A Peculiar Tau Accumulation Pattern Identified Via 18F-Florzolotau PET Imaging in a Patient With Frontotemporal Dementia Caused by a Mutation in the MAPT Gene.

ABSTRACT: We reported imaging findings with a peculiar tau accumulation pattern in a 56 year-old woman with frontotemporal dementia caused by Q351R mutation in the microtubule-associated protein tau (MAPT) gene. She had a 10-year history of gradually worsening memory loss. 18F-FDG PET demonstrated hypometabolism in medial temporal lobes, but 18F-florbetapir PET manifested no abnormal amyloid beta deposition, which ruled out Alzheimer disease. 18F-florzolotau PET showed tau proteins accumulated in medial temporal lobes, basal ganglia brainstem, and cerebellum. The pattern is different from other known MAPT gene mutation. Multitracer imaging can help differentiate between Alzheimer disease and frontotemporal dementia caused by MAPT mutation.

Influence of the Hall-bar geometry on texture-induced topological spin transport in two-dimensional Rashba spin-orbit ferromagnets.

While the recent prediction and observation of magnetic skyrmions bears inspiring promise for next-generation spintronic devices, how to detect and track their position becomes an important issue. In this work, we investigate the spin transport in a two-dimensional magnetic nanoribbon with the Hall-bar geometry in the presence of Rashba spin-orbit coupling and magnetic skyrmions. We employ the Kwant tight-binding code to compute the Hall conductance and local spin-polarized current density. We consider two versions of the model: One with single skyrmion and one with two separate skyrmions. It is found that the size and position of the skyrmions strongly modulate the Hall conductance near the Hall-bar position. The geometry of the Hall bar also has a strong influence on the Hall conductance of the system. With the decreasing of the width of Hall leads, the peak of Hall conductance becomes sharper. We also show the spatial distribution of the spin-polarized current density around a skyrmion located at different positions. We extend this study toward two separate skyrmions, where the Hall conductance also reveals a sizable dependence on the position of the skyrmions and their distance. Our numerical analysis offers the possibility of electrically detecting the skyrmion position, which could have potential applications in ultrahigh-density storage design.

ß-Cyclodextrin-NHC-Au(I)-Catalyzed Enantioconvergent 1,5-Enyne Cycloisomerizations.

Enantioconvergent transformations from racemic mixtures are attractive since they allow the generation of optically active products with full conversion despite the possibly adverse kinetic resolution process. When dealing with gold(I)-catalyzed cycloisomerizations, chirality transfer from the precursor is another possible diverting pathway, which renders enantioconvergence challenging. Not surprisingly, enantioconvergent Au(I)-catalyzed processes have remained extremely rare. Herein we show that cavity-driven catalysis using ß-cyclodextrin-NHC-Au(I) complexes brings opportunities to conduct highly enantioconvergent cycloisomerizations of 1,5-enynes, -enynols, and, -enynyl esters.

Intensity and associated factors of home health care service needs among elderly patients with chronic diseases in the community: A cross-sectional survey.

AIM AND OBJECTIVES: This study aimed to investigate the intensity of needs for home health care services (HHCs) among elderly patients with chronic diseases and to identify the associated factors. DESIGN: A cross-sectional survey was conducted in Wuhou District, Chengdu, Sichuan Province, China, from April to November 2021. METHODS: Convenient sampling was used to screen elderly patients with chronic diseases managed by Yulin Community Health Service Center. The questionnaires included general information and the Chinese version of the Community Healthy Intensity Rating Scale were completed according to patients' conditions. The data were analyzed using descriptive statistics and binary logistic regression. RESULTS: A total of 371 patients (10.40%) completed the survey. The mean age of the elderly patients was 84.04 years (SD = 7.07); these patients suffered from 1 to 7 kinds of chronic diseases, and the most common were hypertension (78.98%) and diabetes (40.97%). The need intensity of patients for HHCs was moderate (41.51%) or severe (58.49%). For each additional chronic disease that patients suffered from, the need intensity increases by 1.289 times (OR = 1.289; 95% CI: 1.055-1.575, p = .013); in additional, those aged more than 90 years, with a personal monthly income less than 2500 yuan ($387.00), with a poor health current status, and with only basic medical insurance presented greater need intensity (p < .05). CONCLUSION: Our data analysis revealed that economic status, insurance condition, poor health status, and multiple comorbidities may be the most common factors associated with the need intensity for HHCs. These characteristics may help medical staff to identify and help those with urgent health problems.

The Value of CEUS LI-RADS combined with AFP in early diagnosis of hepatocellular carcinoma in low- and high-risk patients.

BACKGROUND: We found that the occurrence of hepatocellular carcinoma (HCC) has increased significantly in non-cirrhotic individuals, with HCC being frequently overlooked or misdiagnosed. Contrast-enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI-RADS) is known to have a high diagnostic quality in high-risk HCC patients. Therefore, we aimed to compare the detection accuracy of CEUS LI-RADS for HCC between low- and high-risk individuals, to confirm its value in low-risk patients at increased risk of HCC, but not yet included in the high-risk groups of LI-RADS. In addition, since CEUS LR-4 and LR-M categories contain a relatively high proportion of HCC, and serum alpha-fetoprotein (AFP) is the most commonly used biomarker for HCC, and the clinically valid, we attempted to further improve the early diagnostic capability of CEUS LI-RADS for HCC in the low-risk and high-risk patients by combining CEUS LR-4 and LR-M categories with AFP. METHODS: We defined high-risk groups (HR)-included in the high-risk patients of LI-RADS, low-risk groups (LR)-not included in the high-risk patients of LI-RADS and enrolled 189 HCC patients with LR and HR settings in a retrospective study. All lesions were confirmed histopathologically. The CEUS LI-RADS accuracy for detecting HCC in these two patients was compared. In addition, the diagnostic algorithm in our study was proposed (for CEUS LR-4 and LR-M patients with AFP>20 ng/ml). we analyzed the ability of CEUS LI-RADS as a valid method of establishing the early diagnosis of HCC in LR and HR patients by combining LR-4 and LR-M categories with AFP. RESULTS: Through comparative analysis, the specificity of the CEUS LR-5 category for HCC in the HR group was 78.4%, whereas in the LR group, it was 94.2%. Meanwhile, the sensitivity (63.2% vs. 63.0%) and positive predictive value (PPV) (75.0% vs. 88.7%) did not differ between the LR and HR groups ( P = 0.990, P = 0.299). It is noteworthy that there were the high proportion of HCC in CEUS LR-4 and LR-M categories in our cases and when we combined CEUS LR-4 and LR-M categories with AFP significantly improved the sensitivity by 21.0% (84.2%) in the LR group, and by 16.0% (79.0%) in the HR group, with statistically difference in sensitivity after combination in the HR group ( P = 0.014). CONCLUSIONS: The CEUS LR-5 category has real meaningful utility in the diagnosis of HCC in both LR and HR patients. The early detection power of the CEUS LI-RADS category for HCC patients was further increased when the CEUS LR-4 and LR-M categories were combined with elevated AFP.

Single-cell RNA sequencing reveals reduced intercellular adhesion molecule crosstalk between activated hepatic stellate cells and neutrophils alleviating liver fibrosis in hepatitis B virus transgenic mice post menstrual blood-derived mesenchymal stem cell transplantation.

Liver fibrosis can cause hepatitis B virus (HBV)-associated hepatocellular carcinoma. Menstrual blood-derived mesenchymal stem cells (MenSCs) can ameliorate liver fibrosis through paracrine. Single-cell RNA sequencing (scRNA-seq) may be used to explore the roadmap of activated hepatic stellate cell (aHSC) inactivation to target liver fibrosis. This study established HBV transgenic (HBV-Tg) mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis and demonstrated that MenSCs migrated to the injured liver to improve serological indices and reduce fibrotic accumulation. RNA-bulk analysis revealed that MenSCs mediated extracellular matrix accumulation and cell adhesion. Liver parenchymal cells and nonparenchymal cells were identified by scRNA-seq in the control, CCl4, and MenSC groups, revealing the heterogeneity of fibroblasts/HSCs. A CellChat analysis revealed that diminished intercellular adhesion molecule (ICAM) signaling is vital for MenSC therapy. Specifically, Icam1 in aHSCs acted on Itgal/Itgb2 and Itgam/Itgb2 in neutrophils, causing decreased adhesion. The expression of Itgal, Itgam, and Itgb2 was higher in CCl4 group than in the control group and decreased after MenSC therapy in neutrophil clusters. The Lcn2, Pglyrp1, Wfdc21, and Mmp8 had high expression and may be potential targets in neutrophils. This study highlights interacting cells, corresponding molecules, and underlying targets for MenSCs in treating HBV-associated liver fibrosis.

Pyro-Phototronic Effect Induced Circularly Polarized Light Detection with a Broadband Response.

Photopyroelectric-based circularly polarized light (CPL) detection, coupling the pyro-phototronic effect and chiroptical phenomena, has provided a promising platform for high-performance CPL detectors. However, as a novel detection strategy, photopyroelectric-based CPL detection is currently restricted by the short-wave optical response, underscoring the urgent need to extend its response range. Herein, visible-to-near-infrared CPL detection induced by the pyro-phototronic effect is first realized in chiral-polar perovskites. Specifically, chiral-polar multilayered perovskites (S-BPEA)2FAPb2I7 (1-S, S-BPEA = (S)-1-4-Bromophenylethylammonium, FA = formamidinium) with spontaneous polarization shows intrinsic pyroelectric and photopyroelectric performance. Strikingly, combining its merits of the pyro-phototronic effect and intrinsic wide-spectrum spin-selective effect, chiral multilayered 1-S presents efficient photopyroelectric-based broadband CPL detection performance spanning 405-785 nm. This research first realizes photopyroelectric-based infrared CPL detection and also sheds light on developing high-performance broadband CPL detectors based on the pyro-phototronic effect in the fields of optics, optoelectronics, and spintronics.

Transcutaneous oxygen tension-guided hyperbaric oxygen therapy for preventing skin necrosis after hyaluronic acid filler injections.

Introduction: Hyaluronic acid (HA) fillers, popular for facial cosmetic enhancements, pose risks of vascular complications like skin necrosis due to arterial blockage, necessitating effective treatments such as hyperbaric oxygen therapy (HBOT). Methodology: This study presents a series of cases where measurements of transcutaneous oxygen pressure (TcPO2) informed the application of HBOT for skin necrosis induced by HA. Clinical presentation and outcomes: In cases 1 and 3, following the injection of HA, potential skin necrosis was observed. In addition to standard treatment, TcPO2 revealed values below 40 mmHg, indicating tissue hypoxia. Treatment with HBOT increased TcPO2 levels to above 200 mmHg, suggesting that HBOT could correct the hypoxia. Monitoring TcPO2 levels also aided in determining the optimal time to discontinue HBOT. In cases 2 and 4, patients received standard treatment, resulting in TcPO2 levels above 40 mmHg, indicating adequate tissue oxygenation, and no additional HBOT was administered. All four patients mentioned above showed good clinical recovery. Conclusion: This study investigates the application of TcPO2 measurement technology in aiding decisions on whether to utilize HBOT in the treatment of complications arising from HA fillers, as well as in optimizing HBOT protocols.

Mode-Symmetry-Assisted Optical Pulling by Bound States in the Continuum.

Aside from optical pushing and trapping that have been implemented successfully, the transportation of objects backward to the source by the optical pulling forces (OPFs) has attracted tremendous attention, which was usually achieved by increasing the forward momentum of light. However, the limited momentum transfer between light and object greatly constrains the amplitudes of OPFs. Here, we present a mechanism to generate strong interactions between object and background through the bound states in the continuums, which can generate large OPFs without increasing the forward momentum of light. The underlying physics is the extraction of momentum from the designed background lattice units assisted by mode symmetry. This work paves the way for extraordinary optical manipulations and shows great potential for exploring the momenta of light in media.

Effect of transcranial direct current stimulation with concurrent cognitive performance targeting posterior parietal cortex vs prefrontal cortex on working memory in schizophrenia: a randomized clinical trial.

Working memory deficits are linked to irregularities in the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC) in schizophrenia, effective intervention strategies are lacking. We evaluated the differential efficacy and underlying neuromechanisms of targeting transcranial direct current stimulation (tDCS) at the DLPFC and the PPC with concurrent cognitive performance for working memory in schizophrenia. In a randomized and double-blind clinical trial, sixty clinically stable schizophrenic patients with below-average working memory were randomly assigned to active DLPFC, active PPC, and sham tDCS groups. Two sessions of tDCS during N-back task were delivered daily for five days. The primary outcome was changes in spatial span test scores from baseline to week 1. The secondary outcomes included changes in scores of color delay-estimation task, other cognitive tasks, and mismatch negativity (biomarker of N-methyl-d-aspartate receptor functioning). Compared with the active DLPFC group, the active PPC group demonstrated significantly greater improvement in spatial span test scores (p = 0.008, d = 0.94) and an augmentation in color delay-estimation task capacity at week 1; the latter sustained to week 2. Compared with the sham tDCS group, the active PPC group did not show a significant improvement in spatial span test scores at week 1 and 2; however, significant enhancement was observed in their color delay-estimation task capacity at week 2. Additionally, mismatch negativity amplitude was enhanced, and changes in theta band measures were positively correlated with working memory improvement in the active PPC group, while no such correlations were observed in the active DLPFC group or the sham tDCS group. Our results suggest that tDCS targeting the PPC relative to the DLPFC during concurrent cognitive performance may improve working memory in schizophrenia, meriting further investigation. The improvement in working memory appears to be linked to enhanced N-methyl-d-aspartate receptor functioning.

Four novel mutations identified in the COL4A3, COL4A4 and COL4A5 genes in 10 families with Alport syndrome.

BACKGROUND: Alport syndrome (AS) is an inherited nephropathy caused by mutations in the type IV collagen genes. It is clinically characterized by damage to the eyes, ears and kidneys. Diagnosis of AS is hampered by its atypical clinical picture, particularly when the typical features, include persistent hematuria and microscopic changes in the glomerular basement membrane (GBM), are the only clinical manifestations in the patient. METHODS: We screened 10 families with suspected AS using whole exome sequencing (WES) and analyzed the harmfulness, conservation, and protein structure changes of mutated genes. In further, we performed in vitro functional analysis of two missense mutations in the COL4A5 gene (c.2359G > C, p.G787R and c.2605G > A, p.G869R). RESULTS: We identified 11 pathogenic variants in the type IV collagen genes (COL4A3, COL4A4 and COL4A5). These pathogenic variants include eight missense mutations, two nonsense mutations and one frameshift mutation. Notably, Family 2 had digenic mutations in the COL4A3 (p.G1170A) and UMOD genes (p.M229K). Family 3 had a digenic missense mutation (p.G997E) in COL4A3 and a frameshift mutation (p.P502L fs*151) in COL4A4. To our knowledge, four of the 11 mutations are novel mutations. In addition, we found that COL4A5 mutation relation mRNA levels were significantly decreased in HEK 293 T cell compared to control, while the cellular localization remained the same. CONCLUSIONS: Our research expands the spectrum of COL4A3-5 pathogenic variants, which is helpful for clinical and scientific research.

Baseline hepatobiliary MRI for predicting chemotherapeutic response and prognosis in initially unresectable colorectal cancer liver metastases.

PURPOSE: To evaluate the performance of hepatobiliary MRI parameters as predictors of clinical response to chemotherapy in patients with initially unresectable colorectal cancer liver metastases (CRLM). METHODS: Eighty-five patients with initially unresectable CRLM were retrospectively enrolled from two hospitals and scanned using gadobenate dimeglumine-enhanced MRI before treatment. Therapy response was evaluated based on the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Conventional parameters (i.e., signal intensity [SI]) and radiomics features of portal venous phase (PVP) and hepatobiliary phase (HBP) images were analyzed between the responders and non-responders. Next, the combined model was constructed, and the area under the receiver operating characteristic (ROC) curve (AUC) was calculated. The relationship between the combined model and progression-free survival (PFS) was analyzed using Cox regression. RESULTS: Of the 85 patients from two hospitals, 42 were in the response group, and 43 were in the non-response group. Upon conducting five-fold cross-validation, the normalized relative enhancement (NRE) of CRLM during the PVP yielded an AUC of 0.625. Additionally, a radiomics feature derived from the tumor area in the HBP achieved an AUC of 0.698, while a separate feature extracted from the peritumoral region in the HBP recorded an AUC of 0.709. The model that integrated these three features outperformed the individual features, achieving an AUC of 0.818. Furthermore, the combined model exhibited a significant correlation with PFS (P < 0.001). CONCLUSION: The combined model, based on baseline hepatobiliary MRI, aids in predicting chemotherapeutic response and PFS in patients with initially unresectable CRLM.

Selective measurement of Cl2 and HCl based on dopant-assisted negative photoionization ion mobility spectrometry combined with semiconductor cooling.

This study presents an efficient approach for the precise detection of chlorine gas (Cl2) and hydrogen chloride (HCl), harmful pollutants frequently emitted from chlor-alkali and various industrial processes. These substances, even in trace amounts, pose significant health risks. Ion mobility spectrometry (IMS), known for its sensitivity in pollutant detection, traditionally struggles to differentiate between Cl2 and HCl due to the similarity of their product ions, Cl-. To overcome this limitation, we introduce a novel technique combining dopant-assisted negative photoionization ion mobility spectrometry (DANP-IMS) with an automatic semiconductor cooling system. This unique combination utilizes the differential cryogenic removal efficiencies of Cl2 and HCl to segregate these gases before analysis. By applying DANP-IMS, we achieved selective measurement of Cl- ion signal intensities under both standard and cryogenic conditions, facilitating the accurate quantification of total chlorine and Cl2 levels. We then determined HCl concentrations by deducting the Cl2 signal from the total chlorine readings. Our approach demonstrated detection limits of 2.0 parts per billion (ppb) for Cl2 and 0.8 ppb for HCl, across a linear detection range of 0-200 ppb. Moreover, our method's capability for real-time atmospheric monitoring of Cl2 and HCl near industrial sites underscores its utility for environmental monitoring, offering a robust solution for the separate and precise measurement of these pollutants.

Multi-layered heterogeneous interfaces created in Co0.85Se@Ni3S4/NF to enhance supercapacitor performances by multi-step alternating electrodeposition.

Heterogeneous interface construction is of far-reaching significance to optimize the electrochemical performance of electrodes. Herein, a multi-step alternating electrochemical deposition (MAED) method is proposed to alternately deposit Co0.85Se and Ni3S4 nanosheets on a nickel foam (NF), forming a special alternate layer-by-layer structure with multi-layered heterogeneous interfaces. The creation of the multi-layered heterogeneous interfaces provides a large interfacial area for redox reactions with optimum interstitials facilitating ion diffusion, thus greatly improving the electrochemical energy storage efficiency. With the increase in the layer number, the material exhibits increasingly better energy storage performance, and 8L-Co0.85Se@Ni3S4/NF exhibits the highest specific capacitances of 2508 F g-1 and 1558 F g-1 at a scan rate of 2 mV s-1 and a current density of 1 A g-1. The 8L-Co0.85Se@Ni3S4/NF//polypyrrole (PPy)/NF asymmetric supercapacitor provides a maximum operation potential window of 1.55 V and energy densities of 76.98 and 35.74 W h kg-1 when the power densities are 775.0 and 15 500 W kg-1, respectively, superior to most of the related materials reported. Through MAED, the deposited phase and the layer number can be accurately controlled, thus providing an efficient strategy for interface construction so as to increase the electrochemical activity of the energy storage materials.

Dermatofibrosarcoma Protuberans MRI: A Preliminary Comparison of Different Sequences.

OBJECTIVE: The purpose of this study was to compare the image quality of different MRI sequences regarding the presentation of Dermatofibrosarcoma Protuberans (DFSP). MATERIALS AND METHODS: We retrospectively collected MRI images of 40 patients who had been pathologically diagnosed with DFSP, including 21 primary tumors and 19 recurrent tumors. The image quality of different MRI sequences was assessed subjectively by two radiologists, taking into account the display of the lesions, artifacts, and distortions, as well as the overall impact of the image quality. RESULTS: Among the 40 cases, 22 cases involved the trunk, 14 cases involved the shoulders and limbs, 2 cases involved the head and neck, 1 case involved the breast, and 1 case involved the groin. In terms of image quality, fat suppression T2-weighted images were superior to T1-weighted images and T2-weighted images (P<0.05). The difference between fat suppression T2-weighted images and contrast-enhanced images was not significant (P>0.05). As far as lesion contrast is concerned, diffusion-weighted images, fat suppression T2-weighted images, and contrast-enhanced images did not differ significantly (P>0.05). On the DWI images, there were severe magnetic artifacts and deformations. CONCLUSIONS: Fat suppression T2-weighted images and enhanced sequences produce the highest quality images, while diffusion-weighted images provide the best lesion contrast.

Peripheral inflammatory T cell subsets are effective predictive factors in the development of heterotopic ossification after posttraumatic elbow surgery.

Heterotopic ossification refers to the pathological formation of extra-skeletal bone. It is a common complication of trauma or surgery that can cause disability and has no definitive cure. Furthermore, the mechanisms underlying chronic inflammation during ossification remain unclear. Therefore, this study aimed to elucidate the systemic immune microenvironment status of heterotopic ossification and identify biomarkers of therapeutic efficacy and recurrence. A combination of stereoarthrolysis with prophylactic radiotherapy and non-steroidal anti-inflammatory drugs was used to treat patients with heterotopic ossification. Changes were observed in peripheral blood lymphocyte levels after treatment. The number of IFNγ+CD8+T cells (3.753 % vs 12.90 %, P < 0.0001) and IL17+CD4+T cells (3.420 % vs 5.560 %, P = 0.0281) were was higher in the peripheral blood of relapsed patients with heterotopic ossification than in that of non-relapsed patients. Similarly, the number of these cells was elevated in patients who developed heterotopic ossification after posttraumatic elbow surgery. Peripheral CD8+T cells derived from patients with this pathology promoted osteogenesis through IFNγ expression in vitro. Our findings demonstrate that IFNγ+CD8+T cells and IL17+CD4+T cells are potential biomarkers of heterotopic ossification after posttraumatic elbow surgery. Furthermore, these cells can be used to predict therapeutic efficacy and relapse after combination therapy.

Potency Assay Variability Estimation in Practice.

During the drug development process, testing potency plays an important role in the quality assessment required for the manufacturing and marketing of biologics. Due to multiple operational and biological factors, higher variability is usually observed in bioassays compared with physicochemical methods. In this paper, we discuss different sources of bioassay variability and how this variability can be statistically estimated. In addition, we propose an algorithm to estimate the variability of reportable results associated with different numbers of runs and their corresponding OOS rates under a given specification. Numerical experiments are conducted on multiple assay formats to elucidate the empirical distribution of bioassay variability.