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Cytotoxic neuronal swelling and glutamate excitotoxicity are two hallmarks of ischemic stroke. However, the underlying molecular mechanisms are not well understood. Here, it is reported that SWELL1, the essential subunit of the volume‐regulated anion channel (VRAC), plays a dual role in ischemic injury by promoting neuronal swelling and glutamate excitotoxicity. SWELL1 expression is upregulated in neurons and astrocytes after experimental stroke in mice. The neuronal SWELL1 channel is activated by intracellular hypertonicity, leading to Cl− influx‐dependent cytotoxic neuronal swelling and subsequent cell death. Additionally, the SWELL1 channel in astrocytes mediates pathological glutamate release, indicated by increases in neuronal slow inward current frequency and tonic NMDAR current. Pharmacologically, targeting VRAC with a new inhibitor, an FDA‐approved drug Dicumarol, attenuated cytotoxic neuronal swelling and cell death, reduced astrocytic glutamate release, and provided significant neuroprotection in mice when administered either before or after ischemia. Therefore, these findings uncover the pleiotropic effects of the SWELL1 channel in neurons and astrocytes in the pathogenesis of ischemic stroke and provide proof of concept for therapeutically targeting it in this disease. [ABSTRACT FROM AUTHOR]

Neurodegenerative diseases are increasing in prevalence and place a significant burden on society. The causes are multifactorial and complex, and increasing evidence suggests a dynamic interplay between genes and the environment, emphasizing the importance of identifying and understanding the role of lifelong exposures, known as the exposome, on the nervous system. This review provides an overview of recent advances toward defining neurodegenerative disease exposomes, focusing on Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. We present the current state of the field based on emerging data, elaborate on key themes and potential mechanisms, and conclude with limitations and future directions. ANN NEUROL 2024;95:635–652 [ABSTRACT FROM AUTHOR]

Background: 18F‐fluorodeoxyglucose (FDG) positron emission tomography (PET) is valuable for determining presence of viable tumor, but is limited by geographical restrictions, radiation exposure, and high cost. Purpose: To generate diagnostic‐quality PET equivalent imaging for patients with brain neoplasms by deep learning with multi‐contrast MRI. Study Type: Retrospective. Subjects: Patients (59 studies from 51 subjects; age 56 ± 13 years; 29 males) who underwent 18F‐FDG PET and MRI for determining recurrent brain tumor. Field Strength/Sequence: 3T; 3D GRE T1, 3D GRE T1c, 3D FSE T2‐FLAIR, and 3D FSE ASL, 18F‐FDG PET imaging. Assessment: Convolutional neural networks were trained using four MRIs as inputs and acquired FDG PET images as output. The agreement between the acquired and synthesized PET was evaluated by quality metrics and Bland–Altman plots for standardized uptake value ratio. Three physicians scored image quality on a 5‐point scale, with score ≥3 as high‐quality. They assessed the lesions on a 5‐point scale, which was binarized to analyze diagnostic consistency of the synthesized PET compared to the acquired PET. Statistical Tests: The agreement in ratings between the acquired and synthesized PET were tested with Gwet's AC and exact Bowker test of symmetry. Agreement of the readers was assessed by Gwet's AC. P = 0.05 was used as the cutoff for statistical significance. Results: The synthesized PET visually resembled the acquired PET and showed significant improvement in quality metrics (+21.7% on PSNR, +22.2% on SSIM, −31.8% on RSME) compared with ASL. A total of 49.7% of the synthesized PET were considered as high‐quality compared to 73.4% of the acquired PET which was statistically significant, but with distinct variability between readers. For the positive/negative lesion assessment, the synthesized PET had an accuracy of 87% but had a tendency to overcall. Conclusion: The proposed deep learning model has the potential of synthesizing diagnostic quality FDG PET images without the use of radiotracers. Evidence Level: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

Objectives: Leptospira, the spirochaete causing leptospirosis, can be classified into >250 antigenically distinct serovars. Although knowledge of the animal host species and geographic distribution of Leptospira serovars is critical to understand the human and animal epidemiology of leptospirosis, current data are fragmented. We aimed to systematically review, the literature on animal host species and geographic distribution of Leptospira serovars to examine associations between serovars with animal host species and regions and to identify geographic regions in need of study. Methods: Nine library databases were searched from inception through 9 March 2023 using keywords including Leptospira, animal, and a list of serovars. We sought reports of detection of Leptospira, from any animal, characterised by cross agglutinin absorption test, monoclonal antibody typing, serum factor analysis, or pulsed‐field gel electrophoresis to identify the serovar. Results: We included 409 reports, published from 1927 through 2022, yielding data on 154 Leptospira serovars. The reports included data from 66 (26.5%) of 249 countries. Detections were from 144 animal host species including 135 (93.8%) from the class Mammalia, 5 (3.5%) from Amphibia, 3 (2.1%) from Reptilia, and 1 (0.7%) from Arachnida. Across the animal host species, Leptospira serovars that were detected in the largest number of animal species included Grippotyphosa (n = 39), Icterohaemorrhagiae (n = 29), Pomona (n = 28), Australis (n = 25), and Ballum (n = 25). Of serovars, 76 were detected in a single animal host species. We created an online database to identify animal host species for each serovar by country. Conclusions: We found that many countries have few or no Leptospira serovars detected from animal host species and that many serovars were detected from a single animal species. Our study highlights the importance of efforts to identify animal host species of leptospirosis, especially in places with a high incidence of human leptospirosis. We provide an updated resource for leptospirosis researchers. [ABSTRACT FROM AUTHOR]

Rationale: Video visits became more widely available during the coronavirus disease (COVID‐19) pandemic. However, the ongoing role and value of video visits in care delivery and how these may have changed over time are not well understood. Aims and Objectives: Compare the relative complexity of in‐person versus video visits during the COVID‐19 pandemic and describe the complexity of video visits over time. Methods: We used billing data for in‐person and video revisits from non‐behavioural health specialities with the most video visit utilisation (≥50th percentile) at a large, urban, public healthcare system from 1 January 2021 to 31 March 2022. We used current procedural terminology (CPT) codes as a proxy for information gathering and decision‐making complexity and time spent on an encounter. We compared the distribution of CPT codes 99211–99215 between in‐person and video visits using Fisher's exact tests. We used Spearman correlation to test for trends between proportions of CPT codes over time for video visits. Results: Ten specialities (adult primary care, paediatrics, adult dermatology, bariatric surgery, paediatric endocrinology, obstetrics and gynaecologist, adult haematology/oncology, paediatric allergy/immunology, paediatric gastroenterology, and paediatric pulmonology) met inclusion criteria. For each speciality, proportions of each CPT code for in‐person visits and for video visits varied significantly, and patterns of variation differed by speciality. For example, in adult primary care, video visits had smaller proportions of moderate/high complexity visits (99214 and 99215) and greater proportions of lower complexity visits (99211–99213) compared with in‐person visits (p < 0.001), but in paediatric endocrinology, the opposite was seen (p < 0.001). Trends in CPT codes over time for video visits in each speciality were also mixed. Conclusion: In‐person and video visits had differing proportions of complexity codes (typically skewing towards lower complexity for video visits). The complexity of video visits changed over time in many specialities. Observed patterns for both phenomena varied by speciality. [ABSTRACT FROM AUTHOR]

With the proliferation of information and communication technology in rural areas, rural e‐commerce has gradually become a new economic phenomenon in China. Using the national rural e‐commerce comprehensive demonstration policy as a quasi‐natural experiment, this study examines the causal linkage between rural e‐commerce and county‐level economic development in China. Its findings, which draw on county‐level panel data from 2011 to 2018, indicate that the policy had a positive effect on the county‐level economy in China, resulting in an overall increase in county GDP by 3.5 percent (0.7 percent annually). Our analysis further shows that the impact of the policy differed along the region and human capital dimensions. Further analysis reveals that industrial structure and nonagricultural employment were the main channels for the policy to exert a county‐level economic impact. Infrastructure improvement in China also plays an important role. The findings emphasize the importance of advancing e‐commerce in rural areas to stimulate county‐level economic development. [ABSTRACT FROM AUTHOR]

Background: Many pathways are implicated in pathogenesis of Alzheimer's disease (AD). Stem cells are a promising strategy to simultaneously correct multiple pathways; however, therapeutic mechanisms of stem cells are not well described. Here, we used spatial transcriptomics to quantitate gene expression following intracranial transplantation of human neural stem cells (hNSCs) in a mouse model of AD. Method: The 5XFAD mouse model was utilized. An hNSC cell line (HK532‐IGF1, Palisade Bio) was transplanted into fimbria fornix of the hippocampus (6 total injections, 180,000‐600,000 total cells). Spatial memory was assessed by Morris water maze. Amyloid plaques were assessed by immunofluorescence and ELISA. Hemibrains were submitted for spatial transcriptomics (Visium 10X, 10X Genomics) and significant differentially expressed genes (DEGs) were identified (p < 0.05). Pathway enrichment was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG), and CellChat network analysis examined communication between cell populations. Result: hNSC transplantation restored learning curves of 5XFAD mice in Morris water maze, mimicking wild‐type performance (Fig 1A). However, there were no changes in amyloid‐beta burden (Fig 1B‐C). Spatial transcriptomics elucidated non‐amyloid hNSC therapeutic mechanisms. In hippocampal subregions, we discovered 1061 normalized DEGs. KEGG pathway analysis revealed significant impact on protein processing ("ubiquitin mediated proteolysis", "protein export", and "proteosome"), "long‐term potentiation," and "metabolic pathways" (Fig 2). Plaque induced genes were normalized upon hNSC transplantation, particularly in microglia (Fig 3A). A reduction in stage 1 and stage 2 disease associated microglia (DAM) was seen, without affecting homeostatic microglia (Fig 3B). CellChat analysis showed hNSCs interacted with stage 1 and stage 2 DAM along many pathways (Fig 3C). Pathologic signaling between hippocampus and DAM upregulated in the 5XFAD model was again normalized upon hNSC transplantation. Conclusion: Transplantation of hNSCs rescued memory in 5XFAD mice. No change in amyloid plaque burden was noted, but spatial transcriptomics revealed many genes dysregulated in 5XFAD that were normalized with hNSC transplantation. hNSCs interacted with and normalized populations of stage 1 and stage 2 DAM. Our results suggest that hNSCs exert beneficial effects in part by modulating microglia‐mediated neuroinflammation in AD. [ABSTRACT FROM AUTHOR]

Background: This study aimed to validate early [18F]‐FDG (eFDG) imaging for the quantification of cerebral blood flow (CBF), enabling dual‐marker imaging of perfusion and metabolism with a single tracer. Method: 19 participants with memory concerns underwent simultaneous [18F]‐FDG PET and multi delay pseudo‐continuous arterial spin labeling (eASL) MR imaging on a hybrid 3T PET/MRI scanner. eFDG‐CBF maps were generated from the first 30s, 60s, 120s and 300s after injection, and measurements were compared to ASL‐CBF using voxel‐wise cross correlation and concordance correlation for 7 regions derived from the MNI‐structural atlas. Result: Highest voxel‐wise cross‐correlation to ASL‐CBF maps were reported for 300s (5 min) eFDG (r = 0.77).Concordance correlation (CC) values were strong in all ROIs, ranging from (CC = 0.88) to (CC = 0.65) in temporal and occipital regions respectively. Mean of measurements in all ROIs were in good agreement between eFDG and ASL CBF maps, with a reported voxel‐wise mean absolute error of ±6.73 ml/100g/min between two maps. Conclusion: By simultaneous measurement of hemodynamics across modalities with a TOF‐enabled PET/MRI, we were able to demonstrate that eFDG PET is a reliable measure in mapping CBF based on strong inter‐modality correlation with ASL‐CBF, irrespective of pathophysiological variations in memory patients. [ABSTRACT FROM AUTHOR]

Rationale: During the coronavirus disease pandemic, audio‐only and video telehealth visits became more widely available, but the relative patient satisfaction between telehealth and in‐person modalities is not well‐described. Aims and Objectives: Our objective was to compare patient satisfaction with audio‐only, video, and in‐person adult primary care visits at a large, urban public healthcare system. Methods: In this cross‐sectional study, we used aggregated data from Press Ganey patient satisfaction surveys at 17 primary care facilities at New York City Health + Hospitals for visits between 1 June 2021 to 30 November 2021. We compared mean scores for questions common to surveys for each modality in domains of Access, Care Provider, and Overall Assessment using pairwise comparisons with two‐tailed t‐tests. Results: There were 7,183/79,562 (9.0%) respondents for in‐person visits and 1,009/15,092 (6.7%) respondents for telehealth visits. Compared to respondents for in‐person visits, respondents for telehealth visits were more likely to be aged 35–64 years, Asian, and speak English as their primary language, and less likely to be ≥65 years old, Black or other race, and speak Spanish or another language as their primary language (p < 0.001). Patients reported higher mean satisfaction for Access measures for telehealth visits than in‐person visits (p < 0.001). For Care Provider satisfaction questions, video visits generally had higher mean scores than in‐person and, in turn, audio‐only visits. For Overall Assessment questions, video visits had higher mean scores than in‐person and, subsequently, audio‐only visits. Conclusion: Of the visit modalities, video visits had the highest mean satisfaction scores across all domains. Telehealth may improve experiences with access, but audio‐only visits may provide poorer visit experiences. [ABSTRACT FROM AUTHOR]

Background: Mechanical circulatory support (MCS) has been widely utilized in critically ill cardiac transplant candidates. Few studies have investigated the impact of duration of MCS before heart transplantation (HTx) on long‐term patient survival. Methods: A retrospective HTx database was reviewed between 2009 and 2019. Patients who did not or did undergo MCS before HTx were categorized into two groups: (1) A (did not) and (2) B (did), respectively. A receiver operating characteristic (ROC) curve was plotted to assess the cutoff level of MCS duration before HTx in evaluating 5‐year survival. Result: A total of 270 HTx patients (group A: 120, group B: 150) were analyzed. Group B patients had a higher percentage of blood type O, a higher incidence of resuscitation, a shorter listing duration, and a higher likelihood of having United Network for Organ Sharing (UNOS) 1A status than group A. The ROC curve revealed 24 days as a good cut‐off level for determining the best MCS before HTx timing. Group B was categorized into two subgroups: (1) B1 (MCS < 24 days, n = 65) and (2) B2 (MCS > 24 days, n = 85). B2 had a higher incidence of cardiopulmonary resuscitation (CPR), hemodialysis, longer waiting time after MCS, and better ventricular assist device implantation than B1. However, the survival curves showed that B1 outcomes were significantly worse than in groups A and B2. Groups A and B2 had similar survival curves without an increased incidence of infection. Conclusion: The preliminary data demonstrated that a longer duration of MCS may be associated with better outcomes than urgent HTx. [ABSTRACT FROM AUTHOR]

Background: As the field of stem cell therapy advances, it is important to develop reliable methods to overcome host immune responses in animal models. This ensures survival of transplanted human stem cell grafts and enables predictive efficacy testing. Immunosuppressive drugs derived from clinical protocols are frequently used but are often inconsistent and associated with toxic side effects. Here, using a molecular imaging approach, we show that immunosuppression targeting costimulatory molecules CD4 and CD40L enables robust survival of human xenografts in mouse brain, as compared to conventional tacrolimus and mycophenolate mofetil. Methods: Human neural stem cells were modified to express green fluorescent protein and firefly luciferase. Cells were implanted in the fimbria fornix of the hippocampus and viability assessed by non‐invasive bioluminescent imaging. Cell survival was assessed using traditional pharmacologic immunosuppression as compared to monoclonal antibodies directed against CD4 and CD40L. This paradigm was also implemented in a transgenic Alzheimer's disease mouse model. Results: Graft rejection occurs within 7 days in non‐immunosuppressed mice and within 14 days in mice on a traditional regimen. The addition of dual monoclonal antibody immunosuppression extends graft survival past 7 weeks (p <.001) on initial studies. We confirm dual monoclonal antibody treatment is superior to either antibody alone (p <.001). Finally, we demonstrate robust xenograft survival at multiple cell doses up to 6 months in both C57BL/6J mice and a transgenic Alzheimer's disease model (p <.001). The dual monoclonal antibody protocol demonstrated no significant adverse effects, as determined by complete blood counts and toxicity screen. Conclusions: This study demonstrates an effective immunosuppression protocol for preclinical testing of stem cell therapies. A transition towards antibody‐based strategies may be advantageous by enabling stem cell survival in preclinical studies that could inform future clinical trials. [ABSTRACT FROM AUTHOR]

The central nucleus of the amygdala (CeA) network consists of a heterogeneous population of inhibitory GABAergic neurons distributed across distinct subregions. While the specific roles for molecularly defined CeA neurons have been extensively studied, our understanding of functional heterogeneity within classes of molecularly distinct CeA neurons remains incomplete. In addition, manipulation of genetically defined CeA neurons has produced inconsistent behavioral results potentially due to broad targeting across CeA subregions. Therefore, elucidating heterogeneity within molecularly defined neurons in subdivisions of the CeA is pivotal for gaining a complete understanding of how CeA circuits function. Here, we used a multifaceted approach involving transgenic reporter mice, brain slice electrophysiology, and neuronal morphology to dissect the heterogeneity of corticotropin‐releasing hormone (CRH) neurons in topographically distinct subregions of the CeA. Our results revealed that intrinsic and morphological properties of CRH‐expressing (CRH+) neurons in the lateral (CeL) and medial (CeM) subdivisions of the CeA were significantly different. We found that CeL‐CRH+ neurons are relatively homogeneous in morphology and firing profile. Conversely, CeM‐CRH+ neurons displayed heterogeneous electrophysiological and morphological phenotypes. Overall, these results show phenotypic differences between CRH+ neurons in CeL and CeM. [ABSTRACT FROM AUTHOR]

The rat surgical anterior cruciate ligament transection (ACLT) model is commonly used to investigate intra‐articular osteoarthritis (OA) therapies, and histological assessment is often the primary outcome measure. However, histological changes do not always correlate well with clinical outcomes. Therefore, this study evaluated functional outcomes in the rat surgical ACLT model and compared intra‐articular injection volumes ranging from 20 to 50 μl. Unilateral ACLT was surgically induced and static weight‐bearing, mechanical allodynia, motor function, and gait were assessed in four groups of male, Sprague‐Dawley rats (n = 6 per group). Intra‐articular injections of 20 µl Dulbecco's phosphate‐buffered saline (DPBS), 50 µl DPBS, or 50 µl of synthetic biomimetic boundary lubricant were administered once weekly for 3 weeks postoperatively. Structural changes were evaluated histologically at 20 weeks. Rat cadaver knees were injected with 20, 30, 40, or 50 µl of gadolinium solutions and were imaged using magnetic resonance imaging (MRI). Static weight‐bearing, mechanical allodynia, and gait parameters in ACLT groups revealed differences from baseline and naïve controls for 4 weeks post‐ACLT; however, these differences did not persist beyond 6 weeks. Different intra‐articular DPBS injection volumes did not result in functional or histological changes; however, peri‐articular leakage was documented via MRI following 50, 40, and 30 µl but not 20 µl gadolinium injections. Statement of clinical significance: Differences in functional parameters were predominantly restricted to early, postoperative changes in the rat surgical ACLT model despite evidence of moderate histologic OA at 20 weeks. Injection volumes of 20–30 µl are more appropriate for investigating intra‐articular therapies in the rat knee. [ABSTRACT FROM AUTHOR]

BACKGROUND In China, pesticide retailers have often been accused of providing inaccurate advice on pesticide use to farmers in a chaotic pesticide market. However, it is unclear whether governmental regulation of sales and advice on pesticide use by pesticide retailers induces them to provide accurate advice. RESULTS: Using survey data of 242 pesticide retailers in 2016, this study analyzes how pesticide retailers in China provide advice on pesticide use to farmers and examines whether governmental regulation induces pesticide retailers to provide accurate advice. The surveyed retailers were found to advise farmers to use the correct active ingredients in only 75.6% of observations. Retailers recommended pesticide application rates higher than the scientifically recommended levels among 57.2% of observations. The bivariate probit model estimation results show that highly intensive governmental regulation increases the probability of correct advice on pesticide use of pesticide retailers in the county and township seats by 13% and 19%, respectively. Moreover, highly intensive regulation can also increase the probability of pesticide non‐overuse advice by the retailers from the retailers in the villages by 38%. CONCLUSION: Highly intensive governmental regulation can induce pesticide retailers to provide more accurate advice on pesticide use to farmers, but the effects differ across the locations of pesticide retailers. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Over the last three decades, fiber optic sensors (FOS) have gained a lot of attention for their wide range of monitoring applications across many industries, including aerospace, defense, security, civil engineering, and energy. FOS technologies hold great promise to form the backbone for next‐generation intelligent sensing platforms that offer long‐distance, high‐accuracy, distributed measurement capabilities and multiparametric monitoring with resilience to harsh environmental conditions. The major limitations posed by FOS are 1) cross‐sensitivity, 2) enormous volume and large data generation, 3) low data processing speed, 4) degradation of signal‐to‐noise ratio over the fiber length, and 5) overall cost of sensor and interrogator systems. These challenges can be overcome by building advanced data analytics engines enabled by recent breakthroughs in machine learning (ML) and artificial intelligence (AI). This article presents a comprehensive review of recent studies that integrate ML and AI algorithms with FOS technologies. This review also highlights several FOS technology development directions that promise a significant impact on widespread use for several industrial applications, with an emphasis on energy systems monitoring. A perspective on future directions for further research development is also provided. [ABSTRACT FROM AUTHOR]

Background: Individuals aged 65 and older face unique barriers to adoption of telehealth, and the coronavirus disease 2019 pandemic has provided a "natural experiment" in how to meet the health needs of older patients remotely. Physician perspectives on practical considerations surrounding telehealth adoption, motivations of use, and reasons for nonuse are necessary to inform the future of healthcare delivery. The objective is to understand the experiences of physicians using telemedicine for older patients. Methods: From September to November 2020, we conducted 30‐min semi‐structured interviews using purposeful sampling to identify and enroll participants from diverse settings. We included 48 U.S.‐based physicians (geriatrician, n = 18, primary care, n = 15, emergency, n = 15) from all geographic regions, rural–urban and academic/community settings. Audio‐recorded interviews were professionally transcribed and analyzed using framework analysis. Major themes and subthemes were identified. Results: Participants had a median (interquartile range) age of 37.5 (34–44.5), 27 (56%) were women. Five major themes emerged: (1) telehealth uptake was rapid and iterative, (2) telehealth improved the safety of medical care, (3) use cases were specialty‐specific (for geriatricians and primary care physicians telehealth substituted for in‐person visits; for emergency physicians it primarily supplemented in‐person visits), (4) physicians altered clinical care to overcome older patient barriers to telehealth use, and (5) telehealth use among physicians declined in mid‐April 2020, due primarily to patient needs and administrator preferences, not physician factors. Conclusion: In this qualitative analysis, physicians reported a rapid, iterative uptake of telehealth and attenuation of use as coronavirus disease 2019 prevalence declined. Physician experiences during the pandemic can inform interventions and policies to help buoy telehealth for ongoing healthcare delivery and ensure its accessibility for older Americans. [ABSTRACT FROM AUTHOR]

Diets are key determinants of nutrition and health and play a significant role in the environment. In this article, we aim to (i) describe dietary transitions and health in China and the consequent environmental challenges; (ii) identify differences between current Chinese diets and healthy reference diets; (iii) conduct a systematic review assessing the health impacts of four reference diets on the Chinese population, and (iv) simulate changes in greenhouse gas emissions under different diet scenarios. The results show differences between the Chinese diets and reference diets, with the current Chinese diet including mainly grains (especially refined rice), excessive meat consumption, and insufficient consumption of fruit and milk. If all Chinese consumers adopt one of the healthy reference diets all the time, the incidence of diet‐related chronic disease and mortality would be significantly reduced. Such dietary shifts would also reduce greenhouse gas emissions by 146–202 million tons (18–25 percent) compared with the projected emissions level in 2030. [ABSTRACT FROM AUTHOR]

Chinese migrant workers are very exposed to the shocks caused by the COVID‐19 pandemic. Falling remittances adversely affect their families who rely on remittance incomes. The impacts of COVID‐19 on migrants and remittance‐receiving households are assessed using a nationally representative household dataset and a microsimulation model. We found about 70 percent of migrant workers lost part of their wage income during the pandemic lockdown period and rural migrants working in small and medium enterprises were affected the most. This led to about 50 percent of remittance‐receiving households being affected adversely by falling remittances, and the average decline in such income was more than 45 percent. Nearly 13 percent of pre‐pandemic nonpoor remittance‐receiving households could fall into poverty, raising the poverty rate among remittance‐receiving households by 4 percentage points. Many households that were poor prior to the pandemic became more impoverished. The results indicate that social protection programs targeting vulnerable migrants and their families at home are important. [ABSTRACT FROM AUTHOR]

Monoclonal antibodies (mAbs) are currently used for the treatment of numerous conditions including cancer, psoriasis, arthritis, and atopic dermatitis, among others. All mAbs are currently administered by either intravenous or subcutaneous injections. Herein, the use of a novel ionic liquid and deep eutectic solvent, choline and glycolate (CGLY), as a platform for gastrointestinal administration of therapeutic antibodies is reported. CGLY maintains the stability and structure of TNFα antibody. CGLY significantly enhances paracellular transport of TNFα antibody in vitro. CGLY also reduces the viscosity of the intestinal mucus, another key barrier for antibody transport. In vivo results in rats demonstrate that CGLY effectively delivers TNFα antibody into the intestinal mucosa as well as systemic circulation. One week repeat dose study followed by histology and serum biochemistry analysis indicates that CGLY is well tolerated by rats. Overall, this work illustrates the promise of using choline‐based ionic liquids and deep eutectic solvents as an oral delivery platform for local as well as systemic delivery of therapeutic antibodies. [ABSTRACT FROM AUTHOR]

Disruptions in social behaviour are prevalent in many neuropsychiatric disorders such as schizophrenia, bipolar disorder and autism spectrum disorders. However, the underlying neurochemical regulation of social behaviour is still not well understood. The central cholinergic system has been proposed to contribute to the regulation of social behaviour. For instance, decreased global levels of acetylcholine release in the brain leads to decreased social interaction and an impairment of social memory in mice. Nonetheless, it has been difficult to ascertain the specific brain areas where cholinergic signalling influences social preference and social memory. In this study, we investigated the impact of different forebrain cholinergic regions on social behaviour by examining mouse lines that differ in their regional expression level of the vesicular acetylcholine transporter—the protein that regulates acetylcholine secretion. We found that when cholinergic signalling is highly disrupted in the striatum, hippocampus, cortex and amygdala mice have intact social preference but are impaired in social memory, as they cannot remember a familiar conspecific nor recognize a novel one. A similar pattern emerges when acetylcholine release is disrupted mainly in the striatum, cortex, and amygdala; however, the ability to recognize novel conspecifics is retained. In contrast, cholinergic signalling of the striatum and amygdala does not appear to significantly contribute to the modulation of social memory and social preference. Furthermore, we demonstrated that increasing global cholinergic tone does not increase social behaviours. Together, these data suggest that cholinergic transmission from the hippocampus and cortex are important for regulating social memory. [ABSTRACT FROM AUTHOR]

CASE REPORT The patient is a 75-year-old man with history of myelodysplastic syndrome who received an allogeneic peripheral blood stem cell transplant from a matched unrelated donor after conditioning including fludarabine and total body irradiation (400cGY). Here, we report a case of perianal malakoplakia in an allogeneic stem cell transplant patient. Keywords: cutaneous malakoplakia; malakoplakia; perianal EN cutaneous malakoplakia malakoplakia perianal 829 832 4 06/23/21 20210701 NES 210701 INTRODUCTION Malakoplakia is an unusual granulomatous reaction to bacterial infection, most often occurring in the genitourinary tract.1 Cutaneous malakoplakia is rare, with around 50 cases reported in the literature and 10 cases documented in the perianal region.1 Its infrequent occurrence in the skin can make recognition of this entity a diagnostic challenge for dermatopathologists. [Extracted from the article]

Pandemic outbreaks disrupt agricultural trade. The possible strengthening of import barriers to products from countries at the epicenter of a pandemic by their trade partners could aggravate this situation. This paper examines the responses of the US Food and Drug Administration (FDA), import refusals, and subsequent trade impacts on the agricultural exports from the developing countries that were the epicenters of four pandemics in the past two decades. Using monthly data for the period 2002–2020, we find increased import refusals and amplified trade‐impeding impacts on agricultural exports during pandemic outbreaks. Increased import refusals and the amplification of the trade‐impeding effect of import refusals were especially large when China was the epicenter. We further examine possible differences in these results across products and FDA inspection methods, and the main conclusions remain robust. This paper offers a better understanding of the economic outcomes of pandemic outbreaks and provides policy suggestions for China. [ABSTRACT FROM AUTHOR]

Objective: Prolonged fever‐induced seizures (febrile status epilepticus [FSE]) during early childhood increase the risk for later epilepsy, but the underlying mechanisms are incompletely understood. Experimental FSE (eFSE) in rats successfully models human FSE, recapitulating the resulting epileptogenesis in a subset of affected individuals. However, the powerful viral and genetic tools that may enhance mechanistic insights into epileptogenesis and associated comorbidities, are better‐developed for mice. Therefore, we aimed to determine if eFSE could be generated in mice and if it provoked enduring changes in hippocampal‐network excitability and the development of spontaneous seizures. Methods: We employed C57BL/6J male mice, the strain used most commonly in transgenic manipulations, and examined if early life eFSE could be sustained and if it led to hyperexcitability of hippocampal networks and to epilepsy. Outcome measures included vulnerability to the subsequent administration of the limbic convulsant kainic acid (KA) and the development of spontaneous seizures. In the first mouse cohort, adult naive and eFSE‐experiencing mice were exposed to KA. A second cohort of control and eFSE‐experiencing young adult mice was implanted with bilateral hippocampal electrodes and recorded using continuous video–electroencephalography (EEG) for 2 to 3 months to examine for spontaneous seizures (epileptogenesis). Results: Induction of eFSE was feasible and eFSE increased the susceptibility of adult C57BL/6J mice to KA, thereby reducing latency to seizure onset and increasing seizure severity. Of 24 chronically recorded eFSE mice, 4 (16.5%) developed hippocampal epilepsy with a latent period of ~3 months, significantly different from the expectation by chance (P =.04). The limbic epilepsy that followed eFSE was progressive. Significance: eFSE promotes pro‐epileptogenic network changes in a majority of C57BL/6J male mice and frank "temporal lobe–like" epilepsy in one sixth of the cohort. Mouse eFSE may thus provide a useful tool for investigating molecular, cellular, and circuit changes during the development of temporal lobe epilepsy and its comorbidities. [ABSTRACT FROM AUTHOR]

Objective: Intracranial electrographic localization of the seizure onset zone (SOZ) can guide surgical approaches for medically refractory epilepsy patients, especially when the presurgical workup is discordant or functional cortical mapping is required. Minimally invasive stereotactic placement of depth electrodes, stereoelectroencephalography (SEEG), has garnered increasing use, but limited data exist to evaluate its postoperative outcomes in the context of the contemporaneous availability of both SEEG and subdural electrode (SDE) monitoring. We aimed to assess the patient experience, surgical intervention, and seizure outcomes associated with these two epileptic focus mapping techniques during a period of rapid adoption of neuromodulatory and ablative epilepsy treatments. Methods: We retrospectively reviewed 66 consecutive adult intracranial electrode monitoring cases at our institution between 2014 and 2017. Monitoring was performed with either SEEG (n = 47) or SDEs (n = 19). Results: Both groups had high rates of SOZ identification (SEEG 91.5%, SDE 88.2%, P =.69). The majority of patients achieved Engel class I (SEEG 29.3%, SDE 35.3%) or II outcomes (SEEG 31.7%, SDE 29.4%) after epilepsy surgery, with no significant difference between groups (P =.79). SEEG patients reported lower median pain scores (P =.03) and required less narcotic pain medication (median = 94.5 vs 594.6 milligram morphine equivalents, P =.0003). Both groups had low rates of symptomatic hemorrhage (SEEG 0%, SDE 5.3%, P =.11). On multivariate logistic regression, undergoing resection or ablation (vs responsive neurostimulation/vagus nerve stimulation) was the only significant independent predictor of a favorable outcome (adjusted odds ratio = 25.4, 95% confidence interval = 3.48‐185.7, P =.001). Significance: Although both SEEG and SDE monitoring result in favorable seizure control, SEEG has the advantage of superior pain control, decreased narcotic usage, and lack of routine need for intensive care unit stay. Despite a heterogenous collection of epileptic semiologies, seizure outcome was associated with the therapeutic surgical modality and not the intracranial monitoring technique. The potential for an improved postoperative experience makes SEEG a promising method for intracranial electrode monitoring. [ABSTRACT FROM AUTHOR]

Scar forming wounds are often characterized by higher levels of vascularity than non‐scarring wounds and normal skin, and inhibition of angiogenesis has been shown to inhibit scar formation in some model systems. The rabbit ear hypertrophic scar (HS) model has been widely used to study the mechanisms that underlie the development of HS as well as the effectiveness of various treatments. Although the rabbit ear HS model is well characterized in terms of scar formation, the rate and level of angiogenesis has not been investigated in this model, and the cause‐effect relationship between angiogenesis and rabbit HSs has not been examined. In the current study, full‐thickness excisional wounds were created on the ventral side of New Zealand White rabbit ears to induce HS formation, and the dynamic pattern of angiogenesis and the expression of angiogenic regulatory factors were examined over time. Blood vessel density was found to peak at 2.7% on day 14 post‐wounding, decreasing to 1.7% by day 28. mRNA levels of the proangiogenic factor VEGF‐A peaked at day 14, while the expression of the antiangiogenic factors pigment epithelium‐derived factor (PEDF) and thrombospondin 1 (TSP1) peaked at day 28 post‐wounding. To examine whether inhibition of angiogenesis influences HS formation in this model, wounds were treated with exogenous soluble antiangiogenic agents including recombinant PEDF (rPEDF) and a functional PEDF peptide (PEDF‐335). rPEDF and PEDF‐335 were administered intradermally from day 4 post‐wounding every 3 days until day 19. Intradermal injection of rPEDF or PEDF‐335 both led to decreased angiogenesis and decreased collagen deposition at the wound site. The results support the utility of antiangiogenic therapies, including rPEDF/PEDF‐335, as a potential new strategy for the prevention or treatment of HSs. [ABSTRACT FROM AUTHOR]

We conduct a randomized controlled trial to examine the impacts of delayed premium payment on insurance uptake and the subsequent investment decisions among smallholder farmers in rural China. Our results show uptake among those with the delayed payment option is 10% higher than and three times as high as among those without the option. We also find a positive impact of delayed premium payment and insurance adoption on household investment in production, especially higher risk activities. [ABSTRACT FROM AUTHOR]

Background: While many developmentally relevant enhancers act in a modular fashion, there is growing evidence for nonadditive interactions between distinct cis‐regulatory enhancers. We investigated if nonautonomous enhancer interactions underlie transcription regulation of the Drosophila segment polarity gene, wingless. Results: We identified two wg enhancers active at the blastoderm stage: wg 3613u, located from −3.6 to −1.3 kb upstream of the wg transcription start site (TSS) and 3046d, located in intron two of the wg gene, from 3.0 to 4.6 kb downstream of the TSS. Genetic experiments confirm that Even Skipped (Eve), Fushi‐tarazu (Ftz), Runt, Odd‐paired (Opa), Odd‐skipped (Odd), and Paired (Prd) contribute to spatially regulated wg expression. Interestingly, there are enhancer specific differences in response to the gain or loss of function of pair‐rule gene activity. Although each element recapitulates aspects of wg expression, a composite reporter containing both enhancers more faithfully recapitulates wg regulation than would be predicted from the sum of their individual responses. Conclusion: These results suggest that the regulation of wg by pair‐rule genes involves nonadditive interactions between distinct cis‐regulatory enhancers. Key Findings: Two distinct DNA elements within the Drosophila wingless locus that are associated with DNA‐binding proteins encoded by the pair‐rule segmentation genes mediate regulation by these genes in the early embryo.Neither of these two elements faithfully emulates the full range of wingless regulation in response to manipulations in pair‐rule gene activity.A composite reporter gene construct containing both enhancers more faithfully emulates wingless regulation than is expected from the sum of the expression patterns produced by the two single elements.The ectopic expression produced by the intronic enhancer is suppressed in a reporter gene construct that also contains the upstream enhancer element. [ABSTRACT FROM AUTHOR]

Herein, gallium nitride (GaN) samples implanted with magnesium (Mg) and fluorine (F) ions are investigated by photoluminescence (PL) measurements. In low‐temperature PL measurements, the characteristic green luminescence (GL) band attributable to nitrogen vacancies (VN) is observed in Mg‐ion‐implanted GaN. As VN are likely to act as donors, suppressing their formation is essential to realizing p‐type conductivity. The energy required for a F impurity to replace VN in GaN and eventually form F on a N site decreases when the Fermi level approaches the valence band maximum, and therefore F is employed as a subsequent implantation element to compensate for VN. The GL band peak disappears upon implanting Mg and F ions at a high temperature and adjusting the F concentration to an appropriate value. This result suggests that VN generated by Mg ion implantation can be suppressed using an element with a lower formation energy than that of VN. [ABSTRACT FROM AUTHOR]

Introduction: Direct oral anticoagulants (DOACs) effectively prevent recurrent venous thromboembolism (VTE). However, it is unknown which agents should be used to prevent recurrent VTE and which patients with unprovoked VTE should receive extended anticoagulation. We therefore sought to compare the efficacy and safety among DOACs for secondary prevention of VTE. We also determined a risk‐adapted threshold for initiating extended anticoagulation based on the likelihood of VTE recurrence (without treatment) and bleeding (with treatment) in patients with unprovoked VTE. Methods: Our systematic review of randomized controlled trials compares extended anticoagulation with DOACs to another DOAC, aspirin, or placebo for the prevention of recurrent VTE. We searched PubMed, EMBASE, and Cochrane Registry of Controlled Trials (CENTRAL) in October 2018. Our outcomes of interest were VTE recurrence, major bleeding, and all clinically relevant bleeding. We used network meta‐analysis to make indirect comparisons among DOACs. We populated the threshold decision‐analytic model with data from our meta‐analysis to determine the risk of VTE recurrence above which the benefits of extended anticoagulation outweigh the harms compared with no treatment. Results: We included four, high‐quality, randomized trials comprising 8386 participants. Low‐dose apixaban, full‐dose apixaban, low‐dose rivaroxaban, full‐dose rivaroxaban, and dabigatran reduce VTE recurrence compared with placebo (RR = 0.19, 95% CI, 0.12‐0.31; RR = 0.20, 95% CI, 0.12‐0.32; RR = 0.08, 95% CI, 0.03‐0.27; RR = 0.14, 95% CI, 0.06‐0.35; RR = 0.19, 95% CI, 0.09‐0.40, respectively). No DOACs increased major bleeding risk compared with placebo. A VTE recurrence risk above 0.3% to 0.4% at approximately 1 year is the threshold to treat a patient with unprovoked VTE with extended anticoagulation (with any DOAC). Conclusions: All DOACs exhibit comparable efficacy for the prevention of recurrent VTE. Given that the risk of VTE recurrence is much higher than the calculated threshold for treatment, extended thromboprophylaxis should be considered in all patients with unprovoked VTE who do not have increased bleeding risk. [ABSTRACT FROM AUTHOR]

Summary: Bortezomib in combination with cyclophosphamide and dexamethasone (CyBorD, is a well‐established frontline chemotherapy regimen for patients with multiple myeloma, but prospective data on elderly non‐transplant eligible patients is limited. A total of 155 patients aged 70 years or older with newly diagnosed multiple myeloma who received at least one cycle of CyBorD chemotherapy in three centres across New Zealand were evaluated. Partial response or better was achieved in 79·4%, of whom 52·9% achieved at least a very good partial response. After a median follow‐up of 31·9 months, the median event‐free survival (EFS) was 17·0 months (age 70–80 years, 17·7 months; age above 80 years, 8·6 months; P = 0·002). The median overall survival was 45·1 months (age 70–80, 49·8 months; above 80, 33·3 months; P = 0·003). Amongst those who had seven or more cycles of treatment, those who had a pre‐planned switch to bortezomib‐thalidomide‐dexamethasone (VTD) consolidation had a superior median EFS of 25·4 months, compared with 20·3 months in the CyBorD only group (P = 0·028). This is the largest real‐world dataset on the efficacy of CyBorD in the elderly population, and pre‐planned switch to VTD was associated with better outcomes. [ABSTRACT FROM AUTHOR]

Background: We have previously developed a research pipeline to identify potential suppressors of APOE ε4 risk on Alzheimer's disease (AD), and we have successfully identified an epigenomic factor which may act as ε4 suppressor. However, it is unknown which cell type is more important to contain this ε4 suppressor on the transcriptome level. Method: We included single‐nucleus RNA sequencing (snRNAseq) data of the postmortem human brains from 424 subjects of the Religious Orders Study or the Rush Memory and Aging Project (ROSMAP). Based on this snRNAseq data, we have derived the estimate of the percentage and transcriptomic profiles of different types of brain cells including excitatory neurons, inhibitory neurons, endothelial cells, pericytes, oligodendrocytes, astrocytes, and microglia. Besides the main cell types, we further derived the estimates on the cell subtype level. With the generalized linear regression model, the final prioritized cell types and genes should fulfill two criteria: (1) be associated with AD pathologies (pTAU and neuritic plaque) in all subjects; and (2) reduce the effect of ε4 on AD susceptibility. Result: Based on the transcriptome‐wide association study (TWAS) of the main brain cells, almost all the brain cell types contain at least one genome‐wide significant (P≤6.5×10−6) gene which can act as the APOE ε4 suppressor on AD risk. However, the subtype cellular analysis suggested that neuronal subtypes are more important than the other cell types because almost all the subtypes of the excitatory neuronal cells (15 out of 16) contain the genome‐wide significant ε4 suppressor while this percentage for microglia is only 25% (4 out of 16). The pathway analysis suggested that the top 179 genes expressed in the neuronal cells were involved in the trans‐synaptic signaling by trans‐synaptic complex and synapse assembly. Conclusion: On the transcription level, APOE ε4 suppressor effects are present across a variety of different brain cell types but enriched in neurons where synapse pathways appear to play a predominant role in suppressing the effect of APOE ε4. [ABSTRACT FROM AUTHOR]

The article discusses the magnitude and the nature of analysts' and investors' functional fixation on reporting accounting numbers. The article examines the issue by using a sample of 158 deferred tax adjustments resulting from the Omnibus Budget Reconcillation Act of 1993. The article attempts to test two competing descriptions of investor behavior. The article explores how financial analysts handled the adjustment in their forecasts of third-quarter earnings per share (EPS). The article finds that analysts generally did not include these adjustments in their earnings forecasts. The data in the article is compared to literature on market efficiency and functional fixation.

Purpose: Our goal was to use a generative adversarial network (GAN) with feature matching and task‐specific perceptual loss to synthesize standard‐dose amyloid Positron emission tomography (PET) images of high quality and including accurate pathological features from ultra‐low‐dose PET images only. Methods: Forty PET datasets from 39 participants were acquired with a simultaneous PET/MRI scanner following injection of 330 ± 30 MBq of the amyloid radiotracer 18F‐florbetaben. The raw list‐mode PET data were reconstructed as the standard‐dose ground truth and were randomly undersampled by a factor of 100 to reconstruct 1% low‐dose PET scans. A 2D encoder‐decoder network was implemented as the generator to synthesize a standard‐dose image and a discriminator was used to evaluate them. The two networks contested with each other to achieve high‐visual quality PET from the ultra‐low‐dose PET. Multi‐slice inputs were used to reduce noise by providing the network with 2.5D information. Feature matching was applied to reduce hallucinated structures. Task‐specific perceptual loss was designed to maintain the correct pathological features. The image quality was evaluated by peak signal‐to‐noise ratio (PSNR), structural similarity (SSIM), and root mean square error (RMSE) metrics with and without each of these modules. Two expert radiologists were asked to score image quality on a 5‐point scale and identified the amyloid status (positive or negative). Results: With only low‐dose PET as input, the proposed method significantly outperformed Chen et al.'s method (Chen et al. Radiology. 2018;290:649–656) (which shows the best performance in this task) with the same input (PET‐only model) by 1.87 dB in PSNR, 2.04% in SSIM, and 24.75% in RMSE. It also achieved comparable results to Chen et al.'s method which used additional magnetic resonance imaging (MRI) inputs (PET‐MR model). Experts' reading results showed that the proposed method could achieve better overall image quality and maintain better pathological features indicating amyloid status than both PET‐only and PET‐MR models proposed by Chen et al. Conclusion: Standard‐dose amyloid PET images can be synthesized from ultra‐low‐dose images using GAN. Applying adversarial learning, feature matching, and task‐specific perceptual loss are essential to ensure image quality and the preservation of pathological features. [ABSTRACT FROM AUTHOR]

Objective: To better understand the potential effects after corticotomy accelerated osteogenic orthodontic treatment (CAOOT).Setting and Sample Population: Systematic review with meta-analysis.Materials and Methods: A literature search up to August 2018 was conducted to identify randomized clinical studies (RCTs) on CAOOT reporting periodontal parameters, bone changes, patient-centred and short- and long-term adverse outcomes. A random-effects meta-analysis was performed on various parameters (bone density, buccal bone thickness, anchorage loss, visual analog scale, root resorption and retraction time) to quantify weighted treatment effects.Results: A total of five split mouth, four parallel arms, one regular RCTs and two prospective CCTs were included (206 patients). Pooled data showed increase in bone thickness by 0.68 mm (95% CI: 1.17, 0.19) and reduced retraction time by 2.80 months (95% CI: -4.17, -1.43). There were statistically insignificant differences for root resorption 0.24 mm (95% CI: -0.49, 0.96), anchorage loss 0.49 mm (95% CI: -1.38, 0.40), worsening of periodontal parameters (gingival index) by 0.30 (95% CI: -0.83, 0.23) and mean increase in bone density of 7.07% on the corticotomy side at 6 months (95% CI: -3.24, 17.38).Conclusion: Current evidence suggests a very low to low level of certainty (GRADE assessment) in regard to quantified effects after CAOOT. Although CAOOT procedures show insignificant increase in the density following the use of bone graft and anchorage loss, they appear to accelerate the tooth movement during the first few months, to increase the buccal bone thickness and to show good tolerance by the patients; the clinical significance of these changes may be considered questionable. [ABSTRACT FROM AUTHOR]

Background: Subject motion in positron emission tomography (PET) studies leads to image blurring and artifacts; simultaneously acquired magnetic resonance imaging (MRI) data provides a means for motion correction (MC) in integrated PET/MRI scanners.Purpose: To assess the effect of realistic head motion and MR-based MC on static [18 F]-fluorodeoxyglucose (FDG) PET images in dementia patients.Study Type: Observational study.Population: Thirty dementia subjects were recruited.Field Strength/sequence: 3T hybrid PET/MR scanner where EPI-based and T1 -weighted sequences were acquired simultaneously with the PET data.Assessment: Head motion parameters estimated from high temporal resolution MR volumes were used for PET MC. The MR-based MC method was compared to PET frame-based MC methods in which motion parameters were estimated by coregistering 5-minute frames before and after accounting for the attenuation-emission mismatch. The relative changes in standardized uptake value ratios (SUVRs) between the PET volumes processed with the various MC methods, without MC, and the PET volumes with simulated motion were compared in relevant brain regions.Statistical Tests: The absolute value of the regional SUVR relative change was assessed with pairwise paired t-tests testing at the P = 0.05 level, comparing the values obtained through different MR-based MC processing methods as well as across different motion groups. The intraregion voxelwise variability of regional SUVRs obtained through different MR-based MC processing methods was also assessed with pairwise paired t-tests testing at the P = 0.05 level.Results: MC had a greater impact on PET data quantification in subjects with larger amplitude motion (higher than 18% in the medial orbitofrontal cortex) and greater changes were generally observed for the MR-based MC method compared to the frame-based methods. Furthermore, a mean relative change of ∼4% was observed after MC even at the group level, suggesting the importance of routinely applying this correction. The intraregion voxelwise variability of regional SUVRs was also decreased using MR-based MC. All comparisons were significant at the P = 0.05 level.Data Conclusion: Incorporating temporally correlated MR data to account for intraframe motion has a positive impact on the FDG PET image quality and data quantification in dementia patients.Level Of Evidence: 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1288-1296. [ABSTRACT FROM AUTHOR]

Erratum: "Ultra-low-dose PET reconstruction using generative adversarial network with feature matching and task-specific perceptual loss" Https://doi.org/10.1002/mp.13626 In the Conflicts of Interest section, G.Z. acknowledges funding support from GE Healthcare, consulting fees from Biogen, and equity in Subtle Medical, Inc. E.G. acknowledges equity in Subtle Medical, Inc. The original version of this article erroneously listed G.Z. as affiliated with Subtle Medical, Inc, which was not correct. [Extracted from the article]

Background: Reduced CBF and amyloid update measured by PET imaging have been reported among Alzheimer's disease (AD) patients. Evidence suggested that early amyloid update may reflect the underlying CBF information. In this pilot study, we aimed to compare whether early uptake amyloid PET images can be used to estimate CBF, by comparing them with gold‐standard 15O‐water PET CBF images. Method: Data were collected from an AD patient (female, 74 years) and a normal subject (female, 75 years) using a simultaneous 3T PET/MRI system and injection of 775 MBq of 15O‐water followed by 330 MBq of the amyloid radiotracer 18F‐florbetaben. CBF was computed by fitting the reconstructed PET data to a one‐compartment pharmacokinetic model using an image‐derived AIF. The amyloid PET data were reconstructed from time of injection to 1 and 5 minutes post‐injection yielding two short early duration uptake images, with the OSEM reconstruction parameters set as 2 iterations, 28 subsets, and a 4mm Gaussian post‐reconstruction filter. All images were transformed to the MNI‐152 2mm standard space using non‐linear registration. Result: The figure shows the measured CBF and amyloid PET maps of the patient and normal subject. In the AD patient, a CBF deficit is present in the posterior biparietal regions (indicated by the arrows), in contrast with other regions. This characteristic CBF deficit is not seen in the normal subject. Conclusion: With further investigation and quantification in various tracers and participant populations, using early dynamic data acquired with amyloid PET tracers could be a potential tool for measuring CBF [ABSTRACT FROM AUTHOR]

Background: In neurodegenerative diseases such as Alzheimer's disease, simultaneous PET/MRI provides a "one‐stop shop" to acquire biomarkers as outlined by the AT(N) criteria. However, to enable large‐scale imaging studies of dementia with frequent follow‐ups, a reduction of injected radiotracer dose and the enhancement of the degraded image quality after reconstruction needs to be addressed. With deep learning‐based methods, we have previously demonstrated the use of U‐Net‐based methods that incorporate spatially correlated PET/MRI information to produce high quality 18F‐florbetaben amyloid PET images from scan protocols with markedly reduced injected radiotracer dose (as low as ∼1% dose). However, for tau radiotracers, where the uptake is focal, has greater image noise, and the signal is weaker than that of amyloid, we also aim to investigate whether a generative adversarial network (GAN) can enhance ultra‐low‐dose tau PET images and whether the generated images are of diagnostic quality. Method: 44 participants (18 female, 70.2±7.5 years) were recruited to train the ultra‐low‐dose tau GAN; 221±61 MBq of the tau radiotracer 18F‐PI‐2620 was injected. T1‐weighted and T2‐FLAIR MRI were acquired simultaneously. A subset of the list mode consisting of 1/20 of the events (simulating 5% dose) was reconstructed to produce an ultra‐low‐dose PET image and used as inputs along with the MR images to train the GAN. The image quality of the enhanced PET and the ultra‐low‐dose PET images were compared to the original full‐dose image using three image‐based metrics ; the mean and standard deviation of uptake in the medial temporal lobe and inferior temporal cortex as well as SUVRs were also calculated. Three clinicians were recruited to evaluate tracer uptake on various regions of interest. Result: The enhanced images showed significant noise reduction compared to the low‐dose image (Figure); uptake patterns in the low‐dose and enhanced images were read accurately (Gwet's AC1>0.84 for all relevant regions) compared to their full‐dose counterparts. Conclusion: The deep learning‐enhanced images had marked noise reduction and were able to be read clinically for regional uptake patterns of tau accumulation similarly as the full‐dose images. This technique can potentially increase the utility of hybrid PET/MR imaging in clinical diagnoses and longitudinal studies. [ABSTRACT FROM AUTHOR]

In this work, characterizations are conducted to investigate the threshold voltage (VTH) stability of the normally‐off GaN metal–insulator–semiconductor (MIS‐) field‐effect transistor (FET) with fully recessed gate structure and highly reliable low‐pressure chemical vapor deposition SiNx gate dielectric. We conducted bias‐temperature instability (BTI) tests under both positive and negative gate bias. We demonstrated the highly stable VTH of the high‐performance MIS‐FETs with small BTI, which benefits from the effective interfacial protection layer. More specifically, combining the BTI tests and drain current 1/f noise analysis, we present extensive investigation of the physical origins of BTI. According to the experimental evidence and analysis, we ascribe the VTH instability to the trapping/detrapping of the pre‐existing trap states located at the SiNx/GaN interface and/or in the gate dielectric. [ABSTRACT FROM AUTHOR]

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