"Building bridges"-communication education for residents in radiology: a scoping review.

BACKGROUND: Good communication is an important professional attribute for radiologists. However, explorations of communication education and their outcomes in radiology residents are sparse. This scoping review aims to evaluate the existing literature on communication education for radiology residents, identify gaps in current practices, and suggest directions for future studies. METHODS: A scoping review following the six-step approach of Arksey and O'Malley was undertaken. We searched through PubMed, Embase, ERIC, and Web of Science databases, focusing on communication education in radiology residents. RESULTS: Sixteen of the 3096 identified articles were included in the analysis. Most studies (13/16) originated from the United States. The studies varied in study design, including quantitative, qualitative and mixed-methods approaches. The sample sizes of most studies were small to moderate, with more than half of the studies had fewer than 30 participants. The identified studies predominantly focused on communication with patients and healthcare professionals. The need for communication education, the efficacy of specific communication education programs, and the capability of some assessment tools for evaluating residents' communication skills were investigated. CONCLUSIONS: This scoping review reveals the gap between the need for communication education and the lack of comprehensive education programs in radiology residents globally. Future studies should develop tailored interventions and use reliable assessment tools, engaging more participants with extended follow-up periods, and expand the scope of communication training to include all relevant stakeholders.

Comparison between screw fixation and plate fixation via sinus tarsi approach for displaced intra-articular calcaneal fractures: a systematic review and meta-analysis.

BACKGROUND: Optimal surgical fixation for displaced intra-articular calcaneal fractures (DIACF) remains a subject of debate, particularly regarding the superiority between screw fixation and plate fixation via the sinus tarsi approach (STA). This review aims to determine the preferred treatment for DIACF and compare the outcomes of minimally invasive surgery options. METHODS: Our study involved thorough searches across multiple electronic databases, including PubMed, Cochrane, Embase, and Web of Science, to identify all relevant publications on distal intra-articular fractures of the calcaneus (DIACFs) that were fixed using cannulated screws or plates via STA. Through a comprehensive meta-analysis, we evaluated several outcomes, including post-operative function, radiological measurements, and complications. RESULT: A total of 728 patients from 7 studies met the inclusion criteria. Among them, 435 patients underwent screw fixation via STA, and 373 patients underwent plate fixation via STA. The study found no statistically significant differences between the screw fixation and the plate fixation via sinus tarsi approach (STA) in terms of AOFAS scores, Bohler's angle, Gissane's angle, sural nerve injury, secondary subtalar arthrodesis and reoperation. Compared with screw fixation, plate fixation via STA can reduce reduction loss of Bohler's angle (WMD = - 1.64, 95% CI = [- 2.96, - 0.31], P = 0.06, I2 = 59%), lower the incidence of fixation failure (OR = 0.32, 95% CI = [0.13, 0.81], P = 0.78, I2 = 0%), and decrease intra-articular step-off (WMD = - 0.52, 95% CI = [- 0.87, - 0.17], P = 0.66, I2 = 0%). CONCLUSIONS: Plate fixation demonstrates superior capability in restoring calcaneal width, maintaining Bohler's angle, and minimizing intra-articular step-off, thereby maintaining better reduction of the subtalar articular surface. In addition, plate fixation exhibits the modest complication rate and a low incidence of fixation failure. Therefore, we recommend the use of plate fixation through the STA, especially for complex and comminuted intra-articular calcaneal fractures.

Comparison between anterior-to-posterior screw fixation versus posterolateral approach plate fixation for posterior malleous fracture: A systematic review and meta-analysis.

PURPOSE: There are two main surgical fixation methods for the posterior malleolar fractures (PMFs), the anterior-to-posterior (AP) screws or via the posterolateral (PL) approach utilizing a buttress plate. This review aims to compare the clinical outcome between the AP screw fixation and the PL plate fixation for treating PMFs. METHODS: We searched all relevant publications about PMFs treated with AP screws or PL plates through electronic databases including the PubMed, the Cochrane Library, the Embase, the Wiley online library and the Web of Science. The meta-analysis was conducted to evaluated clinical outcomes including reduction quality, post-operative function and complications. RESULTS: Six studies (one single randomized controlled trial and five retrospective cohort studies) were enrolled. 172 patients underwent AP screw fixation and 214 patients underwent PL plate fixation with a total of 386 patients (169 males and 217 females). The PL plating group yielded better AOFAS scores(MD = 6.97, 95 % CI=[4.68, 9.27], P＜0.00001, I2 =0 %) and was more likely to achieve excellent anatomical reduction(OR=5.49, 95 % CI=[1.06, 28.42], P = 0.04, I2 =80 %). No differences were found in the bad reduction quality, incidences of complications (arthritis, neuralgia, superficial wound healing problems and implant failure), the walking VAS scores and the dorsiflexion restriction degrees. CONCLUSION: We suggest that the PL plate fixation method has the clinical benefit of achieving anatomical reduction and better AOFAS scores over the AP screw fixation for treating PMFs. No differences were found in the incidences of complications ( arthritis, neuralgia, superficial wound healing problems and implant failure), the walking VAS scores and the dorsiflexion restriction degrees. The posterior approach and the direct reduction are recommended for the treatment of the PMFs. LEVEL OF CONFIDENCE: Ⅱb.

Crystalline Dual-Porous Covalent Triazine Frameworks as a New Platform for Efficient Electrocatalysis.

Crystalline covalent triazine frameworks (CTFs) have gained considerable interest in energy and catalysis owing to their well-defined nitrogen-rich π-conjugated porosity and superior physicochemical properties, however, suffer from very limited molecular structures. Herein we report a novel solvent-free FeCl3 -catalyzed polymerization of 2, 6-pyridinedicarbonitrile (DCP) to achieve the first synthesis of crystalline, dual-porous, pyridine-based CTF (Fe-CTF). The FeCl3 could not only act as a highly active Lewis acid catalyst for promoting the two-dimensional ordered polymerization of DCP monomers, but also in situ coordinate with the tridentate chelators generated between pyridine and triazine groups to yield unique Fe-N3 single-atom active sites in Fe-CTF. Abundant few-layer crystalline nanosheets (Fe-CTF NSs) could be prepared through simple ball-milling exfoliation of the bulk layered Fe-CTF and exhibited remarkable electrocatalytic performance for oxygen reduction reaction (ORR) with a half-wave potential and onset potential up to 0.902 and 1.02 V respectively, and extraordinary Zn-air battery performance with an ultrahigh specific capacity and power density of 811 mAh g-1 and 230 mW cm-2 respectively. By combining operando X-ray absorption spectroscopy with density functional theory calculations, we revealed a dynamic and reversible evolution of Fe-N3 to Fe-N2 during the electrocatalytic process, which could further accelerate the electrocatalytic reaction.

Gray matter structural covariance networks patterns associated with autopsy-confirmed LATE-NC compared to Alzheimer's disease pathology.

BACKGROUND: Cases with the limbic-predominant age-related TAR DNA-binding protein 43 (TDP-43) encephalopathy neuropathologic change (LATE-NC), Alzheimer's disease (AD), and mixed AD+TDP-43 pathology (AD+LATE-NC) share similar symptoms, which makes it a challenge for accurate diagnosis. Exploring the patterns of gray matter structural covariance networks (SCNs) in these three types may help to clarify the underlying mechanism and provide a basis for clinical interventions. METHODS: We included ante-mortem MRI data of 10 LATE-NC, 39  AD, and 25  AD+LATE-NC from the ADNI autopsy sample. We used four regions of interest (left posterior cingulate cortex, right entorhinal cortex, frontoinsular and dorsolateral prefrontal cortex) to anchor the default mode network (DMN), salience network (SN), and executive control network (ECN). Finally, we assessed the SCN alternations using a multi-regression model-based linear-interaction analysis. RESULTS: Cases with autopsy-confirmed LATE-NC and AD showed increased structural associations involving DMN, ECN, and SN. Cases with AD+LATE-NC showed increased structural association within DMN while decreased structural association between DMN and ECN. The volume of peak clusters showed significant associations with cognition and AD pathology. CONCLUSIONS: This study showed different SCN patterns in the cases with LATE-NC, AD, and AD+LATE-NC, and indicated the network disconnection mechanism underlying these three neuropathological progressions. Further, SCN may serve as an effective biomarker to distinguish between different types of dementia.

Neuropsychiatric symptoms associated multimodal brain networks in Alzheimer's disease.

Concomitant neuropsychiatric symptoms (NPS) are associated with accelerated Alzheimer's disease (AD) progression. Identifying multimodal brain imaging patterns associated with NPS may help understand pathophysiology correlates AD. Based on the AD continuum, a supervised learning strategy was used to guide four-way multimodal neuroimaging fusion (Amyloid, Tau, gray matter volume, brain function) by using NPS total score as the reference. Loadings of the identified multimodal patterns were compared across the AD continuum. Then, regression analyses were performed to investigate its predictability of longitudinal cognition performance. Furthermore, the fusion analysis was repeated in the four NPS subsyndromes. Here, an NPS-associated pathological-structural-functional covaried pattern was observed in the frontal-subcortical limbic circuit, occipital, and sensor-motor region. Loading of this multimodal pattern showed a progressive increase with the development of AD. The pattern significantly correlates with multiple cognitive domains and could also predict longitudinal cognitive decline. Notably, repeated fusion analysis using subsyndromes as references identified similar patterns with some unique variations associated with different syndromes. Conclusively, NPS was associated with a multimodal imaging pattern involving complex neuropathologies, which could effectively predict longitudinal cognitive decline. These results highlight the possible neural substrate of NPS in AD, which may provide guidance for clinical management.

Current coffee consumption is associated with decreased striatal dopamine transporter availability in Parkinson's disease patients and healthy controls.

BACKGROUND: Coffee is the most widely consumed psychostimulant worldwide. Emerging evidence indicates that coffee consumption habit significantly reduces the risk of developing Parkinson's disease (PD). However, the effect of coffee consumption on nigrostriatal dopaminergic neurodegeneration is still largely unknown. We therefore aim to investigate the role of coffee consumption in nigrostriatal dopaminergic neurodegeneration using dopamine transporter (DAT) imaging in PD and healthy controls (HC). METHODS: A total of 138 PD patients and 75 HC with questionnaires about coffee consumption, and DAT scans were recruited from the Parkinson's Progression Markers Initiative cohort. Demographic, clinical, and striatal DAT characteristics were compared across subgroups of current, former, and never coffee consumers in PD and HC, respectively. Furthermore, partial correlation analyses were performed to determine whether there was a relationship between coffee cups consumed per day and striatal DAT characteristics in each striatal region. In addition, the factors that may have influenced the loss of nigrostriatal dopaminergic neurons were included in multiple linear regression analyses to identify significant contributing factors to DAT availability in each striatal region. RESULTS: PD patients had lower DAT availability in each striatal region than HC (p < 0.001). In PD patients, there were significant differences in DAT availability in the caudate (p = 0.008, Bonferroni corrected) across three PD subgroups. Specifically, post hoc tests showed that current coffee consumers had significantly lower DAT availability in the caudate than former coffee consumers (p = 0.01) and never coffee consumers (p = 0.022). In HC, there were significant differences in DAT availability in the caudate (p = 0.031, Bonferroni uncorrected) across three HC subgroups. Specifically, post hoc tests showed that current coffee consumers had significantly lower DAT availability in the caudate than former coffee consumers (p = 0.022). Moreover, correlation analysis revealed that cups per day were negatively correlated with DAT availability in the caudate in current consumers of PD patients (r = - 0.219, p = 0.047). In addition, multiple linear regression analyses showed that current coffee consumption remained an independent predictor of decreased DAT availability in the caudate in PD patients and HC. CONCLUSIONS: This study demonstrates that current coffee consumption is associated with decreased striatal DAT availability in the caudate. However, the effects of caffeine on striatal DAT may fade and disappear after quitting coffee consumption. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01141023.

Increased iron deposition in nucleus accumbens associated with disease progression and chronicity in migraine.

BACKGROUND: Migraine is one of the world's most prevalent and disabling diseases. Despite huge advances in neuroimaging research, more valuable neuroimaging markers are still urgently needed to provide important insights into the brain mechanisms that underlie migraine symptoms. We therefore aim to investigate the regional iron deposition in subcortical nuclei of migraineurs as compared to controls and its association with migraine-related pathophysiological assessments. METHODS: A total of 200 migraineurs (56 chronic migraine [CM], 144 episodic migraine [EM]) and 41 matched controls were recruited. All subjects underwent MRI and clinical variables including frequency/duration of migraine, intensity of migraine, 6-item Headache Impact Test (HIT-6), Migraine Disability Assessment (MIDAS), and Pittsburgh Sleep Quality Index (PSQI) were recorded. Quantitative susceptibility mapping was employed to quantify the regional iron content in subcortical regions. Associations between clinical variables and regional iron deposition were studied as well. RESULTS: Increased iron deposition in the putamen, caudate, and nucleus accumbens (NAC) was observed in migraineurs more than controls. Meanwhile, patients with CM had a significantly higher volume of iron deposits compared to EM in multiple subcortical nuclei, especially in NAC. Volume of iron in NAC can be used to distinguish patients with CM from EM with a sensitivity of 85.45% and specificity of 71.53%. As the most valuable neuroimaging markers in all of the subcortical nuclei, higher iron deposition in NAC was significantly associated with disease progression, and higher HIT-6, MIDAS, and PSQI. CONCLUSIONS: These findings provide evidence that iron deposition in NAC may be a biomarker for migraine chronicity and migraine-related dysfunctions, thus may help to understand the underlying vascular and neural mechanisms of migraine. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT04939922.

Associations of Alzheimer's Disease Pathology and Small Vessel Disease With Cerebral White Matter Degeneration: A Tract-Based MR Diffusion Imaging Study.

BACKGROUND: White matter (WM) degeneration is a key feature of Alzheimer's disease (AD). However, the underlying mechanism remains unclear. PURPOSE: To investigate how amyloid-ß (Aß), tau, and small vascular disease (SVD) jointly affect WM degeneration in subjects along AD continuum. STUDY TYPE: Retrospective. SUBJECTS: 152 non-demented participants (age: 55.8-91.6, male/female: 66/86) from the ADNI database were included, classified into three groups using the A (Aß)/T (tau)/N pathological scheme (Group 1: A-T-; Group 2: A+T-; Group 3: A+T+) based on positron emission tomography data. FIELD STRENGTH/SEQUENCE: 3T; T1-weighted images, T2-weighted fluid-attenuated inversion recovery images, T2*-weighted images, diffusion-weighted spin-echo echo-planar imaging sequence (54 diffusion directions). ASSESSMENT: Free-water diffusion model (generated parameters: free water, FW; tissue fractional anisotropy, FAt; tissue mean diffusivity, MDt); SVD total score; Neuropsychological tests. STATISTICAL TESTS: Linear regression analysis was performed to investigate the independent contribution of AD (Aß and tau) and SVD pathologies to diffusion parameters in each fiber tract, first in the entire population and then in each subgroup. We also investigated associations between diffusion parameters and cognitive functions. The level of statistical significance was set at p < 0.05 (false discovery rate corrected). RESULTS: In the entire population, we found that: 1) Increased FW was significantly associated with SVD and tau, while FAt and MDt were significantly associated with Aß and tau; 2) The spatial pattern of fiber tracts related to a certain pathological marker is consistent with the known distribution of that pathology; 3) Subgroup analysis showed that Group 2 and 3 had more alterations of FAt and MDt associated with Aß and tau; 4) Diffusion imaging indices showed significant associations with cognitive score in all domains except memory. DATA CONCLUSION: WM microstructural injury was associated with both AD and SVD pathologies, showing compartment-specific, tract-specific, and stage-specific WM patterns. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

FGF-21 and GDF-15 are increased in migraine and associated with the severity of migraine-related disability.

BACKGROUND: Migraine is a prevalent disorder with significant socioeconomic impact. The impairment of metabolic homeostasis in migraine warrants further investigation. Changes in serum levels of Fibroblast-growth-factor 21 (FGF-21) and Growth-differentiation-factor 15 (GDF-15) are characteristic of some metabolic and mitochondrial diseases. This study aimed to assess whether the presence of migraine affects serum levels of FGF-21 and GDF-15, and taking metabolic disorders into account as potential confounding factors. METHODS: We collected serum samples from 221 migraine patients (153 episodic migraineurs and 68 chronic migraineurs) and 124 healthy controls. The serum concentrations of FGF-21 and GDF-15 were measured using an enzyme-linked immunosorbent assay (ELISA) based approach. Clinical variables, including monthly headache days, peak headache pain intensity, the 6-item Headache Impact Test (HIT-6), and the Migraine Disability Assessment (MIDAS), were also addressed. The associations between the clinical variables of migraine patients and serum levels of FGF-21 and GDF-15 were studied. RESULTS: In the multiple regression that corrected for age, we found that the serum levels of FGF-21 and GDF-15 were significantly higher in migraine sufferers than in healthy controls. A significant elevation in serum concentration of FGF-21, but not GDF-15, was observed in patients with chronic migraine (CM) compared to those with episodic migraine (EM). Regarding migraine-related disability, higher scores on the HIT-6 and MIDAS were associated with higher levels of FGF-21 and GDF-15. For the receiver operating characteristic (ROC) analysis, the diagnosis of migraine using GDF-15 showed that the area under the ROC curve (AUC) was 0.801 and the AUC of chronic migraine was 0.880. CONCLUSION: Serum GDF-15 and FGF-21 levels are increased in patients with migraine and associated with the severity of migraine-related disability.

The association of enlarged perivascular space with microglia-related inflammation and Alzheimer's pathology in cognitively normal elderly.

BACKGROUND: Glymphatic dysfunction may contribute to the accumulation of Alzheimer's disease (AD) pathologies. Conversely, AD pathologic change might also cause neuroinflammation and aggravate glymphatic dysfunction, forming a loop that accelerates AD progression. In vivo validations are needed to confirm their relationships. METHODS: In this study, we included 144 cognitively normal participants with AD pathological biomarker data (baseline CSF Aß1-42, T-Tau, P-Tau181; plasma P-Tau181 at baseline and at least one follow-up) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Each subject had completed structural MRI scans. Among them, 117 subjects have available neuroinflammatory biomarker (soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and 123 subjects have completed two times [18F]-florbetapir PET. The enlarged PVS (EPVS) visual rating scores in basal ganglia (BG) and centrum semiovale (CS) were assessed on T1-weighted images to reflect glymphatic dysfunction. Intracranial volume and white matter hyperintensities (WMH) volume were also calculated for further analysis. We performed stepwise linear regression models and mediation analyses to estimate the association between EPVS severity, sTREM2, and AD biomarkers. RESULTS: CS-EPVS degree was associated with CSF sTREM2, annual change of plasma P-tau181 and total WMH volume, whereas BG-EPVS severity was associated with age, gender and intracranial volume. The sTREM2 mediated the association between CSF P-tau181 and CS-EPVS. CONCLUSION: Impaired glymphatic dysfunction could contribute to the accumulation of pathological tau protein. The association between tauopathy and glymphatic dysfunction was mediated by the microglia inflammatory process. These findings may provide evidence for novel treatment strategies of anti-neuroinflammation therapy in the early stage.

Altered functional connectivity pattern of hippocampal subfields in individuals with objectively-defined subtle cognitive decline and its association with cognition and cerebrospinal fluid biomarkers.

Recent studies have shown that in the preclinical phase of Alzheimer's disease (AD), subtle cognitive changes can be detected using sensitive neuropsychological measures, and have proposed the concept of objectively-defined subtle cognitive decline (Obj-SCD). We aimed to assess the functional alteration of hippocampal subfields in individuals with Obj-SCD and its association with cognition and pathological biomarkers. Forty-two participants with cognitively normal (CN), 29 with Obj-SCD, and 55 with mild cognitive impairment (MCI) were retrospectively collected from the ADNI database. Neuropsychological performance, functional MRI, and cerebrospinal fluid (CSF) data were obtained. We calculated the seed-based functional connectivity (FC) of hippocampal subfields (cornu ammonis1 [CA1], CA2/3/dentate gyrus [DG], and subiculum) with whole-brain voxels. Additionally, we analyzed the correlation between FC values of significantly altered regions and neuropsychological performance and CSF biomarkers. The Obj-SCD group showed lower FC between left CA1-CA2/3/DG and right thalamus and higher FC between right subiculum and right superior parietal gyrus (SPG) compared with the CN and MCI groups. In the Obj-SCD group, FC values between left CA2/3/DG and right thalamus were positively associated with Auditory Verbal Learning Test (AVLT) recognition (r = 0.395, p = 0.046) and CSF Aß1-42 levels (r = 0.466, p = 0.019), and FC values between left CA1 and right thalamus were positively correlated with CSF Aß1-42 levels (r = 0.530, p = 0.006). Taken together, dysfunction in CA1-CA2/3/DG subregions suggests subtle cognitive impairment and AD-specific pathological changes in individuals with Obj-SCD. Additionally, increased subiculum connectivity may indicate early functional compensation for subtle cognitive changes.

A single-component light sensor system allows highly tunable and direct activation of gene expression in bacterial cells.

Light-regulated modules offer unprecedented new ways to control cellular behaviour with precise spatial and temporal resolution. Among a variety of bacterial light-switchable gene expression systems, single-component systems consisting of single transcription factors would be more useful due to the advantages of speed, simplicity, and versatility. In the present study, we developed a single-component light-activated bacterial gene expression system (eLightOn) based on a novel LOV domain from Rhodobacter sphaeroides (RsLOV). The eLightOn system showed significant improvements over the existing single-component bacterial light-activated expression systems, with benefits including a high ON/OFF ratio of >500-fold, a high activation level, fast activation kinetics, and/or good adaptability. Additionally, the induction characteristics, including regulatory windows, activation kinetics and light sensitivities, were highly tunable by altering the expression level of LexRO. We demonstrated the usefulness of the eLightOn system in regulating cell division and swimming by controlling the expression of the FtsZ and CheZ genes, respectively, as well as constructing synthetic Boolean logic gates using light and arabinose as the two inputs. Taken together, our data indicate that the eLightOn system is a robust and highly tunable tool for quantitative and spatiotemporal control of bacterial gene expression.

Quantity and Morphology of Perivascular Spaces: Associations With Vascular Risk Factors and Cerebral Small Vessel Disease.

BACKGROUND: Perivascular spaces (PVSs) are important component of the brain glymphatic system. While visual rating has been widely used to assess PVS, computational measures may have higher sensitivity for capturing PVS characteristics under disease conditions. PURPOSE: To compute quantitative and morphological PVS features and to assess their associations with vascular risk factors and cerebral small vessel disease (CSVD). STUDY TYPE: Prospective. POPULATION: One hundred sixty-one middle-aged/later middle-aged subjects (age = 60.4 ± 7.3). SEQUENCE: 3D T1-weighted, T2-weighted and T2-FLAIR sequences, and susceptibility-weighted multiecho gradient-echo sequence on a 3 T scanner. ASSESSMENT: Automated PVS segmentation was performed on sub-millimeter T2-weighted images. Quantitative and morphological PVS features were calculated in white matter (WM) and basal ganglia (BG) regions, including volume, count, size, length (Lmaj ), width (Lmin ), and linearity. Visual PVS scores were also acquired for comparison. STATISTICAL TESTS: Simple and multiple linear regression analyses were used to explore the associations among variables. RESULTS: WM-PVS visual score and count were associated with hypertension (ß = 0.161, P < 0.05; ß = 0.193, P < 0.05), as were BG-PVS rating score, volume, count and Lmin (ß = 0.197, P < 0.05; ß = 0.170, P < 0.05; ß = 0.200, P < 0.05; ß = 0.172, P < 0.05). WM-PVS size was associated with diabetes (ß = 0.165, P < 0.05). WM-PVS and BG-PVS were associated with CSVD markers, especially white matter hyperintensities (WMHs) (P < 0.05). Multiple regression analysis showed that WM/BG-PVS quantitative measures were widely associated with vascular risk factors and CSVD markers (P < 0.05). Morphological measures were associated with WMH severity in WM region and also associated with lacunes and microbleeds (P < 0.05) in BG region. DATA CONCLUSION: These novel PVS measures may capture mild PVS alterations driven by different pathologies. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Progressive Memory Circuit Impairments along with Alzheimer's Disease Neuropathology Spread: Evidence from in vivo Neuroimaging.

During the progression of Alzheimer's disease (AD), neuropathology may propagate transneuronally, cause disruption in memory circuit, and lead to memory impairment. However, there is a lack of in vivo evidence regarding this process. Thus, we aim to simulate and observe the progression of neuropathology in AD continuum. We included cognitively normal (CN), mild cognitive impairments (MCI), and AD subjects, and further classified them using the A/T/N scheme (Group 0: CN, A - T-; Group 1: CN, A + T-; Group 2: CN, A + T+; Group 3: MCI, A + T+; Group 4: AD, A + T+). We investigated alterations of three core memory circuit structures: hippocampus (HP) subfields volume, cingulum-angular bundles (CAB) fiber integrity, and precuneus cortex volume. HP subfields volume showed the trend of initially increased and then decreased (starting from Group 2), while precuneus volume decreased in Groups 3 and 4. The CAB integrity degenerated in Groups 3 and 4 and aggravated with higher disease stages. Further, memory circuit impairments were correlated with neuropathology biomarkers and memory performance. Conclusively, our results demonstrated a pattern of memory circuit impairments along with AD progression: starting from the HP, then propagating to the downstream projection fiber tract and cortex. These findings support the tau propagation theory to some extent.

Characterization of functions in parasite growth and virulence of four Toxoplasma gondii genes involved in lipid synthesis by CRISPR-Cas9 system.

Fatty acid uptake is extremely important for the survival and growth of the intracellular parasite Toxoplasma gondii. In this study, CRISPR-Cas9 gene editing technology was used to investigate the role of four lipid synthesis enzymes, namely, glycerol-3-phosphate dehydrogenase (G3PDH), malonyl CoA-acyl carrier protein transacylase (FabD), acyl-ACP thiolesterase (TE), and diacylglycerol acyltransferase (DGAT), in the virulence and infectivity of Type I RH and Type II Prugniaud (Pru) strains of T. gondii. Immunofluorescence analysis of the tachyzoite stage showed that FabD protein was located in the apicoplast; however, the expression level of the other three proteins was undetectable. Compared with wild-type (WT) strains, the growth of RHΔG3PDH, RHΔTE, and RHΔDGAT in vitro and their virulence in vivo were not significantly different. However, RHΔFabD exhibited a significantly reduced growth rate, compared with the WT strain. The deletion of FabD attenuated the virulence of Type II Pru strain and reduced the formation of cysts in vivo. These data improved our understanding of the role of lipid synthesis enzymes in the pathogenesis of T. gondii.

Long intergenic noncoding RNA SNHG16 interacts with miR-195 to promote proliferation, invasion and tumorigenesis in hepatocellular carcinoma.

Long non-coding RNAs (lncRNAs) have been confirmed crucial regulators in tumorgenesis. Small nucleolar RNA host gene 16 (SNHG16) has been recently shown to be dysregulated, which uncovered to be a potential oncogene in some cancers. However, the biological function and potential mechanism of SNHG16 in hepatocellular carcinoma (HCC) remain unclear. In our study, our observations showed that the expression level of SNHG16 in HCC tissues and cell lines was upregulated compared with adjacent noncancerous tissues and normal cells. In vitro, loss-of-function experiments revealed that SNHG16 knockdown suppressed the proliferation and weakened invasion of SMMC7721 and HepG2 cells. miR-195 expression was significantly decreased in HCC tissues and negatively correlated with SNHG16 expression. Furthermore, RIP and dual luciferase reporter assays showed that SNHG16 acted as an endogenous sponge by directly binding to miR-195 and downregulated its expression. SNHG16 overexpression inverted the inhibitory effect of miR-195 on proliferation and invasion of SMMC7721 and HepG2 cells. Additionally, SNHG16 depletion resulted in lower tumor growth and weight loss, in vivo. In conclusion, our findings reported that the oncogenic role of SNHG16 in HCC tumorigenesis through a novel SNHG16-miR-195 axis, which provided a novel insight for HCC and helped to probe a potential therapeutic target for the deadly disease.

Apparent Diffusion Coefficient as an Imaging Biomarker for Spinal Disease Activity in Axial Spondyloarthritis.

Background A quantifiable imaging measure to gauge the intensity of individual inflammatory lesions in axial spondyloarthritis (SpA) has not been well established. Previous studies have shown that diffusion-weighted (DW) MRI reflects disease activity in axial SpA. Purpose To determine the association between apparent diffusion coefficient (ADC) at MRI of discovertebral lesions and disease activity in individuals with axial SpA. Materials and Methods In this prospective study, 243 study participants (mean age ± standard deviation, 43.2 years ± 13.5) with back pain who fulfilled the Assessment of SpondyloArthritis International Society criteria for SpA were recruited from four rheumatology centers between April 2014 and March 2018. There were 132 men (mean age, 41.4 years ± 13.3) and 111 women (mean age, 45.3 years ± 13.4). Clinical, biochemical, and radiologic parameters were collected. All participants underwent whole-spine MRI by using a short inversion time inversion-recovery sequence and DW imaging. Two independent readers identified the presence of discovertebral lesions. ADCs were measured and normalized with normal bone marrow. Regression analysis was performed to determine association between the mean, maximum, and normalized mean and maximum ADCs of the discovertebral lesions and disease activity and functional parameters (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Bath Ankylosing Spondylitis Functional Index [BASFI], and Bath Ankylosing Spondylitis Global Index [BASGI]). Results Ninety-one discovertebral lesions (five cervical, 61 thoracic, 25 lumbar) were present in 55 of the 243 study participants (22.6%). After adjusting for confounding factors, increased maximum ADC was independently associated with increased BASFI (regression coefficient [ß] = 1.94 [×10-3 mm2/sec], P = .04). Increased normalized maximum ADC was independently associated with BASDAI question 2 (ie, back pain score) (ß = 0.45, P = .01), mean stiffness score (ß = 0.41, P = .04), and BASGI (ß = 0.43, P = .04). Increased normalized mean ADC was independently associated with BASDAI question 2 (ß = 0.61, P = .04). Conclusion Apparent diffusion coefficients at MRI of discovertebral lesions were associated with disease activity, functional impairment, and patient global assessment in axial spondyloarthritis. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Guermazi and Roemer in this issue.

Hepatitis B virus X protein promotes proliferation of hepatocellular carcinoma cells by upregulating miR-181b by targeting ING5.

Hepatitis B virus X protein (HBx) played a key role in the development of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Emerging evidence has demonstrated that miR-181b and the inhibitor of growth protein 5 (ING5) participated in the pathophysiological process. However, the regulatory mechanism of HBx remained unknown. The expression of miR-181b and ING5 in HCC tissues and cell lines were examined using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Cell viability was determined using the MTT method following HCC cell lines transfection. The interaction between miR-181b and ING5 was assessed by luciferase reporter assay. The nude mice tumor model was well established to evaluate the role and biological functions of HBx on the progression of HBV-related HCC in vivo. MiR-181b was upregulated and ING5 was downregulated in HCC tissues and cell lines. As suggested by the results from in vitro and in vivo experiments, HBx downregulates the expression of the miR-181b target gene ING5, resulting in the promotion of HCC cell proliferation. HBx accelerates proliferation activity of HCC cells by increasing miR-181b expression via targeting ING5, thereby influencing the progression of HBV-related HCC.

Concordance of FDG PET/CT metabolic tumour volume versus DW-MRI functional tumour volume with T2-weighted anatomical tumour volume in cervical cancer.

BACKGROUND: 18F-fluoro-deoxyglucose positron emission tomography with computed tomography (FDG PET/CT) has been employed to define radiotherapy targets using a threshold based on the standardised uptake value (SUV), and has been described for use in cervical cancer. The aim of this study was to evaluate the concordance between the metabolic tumour volume (MTV) measured on FDG PET/CT and the anatomical tumour volume (ATV) measured on T2-weighted magnetic resonance imaging (T2W-MRI); and compared with the functional tumour volume (FTV) measured on diffusion-weighted MRI (DW-MRI) in cervical cancer, taking the T2W-ATV as gold standard. METHODS: Consecutive newly diagnosed cervical cancer patients who underwent FDG PET/CT and DW-MRI were retrospectively reviewed from June 2013 to July 2017. Volumes of interest was inserted to the focal hypermetabolic activity corresponding to the cervical tumour on FDG PET/CT with automated tumour contouring and manual adjustment, based on SUV 20%-80% thresholds of the maximum SUV (SUVmax) to define the MTV20-80, with intervals of 5%. Tumour areas were manually delineated on T2W-MRI and multiplied by slice thickness to calculate the ATV. FTV were derived by manually delineating tumour area on ADC map, multiplied by the slice thickness to determine the FTV(manual). Diffusion restricted areas was extracted from b0 and ADC map using K-means clustering to determine the FTV(semi-automated). The ATVs, FTVs and the MTVs at different thresholds were compared using the mean and correlated using Pearson's product-moment correlation. RESULTS: Twenty-nine patients were evaluated (median age 52 years). Paired difference of mean between ATV and MTV was the closest and not statistically significant at MTV30 (-2.9cm3, -5.2%, p = 0.301). This was less than the differences between ATV and FTV(semi-automated) (25.0cm3, 45.1%, p < 0.001) and FTV(manual) (11.2cm3, 20.1%, p = 0.001). The correlation of MTV30 with ATV was excellent (r = 0.968, p < 0.001) and better than that of the FTVs. CONCLUSIONS: Our study demonstrated that MTV30 was the only parameter investigated with no statistically significant difference with ATV, had the least absolute difference from ATV, and showed excellent positive correlation with ATV, suggesting its superiority as a functional imaging modality when compared with DW-MRI and supporting its use as a surrogate for ATV for radiotherapy tumour contouring.