including cryo-EM, AI, GPCR drug screening, gene therapy vectors, and CRISPR editing technology, as well as discuss in depth the future direction of novel GPCR-based drug development and gene therapy for cochlear hearing loss. Collectively, this review is to facilitate basic and (pre-) clinical research in this area, and provide beneficial help for emerging GPCR-based cochlear therapies.
Effects of four cooking methods on flavor and sensory characteristics of scallop muscle
Authors: Wang Yueyao , Tian Guifang , Mao Kemin , Chitrakar Bimal , Wang Zhongxuan , Liu Jie , Bai Xinzhong , Sang Yaxin , Gao Jie
Published: October 2022

This work aimed to explore the influence of four different cooking methods (Boiling, roasting, frying, and microwaving) on the sensory characteristics of scallop muscles. Headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) and electronic nose (e-nose) were combined to analyze the aroma of scallops. Combined with the results of free amino acids and electronic tongue (e-tongue), the taste changes of different samples were analyzed. Furthermore, texture profile and microstructure analysis jointly showed the influence of cooking methods on texture. The results showed that frying was the most suitable cooking method for scallop muscle because it resulted the best tasted products, boiled scallops retain the highest similarity to fresh scallops. Besides, a higher level of lipid oxidation and Maillard reaction resulted in significant increase in aldehydes, ketones, furans, umami, and sweet amino acid. For the boiled sample, the loss of water-soluble compounds and less fat oxidation resulted in fewer flavor substances and free amino acids, along with looser organizational structure and poorer sensory quality. The research showed that besides the texture of scallop muscle, volatile organic compounds and free amino acids as well as their mutual roles in taste and smell were also important to sensory receptivity.
Extracellular vesicle miRNAs in breast milk of obese mothers
Authors: Cho Young Eun , Vorn Rany , Chimenti Michael , Crouch Keith , Shaoshuai Chen , Narayanaswamy Janhavi , Harken Alaria , Schmidt Reegan , Gill Jessica , Lee Hyangkyu
Published: October 2022

Background

Breast milk has abundant extracellular vesicles (EVs) containing various biological molecules (cargo), including miRNAs. EVs are not degraded in the gastrointestinal system and circulation; thus, breast milk EVs (bEVs) are expected to interact with other organs in breastfed infants and modify the gene expression of recipient cells using miRNAs. Maternal pre-pregnancy BMI is a critical factor influencing the composition of breast milk. Thus, in mothers with obesity, miRNAs in bEVs can be altered, which might be associated with adverse health outcomes in infants. In this study, we examined 798 miRNAs to determine which miRNAs are altered in the bEVs of mothers with obesity and their potential impact on breastfed infants.

Methods

We recruited healthy nursing mothers who were either of normal weight (BMI < 25) or with obesity (BMI ≥ 30) based on their pre-pregnancy BMI, and delivered a singleton baby in the prior 6 months. EVs were isolated from breast milk with ultracentrifugation. bEV characteristics were examined by flow cytometry and fluorescence imaging of EV markers. A total of 798 miRNAs were screened using a NanoString human miRNA panel to find differentially expressed miRNAs in bEVs of mothers with obesity compared to mothers of normal weight.

Results

We included 65 nursing mothers: 47 of normal weight and 18 with obesity based on pre-pregnancy BMI. After bEV isolation, we confirmed the expression of various EV markers. Out of 37 EV markers, CD326 (EpCaM) was the most highly expressed in bEVs. The most abundant miRNAs in bEVs include miR-30b-5p, miR-4454, miR-494-3p, and let-7 miRNAs. Target genes of the top 10 miRNAs were associated with cancer, prolactin pathway, EGFR, ErbB, and FoxO signaling pathway. In bEVs of mothers with obesity, 19 miRNAs were differentially expressed (adjusted p < 0.05 cut-off), which include miR-575, miR-630, miR-642a-3p, and miR-652-5p. These miRNAs and their target genes were associated with neurological diseases and psychological disorders.

Conclusion

In this study, we characterized bEVs and demonstrated altered miRNAs in bEVs of mothers with obesity and identified the pathways of their potential target genes. Our findings will provide insight for future studies investigating the role of bEVs in breastfed infants.
Mechanisms of venetoclax resistance and solutions
Authors: Liu Jiachen , Chen Yidong , Yu Lihua , Yang Lihua
Published: October 2022

The BCL-2 inhibitor venetoclax is currently approved for treatment of hematologic diseases and is widely used either as monotherapy or in combination strategies. It has produced promising results in the treatment of refractory or relapsed (R/R) and aged malignant hematologic diseases. However, with clinical use, resistance to venetoclax has emerged. We review the mechanism of reduced dependence on BCL-2 mediated by the upregulation of antiapoptotic proteins other than BCL-2, such as MCL-1 and BCL-XL, which is the primary mechanism of venetoclax resistance, and find that this mechanism is achieved through different pathways in different hematologic diseases. Additionally, this paper also summarizes the current investigations of the mechanisms of venetoclax resistance in terms of altered cellular metabolism, changes in the mitochondrial structure, altered or modified BCL-2 binding domains, and some other aspects; this article also reviews relevant strategies to address these resistance mechanisms.
A predictive signature based on enhancer RNA associates with immune infiltration and aids treatment decision in clear cell renal cell carcinoma
Authors: Li Qinyu , Xiao Xueyan , Chen Bingliang , Song Guoda , Zeng Kai , Li Beining , Miao Jianping , Liu Chaofan , Luan Yang , Liu Bo
Published: October 2022

Clear cell renal cell carcinoma (ccRCC) is a prevalent urinary malignancy. Despite the recent development of better diagnostic tools and therapy, the five-year survival rate for individuals with advanced and metastatic ccRCC remains dismal. Unfortunately, ccRCC is less susceptible to radiation and chemotherapy. Consequently, targeted therapy and immunotherapy play a crucial role in the treatment of ccRCC. Enhancer RNAs (eRNAs) are noncoding RNAs transcribed by enhancers. Extensive research has shown that eRNAs are implicated in a variety of cancer signaling pathways. However, the biological functions of eRNAs have not been systematically investigated in ccRCC. In this study, we conducted a comprehensive investigation of the role of eRNAs in the onset and management of ccRCC. Patient prognosis-influencing eRNAs and target genes were chosen to construct a predictive signature. On the basis of the median riskscore, ccRCC patients were split into high- and low-risk subgroups. The prediction efficiency was assessed in several cohorts, and multi-omics analysis was carried out to investigate the differences and underlying mechanisms between the high- and low-risk groups. In addition, we investigated its potential to facilitate clinical treatment choices. The riskscore might be used to forecast a patient’s response to immunotherapy and targeted therapy, giving a revolutionary method for selecting treatment regimens with pinpoint accuracy.
Recent progress of the tumor microenvironmental metabolism in cervical cancer radioresistance
Authors: Zhou Junying , Lei Ningjing , Tian Wanjia , Guo Ruixia , Chen Mengyu , Qiu Luojie , Wu Fengling , Li Yong , Chang Lei
Published: October 2022

Radiotherapy is widely used as an indispensable treatment option for cervical cancer patients. However, radioresistance always occurs and has become a big obstacle to treatment efficacy. The reason for radioresistance is mainly attributed to the high repair ability of tumor cells that overcome the DNA damage caused by radiotherapy, and the increased self-healing ability of cancer stem cells (CSCs). Accumulating findings have demonstrated that the tumor microenvironment (TME) is closely related to cervical cancer radioresistance in many aspects, especially in the metabolic processes. In this review, we discuss radiotherapy in cervical cancer radioresistance, and focus on recent research progress of the TME metabolism that affects radioresistance in cervical cancer. Understanding the mechanism of metabolism in cervical cancer radioresistance may help identify useful therapeutic targets for developing novel therapy, overcome radioresistance and improve the efficacy of radiotherapy in clinics and quality of life of patients.
The risk of serious bacterial infections among young ex-premature infants with fever
Authors: Barak-Corren Yuval , Elizur Yoav , Yuval Shira , Burstyn Amalia , Deri Noy , Schwartz Shepard , Megged Orli , Toker Ori
Published: October 2022

Background and Objectives

To determine the rate of serious-bacterial-infections (SBI) in young ex-premature infants with fever, and to develop a risk-stratification algorithm for these patients.

Methods

A retrospective cohort study including all infants who presented to the pediatric emergency department (ED) of a tertiary-care university-hospital between 2010 and 2020 with fever (≥38°C), were born prematurely (<37-weeks), had post-conception age of <52-weeks, and had available blood, urine, or CSF cultures. The rates of SBI by age-of-birth and age-at-visit were calculated and compared to a cohort of matched full-term controls.

Results

The study included a total of 290 ex-premature cases and 290 full-term controls. There were 11 cases (3.8%) with an invasive bacterial infection (IBI) of either bacteremia, meningitis or both and only six controls (2.1%) with IBI (p = 0.32). Over 28-days chronologic-age, there were 10 (3.6%) IBIs among cases and no IBIs among the controls (p = 0.02). There were eight (3%) cases and three (1%) controls with IBI who were well-appearing on physical examination (p = 0.19). All eight well-appearing ex-premature infants were under 60-days adjusted-age, seven of whom (88%) were also under 28-days adjusted-age. There were 28 (10.6%) cases and 34 (12%) controls with urinary tract infection (UTI) (p = 0.5). Among cases under 60-days adjusted-age, urinalysis was not reliable to exclude UTI (50% negative).

Conclusions

Well-appearing ex-preterm infants have a significant risk for IBI until the adjusted age of 28-days and for UTI until the adjusted age of 60-days. Further studies are needed to evaluate the approach to fever in this unique population.
CLCA1 mediates the regulatory effect of IL-13 on pediatric asthma
Authors: Xu Yanan , Cao Lili , Chen Jiong , Jiang Danyan , Ruan Peisen , Ye Qinsong
Published: October 2022

Objective

CLCA1 is a secreted protein with protease activity, and its expression is associated with inflammatory airway diseases. This study aimed to investigate the role of CLCA1 and IL-13 in pediatric asthma.

Methods

In asthmatic and healthy children, the correlation between CLCA1 expression and blood IL-4, and IL-13 levels were investigated by serological analyses such as RT-qPCR and ELISA. The effects on the activity and apoptosis of bronchial epithelial cells following IL-13 stimulation were explored in vitro by the CCK-8 assay and flow cytometry, respectively. CLCA1 siRNA was used to knock down the expression level of bronchial epithelial cells and the effect of IL-13 stimulation on these cells was assessed by the CCK-8 assay and flow cytometry.

Results

CLCA1, IL-4, and IL-13 were highly expressed in the serum of children with asthma. CLCA1 expression was highly correlated to serum IL-13. IL-13 stimulation reduced the activity of bronchial epithelial cells in vitro and promoted apoptosis. Lastly, knockdown of CLCA1 rescued the IL-13-induced decrease in activity and apoptosis.

Conclusion

CLCA1 is highly expressed in children with asthma and mediates the contributory effect of IL-13 on the occurrence and development of pediatric asthma.
Effectiveness of ertapenem for treatment of infections in children: An evidence mapping and meta-analysis
Authors: Zhao Ruiqiu , Long Xiaoru , Wang Jiangxia , Zhu Jing , Liu Cong , Shang Tingting , Zhang Zhenzhen , Obi Engels , Osadebe Lynda , Kang Yue , Liu Jie , Chen Xiaodi , Xu Hongmei
Published: October 2022

Objectives

To assess and summarize current evidence on the effectiveness and safety of ertapenem for treatment of childhood infections, in consideration of high infection prevalence in children and wide use of ertapenem.

Methods

The following 8 databases were searched on 13th May 2021: Web of Science, Embase via Ovid SP, PubMed, The Cochrane Library (CENTRAL), Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP and Wanfang. The primary outcome was treatment success rate. Risk ratios (RRs) and 95% confidence interval (CI) were estimated using random-effect models. Subgroup analysis was conducted where heterogeneity was found.

Results

Fifteen studies (8 randomized controlled trials, 1 observational comparative study, and 6 before and after studies) involving 2,528 patients were included in the final review. Ertapenem had similar treatment success rates with β-lactam antibiotics [relative risk (RR) = 1.08, 95% CI: 0.99–1.19]. In a subgroup analysis, similar efficacy (RR = 1.08, 95% CI: 0.97–1.20) between ertapenem and other carbapenems. Compared with β-lactam antibiotics, ertapenem did not increase the risk of any adverse events (RR = 1.02, 95%CI: 0.71–1.48), drug-related diarrhea (all non-Asian children, RR = 0.62, 95%CI: 0.31–1.25), or injection site pain (all non-Asian children, RR = 1.66, 95%CI: 0.59–4.68). Subgroup analysis showed no obvious difference between ertapenem group and carbapenems or non-carbapenems group on risk of adverse events.

Conclusion

Our findings suggest that ertapenem is effective and safe in treatment for children with infection. Further comparative real-world data is needed to supplement clinical evidence on the overall benefits of ertapenem in this population.