Selective vulnerability of hippocampal sub-regions in patients with subcortical vascular mild cognitive impairment.

Early diagnosis of subcortical vascular mild cognitive impairment (svMCI) is clinically essential because it is the most reversible subtype of all cognitive impairments. Since structural alterations of hippocampal sub-regions have been well studied in neurodegenerative diseases with pathophysiological cognitive impairments, we were eager to determine whether there is a selective vulnerability of hippocampal sub-fields in patients with svMCI. Our study included 34 svMCI patients and 34 normal controls (NCs), with analysis of T1 images and Montreal Cognitive Assessment (MoCA) scores. Gray matter volume (GMV) of hippocampal sub-regions was quantified and compared between the groups, adjusting for age, sex, and education. Additionally, we explored correlations between altered GMV in hippocampal sub-fields and MoCA scores in svMCI patients. Patients with svMCI exhibited selectively reduced GMV in several left hippocampal sub-regions, such as the hippocampal tail, hippocampal fissure, CA1 head, ML-HP head, CA4 head, and CA3 head, as well as decreased GMV in the right hippocampal tail. Specifically, GMV in the left CA3 head was inversely correlated with MoCA scores in svMCI patients. Our findings indicate that the atrophy pattern of patients with svMCI was predominantly located in the left hippocampal sub-regions. The left CA3 might be a crucial area underlying the distinct pathophysiological mechanisms of cognitive impairments with subcortical vascular origins.

Hotspots and Trends in Research on Treating Pain with Electroacupuncture: A Bibliometric and Visualization Analysis from 1994 to 2022.

Purpose: Electroacupuncture is widely used to pain management. A bibliometric analysis was conducted to identify the hotspots and trends in research on electroacupuncture for pain. Methods: We retrieved studies published from 1994-2022 on the topic of pain relief by electroacupuncture from the Web of Science Core Collection database. We comprehensively analysed the data with VOSviewer, CiteSpace, and bibliometrix. Seven aspects of the data were analysed separately: annual publication outputs, countries, institutions, authors, journals, keywords and references. Results: A total of 2030 papers were analysed, and the number of worldwide publications continuously increased over the period of interest. The most productive country and institution in this field were China and KyungHee University. Evidence-Based Complementary and Alternative Medicine was the most productive journal, and Pain was the most co-cited journal. Han Jisheng, Fang Jianqiao, and Lao Lixing were the most representative authors. Based on keywords and references, three active areas of research on EA for pain were mechanisms, randomized controlled trials, and perioperative applications. Three emerging trends were functional magnetic resonance imaging (fMRI), systematic reviews, and knee osteoarthritis. Conclusion: This study comprehensively analysed the research published over the past 28 years on electroacupuncture for pain treatment, using bibliometrics and science mapping analysis. This work presents the current status and landscape of the field and may serve as a valuable resource for researchers. Chronic pain, fMRI-based mechanistic research, and the perioperative application of electroacupuncture are among the likely foci of future research in this area.

Automated Fragmentation Quantum Mechanical Calculation of 15N and 13C Chemical Shifts in a Membrane Protein.

In this work, we developed an accurate and cost-effective automated fragmentation quantum mechanics/molecular mechanics (AF-QM/MM) method to calculate the chemical shifts of 15N and 13C of membrane proteins. The convergence of the AF-QM/MM method was tested using Krokinobacter eikastus rhodopsin 2 as a test case. When the distance threshold of the QM region is equal to or larger than 4.0 Å, the results of the AF-QM/MM calculations are close to convergence. In addition, the effects of selected density functionals, basis sets, and local chemical environment of target atoms on the chemical shift calculations were systematically investigated. Our results demonstrate that the predicted chemical shifts are more accurate when important environmental factors including cross-protomer interactions, lipid molecules, and solvent molecules are taken into consideration, especially for the 15N chemical shift prediction. Furthermore, with the presence of sodium ions in the environment, the chemical shift of residues, retinal, and retinal Schiff base are affected, which is consistent with the results of the solid-state nuclear magnetic resonance (NMR) experiment. Upon comparing the performance of various density functionals (namely, B3LYP, B3PW91, M06-2X, M06-L, mPW1PW91, OB95, and OPBE), the results show that mPW1PW91 is a suitable functional for the 15N and 13C chemical shift prediction of the membrane proteins. Meanwhile, we find that the improved accuracy of the 13Cß chemical shift calculations can be achieved by the employment of the triple-ζ basis set. However, the employment of the triple-ζ basis set does not improve the accuracy of the 15N and 13Cα chemical shift calculations nor does the addition of a diffuse function improve the overall prediction accuracy of the chemical shifts. Our study also underscores that the AF-QM/MM method has significant advantages in predicting the chemical shifts of key ligands and nonstandard residues in membrane proteins than most widely used empirical models; therefore, it could be an accurate computational tool for chemical shift calculations on various types of biological systems.

Hippocampal subfield volumes in mild cognitive impairment and alzheimer's disease: a systematic review and meta-analysis.

The hippocampus is a complex structure that consists of several subfields with distinct and specialized functions. Although numerous studies have been performed to explore hippocampal atrophy at the sub-regional level in mild cognitive impairment (MCI) and Alzheimer's disease (AD), the results have been inconsistent especially for whether and which subfields can be served as the most potential biomarkers in MCI and AD. Herein, we used a meta-analytic approach to synthesize the extant literatures on hippocampal subfields in MCI and AD through PubMed, Web of Science, and Embase (PROSPERO CRD42021257586). As a result, a total of twenty studies using Freesurfer 5 and Freesurfer 6 were included in this investigation. These studies revealed that at the sub-regional level, hippocampal subfield volume reductions in MCI and AD were not restricted to specific subfields, and subiculum and presubiculum had the largest z-scores across most comparisons. However, none of the subfield performed much better in discriminating MCI and HC, AD and MCI, AD and HC as compared to whole hippocampus volume. These results suggested that we should explore the changes in the hippocampal subfields in subtypes of MCI or even at an earlier stage, that is subjective cognitive impairment.

Functional magnetic resonance imaging studies of acupuncture at ST36: a coordinate-based meta-analysis.

Background: Functional magnetic resonance imaging (fMRI) has been widely used to investigate the brain effect of acupuncture point Stomach 36 (ST36, Zusanli). However, inconsistent results have hindered our understanding of the neural mechanisms of acupuncture at ST36. Objective: To perform a meta-analysis of fMRI studies on acupuncture at ST36 to assess the brain atlas of acupuncture at ST36 from available studies. Method: Based on a preregistered protocol in PROSPERO (CRD42019119553), a large set of databases was searched up to August 9, 2021, without language restrictions. Peak coordinates were extracted from clusters that showed significant signal differences before and after acupuncture treatment. A meta-analysis was performed using seed-based d mapping with permutation of subject images (SDM-PSI), a newly improved meta-analytic method. Results: A total of 27 studies (27 ST36) were included. This meta-analysis found that ST36 could activate the left cerebellum, the bilateral Rolandic operculum, the right supramarginal gyrus, and the right cerebellum. Functional characterizations showed that acupuncture at ST36 was mainly associated with action and perception. Conclusion: Our results provide a brain atlas for acupuncture at ST36, which, besides offering a better understanding of the underlying neural mechanisms, also provides the possibility of future precision therapies.

Combining amide proton transfer-weighted and arterial spin labeling imaging to differentiate solitary brain metastases from glioblastomas.

PURPOSE: To evaluate the clinical utility of amide proton transfer-weighted imaging (APTw) and arterial spin labeling (ASL) in differentiating solitary brain metastases (SBMs) from glioblastomas (GBMs). METHODS: Forty-eight patients diagnosed with brain tumors were enrolled. All patients underwent conventional MRI, APTw, and ASL scans on a 3.0 T MRI system. The mean APTw value and mean cerebral blood flow (CBF) value were measured. The differences in various parameters between GBMs and SBMs were assessed using the independent-samples t-test. The quantitative performance of these MRI parameters in distinguishing between GBMs and SBMs was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: GBMs exhibited significantly higher APTw and CBF values in peritumoral regions compared with SBMs (P < 0.05). There was no significant difference between SBMs and GBMs in tumor cores. APTw MRI had a higher diagnostic efficiency in differentiating SBMs from GBMs (area under the curve [AUC]: 0.864; 75.0% sensitivity and 81.8% specificity). Combined use of APTw and CBF value increased the AUC to 0.927. CONCLUSION: APTw may be superior to ASL for distinguishing between SBMs and GBMs. Combination of APTw and ASL showed better discrimination and a superior diagnostic performance.

A multi-calibration potentiometric sensing array based on diboronic acid-PtAu/CNTs nanozyme for home monitoring of urine glucose.

All-solid-state potentiometric sensors that are easily miniaturized and arrayed are widely used in home diagnostics. However, changes in sample matrix compositions tend to affect the basic potential of the potentiometric sensor, and pH of sample could change the response slope, thus affecting the detection reliability. This study takes the detection of glucose in urine as a model to increase the reliability of potentiometric sensors in home detection. PtAu/CNTs nanozyme modified by diboronic acid has been designed, showing better catalytic selectivity for glucose by experiments and theoretical calculations. Moreover, glucose electrode group in a multi-calibration glucose potentiometric sensing array can realize the basic potential calibration of sensing channel by the calibration channel. Meanwhile, the pH electrode group can not only measure the urine pH, but also calibrate the response slope of the glucose electrode group, thus improving the reliability of home detection.

Volume of hippocampus-amygdala transition area predicts outcomes of electroconvulsive therapy in major depressive disorder: high accuracy validated in two independent cohorts.

BACKGROUND: Although many previous studies reported structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy (ECT) in major depressive disorder (MDD), yet the exact roles of both areas for antidepressant effects are still controversial. METHODS: In the current study, segmentation of amygdala and hippocampal sub-regions was used to investigate the longitudinal changes of volume, the relationship between volume and antidepressant effects, and prediction performances for ECT in MDD patients before and after ECT using two independent datasets. RESULTS: As a result, MDD patients showed selectively and consistently increased volume in the left lateral nucleus, right accessory basal nucleus, bilateral basal nucleus, bilateral corticoamygdaloid transition (CAT), bilateral paralaminar nucleus of the amygdala, and bilateral hippocampus-amygdala transition area (HATA) after ECT in both datasets, whereas marginally significant increase of volume in bilateral granule cell molecular layer of the head of dentate gyrus, the bilateral head of cornu ammonis (CA) 4, and left head of CA 3. Correlation analyses revealed that increased volume of left HATA was significantly associated with antidepressant effects after ECT. Moreover, volumes of HATA in the MDD patients before ECT could be served as potential biomarkers to predict ECT remission with the highest accuracy of 86.95% and 82.92% in two datasets (The predictive models were trained on Dataset 2 and the sensitivity, specificity and accuracy of Dataset 2 were obtained from leave-one-out-cross-validation. Thus, they were not independent and very likely to be inflated). CONCLUSIONS: These results not only suggested that ECT could selectively induce structural plasticity of the amygdala and hippocampal sub-regions associated with antidepressant effects of ECT in MDD patients, but also provided potential biomarkers (especially HATA) for effectively and timely interventions for ECT in clinical applications.

Acupuncture Treatment Modulate Regional Homogeneity of Dorsal Lateral Prefrontal Cortex in Patients with Amnesic Mild Cognitive Impairment.

BACKGROUND: Although acupuncture is widely used to improve cognitive and memory in the amnesic mild cognitive impairment (aMCI) patients with impressive effectiveness, its neural mechanism remains largely unclear. OBJECTIVE: We aimed to explore functional magnetic resonance imaging (fMRI) mechanism of acupuncture for aMCI. METHODS: A randomized, controlled, single-blind research was performed. A total of 46 aMCI patients were randomly assigned into verum and sham acupuncture group, who received a total of 24 times treatments (3 times/week, 8 weeks). Clinical evaluation and fMRI scanning were performed at baseline and after treatment for all aMCI patients. The interaction effects and inter-group effects of regional homogeneity (ReHo) were performed using mixed effect models, and the correlations between clinical improvement and neuroimaging changes before and after verum acupuncture treatment were analyzed using Pearson correlations. RESULTS: As a result, interaction effects showed increased ReHo value in left dorsal lateral prefrontal cortex (DLPFC), increased functional connectivity between left DLPFC and left precuneus, and decreased functional connectivity between left DLPFC and left inferior temporal gyrus after verum acupuncture but inversely after sham acupuncture in the aMCI. Condition effects showed increased ReHo in right lingual gyrus, and bilateral post-central gyrus after verum and sham acupuncture in the aMCI. In addition, the changed Montreal Cognitive Assessment scores in verum acupuncture group were significantly correlated with changed ReHo values in left DLPFC. CONCLUSION: Together, our findings further confirmed that acupuncture could be used as a promising complementary therapy for aMCI by modulating function of left DLPFC to improve cognitive symptoms.

Antigen-Down PEC Immunosensor for CYFRA21-1 Detection Based on Photocurrent Polarity Switching Strategy.

In this work, an antigen-down photoelectrochemical (PEC) immunosensor based on a signal polarity switching strategy for the detection of cytokeratin 19 fragment 21-1 (CYFRA21-1) was proposed. 3,4,9,10-Perylene tetracarboxylic acid (PTCA) is a conjugated organic dye containing five benzene nuclei, which has excellent film-forming and optical properties. PTCA sensitized by SnS2 can further improve the basal signal and the stability of the PEC immunosensor. Moreover, avidin-functionalized CuInS2 as a signal probe can convert the basal anodic photocurrent to a cathodic photocurrent. Therefore, the PEC sensor realized the photocurrent polarity conversion before and after labeling. With avidin-functionalized CuInS2, the polarity of the photocurrent was changed once CYFRA21-1 was detected. Therefore, the PEC immunosensor owns high sensitivity. The linear range of the immunosensor for the detection of CYFRA21-1 is 0.00001-500 ng·mL-1, and the detection limit is 3.5 fg·mL-1. The PEC immunosensor has good stability, high selectivity, and good repeatability. This work may provide a new way for the detection of CYFRA21-1 and other proteins.

Synergistic Effect of Bio-Inspired Nanochannels: Hydrophilic DNA Probes at Inner Wall and Hydrophobic Coating at Outer Surface for Highly Sensitive Detection.

During the past few decades, bio-inspired nanochannels have been well developed and applied in biosensing, energy transfer, separation, and so on. Here, inspired by the synergistic effect of biological nanopores, biomimetic solid-state nanochannels with hydrophilic DNA probes at the inner wall (DNA@IWHydrophilic ) and hydrophobic coating at the outer surface (None@OSHydrophobic ) are designed. To demonstrate their prompted sensing properties, Hg2+ and its specific probe are selected as target and hydrophilic DNA probes, respectively. Compared with the traditional solid-state nanochannels with hydrophilic probes distributed on both the inner wall and outer surface, the nanochannels with DNA@IWHydrophilic +None@OSHydrophobic significantly decrease the limit of detection (LOD) by 105 -fold. The obvious improvement of sensitivity (with LOD of 1 nM) is attributed to the synergistic effect: None@OSHydrophobic results in the nanochannel's effective diameter decrease and DNA@IWHydrophilic induces a specific sensing target. Meanwhile, nanomolar detection of Hg2+ in human serum and in vivo fish muscle are achieved. Through molecular dynamics simulation, the synergistic effect can be confirmed by ion fluxes increasement; the relative carbon nanotube increases from 135.64% to 135.84%. This work improves the understanding of nanochannels' synergistic effect and provides a significant insight for nanochannels with improved sensitivity.

Structural and Functional Trajectories of Middle Temporal Gyrus Sub-Regions During Life Span: A Potential Biomarker of Brain Development and Aging.

Although previous studies identified a similar topography pattern of structural and functional delineations in human middle temporal gyrus (MTG) using healthy adults, trajectories of MTG sub-regions across lifespan remain largely unknown. Herein, we examined gray matter volume (GMV) and resting-state functional connectivity (RSFC) using datasets from the Nathan Kline Institute (NKI), and aimed to (1) investigate structural and functional trajectories of MTG sub-regions across the lifespan; and (2) assess whether these features can be used as biomarkers to predict individual's chronological age. As a result, GMV of all MTG sub-regions followed U-shaped trajectories with extreme age around the sixth decade. The RSFC between MTG sub-regions and many cortical brain regions showed inversed U-shaped trajectories, whereas RSFC between MTG sub-regions and sub-cortical regions/cerebellum showed U-shaped way, with extreme age about 20 years earlier than those of GMV. Moreover, GMV and RSFC of MTG sub-regions could be served as useful features to predict individual age with high estimation accuracy. Together, these results not only provided novel insights into the dynamic process of structural and functional roles of MTG sub-regions across the lifespan, but also served as useful biomarkers to age prediction.

Progressive cortical and sub-cortical alterations in patients with anti-N-methyl-D-aspartate receptor encephalitis.

BACKGROUND: Advanced structural analyses are increasingly being highly valued to uncover pathophysiological understanding of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Therefore, we aimed to explore whether and how antibody-mediated NMDAR dysfunction affected cortical and sub-cortical brain morphology and their relationship with clinical symptoms. METHODS: We performed surface-based morphometry analyses, hippocampal segmentation, and correlational analyses in 24 patients with anti-NMDAR encephalitis after acute disease stage and 30 normal controls (NC) in this case-control study. RESULTS: Patients showed significantly decreased cortical alterations mainly in language network (LN) and default mode network (DMN), as well as decreased gray matter volume in left cornu ammonis 1 (CA1) body of hippocampus. Further correlation analyses showed that the decreased cortical thickness in the right superior frontier gyrus was associated with decreased cognitive scores, the decreased cortical volume in the right pars triangulari and decreased surface area in the right pars operculari were associated with decreased memory scores, whereas decreased gray matter volume in the left CA1 body was significantly correlated with longer time between first symptom and imaging in the patients. CONCLUSION: These results suggested that cognitive impairments resulted from long-term sequelae of the encephalitis were mainly associated with cortical alterations in LN and DMN and sub-cortical atrophy of left CA1 body, which can be served as effective features to assess disease progression in clinical routine examination.

Progress of Acupuncture Therapy in Diseases Based on Magnetic Resonance Image Studies: A Literature Review.

The neural mechanisms of acupuncture are not well-understood. Over the past decades, an increasing number of studies have used MRI to investigate the response of the brain to acupuncture. The current review aims to provide an update on acupuncture therapy in disease. The PubMed, Embase, Web of Science, and Cochrane Library databases were searched from inception to January 31, 2021. Article selection and data extraction were conducted by two review authors. A total of 107 publications about MRI in acupuncture were included, the collective findings of which were as follows: (1) stroke and GB34 (Yanglingquan) are the most studied disease and acupoint. Related studies suggested that the mechanism of acupuncture treatment for stroke may associate with structural and functional plasticity, left and right hemispheres balance, and activation of brain areas related to movement and cognition. GB34 is mainly used in stroke and Parkinson's disease, which mainly activates brain response in the premotor cortex, the supplementary motor area, and the supramarginal gyrus; (2) resting-state functional MRI (rs-fMRI) and functional connectivity (FC) analysis are the most frequently used approaches; (3) estimates of efficacy and brain response to acupuncture depend on the type of sham acupuncture (SA) used for comparison. Brain processing after acupuncture differs between patients and health controls (HC) and occurs mainly in disorder-related areas. Factors that influence the effect of acupuncture include depth of needling, number and locations of acupoints, and deqi and expectation effect, each contributing to the brain response. While studies using MRI have increased understanding of the mechanism underlying the effects of acupuncture, there is scope for development in this field. Due to the small sample sizes, heterogeneous study designs, and analytical methods, the results were inconsistent. Further studies with larger sample sizes, careful experimental design, multimodal neuroimaging techniques, and standardized methods should be conducted to better explain the efficacy and specificity of acupuncture, and to prepare for accurate efficacy prediction in the future.

Magnetic Resonance Imaging Studies on Acupuncture Therapy in Depression: A Systematic Review.

Accumulating studies had been performed using magnetic resonance imaging (MRI) to understand the neural mechanism of acupuncture therapy for depression. However, inconsistencies remain due to differences in research designs and MRI analytical methods. Therefore, we aim to summarize the current MRI research and provide useful information for further research by identifying papers published in English and Chinese about MRI studies on acupuncture for depression up to November 2020. A total of 22 studies met the inclusion criteria, including 810 depression patients and 416 health controls (HCs). The applied designs of these studies are mainly random control trial and pre-post designs. The MRI analytical methods are mainly (fractional) amplitude of low-frequency fluctuation (fALFF/ALFF) and functional connectivity (FC), whereas a small subset of studies used voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). The most consistent functional MRI (fMRI) results showed increased N-acetylaspartate/creatine (NAA/Cr) ratios, increased ALFF in the right precuneus, decreased ALFF in the inferior frontal gyrus (IFG), and increased FC of the anterior cingulate cortex (ACC). In contrast, no significant neurological changes were identified in any of the DTI or VBM studies. However, clear, reliable conclusions cannot be drawn due to the use of different designs, analytical methods, seed points selected, types of depression, acupuncture points, and so on. Improved report specifications, well-designed studies, consistent analytical methods, and larger sample sizes will enable the field to better elucidate the underlying mechanisms of acupuncture in depressed patients.

Art Therapy: A Complementary Treatment for Mental Disorders.

Art therapy, as a non-pharmacological medical complementary and alternative therapy, has been used as one of medical interventions with good clinical effects on mental disorders. However, systematically reviewed in detail in clinical situations is lacking. Here, we searched on PubMed for art therapy in an attempt to explore its theoretical basis, clinical applications, and future perspectives to summary its global pictures. Since drawings and paintings have been historically recognized as a useful part of therapeutic processes in art therapy, we focused on studies of art therapy which mainly includes painting and drawing as media. As a result, a total of 413 literature were identified. After carefully reading full articles, we found that art therapy has been gradually and successfully used for patients with mental disorders with positive outcomes, mainly reducing suffering from mental symptoms. These disorders mainly include depression disorders and anxiety, cognitive impairment and dementias, Alzheimer's disease, schizophrenia, and autism. These findings suggest that art therapy can not only be served as an useful therapeutic method to assist patients to open up and share their feelings, views, and experiences, but also as an auxiliary treatment for diagnosing diseases to help medical specialists obtain complementary information different from conventional tests. We humbly believe that art therapy has great potential in clinical applications on mental disorders to be further explored.

Neuroplasticity of Acupuncture for Stroke: An Evidence-Based Review of MRI.

Acupuncture is widely recognized as a potentially effective treatment for stroke rehabilitation. Researchers in this area are actively investigating its therapeutic mechanisms. Magnetic resonance imaging (MRI), as a noninvasive, high anatomical resolution technique, has been employed to investigate neuroplasticity on acupuncture in stroke patients from a system level. However, there is no review on the mechanism of acupuncture treatment for stroke based on MRI. Therefore, we aim to summarize the current evidence about this aspect and provide useful information for future research. After searching PubMed, Web of Science, and Embase databases, 24 human and five animal studies were identified. This review focuses on the evidence on the possible mechanisms underlying mechanisms of acupuncture therapy in treating stroke by regulating brain plasticity. We found that acupuncture reorganizes not only motor-related network, including primary motor cortex (M1), premotor cortex, supplementary motor area (SMA), frontoparietal network (LFPN and RFPN), and sensorimotor network (SMN), as well as default mode network (aDMN and pDMN), but also language-related brain areas including inferior frontal gyrus frontal, temporal, parietal, and occipital lobes, as well as cognition-related brain regions. In addition, acupuncture therapy can modulate the function and structural plasticity of post-stroke, which may be linked to the mechanism effect of acupuncture.

Cinnamolide sesquiterpene lactone suppresses in vitro and in vivo cancer cell growth in cisplatin-resistant human cervical carcinoma cells by inducing mitochondrial mediated apoptosis, caspase activation, loss of MMP and targeting Akt/ß-Catenin signaling pathway.

The Editors of JBUON issue an Expression of Concern to 'Cinnamolide sesquiterpene lactone suppresses in vitro and in vivo cancer cell growth in cisplatin-resistant human cervical carcinoma cells by inducing mitochondrial mediated apoptosis, caspase activation, loss of MMP and targeting Akt/ß-Catenin signaling pathway', by Jing Hou, Changli Kan, Yanju Zhu, Yi Zhang, Bingfeng Zhou, Chunli Ren, Jiuyuan Fu, Yanwei Guo, Jinhuan Zhang; JBUON 2020;25(2):709-715; PMID: 32521857. Following the publication of the above article, readers drew to our attention that part of the data was possibly unreliable. We sent emails to the authors with a request to provide the raw data to prove the originality, but received no reply. Therefore, as we continue to work through the issues raised, we advise readers to interpret the information presented in the article with due caution. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

Gray Matter Atrophy in Amnestic Mild Cognitive Impairment: A Voxel-Based Meta-Analysis.

Background: Voxel-based morphometry (VBM) has been widely used to investigate structural alterations in amnesia mild cognitive impairment (aMCI). However, inconsistent results have hindered our understanding of the exact neuropathology related to aMCI. Objectives: Our aim was to systematically review the literature reporting VBM on aMCI to elucidate consistent gray matter alterations, their functional characterization, and corresponding co-activation patterns. Methods: The PubMed, Web of Science, and EMBASE databases were searched for VBM studies on aMCI published from inception up to June 2020. Peak coordinates were extracted from clusters that showed significant gray matter differences between aMCI patients and healthy controls (HC). Meta-analysis was performed using seed-based d mapping with the permutation of subject images (SDM-PSI), a newly improved meta-analytic method. Functional characterization and task-based co-activation patterns using the BrainMap database were performed on significant clusters to explore their functional roles. Finally, VBM was performed based on the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset to further support the findings. Results: A total of 31 studies with 681 aMCI patients and 837 HC were included in this systematic review. The aMCI group showed significant gray matter atrophy in the left amygdala and right hippocampus, which was consistent with results from the ADNI dataset. Functional characterization revealed that these regions were mainly associated with emotion, cognition, and perception. Further, meta-regression analysis demonstrated that gray matter atrophy in the left inferior frontal gyrus and the left angular gyrus was significantly associated with cognitive impairment in the aMCI group. Conclusions: The findings of gray matter atrophy in the left amygdala and right hippocampus are highly consistent and robust, and not only offer a better understanding of the underlying neuropathology but also provide accurate potential biomarkers for aMCI.

Pre-pregnancy body mass index in mothers, birth weight and the risk of type I diabetes in their offspring: A dose-response meta-analysis of cohort studies.

BACKGROUND: The incidence of type I diabetes among children has increased significantly and the relationship between maternal pre-pregnancy Body Mass Index (BMI), Birth weight and risk of Type 1 diabetes in children (T1DMC) is controversial. OBJECTIVE: This dose-response meta-analysis was performed to investigate the association between maternal Pre-Pregnancy Body-Mass Index, Birth Weight and the Risk of Childhood Type I Diabetes. SEARCH STRATEGY: A comprehensive systematic search was conducted in MEDLINE/PubMed, SCOPUS, Cochrane, and Web of Science databases from inception to April 2019. Key search terms included "body mass index" OR "Birth weight" AND "Type 1 diabetes". SELECTION CRITERIA: Peer-reviewed studies that reporting association between BMI or birth weight and type I diabetes in a retrospective or prospective study by appropriate estimates such as the hazard ratio (HR), risk ratio (RR), or odds ratio (OR) and the corresponding 95 % confidence intervals (CI). DATA COLLECTION AND ANALYSIS: MOOSE guidelines were followed. Data were extracted by 2 researchers, independently. Combined hazard ratios (HRs) was evaluated by DerSimonian and Laird Random-effects model. RESULTS: Two studies continuing four arms with 1,209,122 participants were eligible for pre-pregnancy BMI section meta-analysis and six studies were eligible for inclusion, providing 10,340,036 participants for birth weight section meta-analysis. Pooled results demonstrated a significant association between obesity and risk of T1DMC (HR: 1.30, 95 % CI: 1.16-1.46, I2 = 7%). The combined HR (95 % CI) showed lower risk of T1DMC in low birth weight infants (HR: 0.78, 95 % CI: 0.69-0.88, I2 = 0%) and higher risk of T1DMC in the high birth weight infants versus the normal category of birth weight (HR: 1.08, 95 % CI: 1.00-1.17, I2 = 31 %). There was a significant non-linear association between birth weight and risk of T1DMC in children (Coef =-0.00032, p = 0.001). CONCLUSIONS AND RELEVANCE: This systematic review and meta-analysis identified high maternal BMI and High birth weight (HBW) increase risk of childhood T1DMC.