CN Group Research Articles

Fully automatic deep‐learning based segmentation of Hippocampal subfields from standard resolution T1W MRI in Alzheimer’s Disease

AbstractBackgroundHippocampal subfield volumes are of interest in Alzheimer’s disease (AD) as sub‐regions are affected at different points in the disease trajectory and may provide increased sensitivity as biomarkers compared to the whole hippocampus alone. Subfield volume estimation typically requires a high‐resolution T2‐weighted MRI to ensure accurate anatomical parcellation; however, this increases scan times and may not be present in historical datasets. Automatic methods exist for subfield segmentation from mono‐modal standard resolution T1W MRI, with deep‐learning approaches providing the most promising results to date. Here we extend such work employing deep learning approaches to provide flexible hippocampal subfield segmentation of standard resolution (1mm3) T1W MRI.MethodWe trained a collection of deep‐learning segmentation models to perform binary segmentation of the CA1‐3, CA4/DG, Subiculum, and whole Hippocampus, using a publicly available dataset of 25 subjects with manually segmented region labels on T1 MRI (1mm3). Multilabel segmentations were generated from combination of segmentation outputs.ResultTotal hippocampal and subfield multi‐label segmentations were generated for all test subjects in each cross validated loop and DICE overlap with the ground truth label computed. Preliminary results, computed using a 5‐fold cross validation, report mean DICE in whole Hippocampus = 0.904(std: 0.014), CA1‐3 = 0.842(std:0.019), CA4/DG = 0.767(std:0.04), and Subiculum = 0.791(std:0.033).Segmentation models were applied to 947 subjects with standard T1 MRI from the ADNI cohort and either a CN or MCI label. Subjects were selected with pre‐existing hippocampal subfield volumes, provided by ADNI, computed with the ASHS method using a multi‐modal T1 and hi‐res T2 MRI image. While the proposed method and ASHS employ subtly different parcellation schema we note significant correlation across similar regions between methods.Logistic regression of ICV corrected volumes and MMSE, correcting for age and sex, reveal both ASHS and the proposed method can significantly discriminate between CN and MCI groups (Table 1), with subfields areas providing greater discrimination that of the whole hippocampus.ConclusionHere we present preliminary results for a flexible deep‐learning approach to segmentation of hippocampal subfields from standard resolution T1 MRI alone; indicating comparable performance for group discrimination to an established multi‐modal standard.

Hippocampus‐associated tract degradation follows differential DTI patterns and is influenced by amyloid in MCI patients

AbstractBackgroundDiffusion tensor imaging (DTI) has been leveraged to understand microstructural alterations to limbic and cortico‐cortical tracts in Alzheimer’s disease (AD). However, investigation into the key changes and patterns of fractional anisotropy (FA) and mean diffusivity (MD) metrics in the early stages of MCI has not been widely investigated. This study aimed to establish whether the early DTI white matter tract changes in MCI patients are decoupled and whether amyloid positivity (Aβ+/Aβ‐) is associated with early tract degradation.Method171 participants (103 MCI & 73 CN) were recruited from the AD Neuroimaging Initiative (ADNI; adni.loni.usc.edu) database. For each participant, FA and MD maps were obtained at their baseline scan and voxel wise analysis was carried out using FSL (https://fsl.fmrib.ox.ac.uk/fsl/) and Tract‐Based Spatial Statistics (https://fsl.fmrib.ox.ac.uk/fsl/fslwiki/TBSS). Students t‐tests were conducted on the FA and MD changes in hippocampal WM tracts, previously identified as areas of potential early degradation. Comparisons between CN and MCI groups were made along Aβ+ and Aβ‐ groups.ResultWe found evidence for WM degradation, indicated by lower FA scores in MCI participants compared with controls, in the specific regions of interest of the fornix (p = 0.004) and tapetum (p = 0.012). Mean diffusivity was increased in the MCI group compared to CN in areas of the fornix (p < 0.001), consistent with FA alterations, yet differed from areas identified in FA changes owing to changes in the uncinate fasciculus (p = 0.022) and cingulum (p = 0.003). Comparison of DTI metrics in the fornix between amyloid status groups revealed that Aβ+ participants had significantly lower FA compared to Aβ‐ participants (p = 0.047), but MD did not significantly differ.ConclusionThese results confirm the notion that WM tract integrity degradation in the tract apparatus surrounding the hippocampus occur early in the AD trajectory. However, results indicate that FA alterations occur in different patterns to that of MD and that amyloid may influence these patterns. This supports the idea that efforts to develop therapeutics which maintain WM tract integrity early may be key to slowing AD progression.

18F]MK6240 and [18F]PI2620 autoradiography on postmortem human brain tissue in AD

AbstractBackgroundTo compare the post mortem uptake of [18F]MK6240 and [18F]PI2620 in the brain hemisphere, of A‐T‐ (CN) and A+T+ tissueMethodAutoradiography (ARG) imaging using [18F]MK6240 and [18F]PI2620 was used to assess uptake of CN and AD tissues. One study used sections of whole‐hemisphere of one CN tissue and one AD tissue. The uptake value of [18F]MK6240 was calculated from a regions of interest (ROI) drawn manually from the area of cortex gray matter (GM), cortex white matter (WM), and background (BG).Other study was 24 tissues from the prefrontal cortex (Pfc) (12CN, 12AD), hippocampus (Hip) (12 CN, 12 AD) and cerebellum (Cer) (12 CN, 12 AD) were evaluated with [18F]MK6240, and [18F]PI2620. The uptake value of [18F]MK6240 and [18F]PI2620 was calculated from ROI drawn manually from the area of pfc GM, hip GM and cer GM.ResultThe ARG showed greater [18F]MK6240 uptake in AD than in CN tissue. There were significant differences between CN and AD tissue in terms of cortex gray GM distribution and cortex WM, but no significant differences in BG. These results also, there is no correlation between the specific activity of [18F]MK6240 and the uptake value in CN and AD tissues. In a second experiment, based on our findings there was a significant difference between CN and AD groups when assessed by [18F]MK6240 as well as [18F]PI2620 in the pfc_GM and hip_GM. Furthermore, we found no difference between AD and CN tissues when assessed by [18F]MK6240 and [18F]PI2620 in cerebellum GM. Ratio values Pfc/Cer and Hip/Cer assessed by [18F]MK6240 as well as there were significant differences between CN and AD. [18F]MK6240 and [18F]PI2620 were highly correlated in AD but not in CN brain tissues.ConclusionWe also found that [18F]PI2620 and [18F]MK6240 have similar brain uptake in post‐mortem tissue.

Association of Polygenic Risk Score of Alzheimer’s disease with A/T/N Biomarkers and Cognitive Decline

AbstractBackgroundPolygenic risk scores (PRS) quantify the combined effects of genetic variants to enable the prediction of an individual’s risk of developing the disease. Alzheimer’s disease (AD) is a complex disorder in which the relationship among PRS, neuropathological substrates, and related cognitive decline remain especially understudied in Asian populations. We investigated the associations of PRS with AD neuroimaging biomarkers and cognitive phenotypes in a Korean Cohort.MethodThe study included 501 older adults (264 cognitively normal [CN], 146 mild cognitive impairment [MCI], and 91 AD dementia) from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE). Comprehensive clinical and neuropsychological evaluations, as well as multi‐modal neuroimaging including 3T MRI and 11C‐PiB‐PET were administered. A subset of participants underwent 18F‐AV‐1451 PET (n = 167). Imaging phenotypes including beta‐amyloid (Aβ) positivity, global tau deposition, and adjusted hippocampal volume (HVa) were used for amyloid (A), tau (T), and neurodegeneration (N) biomarkers, respectively., which was imputed using the TOPMed reference panel. PRS was calculated using the summary statistics of a recent large‐scale GWAS study for AD by PRS‐CS. The Apolipoprotein E (APOE) region was excluded in the calculation. The associations between standardized PRS and imaging/cognitive phenotypes were examined using either multiple linear or logistic regression analysis with covariates (age and sex for neuroimaging biomarker phenotypes; age, sex and education for cognitive phenotypes).ResultPRS was significantly higher in the AD dementia group compared to the CN group. Higher PRS was associated with greater CDR‐sum‐of‐boxes (β[SE] = 0.233[0.083], t = 2.818, p = 0.005) and lower MMSE scores (β[SE] = ‐0.648[0.198], t = ‐3.271, p = 0.001). In terms of AD neuroimaging biomarkers (Figure 1), higher PRS was significantly associated with an increased likelihood of Aβ positivity (OR = 1.233, 95%CI = 1.024‐1.491), and lower HVa (β[SE] = ‐132.79[49.624], t = ‐2.676, p = 0.008), but not with global tau deposition (β[SE] = 0.075[0.048], t = 1.573, p = 0.118).ConclusionThese findings suggest that higher PRS predicts increased pathological Aβ deposition and accelerated neurodegeneration, as well as greater cognitive decline. Further investigation in larger and multiethnic samples are needed to determine generalizability to other ethnoracial populations.

Association Between Age and Cognitive Severity in Participants from the Longitudinal Early‐Onset Alzheimer’s Disease Study

AbstractBackgroundAge‐related cognitive declines are well‐documented in cognitively normal adults (van der Willik et al., 2021), as are greater cognitive impairments with advancing age in traditional‐ (or “late‐”) onset Alzheimer’s disease (LOAD; Davis et al., 2018). Early‐onset Alzheimer’s disease (EOAD; diagnosis ≤65 years old) possesses a unique disease course and underlying pathology relative to LOAD (Mendez, 2012), consequently it is unknown if the association between age and cognitive severity is similar. The objective of the current study is to examine the relationship between cognition and age‐at‐baseline in participants enrolled in the Longitudinal Early‐Onset Alzheimer’s Disease Study (LEADS; Apostolova et al., 2019).MethodCross‐sectional cognitive data from 371 participants (aged 40‐64) enrolled in the LEADS protocol were analyzed, using composites for the domains of Episodic Memory, Speed/Attention, Visuospatial skills, Language, and Executive skills. Relationships between age‐at‐baseline and cognition were examined using linear regression based on diagnostic group classification (cognitively normal [CN], amyloid‐positive EOAD, and amyloid‐negative Early‐Onset non‐Alzheimer’s disease [EOnonAD]), controlling for the effects of age and education years.ResultDemographic characteristics for each group are shown in Table 1. Across cognitive domains, the CN group displayed either non‐significant or negative relationships (Executive skills; r = ‐0.30, p = .006) between age‐at‐baseline and cognitive performance (Figure 1 and Table 2). Conversely, the EOAD group showed consistent positive relationships for domains of Speed/Attention (r = 0.23, p<.001), Visuospatial Skills (r = 0.19, p = .01), and Episodic Memory (r = 0.16, p = .02). A similar non‐significant trend was observed for the EOnonAD group for Speed/Attention (r = 0.17, p = .19). When considering those with amnestic‐variant early‐onset dementia across diagnostic groups, positive relationships between age‐at‐baseline and cognition were observed for Speed/Attention (r = 0.19, p = .006) and Visuospatial skills (non‐significant trend; r = 0.14, p = .05), but not for Episodic Memory (r = ‐0.06, p = .35).ConclusionWorse cognitive severity was associated with younger age‐at‐baseline for EOAD participants in LEADS. Similar trends were observed for EOnonAD participants, though to a lesser magnitude. These results were counter to those observed for CN participants, and to what is known about cognitive trajectories in normal aging or LOAD. These findings further support previous suggestions that EOAD appears to be a distinct entity relative to LOAD.

The Pattern of Hippocampus and Entorhinal Cortex Subregion Atrophy in Early Alzheimer’s Disease

AbstractBackgroundAtrophy of the hippocampus and entorhinal cortex (EC) develops early in Alzheimer’s disease (AD). The nature of atrophy along the anterior‐posterior longitudinal axis of the hippocampus and EC in individuals with amnestic mild cognitive impairment (aMCI) with positive AD biomarkers (AD aMCI) has been less researched. We aimed to reveal a possible different pattern of atrophy in longitudinal axis of the hippocampus and EC between AD aMCI individuals and those with AD biomarker negative aMCI (non‐AD aMCI).MethodIn total, 100 older adults with AD aMCI (n = 26), non‐AD aMCI (n = 23), mild AD dementia (n = 22) and cognitively normal (CN; n = 29) from the Czech Brain Aging Study (CBAS) underwent clinical and cognitive testing, and brain MRI with the 3‐dimensional T1‐weighted high‐resolution magnetization‐prepared rapid gradient echo sequences. An automated processing pipeline using the Advanced Normalization Tools based on the CBAS population template and a manual segmentation protocol were used to measure left and right subregional hippocampus and EC volumes including hippocampus head (HH), body (HB) and tail (HT), and anterolateral (alEC) and posteromedial (pmEC) entorhinal cortex volumes, respectively. Volumes were normalized to estimated total intracranial volume.ResultCompared to the CN group, the AD aMCI group had lower subregional hippocampus and EC volumes (p<0.05) except for right and left HH volumes. Compared to the non‐AD aMCI group, the AD aMCI group had lower right HB (p<0.05), right and left HT (p<0.01), right alEC (p<0.05), and right (p<0.01) and left (p<0.05) pmEC volumes. The mild AD dementia group had lower all subregional hippocampus and EC volumes compared to the CN group (p<0.05).ConclusionThese results are in line with previous research that demonstrated atrophy of the hippocampus and EC in early AD and indicate that atrophy of the posterior hippocampus and EC subregions may reflect AD pathology in aMCI individuals. Volumetric differences along the anterior‐posterior axis of the hippocampus and EC could serve as a potential biomarker to identify the underlying pathology in different neurodegenerative diseases.

Visualizing Braak stages with deformation‐based morphometry in super‐sampled MRI

AbstractBackgroundUnlike MRI data, histological data collected post‐mortem can’t be used to study the longitudinal formation of neurofibrillary tangles (NFT) and corresponding brain changes over time for individuals. Although structural MRI offers the possibility of non‐invasive longitudinal antemortem imaging, its resolution is a limiting factor. Using image processing and super‐sampling techniques, we examined the possibility of employing structural MRI to observe the NFT footprints in the brain.MethodData included baseline MRI scans of 1473 subjects from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset including ADNI1, 2, and GO. Voxel size was super‐sampled to 0.5×0.5×0.5mm (Manjón et al. 2010) before non‐linear registration to an ADNI‐based unbiased symmetric MRI template. The resulting deformation fields were used to compute the Jacobian determinant map for each subject as a proxy for local volume. For each subject, the sex‐ and age‐corrected z‐scored Jacobian maps were then calculated and averaged for each diagnostic group: normal subjects(CN), early MCI, late MCI, and AD. The average map for CN group was subtracted from the other average maps to show the AD‐stage differences.ResultThe Braak tau staging pattern (Braak & Braak, 1995) is seen in average Jacobian maps as the disease progresses. Subjects in the MCI groups showed on average more pronounced neurodegeneration in the transentorhinal and entorhinal region (Braak Stages 1‐2), followed by degeneration in the hippocampus (Stages 3‐4). Later on, this neurodegeneration progresses toward the neocortex (Stages 5‐6). Figure 1 illustrates these results: A) the template, B)EMCI vs CN, C) LMCI vs EMCI, D) LMCI vs CN, E) AD vs CN. Red color shows an increase and blue indicates a decrease in local volume.ConclusionUsing novel image processing techniques, we were able to verify the staging of AD‐related neurofibrillary pathology progression in MRI data. This shows that structural MRI data, although limited in resolution, can still offer in‐depth insight into the brain antemortem which will in return allow the longitudinal and possible lifespan studies with an accuracy close to histological data.

Synthesis of pH responsive malononitrile functionalized metal organic framework MIL-100(Fe) for efficient adsorption of uranium U(VI) from real-life alkaline leach liquor

The porous framework of MIL-100(Fe) was functionalized using malononitrile (MN), through an in-situ Knoevenagel condensation reaction to introduce abundant –CN groups on the surface of the developed adsorbent. The resultant MN-functionalized MIL-100(Fe) exhibited excellent Uranium (U(VI)) removal capacity (i.e., 270 mg/g) at highly alkaline pH (⁓ 10). Different coexisting cations and anions show negligible influence on the U-removal and it was 92.1–99.7 % in presence of different co-ions, with the concentration from 10 to 50 mg/L. Moreover, MIL-100(Fe)_MN showed extremely selective U removal from the actual alkaline leach liquor (⁓ 97 %), without any pH adjustment and leaching of the constituent Fe. The surface-grafted –CN groups were predominantly active towards the coordinative interactions with the U(VI) ionic moieties, as evident from the XPS and FTIR analysis. The MIL-100(Fe)_MN adsorbent was also subjected to five consecutive adsorption-desorption cycles, with >90 % U removal after 5th cycle. Moreover, the regenerated MIL-100(Fe)_MN was structurally and functionally resilient, as observed from the morphological and crystallographic analysis. A convection-pore diffusion based transport model was used to analyze the optimized mass transfer parameters. Overall, the present study highlights the simple design and development of malononitrile-functionalized MIL-100(Fe) as an efficient and selective adsorbent for U(VI) removal from U-rich alkaline leach liquor.

Edge-modified phosphorene nanoribbons enhance interfacial carrier extraction in perovskite solar cells

The search for cheap, stable and efficient electron and hole transport layers (ETL and HTL) of perovskite solar cells (PVSCs) remains a significant challenge. In this study, we construct a series of edge-modified phosphorene nanoribbons (PNRs) and explore their potentials as either ETL or HTL in PVSCs using PNRs/MAPbI3 heterojunction. The results reveal that the different functional groups have distinct effects on the electronic structures of individual PNRs. When combined with MAPbI3, the electronic structures of PNRs are further regulated due to the strong interaction. Considering the combined influence of both modifying groups and MAPbI3, several PNRs/MAPbI3 including COH-PNR/MAPbI3, OCN-PNR/MAPbI3 and CN-PNR/MAPbI3 show the tendency for electron transfer from MAPbI3 to PNRs. Conversely, NH2-PNR/MAPbI3 has a possibility for hole transfer. The time-domain noncollinear DFT-based nonadiabatic carrier dynamics simulations for H-PNR/MAPbI3, CN-PNR/MAPbI3 and NH2-PNR/MAPbI3 validate that the –CN group facilitates interfacial electron transfer, while the –NH2 group promotes hole transfer compared to H-PNR/MAPbI3. The addition of modifying groups increases the number of states of the PNRs in PNRs/MAPbI3 that are capable of accepting electron or hole from MAPbI3, thereby enhancing the carrier extraction capacity. This computational work proposes a design strategy to enhance the efficiency of ETL and HTL in PVSCs.

Synthesis of a novel microplastic trap with abundant oxime groups based on MOF-545 post-engineering for the environmental pollution control and water remediation

The elimination of microplastics (MPs) from aquatic systems is a great challenge because of its miniature dimension and exorbitant stability. Hence, a novel MP trap with abundant oxime groups (MOF-545-oxime) was triumphantly synthesized based on MOF-545 post-engineering. The supreme MP adsorption capacity of MOF-545-oxime was 294.6 mg/g, which also manifested excellent selectivity and reusability for MP adsorption. Moreover, the kinetic, isothermal and thermodynamic models were used to inquiry the MP adsorption mechanism, which was governed by electrostatic attraction, coordination, and π–π interactions. The XPS spectra and adsorption energy calculations upheld the CN–OH and CN groups executed a pivotal part in the MP adsorption process of MOF-545-oxime. MOF-545-oxime also possessed splendid anti-biofouling activity and environmental safety, which efficaciously diminished the pessimistic influences of Halamphora upon the MP adsorption capacity and complied with the requirements for non-toxicity and innocuousness in the adsorbent application. The superb anti-biofouling activity and environmental safety of MOF-545-oxime might be due to the abundant functional groups and stable chemical structure. Indubitably, the development of efficacious adsorbents is crucial for the MP removal from aquatic systems. The originally proposed MOF-545-oxime has a great potential to remove MPs from aquatic systems, which also offers an inspiration for perfect high-efficiency adsorbents.

Exploration of violet-to-blue thermally activated delayed fluorescence emitters based on "CH/N" and "H/CN" substitutions at diphenylsulphone acceptor. A DFT study.

The violet-to-blue thermally activated delayed fluorescence (TADF) emitters were created employing several substituents based on 5,5-dimethyl-5,10-dihydropyrido [2,3-b][1,8] naphthyridine-diphenylsulphone (DMDHPN-DPS) called 1a via "CH/N" and "H/CN" substitutions at the diphenylsulphone acceptor (DPS) moiety. The parent compound 1a was selected from our former work after extensive research employing "CH/N" substitution on Dimethyl-acridine (DMAC) donor moiety. There is a little overlap amid the highest occupied molecular orbitals (HOMOs) and lowest un-occupied molecular orbitals (LUMOs) due to the distribution of HOMOs and LUMOs primarily on the DMDHPN donor and the DPS acceptor moieties, respectively. It resulted in a narrower energy gap (∆E ST) between the lowest singlet (S1) and triplet (T1) excited state. In nearly all derivatives, the steric hindrance results in a larger torsional angle (85°-98°) between the plane of the DMDHPN and the DPS moieties. The predicted ΔE ST values of the compounds with "H/CN" substitution were lower than those of the comparable "CH/N" substituents, demonstrating the superiority of the reversible inter-system crossing (RISC) from the T1 → S1 state. All derivatives have emission wavelengths (λ em) in the range of 357-449nm. The LUMO → HOMO transition energies in the S1 states are lowered by the presence of -CN groups or -N = atoms at the ortho or meta sites of a DPS acceptor unit, causing the λ em values to red-shift. Furthermore, the λ em showed a greater red-shift as there were more-CN groups or -N = atoms. Three of the derivatives named 1b, 1g, and 1h, emit violet (394nm, 399nm, and 398nm, respectively), while two others, 1f and 1i, emit blue shade (449nm each) with reasonable emission intensity peak demonstrating that these derivatives are effective violet-to-blue TADF nominees. The lower ΔE ST value for derivative 1i (0.01eV) with λ em values of 449nm make this molecule the finest choice for blue TADF emitter amongst all the studied derivatives. We believe our research might lead to the development of more proficient blue TADF-OLEDs in the future.

Identification of novel diagnostic panel for mild cognitive impairment and Alzheimer’s disease: findings based on urine proteomics and machine learning

BackgroundAlzheimer’s disease is a prevalent disease with a heavy global burden. Proteomics is the systematic study of proteins and peptides to provide comprehensive descriptions. Aiming to obtain a more accurate and convenient clinical diagnosis, researchers are working for better biomarkers. Urine is more convenient which could reflect the change of disease at an earlier stage. Thus, we conducted a cross-sectional study to investigate novel diagnostic panels.MethodsWe firstly enrolled participants from China-Japan Friendship Hospital from April 2022 to November 2022, collected urine samples, and conducted an LC–MS/MS analysis. In parallel, clinical data were collected, and clinical examinations were performed. After statistical and bioinformatics analyses, significant risk factors and differential urinary proteins were determined. We attempt to investigate diagnostic panels based on machine learning including LASSO and SVM.ResultsFifty-seven AD patients, 43 MCI patients, and 62 CN subjects were enrolled. A total of 3366 proteins were identified, and 608 urine proteins were finally included in the analysis. There were 33 significantly differential proteins between the AD and CN groups and 15 significantly differential proteins between the MCI and CN groups. AD diagnostic panel included DDC, CTSC, EHD4, GSTA3, SLC44A4, GNS, GSTA1, ANXA4, PLD3, CTSH, HP, RPS3, CPVL, age, and APOE ε4 with an AUC of 0.9989 in the training test and 0.8824 in the test set while MCI diagnostic panel included TUBB, SUCLG2, PROCR, TCP1, ACE, FLOT2, EHD4, PROZ, C9, SERPINA3, age, and APOE ε4 with an AUC of 0.9985 in the training test and 0.8143 in the test set. Besides, diagnostic proteins were weakly correlated with cognitive functions.ConclusionsIn conclusion, the procedure is convenient, non-invasive, and useful for diagnosis, which could assist physicians in differentiating AD and MCI from CN.

Design and application of zirconium-based coordination polymers for selective capture of copper

The heavy metal copper in the wastewater is extremely harmful to human and ecological environment. The new metal coordination polymer (Zr-TPTA) adsorbent is prepared to capture copper ion from aqueous medium. The effects of reaction time, initial concentration of Cu(II) ion, pH value and temperature on adsorption efficiency of Cu(II) ion by Zr-TPTA are studied. The maximum adsorption capacity of Zr-TPTA is 148.32 mg/g at pH 3.0. The thermoisopleth and kinetic data conform to Langmuir and pseudo-second-order models, indicating that the adsorption mode is monolayer chemisorption. The capture of Cu(II) ion on Zr-TPTA surface is a spontaneous exothermic process according to thermodynamic parameter calculation results. The strength of interaction force between adsorbent and Cu(II) ion (15,649 mL/g) shows that the Zr-TPTA adsorbent has selective adsorption for Cu(II) ion. The consecutive adsorption-desorption experiment demonstrates the excellent reusability of Zr-TPTA. The X-ray photoelectron spectroscopy (XPS), zeta potential and density functional theory (DFT) prove that the adsorption mechanism is the complexation reaction of Cu(II) ion with CS and CN groups. This work illustrates the value of self-designed novel metal coordination polymer in adsorbent materials with selective capture of copper ion.

Cytomegalovirus-Seronegative Plus Leukoreduced Blood Products Are Still Superior to Only Leukoreduced Products in Preventing Transfusion-Transmitted Cytomegalovirus Infection

Introduction Cytomegalovirus (CMV) is one of the most important pathogens causing complications after hematopoietic stem cell transplantation (HSCT). Transfusion-transmitted CMV infection (TT-CMV) in CMV-seronegative patients is a major issue. Leukoreduced (LR) blood products were unavailable before 2004. However, they have gradually become widespread, and all blood products in Japan have been LR since 2007. This study aimed to assess the incidence of TT-CMV in CMV-seronegative HSCT recipients undergoing autologous HSCT (auto-HSCT) or allogeneic HSCT (allo-HSCT) from CMV-seronegative stem cell donors, who received transfusions with “CMV-seronegative products” from CMV-seronegative donors or “random donor products” from donors not tested for anti-CMV antibodies during the periods of availability and unavailability of LR products. Methods We retrospectively evaluated 3590 CMV-seronegative recipients registered in the TRUMP database of the Japanese Society for Transplantation and Cellular Therapy from 1999 to 2018. The recipients undergoing HSCT were categorized into three periods: Period A (when LR products were unavailable), 1999-2003 (n = 136); Period B (when there were both non-LR and LR products), 2004-2006 (n = 200); and Period C (when only LR products were available), 2007-2018 (n = 3254). TT-CMV was defined by the presence of CMV antigenemia and/or CMV diseases. This study was approved by the Ethics Committee of Kobe University Hospital and was conducted in accordance with the principles of the Declaration of Helsinki. Results The median age of the patients at HSCT was 40 years (range, 0-79 years). Among auto-HSCT patients (n = 1628) transfused with “CMV-negative products”(CN group) and “random donor products” (RD group), the incidences of TT-CMV in the CN and RD groups were 0% (0/4) and 3.1% (1/32) during Period A (P = 1.0), 22.2% (2/9) and 10.6% (7/66) during Period B (P = 0.29), and 3.8% (4/105) and 5.0% (71/1412) during Period C (P = 0.81), respectively. Among the allo-HSCT patients (n = 1962), the incidences of TT-CMV in the CN and RD groups were 10.0% (3/30) and 27.1% (19/70) during Period A (P = 0.07), 17.9% (5/28) and 29.9% (29/97) during Period B (P = 0.24), and 11.6% (41/355) and 28.0% (387/1382) during Period C (P < 0.001), respectively. During Period C, 99 patients in the CN group always underwent transfusion with leukocyte reduction filters, of which 11 (11.1%) were diagnosed with TT-CMV. In contrast, 202 patients in the CN group always underwent transfusion without the filters, of which 26 (12.9%) were diagnosed with TT-CMV (P = 0.78). In the RD group, 494 patients always underwent transfusion with leukocyte reduction filters, of which 124 (25.1%) were diagnosed with TT-CMV. On the other hand, 807 patients in the RD group always underwent transfusion without the filters, of which 245 (30.4%) were diagnosed with TT-CMV (P = 0.10). Multivariate analysis revealed that random donor products (hazard ratio [HR]: 3.11, 95% confidence interval [CI]: 2.13-4.52; P < 0.001) and age ≥16 years (HR: 2.90, 95% CI: 2.06-4.09; P < 0.001) were associated with an increased risk of TT-CMV in allo-HSCT. No significant difference was observed in the incidence of CMV diseases between the CN group (3.7%; 13/355) and the RD group (3.8%; 52/1382) (P = 1.00). The major CMV diseases included CMV colitis (n = 5) and pneumonia (n = 2) in the CN group, and CMV colitis (n = 30), pneumonia (n = 9), and retinitis (n = 4) in the RD group. Interestingly, among the patients with TT-CMV during Period C, 27/41 patients (65.9%) in the CN group and 333/387 patients (86.1%) in the RD group received early intervention with anti-CMV agents (P = 0.002). The limitation included that complement-fixation test for anti-CMV antibody was used in Japan Marrow Donor Program in this cohort. Conclusion This is the largest study demonstrating that CMV-seronegative plus LR products are still superior to only LR products from random donors in terms of TT-CMV prevention among allo-HSCT CMV-seronegative recipients. However, no significant difference was observed in the incidence of CMV diseases, possibly because of early intervention with anti-CMV agents.

52 Open Access, Normative Morphometric Software Indicate Neurodegeneration Associated with Episodic Memory Dysfunction in Amnestic MCI

Objective:Neurodegeneration in Alzheimer’s disease (AD) is typically assessed through brain MRI, and proprietary software can provide normative quantification of regional atrophy. However, proprietary software can be cost-prohibitive for research settings. Thus, we used the freely available software NOrmative Morphometry Image Statistics (NOMIS) which generates normative z-scores of segmented T1-weighted images from FreeSurfer to determine if these scores replicate established patterns of neurodegeneration in the context of amnestic mild cognitive impairment (aMCI), and whether these measures correlate with episodic memory test performance.Participants and Methods:Patients with aMCI (n = 25) and cognitively normal controls (CN; n = 74) completed brain MRI and two neuropsychological tests of episodic memory (the Rey Auditory Verbal Learning Test and the Wechsler Logical Memory Tests I & II), from which a single composite of normed scores was computed. A subset returned for follow-up (aMCI n = 11, CN n = 52) after ∼15 months and completed the same procedures. T1-weighted images were segmented using FreeSurfer v6.0 and the outputs were submitted to NOMIS to generate normative morphometric estimates for AD-relevant regions (i.e., hippocampus, parahippocampus, entorhinal cortex, amygdala) and control regions (i.e., cuneus, lingual gyrus, pericalcarine gyrus), controlling for age, sex, head size, scanner manufacturer, and field strength. Baseline data were used to test for differences in ROI volumes and memory between groups and to assess the within-group associations between ROI volumes and memory performance. We also evaluated changes in ROI volumes and memory over the follow-up interval by testing the main effects of time, group, and the group X time interactions. Lastly, we tested whether change in volume was associated with declines in memory.Results:At baseline, the aMCI group performed 2 SD below the CN group on episodic memory and exhibited smaller volumes in all AD-relevant regions (volumes 0.4 - 1.2 SD below CN group, ps < .041). There were no group differences in control region volumes. Memory performance was associated with volumes of the AD-relevant regions in the aMCI group (average rho = .51) but not with control regions. ROI volumes were not associated with memory in the CN group. At follow-up, the aMCI group continued to perform 2 SD below the CN group on episodic memory tests; however, change of performance over time did not differ between groups. The aMCI group continued to exhibit smaller volumes in all AD-relevant regions than the CN group, with greater declines in hippocampal volume (17% annual decline vs. 8% annual decline) and entorhinal volume (54% annual decline vs. 5% annual decline). There was a trending Group X Time interaction such that decrease in hippocampal volume was marginally associated with decline in memory for the aMCI group but not the CN group.Conclusions:Normative morphometric values generated from freely available software demonstrated expected patterns of group differences in AD-related volumes and associations with memory. Significant effects were localized to AD-relevant brain regions and only occurred in the aMCI group. These findings support the validity of these free tools as reliable and cost-effective alternatives to proprietary software.

5 Cross-cultural Diagnostic Validity of the Multilingual Naming Test (MINT) in a Sample of Older Adults.

Objective:The current study aimed to evaluate the psychometric properties and diagnostic accuracy of the 32-item version of the Multilingual Naming Test (MINT) in a sample of English and Spanish monolinguals and bilingual older adults from two ethnic groups (EA; European Americans and HA; Hispanic American) with typical and atypical aging. An IRT model was used to identify 24 MINT Items assessed across ethnicity and language testing groups (Spanish and English). We analyzed the discriminant and predictive validity of the 32-item and 24-item scales across diagnostic groups (cognitively normal [CN], mild cognitive impairment [MCI], and dementia [AD]). Diagnostic accuracy was then assessed with both versions applying ROC (Receiver Operating Characteristics) curve reporting using AUC (Area Under the Curve). We expected the MINT to distinguish between the CN and AD groups but not between CN and MCI and the MCI and AD. We conducted IRT analyses to evaluate the cross-language validity of the items from the 32-item MINT in English and Spanish through Rasch Analysis across our two ethnic groups. Finally, we tested the association between MINT scores and MRI volumetric measures of language-related areas in both cerebral hemispheres’ temporal and frontal lobes.Participants and Methods:The sample comprised 281 participants (178 females) enrolled in the 1Florida Alzheimer’s Disease Research Center (ADRC), with 175 participants self-identified as HA (51 tested in English and 124 in Spanish) and 106 EA, all of them monolingual English speakers. The participants were classified into three diagnostic groups: 1. CN (n = 94); 2. MCI (n = 148); and 3. AD (n = 39). Participants are evaluated yearly through a comprehensive neuropsychological battery, including the MINT is a standard CN task that requires patients to retrieve words upon presentation of a line drawing.Results:We obtained a ceiling effect in four items (Butterfly, Glove, Watch, and Candle). Four items were easier in English (Blind, Gauge, Porthole, and Pestle) and four in Spanish (Dustpan, Funnel, Anvil, and Mortar). In the 32-item version of the MINT, EA scored significantly higher than HA, but when removing those eight items, the ethnic difference was attenuated and no longer statistically significant (controlling for education). The ROC curves showed that both versions of the MINT had poor accuracy when identifying CN participants and were acceptable in identifying dementia participants but unacceptable for classifying MCI participants. The 32-item MINT in English and Spanish and the 24-item MINT in Spanish were significantly correlated with the bilateral MTG. However, the 24-item MINT in English was only correlated with this area’s volume in the right hemisphere. The left FG correlated with MINT scores regardless of language and MINT version. We also found some differential correlations depending on the language of administration. The bilateral hippocampi, STG, MTG and FG, and right ITG were significantly correlated only with MINT Spanish scores, while the left ITG was significant only when either version of the MINT was administered in English.Conclusions:Our results highlight the importance of analyzing cross-cultural samples when implementing neuropsychological tests.

일상생활 수행능력 평가도구의 유효성 분석 연구

Objective: The study’s aim was to evaluate the validity of the Korean version of the University of California San Diego Performance- based Skills Assessment, Validation of Intermediate Measures (K-UPSA-2-VIM) in patients with dementia (D), mild cognitive impairment (MCI), and cognitive normal control group (CN).
 Methods: Study participants were 25 patients with D, 43 patients with MCI, and 111 controls with CN group, respectively. For cognitive assessment, Mini Mental State Examination, Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological battery, and Clinical Dementia Rating were used. For functional assessment, Barthel-Activities of Daily Living, Instrumental Activities of Daily Living, Dementia Screening questionnaire, and K-UPSA-2-VIM were used.
 Results: Statistically significant differences were observed in all subdomains and total score of the K-UPSA-2-VIM among three cognitive groups. K-UPSA-2-VIM demonstrated 75.7% of sensitivity and 65.1% of specificity, with an area under the curve (AUC) of 0.731 (95% confidence interval [CI]: 0.641-0.821, p<0.001) in discriminating between CN and MCI groups. In discriminating between MCI and D groups, 76.7% of sensitivity and 64.0% of specificity, with an AUC of 0.706 (95% CI: 0.580-0.833, p=0.005) were demonstrated.
 Conclusion: The K-UPSA-2-VIM is useful to evaluate activities of daily living function in Korean patients with D and MCI.

Exploring diaminomaleonitrile-derived Schiff base ligand and its complexes: Synthesis, characterization, computational insights, biological assessment, and molecular docking

A tetra dentate ONNO donor diaminomaleonitrile-based Schiff base ligand along with its four new complexes of Co(II), Ni(II), Cu(II), and Zn(II) have been synthesized. The computational approach has been utilized to provide a theoretical framework for understanding the electronic structure and properties of these complexes. The distorted octahedral geometry of the Schiff base metal complexes indicates that the metal ions are coordinated with the ligand through ONNO donor sites, which is further confirmed by characterization using physiochemical and spectroscopic techniques like elemental analysis, mass, electronic, infrared, 1H, and 13C spectra. In addition, magnetic behavior is analyzed using the Vibrating Sample Magnetometer(VSM). To evaluate the potential modes of biomolecular interactions with the synthesized complexes utilizing Deoxyribo Nucleic Acid(DNA) and to assess the corresponding binding constants, an absorption spectroscopic technique has been utilized. Metal complexes are reported to have a range of binding constant values from 5.45 × 104 M−1 to 4.35 × 105 M−1 with different binding modes, such as intercalation, mixed mode, and electrostatic contact. In addition, in-vitro tests for antibacterial and anti-inflammatory activity have been employed to assess the bioactivities. With an IC50 value of 209.24 µg/mL, the Zn(II) complex is found to show considerable anti-inflammatory action as well as has superior antibacterial activity among all other complexes. The existence of electron-withdrawing CN groups together with other factors can be accounted for biological activity in our reported complexes. Further, molecular docking simulations are conducted to gain insights into the molecular-level interactions and to determine the potential binding energies of inhibitors whose results are in consistent with the in-vitro investigations.

Mechanofluorochromic properties of 1-phenylanthracene derivatives with extremely simple structures

Several types of 1-phenylanthracene derivatives 1–4 were prepared and their photophysical properties were observed in the solution and solid states. Interestingly, the fluorine-substituted 1-phenylanthracene derivative 1c was found to exhibit a higher fluorescence quantum yield (Φf=0.57) in the solid state than in the solution state, probably due to the formation of intermolecular Ar–F•••H–Ar hydrogen bonds. Additionally, some of the 1-phenylanthracene derivatives exhibited mechanofluorochromic properties depending on the substituents of the phenyl group, with the derivatives having CF3, OMe, and CN substituents (1d-1f, 2, 3) showing a significant change in luminous color from a bluish to greenish color at “room temperature” after grinding. However, no change in the luminous color was observed for the derivatives having H, Me, and F substituents (1a-1c) at “room temperature” but luminous color change was observed with low temperature grinding (−78 °C), especially for the CN substituent, in which a significant change in the luminous color was observed at “room temperature” probably due to the formation of Ar-CN•••H–Ar hydorogen bond interactions. Interestingly, for the 1-phenylanthracene derivative 3 substituted with two CN groups, which exhibited a solvatochromic phenomenon, the luminous color recovered with controllable rate from green to bluish when heated and fumed with solvent vapor in the solid state, and the luminous color change with controllable recovery rate was repeatedly successfully observed. These anthracene derivatives have extremely simple structures and could probably be applied as new mechanofluorochromic materials.

Nitriles with exceptionally high proton affinity due to a C–N bond formation upon protonation

In this work, we show that nitriles whose CN group is in the vicinity of an electron pair-donating group exhibit exceptional higher proton affinity than the ordinary nitriles in the gas phase and solution. The exceptional proton affinity of these compounds is partly due to the formation of a new bond between the C atom of CN and the atom with the electron pair upon protonation of the N atom of the CN group. The calculated proton affinities and gas phase basicities confirm that these compounds have comparable or even higher basicities than simple organic superbases such as proton sponges, guanidine, and phosphazene derivatives. The calculations in acetonitrile showed that some of these nitriles also exhibit high basicity in solution with pKa(BH+) ≥ 25.