| 1. |
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| 2. |
- He, YQ, et al.
(författare)
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A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1, s. 1966-
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Tidskriftsartikel (refereegranskat)abstract
- Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10−7 to 4.79 × 10−44). By incorporating the PRS into EBV-serology-based NPC screening, the test’s positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.
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| 3. |
- Wang, Bei, et al.
(författare)
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High-Performance Liquid Alloy Patterning of Epidermal Strain Sensors for Local Fine Skin Movement Monitoring
- 2019
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Ingår i: SOFT ROBOTICS. - : MARY ANN LIEBERT, INC. - 2169-5172 .- 2169-5180. ; 6:3, s. 414-421
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Tidskriftsartikel (refereegranskat)abstract
- Nowadays, stretchable/epidermal electronics based on liquid alloys has attracted more and more attention, and various processing techniques have subsequently been developed to demonstrate diverse applications never seen before. However, to fully exploit its potential advantages, epidermal electronics is still searching for a technique meeting all demands on resolution, pattern complexity, and operational flexibility. In this study, we propose a technique that allows for complex and high-density patterns on thin stretchable substrates by combining ultraviolet laser patterning of a modified water-soluble mask, atomized spray deposition of liquid alloys on a flexible temporary substrate, lift-off by water dissolving, and finally, component integration and encapsulation. With this new technique, it was possible to make epidermal precision strain sensors with liquid alloy patterns of high density, which were capable of monitoring fine local skin movements such as the detailed process of wrinkle formation as well as the overall motion of the body part. In addition, this process is highly efficient and well controllable, with high potential for possible industrial automation and massive production.
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| 4. |
- Zhang, Shuo, et al.
(författare)
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High-Fidelity Conformal Printing of 3D Liquid Alloy Circuits for Soft Electronics
- 2019
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Ingår i: ACS Applied Materials and Interfaces. - : AMER CHEMICAL SOC. - 1944-8244 .- 1944-8252. ; 11:7, s. 7148-7156
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Tidskriftsartikel (refereegranskat)abstract
- Owing to the great deformability from fluid, liquid alloy-based soft electronics has inherent advantages over rigid-based ones for applications such as stretchable intelligence or soft robotics, where high fidelity of three-dimensional (3D) conformability or dynamic morphology is required. However, current fabrications heavily rely on planar techniques, which severely limit their great potential in such attracting applications. By tuning the wettability of liquid alloy on a soft substrate through a selective surface morphology modification, we present a flexography printing technique of liquid alloy circuits on both planar (from diverse materials) and 3D complex surfaces and investigate the tuning mechanism and the relation between liquid alloy wettability and surface morphology modification. In a demonstration, high-fidelity printing of liquid alloy circuits can be deployed not only on the outline but also on small pits of strawberry surface, and the circuits work well in a dynamic deformation. Furthermore, being compatible with current industry process, our technique can be highly potential for future mass manufacturing of liquid alloy-based soft electronics.
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| 5. |
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| 6. |
- Corazzini, Kirsten N., et al.
(författare)
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Toward Common Data Elements for International Research in Long-term Care Homes : Advancing Person-Centered Care
- 2019
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier. - 1525-8610 .- 1538-9375. ; 20:5, s. 598-603
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Tidskriftsartikel (refereegranskat)abstract
- To support person-centered, residential long-term care internationally, a consortium of researchers in medicine, nursing, behavioral, and social sciences from 21 geographically and economically diverse countries have launched the WE-THRIVE consortium to develop a common data infrastructure. WE-THRIVE aims to identify measurement domains that are internationally relevant, including in low-, middle-, and high-income countries, prioritize concepts to operationalize domains, and specify a set of data elements to measure concepts that can be used across studies for data sharing and comparisons. This article reports findings from consortium meetings at the 2016 meeting of the Gerontological Society of America and the 2017 meeting of the International Association of Gerontology and Geriatrics, to identify domains and prioritize concepts, following best practices to identify common data elements (CDEs) that were developed through the US National Institutes of Health/National Institute of Nursing Research's CDEs initiative. Four domains were identified, including organizational context, workforce and staffing, person-centered care, and care outcomes. Using a nominal group process, WE-THRIVE prioritized 21 concepts across the 4 domains. Several concepts showed similarity to existing measurement structures, whereas others differed. Conceptual similarity (convergence; eg, concepts in the care outcomes domain of functional level and harm-free care) provides further support of the critical foundational work in LTC measurement endorsed and implemented by regulatory bodies. Different concepts (divergence; eg, concepts in the person-centered care domain of knowing the person and what matters most to the person) highlights current gaps in measurement efforts and is consistent with WE-THRIVE's focus on supporting resilience and thriving for residents, family, and staff. In alignment with the World Health Organization's call for comparative measurement work for health systems change, WE-THRIVE's work to date highlights the benefits of engaging with diverse LTC researchers, including those in low-, middle-, and high-income countries, to develop a measurement infrastructure that integrates the aspirations of person-centered LTC.
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| 7. |
- Ding, Xue Bing, et al.
(författare)
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Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson’s disease
- 2021
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27:3, s. 411-418
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Tidskriftsartikel (refereegranskat)abstract
- Animal studies implicate meningeal lymphatic dysfunction in the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease (PD). However, there is no direct evidence in humans to support this role1–5. In this study, we used dynamic contrast-enhanced magnetic resonance imaging to assess meningeal lymphatic flow in cognitively normal controls and patients with idiopathic PD (iPD) or atypical Parkinsonian (AP) disorders. We found that patients with iPD exhibited significantly reduced flow through the meningeal lymphatic vessels (mLVs) along the superior sagittal sinus and sigmoid sinus, as well as a notable delay in deep cervical lymph node perfusion, compared to patients with AP. There was no significant difference in the size (cross-sectional area) of mLVs in patients with iPD or AP versus controls. In mice injected with α-synuclein (α-syn) preformed fibrils, we showed that the emergence of α-syn pathology was followed by delayed meningeal lymphatic drainage, loss of tight junctions among meningeal lymphatic endothelial cells and increased inflammation of the meninges. Finally, blocking flow through the mLVs in mice treated with α-syn preformed fibrils increased α-syn pathology and exacerbated motor and memory deficits. These results suggest that meningeal lymphatic drainage dysfunction aggravates α-syn pathology and contributes to the progression of PD.
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| 8. |
- Edvardsson, David, et al.
(författare)
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Advancing Long-Term Care Science Through Using Common Data Elements : Candidate Measures for Care Outcomes of Personhood, Well-Being, and Quality of Life
- 2019
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Ingår i: Gerontology and geriatric medicine. - : Sage Publications. - 2333-7214. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- To support the development of internationally comparable common data elements (CDEs) that can be used to measure essential aspects of long-term care (LTC) across low-, middle-, and high-income countries, a group of researchers in medicine, nursing, behavioral, and social sciences from 21 different countries have joined forces and launched the Worldwide Elements to Harmonize Research in LTC Living Environments (WE-THRIVE) initiative. This initiative aims to develop a common data infrastructure for international use across the domains of organizational context, workforce and staffing, person-centered care, and care outcomes, as these are critical to LTC quality, experiences, and outcomes. This article reports measurement recommendations for the care outcomes domain, focusing on previously prioritized care outcomes concepts of well-being, quality of life (QoL), and personhood for residents in LTC. Through literature review and expert ranking, we recommend nine measures of well-being, QoL, and personhood, as a basis for developing CDEs for long-term care outcomes across countries. Data in LTC have often included deficit-oriented measures; while important, reductions do not necessarily mean that residents are concurrently experiencing well-being. Enhancing measurement efforts with the inclusion of these positive LTC outcomes across countries would facilitate international LTC research and align with global shifts toward healthy aging and person-centered LTC models.
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| 9. |
- Jiang, Jiajun, et al.
(författare)
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Hydroprinted Liquid-Alloy-Based Morphing Electronics for Fast-Growing/Tender Plants : From Physiology Monitoring to Habit Manipulation
- 2020
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Ingår i: Small. - : WILEY-V C H VERLAG GMBH. - 1613-6810 .- 1613-6829. ; 16:39
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Tidskriftsartikel (refereegranskat)abstract
- Monitoring physiological signals and manipulating growth habits of living plants in real time are important for botany research, biohybrid plant robots, and precision agriculture. Although emerging epidermal electronics that can conveniently acquire vital signals of living organisms exhibit a high potential for such scenarios, it is a significant challenge to adapt such devices for plants, because they are fragile and usually have complex surfaces that can change significantly during rapid growth. A gentle fabrication process is critical in order to employ compliant electronic systems to adapt to this highly dynamic situation. In this study, a hydroprinted liquid-alloy-based morphing electronics (LAME) process is employed for fast-growing plants that will sense physiological signals and even function as a biohybrid to determine plant behavior on demand. Besides various surfaces of inorganic targeting substrates, pinning liquid alloy circuits onto the complex plant epidermis is enhanced by introducing high-surface-energy liquid. Functionally, the new developed LAME can be used to monitor leaf moisture content and length, and manipulate leaf and bean sprout orientation. This study lays the foundation for a new form of morphing electronics for botany or biohybrid plant robots, potentially impacting the next generation of precision agriculture and smart hybrid robots.
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| 10. |
- Li, Wei, et al.
(författare)
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Non-lab and semi-lab algorithms for screening undiagnosed diabetes : A cross-sectional study
- 2018
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Ingår i: EBioMedicine. - : ELSEVIER SCIENCE BV. - 2352-3964. ; 35, s. 307-316
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Tidskriftsartikel (refereegranskat)abstract
- Background: The terrifying undiagnosed rate and high prevalence of diabetes have become a public emergency. A high efficiency and cost-effective early recognition method is urgently needed. We aimed to generate innovative, user-friendly nomograms that can be applied for diabetes screening in different ethnic groups in China using the non-lab or noninvasive semi-lab data. Methods: This multicenter, multi-ethnic, population-based, cross-sectional study was conducted in eight sites in China by enrolling subjects aged 20-70. Sociodemographic and anthropometric characteristics were collected. Blood and urine samples were obtained 2 h following a standard 75 g glucose solution. In the final analysis, 10,794 participants were included and randomized into model development (n - 8096) and model validation (n = 2698) group with a ratio of 3:1. Nomograms were developed by the stepwise binary logistic regression. The nomograms were validated internally by a bootstrap sampling method in the model development set and externally in the model validation set. The area under the receiver operating characteristic curve (AUC) was used to assess the screening performance of the nomograms. Decision curve analysis was applied to calculate the net benefit of the screening model. Results: The overall prevalence of undiagnosed diabetes was 9.8% (1059/10794) according to ADA criteria. The non-lab model revealed that gender, age, body mass index, waist circumference, hypertension, ethnicities, vegetable daily consumption and family history of diabetes were independent risk factors for diabetes. By adding 2 h post meal glycosuria qualitative to the non-lab model, the semi-lab model showed an improved Akaike information criterion (AIC: 4506 to 3580). The AUC of the semi-lab model was statistically larger than the non-lab model (0.868 vs 0.763, P < 0.001). The optimal cutoff probability in semi-lab and non-lab nomograms were 0.088 and 0.098, respectively. The sensitivity and specificity were 76.3% and 81.6%, respectively in semi-lab nomogram, and 72.1% and 673% in non-lab nomogram at the optimal cut off point. The decision curve analysis also revealed a bigger decrease of avoidable OGTT test (52 per 100 subjects) in the semi-lab model compared to the non-lab model (36 per 100 subjects) and the existed New Chinese Diabetes Risk Score (NCDRS, 35 per 100 subjects). Conclusion: The non-lab and semi-lab nomograms appear to be reliable tools for diabetes screening, especially in developing countries. However, the semi-lab model outperformed the non-lab model and NCDRS prediction systems and might be worth being adopted as decision support in diabetes screening in China.
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| 11. |
- Liu, Jin-ming, et al.
(författare)
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Mid-term effects of lung volume reduction surgery on pulmonary function in patients with chronic obstructive pulmonary disease
- 2007
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Ingår i: Chinese Medical Journal. - 0366-6999. ; 120:8, s. 658-662
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Tidskriftsartikel (refereegranskat)abstract
- Background Now lung volume reduction surgery (LVRS) has become one of the most effective methods for the management of some cases of severe chronic obstructive pulmonary disease (COPD). We evaluated the mid-term effects of LVRS on pulmonary function in patients with severe COPD. Methods Ten male patients with severe COPD aged 38-70 years underwent LVRS and their pulmonary function was assessed before, 3 months and 3 years after surgery. The spirometric and gas exchange parameters included residual volume, total lung capacity, inspiratory capacity, forced vital capacity, forced expiratory volume in one second, diffusion capacity for CO, and arterial blood gas. A 6-minute walk distance (6MWD) test was performed. Results As to preoperative assessment, most spirometric parameters and 6MWD were significantly improved after 3 months and slightly 3 years after LVRS. Gas exchange parameters were significantly improved 3 months after surgery, but returned to the preoperative levels after 3 years. Conclusions LVRS may significantly improve pulmonary function in patients with severe COPD indicating for LVRS. Mid-term pulmonary function 3 years after surgery can be decreased to the level at 3 months after surgery. Three years after LVRS, lung volume and pulmonary ventilation function can be significantly improved, but the improvement in gas exchange function was not significant.
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| 12. |
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| 13. |
- Qin, Bei, et al.
(författare)
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Media Bias in China
- 2018
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Ingår i: The American Economic Review. - : American Economic Association. - 0002-8282 .- 1944-7981. ; 108:9, s. 2442-2476
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Tidskriftsartikel (refereegranskat)abstract
- This paper examines whether and how market competition affected the political bias of government-owned newspapers in China from 1981 to 2011. We measure media bias based on coverage of government mouthpiece content (propaganda) relative to commercial content. We first find that a reform that forced newspaper exits (reduced competition) affected media bias by increasing product specialization, with some papers focusing on propaganda and others on commercial content. Second, lower-level governments produce less-biased content and launch commercial newspapers earlier, eroding higher-level governments' political goals. Third, bottom-up competition intensifies the politico-economic tradeoff, leading to product proliferation and less audience exposure to propaganda.
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| 14. |
- Qin, Bei, et al.
(författare)
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Why Does China Allow Freer Social Media? Protests versus Surveillance and Propaganda
- 2017
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Ingår i: Journal of Economic Perspectives. - : American Economic Association. - 0895-3309 .- 1944-7965. ; 31:1, s. 117-140
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we document basic facts regarding public debates about controversial political issues on Chinese social media. Our documentation is based on a dataset of 13.2 billion blog posts published on Sina Weibo—the most prominent Chinese microblogging platform—during the 2009–2013 period. Our primary finding is that a shockingly large number of posts on highly sensitive topics were published and circulated on social media. For instance, we find millions of posts discussing protests, and these posts are informative in predicting the occurrence of specific events. We find an even larger number of posts with explicit corruption allegations, and that these posts predict future corruption charges of specific individuals. Our findings challenge a popular view that an authoritarian regime would relentlessly censor or even ban social media. Instead, the interaction of an authoritarian government with social media seems more complex.
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| 15. |
- Siegel, Elena O., et al.
(författare)
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Understanding Contextual Differences in Residential LTC Provision for Cross-National Research : Identifying Internationally Relevant CDEs
- 2019
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Ingår i: Gerontology and geriatric medicine. - : Sage Publications. - 2333-7214. ; 5, s. 1-8
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Forskningsöversikt (refereegranskat)abstract
- Long-term care (LTC) reflects a growing emphasis on person-centered care (PCC), with services oriented around individuals' needs and preferences. Addressing contextual and cultural differences across countries offers important insight into factors that facilitate or hinder application of PCC practices within and across countries. This article takes an international lens to consider country-specific contexts of LTC, describing preliminary steps to develop common data elements that capture contextual differences across LTC settings globally. Through an iterative series of online, telephone, and in-person sessions, we engaged in in-depth discussions with 11 colleague experts in residential LTC and coauthors from six countries (China and Hong Kong, England, Sweden, Thailand, Trinidad and Tobago, and the United States). Our discussions yielded rich narrative describing a vast range in types of LTC settings, leading to our development of a working definition of residential LTC. Scope of services, funding, ownership, and regulations varied greatly across countries and across different residential LTC settings within countries. Moving forward, we recommend expanding our activities to countries that reflect different stages of residential LTC development. Our goal is to contribute to a larger initiative underway by the WE-THRIVE consortium to establish a global research measurement infrastructure that advances PCC internationally.
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| 16. |
- Tian, Xiaohe, et al.
(författare)
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Probe for simultaneous membrane and nucleus labeling in living cells and in vivo bioimaging using a two-photon absorption water-soluble Zn(II) terpyridine complex with a reduced pi-conjugation system
- 2017
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Ingår i: Chemical Science. - : ROYAL SOC CHEMISTRY. - 2041-6520 .- 2041-6539. ; 8:1, s. 142-149
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Tidskriftsartikel (refereegranskat)abstract
- Small, biocompatible and water-soluble molecules with high two-photon absorption (2PA) cross-section values (delta) are in high demand for specific bioimaging applications. Here, two novel terpyridine derivative ligands with donor-acceptor (D-A) (L1) and donor-pi-acceptor (D-pi-A) (L2) models, and their corresponding Zn(II) complexes are designed and characterized. It was found that the two-photon absorption cross section values (d) in the near-infrared region (NIR, about 800 nm) are significantly enhanced for complexes 1 and 2 compared to their free D-A type ligand L1, while those of complexes 3 and 4 were greatly decreased relative to their free ligand L2, thus confirming that the smaller ligand (D-A type) displays a suitable Turn-ON fluorescence pair for two-photon fluorescence microscopy (2PFM). Firstly, the potential of simultaneously labeling a live cell plasma membrane and nucleus using complex 1 is demonstrated. In addition, live larval and adult zebrafish incubated with an optimal concentration of 1 demonstrated clear brain uptake. Lastly and importantly, using such a probe to visualize the blood-brain- barrier (BBB) capillary endothelial cells and penetrate the BBB into the central nervous system (CNS) intravenously in a mouse model is also explored.
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| 17. |
- Wang, Bei, et al.
(författare)
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Liquid Metal Microscale Deposition enabled High Resolution and Density Epidermal Microheater for Localized Ectopic Expression in Drosophila
- 2022
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Ingår i: Advanced Materials Technologies. - : John Wiley & Sons. - 2365-709X. ; 7:3, s. 2100903-
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Tidskriftsartikel (refereegranskat)abstract
- Localized ectopic expression of enteroendocrine cells in fruit flies provides a convenient model for studying human intestinal diseases, e.g., inflammatory bowel disease, that need urgent attention. Due to its noninvasive feature, thermal activating ectopic expression is an excellent option, but it demands local heating of the tiny and delicate live flies’ abdomen (≈1 × 1 mm2) without blocking their breath, instead of global heating of the whole body. This work proposes a thin, high-resolution, and density liquid metal (LM) microheater with gas permeability and sufficient compliance to provide homogenous local heating to the fly's tiny abdomen. A depositing technique is developed that can make microscale thin (5 µm), smooth (Sa = 0.8 µm), gas permeable LM film for such microheater by introducing LM micrometer/sub-micrometer particles. Collision induced LM particle merging and hence sintering is proposed to solve low conductivity due to their particular shells of micrometer/sub-micrometer particles. The deposition can conformally print on the wavy or rough surface due to the fine particle size. With a shadow mask, this microscale deposition can enable high yield and reproducible thin LM patterning with high resolution, density, and precision simultaneously. Furthermore, it is demonstrated that epidermal patches can compliantly attach onto the wrinkle skin and fingerprint. Finally, by applying such a microheater on the fly abdomen, localized ectopic expression of enteroendocrine cells is successfully demonstrated.
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| 18. |
- Wang, Bei
(författare)
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Liquid metal microscale deposition for soft and stretchable skin-like electronics : Providing a soft and gentle contact to living beings
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Skin-like electronics could provide a soft and gentle contact with living beings for perceiving and delivering the information of pressure, strain, temperature with higher spatial resolution and sensitivity than our skin, without disturbing the user. Gallium-based liquid metal (LM) is an excellent material for soft and stretchable skin-like devices, since it has high electrical and thermal conductivity, flowability, and self-healable capability. However, the LM patterning technique is not well developed and has challenges due to its high surface tension. This thesis presents several methods to advance LM patterning capability, targeting thin, homogenous, high-resolution, and high-density skin-like electronics. Especially, masked deposition is a versatile technique in microsystem fabrication but has been limited by the masking and deposition. Firstly, a mask material that is well suited for lift-off processing at high resolution has been sought for. In this thesis, we introduced the use of a water dissolvable sacrificial thin polyvinyl alcohol (PVA) film for LM masked deposition. The dyed PVA film could be cut by laser and the fabricated mask had a resolution down to 20 µm in width. Secondly, our previously demonstrated LM atomization has a large variation of the droplets size generated by the airbrush, which severely hinder the depositing uniformity at microscale. Sonication produced LM particles has a narrow size distribution, but the particles are insulating. We proposed a simple and effective technique to merge these particles by precise spraying, depositing a LM layer that is microscale thin (5 µm), smooth (area roughness, Sa=0.8 µm), and gas permeable. More importantly, it has conductivity similar to pure LM. With this technique, a skin-like high resolution sensor was fabricated, which is able to monitor the local wrinkle skin movement. Moreover, a high-resolution skin-like micro-heater was made and placed on the fragile and oval abdomen of Drosophila for localized ectopic genetic expression in its gut. In addition, printing LM based skin-like electronics on a 3D surface is also challenging. Hence, we developed two complementary techniques that could gently and conformally transfer a planar pattern to a 3-D surface: A PDMS-based flexible stamp that could transfer a 2-D pattern to a 3-D surface and hydro printing with PVA film as a medium. Using hydro printing, the circuit that was transferred on delicate plants could monitor their physiological information and control their growth.
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| 19. |
- Wang, Bei, et al.
(författare)
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Sandwiched Polyethylene Shrink Film Masking with Tunable Resolution and Shape for Liquid Alloy Patterning
- 2019
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Ingår i: ACS APPLIED POLYMER MATERIALS. - : American Chemical Society (ACS). - 2637-6105. ; 1:2, s. 145-151
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Tidskriftsartikel (refereegranskat)abstract
- Among numerous patterning techniques, masked liquid alloy printing is one of the most promising techniques for scalable fabrication of liquid-alloy-based stretchable electronics. Like any other mask-based process, its resolution is often constrained by the quality of the mask, and the fabrication cost increases drastically with increased resolution. In this work, by introducing a sandwiched thermal shrink polymer film masking technique and a corresponding intermediate release agent, fine liquid alloy patterns were demonstrated by using a mechanical cutting plotter together with a common oven. The final resolution and shape of the mask could be tuned based on the anisotropy of the shrink polymer film and other operational parameters of the technique. After shrinkage, the width of the patterned liquid alloy lines and space in-between could be tuned to less than one third of the original cut pattern, to about 35 and 60 mu m, respectively, according to requirements. To better predict the final structure, several parameters were investigated experimentally and numerically. Finally, a liquid alloy strain sensor and three-dimensional conformal masking were demonstrated, showing the potential of the developed technique.
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| 20. |
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| 21. |
- Wang, Xue Jing, et al.
(författare)
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Autonomic ganglionic injection of α-synuclein fibrils as a model of pure autonomic failure α-synucleinopathy
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- α-Synucleinopathies are characterized by autonomic dysfunction and motor impairments. In the pure autonomic failure (PAF), α-synuclein (α-Syn) pathology is confined within the autonomic nervous system with no motor features, but mouse models recapitulating PAF without motor dysfunction are lacking. Here, we show that in TgM83+/− mice, inoculation of α-Syn preformed fibrils (PFFs) into the stellate and celiac ganglia induces spreading of α-Syn pathology only through the autonomic pathway to both the central nervous system (CNS) and the autonomic innervation of peripheral organs bidirectionally. In parallel, the mice develop autonomic dysfunction, featured by orthostatic hypotension, constipation, hypohidrosis and hyposmia, without motor dysfunction. Thus, we have generated a mouse model of pure autonomic dysfunction caused by α-Syn pathology. This model may help define the mechanistic link between transmission of pathological α-Syn and the cardinal features of autonomic dysfunction in α-synucleinopathy.
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