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•Safety data via smartphones collection assists in understanding vaccine reactions.•Most reactogenicity were mild and self-limited.•Fever and local swelling were more common in V-Watch survey than in clinical trials. The ChAdOx1 nCoV-19 (ChAd), mRNA-1273 (m1273), MVC-COV1901 (MVC), and BNT162b2 (BNT) COVID-19 vaccines received authorization for emergency use in Taiwan beginning in February 2021. We investigated acute reactions to homologous primary COVID-19 vaccination series in adults aged ≥ 18 years. In this prospective observational study based on smartphone data (Taiwan V-Watch), we calculated the frequencies of self-reported local and systemic acute reactions within 7 days of a COVID-19 vaccination, and the health effects up to 3 weeks after each dose. Those who reported adverse reactions after both doses were assessed by the McNemar test. During 22 March 2021–13 December 2021, 77,468 adults were enrolled; 59.0 % were female and 77.8 % were aged 18–49 years. For both doses of all four vaccines, the local and systemic reactions were minor in severity and highest on days 1 and 2 after vaccination, and declined markedly until day 7. For 65,367 participants who provided data after the first and second doses, systemic reactions were more frequent after dose 2 of the BNT and m1273 vaccines (McNemar tests: both p < 0.001), while local reactions were more frequent after dose 2 of the m1273 and MVC vaccines (both p < 0.001), compared with dose 1 of the homologous vaccine. Among the participants aged 18–49 years, the percentage who missed work on the day after vaccination was slightly higher among women (9.3 %) than among men (7.0 %). Acute reactogenicity and impact of work absenteeism for the four COVID vaccines in the V-Watch survey were mild and of short duration.

Purifying selection during dengue viral infection has been suggested as the driving force of viral evolution and the higher complexity of the intra-host quasi-species is thought to offer an adaptive advantage for arboviruses as they cycle between arthropod and vertebrate hosts. However, very few studies have been performed to investigate the viral genetic changes within (intra-host) and between (inter-host) humans in a spatio-temporal scale. Viruses of different serotypes from various countries imported to Taiwan cause annual outbreaks. During 2001-2003, two consecutive outbreaks were caused by dengue virus serotype 2 (DENV-2) and resulted in a larger-scale epidemic with more severe dengue cases in the following year. Phylogenetic analyses showed that the viruses from both events were similar and related to the 2001 DENV-2 isolate from the Philippines. We comprehensively analyzed viral sequences from representative dengue patients and identified three consensus genetic variants, group Ia, Ib and II, with different spatio-temporal population dynamics. The phylodynamic analysis suggested group Ib variants, characterized by lower genetic diversity, transmission rate, and intra-host variant numbers, might play the role of maintenance variants. The residential locations among the patients infected by group Ib variants were in the outer rim of case clusters throughout the 2001-2003 period whereas group Ia and II variants were located in the centers of case clusters, suggesting that group Ib viruses might serve as \"sheltered overwintering\" variants in an undefined ecological niche. Further deep sequencing of the viral envelope (E) gene directly from individual patient serum samples confirmed the emergence of variants belonging to three quasi-species (group Ia, Ib, and II) and the ancestral role of the viral variants in the latter phase of the 2001 outbreak contributed to the later, larger-scale epidemic beginning in 2002. These findings enhanced our understanding of increasing epidemic severity over time in the same epidemic area. It also highlights the importance of combining phylodynamic and deep sequencing analysis as surveillance tools for detecting dynamic changes in viral variants, particularly searching for and monitoring any specific viral subpopulation. Such subpopulations might have selection advantages in both fitness and transmissibility leading to increased epidemic severity.

This research provides the first empirical study examining the actual role that the Chinese Righteous War Tradition (CRWT) played in Chinese decisions for external war between 1950 and 1979. It aims to answer particularly whether the consideration of righteous war was treated as the decisive influence or simply as an instrument for legitimating such a decision. This research traces the role that the CRWT played in successive Chinese leaders’ decision in three cases—the Korean War, the Sino-Indian War, and the Sino-Vietnamese War. The findings indicate that the ideas of the CRWT were largely used to assess and legitimate the decision for external war. However, the assessment of righteous causes generally occupied a lower priority and did not play the decisive role in determining the decision for external war. The actual role of the CRWT may largely be an instrument to help the Chinese to find legitimacy, and the legitimacy may have the potential to assist the Chinese to choose what should be done from among the options based on different pragmatic calculations.

The largest epidemic of avian influenza (AI) in history attacked poultry and wild birds throughout Taiwan starting January 6, 2015. This study analyzed surveillance results, epidemiologic characteristics, and viral sequences by using government-released information, with the intention to provide recommendations to minimize future pandemic influenza. The H5 clade 2.3.4.4 highly pathogenic AI viruses (HPAIVs) had not been detected in Taiwan before 2015. During this epidemic, four types of etiologic agents were identified: the three novel subtypes H5N2, H5N8, and H5N3 clade 2.3.4.4 HPAIVs and one endemic chicken H5N2 subtype (Mexican-like lineage) of low pathogenic AI viruses. Cocirculation of mixed subtypes also occurred, with H5N2 clade 2.3.4.4 HPAIVs accompanied by the H5N8 and H5N3 subtypes or old H5N2 viruses in the same farm. More than 90% of domestic geese died from this AI epidemic; geese were affected the most at the early outbreaks. The epidemic peaked in mid-January for all three novel H5 subtypes. Spatial epidemiology found that most affected areas were located in southwestern coastal areas. In terrestrial poultry (mostly chickens), different geographic distributions of AI virus subtypes were detected, with hot spots of H5N2 clade 2.3.4.4 vs. past-endemic old H5N2 viruses in Changhwa (P = 0.03) and Yunlin (P = 0.007) counties, respectively, of central Taiwan. Phylogenetic and sequence analyses of all the early 10 Taiwan H5 clade 2.3.4.4 isolates covering the three subtypes showed that they were very different from the HA of the past local H5 viruses from domestic ducks (75%–80%) and chickens (70%–75%). However, they had the highest sequence identity percentages (99.53%–100%), with the HA of A/crane/Kagoshima/KU13/2014(H5N8) isolated on December 7, 2014, in Japan being higher than those of recent American and Korean H5 HPAIVs [A/Northern pintail/Washington/40964/2014 (H5N2) and A/gyrfalcon/Washington/41088-6/2014 (H5N8): 99.02%–99.54% and A/Baikal teal/Korea/Donglim3/2014 (H5N8): 98.61%–99.08%], implying a likely common ancestor of these H5 clade 2.3.4.4 viruses. The multiple subtypes of H5 clade 2.3.4.4 HPAIVs imply high viral reassortment. We recommend establishing an integrated surveillance system, involving clinical, virologic, and serologic surveillance in poultry and wild birds, swine and other mammals prevalent on multiple-animal mixed-type traditional farms, and high-risk human populations, as a crucially important step to minimize future pandemic influenza.

This dissertation engages the question of what role the Chinese Righteous War Tradition (CRWT) played in the process of Chinese decision-making regarding the decisions to go to war during the period from 1950 to 1979. It asks whether, in their decision-making, the Chinese leaders identified \"just cause\" through a frame of reference provided by the CRWT; it asks further under what circumstances the identified \"just cause\" may have exerted influence upon their decision for war. This dissertation presents the first empirical study exploring the application and influence of the traditional Chinese concept of righteous war to China's modern history. The CRWT is my label for a set of ideas found in the ancient Chinese classics. These ideas suggest that two major standards, righteousness-based justifications and competent authority, were a frame of reference for the Chinese leaders in their assessment of the legitimacy of a decision for war. The justifications of stopping violence, punishing a disobedient state, helping a weaker state against a stronger state's invasion, and self-defense are regularly defined in the CRWT as righteous causes for going to war. The identification of competent authority is often related to the perception of moral standing, in which a war can be justified by confronting an opponent who is morally inferior to oneself. This dissertation employs the methods of most similar systems and process tracing to explore the role that the CRWT played in successive Chinese leaders' decision to use force in six cases – the Korean War, the Second Taiwan Strait Crisis, the Sino-Indian War, the Vietnam War between 1964 and 1965, the Sino-Soviet Border Conflict, and the Sino-Vietnamese War. This dissertation also examines the pattern of the Chinese government's use of wording, presented in the People's Daily, morally condemning its opponents, which provides supplementary evidence to explore China's presentation of its own righteous legitimacy. The findings of this research suggest that when the decision for war has been justified within this frame of reference, the Chinese are prone to put that legitimized decision into action. The Chinese concept of righteous war may play a more important role in the decision for war when Chinese leaders encounter an impasse in which two opposite courses of action are suggested by their calculations based on Realpolitik. A sense of the righteous legitimacy of their decision may encourage Chinese leaders to enter a war even when the likely consequence may not appear to favor the Chinese. Furthermore, these findings may well enrich Johnson and Tierney's theory about the shift of actors' mind-sets in decision-making because the CRWT may function as a catalyst for the shift. This research also reveals that the CRWT had limited influence when Chinese leaders faced the danger of a possible invasion by a superior opponent or that of nuclear attack. When the need for a decision for war was not open to debate, then, they were not influenced by the consideration of just cause when making their decision.

Cerebral ischemia not only causes pathological changes in the ischemic areas but also induces a series of secondary changes in more distal brain regions（such as the contralateral cerebral hemisphere）. The impact of supratentorial lesions, which are the most common type of lesion, on the contralateral cerebellum has been studied in patients by positron emission tomography, single photon emission computed tomography, magnetic resonance imaging and diffusion tensor imaging. In the present study, we investigated metabolite changes in the contralateral cerebral hemisphere after supratentorial unilateral ischemia using nuclear magnetic resonance spectroscopy-based metabonomics. The permanent middle cerebral artery occlusion model of ischemic stroke was established in rats. Rats were randomly divided into the middle cerebral artery occlusion 1-, 3-, 9-and 24-hour groups and the sham group. ~1H nuclear magnetic resonance spectroscopy was used to detect metabolites in the left and right cerebral hemispheres. Compared with the sham group, the concentrations of lactate, alanine, γ-aminobutyric acid, choline and glycine in the ischemic cerebral hemisphere were increased in the acute stage, while the concentrations of N-acetyl aspartate, creatinine, glutamate and aspartate were decreased. This demonstrates that there is an upregulation of anaerobic glycolysis（shown by the increase in lactate）, a perturbation of choline metabolism（suggested by the increase in choline）, neuronal cell damage（shown by the decrease in N-acetyl aspartate） and neurotransmitter imbalance（evidenced by the increase in γ-aminobutyric acid and glycine and by the decrease in glutamate and aspartate） in the acute stage of cerebral ischemia. In the contralateral hemisphere, the concentrations of lactate, alanine, glycine, choline and aspartate were increased, while the concentrations of γ-aminobutyric acid, glutamate and creatinine were decreased. This suggests that there is a difference in the metabolite changes induced by ischemic injury in the contralateral and ipsilateral cerebral hemispheres. Our findings demonstrate the presence of characteristic changes in metabolites in the contralateral hemisphere and suggest that they are most likely caused by metabolic changes in the ischemic hemisphere.

Porcine epidemic diarrhea (PED) is a highly contagious swine disease caused by porcine epidemic diarrhea virus (PEDV). PED causes enteric disorders with an exceptionally high fatality in neonates, bringing substantial economic losses in the pork industry. The trimeric spike (S) glycoprotein of PEDV is responsible for virus-host recognition, membrane fusion, and is the main target for vaccine development and antigenic analysis. The atomic structures of the recombinant PEDV S proteins of two different strains have been reported, but they reveal distinct N-terminal domain 0 (D0) architectures that may correspond to different functional states. The existence of the D0 is a unique feature of alphacoronavirus. Here we combined cryo-electron tomography (cryo-ET) and cryo-electron microscopy (cryo-EM) to demonstrate in situ the asynchronous S protein D0 motions on intact viral particles of a highly virulent PEDV Pintung 52 strain. We further determined the cryo-EM structure of the recombinant S protein derived from a porcine cell line, which revealed additional domain motions likely associated with receptor binding. By integrating mass spectrometry and cryo-EM, we delineated the complex compositions and spatial distribution of the PEDV S protein N-glycans, and demonstrated the functional role of a key N-glycan in modulating the D0 conformation. Hsu and co-workers integrate cryo-electron tomography, cryo-electron microscopy and mass spectrometry to reveal the structural polymorphism of a pig coronavirus spike protein within intact viral particles, and how glycosylation modulates the conformational changes pertinent to host recognition.

MEC-17, a newly identified alpha-tubulin-N-acetyltransferase 1, serves as the major α-tubulin acetyltransferase to promote α-tubulin acetylation in vitro and in vivo . Alteration of α-tubulin acetylation may be involved in morphology regulation, cell migration, and tumour metastasis. However, MEC-17’s role in cell physiology and its effect on epithelial–mesenchymal transition (EMT) and cell polarity remain elusive. In the present study, we characterized the overexpressed or downregulated cell models through gene targeting as MEC-17 gain- or loss-of-function. Overexpression of MEC-17 enhanced the cell spreading area, suppressed pseudopods formation in a three-dimensional (3D) culture system, and inhibited cancer cell migratory and invasive ability and tumour metastasis by orthotopic lung cancer animal model. Furthermore, morphological change and migration inhibition of cancer cells were accompanied by EMT repression, Golgi reorientation, and polarity disruption caused by alteration of cdc42 activity via a decrease in Rho-GAP, ARHGAP21. By contrast, a reduction in endogenous MEC-17 accelerated the pseudopods formation and EMT, and facilitated cell migration and invasion. These results demonstrated the crucial role of MEC-17 in the modulation of intrinsic cell morphogenesis, migration, and invasive function through regulation of EMT and cell polarity.

Alzheimer's disease (AD) and other dementias have become the fifth leading cause of death worldwide. Accurate early detection of the disease and its precursor, Mild Cognitive Impairment (MCI), is crucial to alleviate the burden on the healthcare system. While most of the existing work in the literature applied neural networks directly together with several data pre-processing techniques, we proposed in this paper a screening system that is to perform classification based on automatic processing of the transcripts of speeches from the subjects undertaking a neuropsychological test. Our system is also shown applicable to different datasets and languages, suggesting that our system holds a high potential to be deployed widely in hospitals across regions. We conducted comprehensive experiments on two different languages datasets, the Pitt dataset and the NTUHV dataset, to validate our study. The results showed that our proposed system significantly outperformed the previous works on both datasets, with the score of the area under the receiver operating characteristic curve (AUROC) of classifying AD and healthy control (HC) being as high as 0.92 on the Pitt dataset and 0.97 on the NTUHV dataset. The performance on classifying MCI and HC remained promising, with the AUROC being 0.83 on the Pitt dataset and 0.88 on the NTUHV dataset.

Vascular calcification is one of the most common effects of macrovascular complications in patients in aging with chronic kidney disease and diabetes. Previous studies showed that HOTAIR attenuated vascular calcification via the Wnt/β-catenin-signaling pathway, yet the molecular mechanism has not been fully elucidated. This study aimed to identify the explicit molecular mechanism underlying HOTAIR regulated vascular calcification. In the phosphate (Pi)-induced calcification model of human aortic smooth muscle cells (HASMCs), we investigated whether HOTAIR was involved in the regulation of miR-126. The luciferase reporter was used to examine the effect of HOTAIR on miR-126 and miR-126 on Klotho 3ʹ-UTR. Furthermore, we overexpressed Klotho to verify the regulation of Klotho on SIRT1, as well as their roles in mediating Pi-induced calcification in HASMCs via the Wnt/β-catenin signaling pathway. Finally, the results were verified in an in vivo mice calcification model. Overexpression of HOTAIR reduced the expression of miR-126 in Pi-induced HASMCs. Additionally, knockdown of miR-126 increased SIRT1 expression by regulating Klotho expression. An increased level of Klotho inhibited Wnt/β-catenin signaling pathway, which eventually attenuated Pi-induced HASMCs calcification. Luciferase reporter assay revealed that HOTAIR targeted miR-126 and miR-126 could directly target Klotho. Eventually, HOTAIR overexpression reversed Pi-induced calcium calcification in vivo mouse models. This study demonstrated that HOTAIR overexpression attenuated Pi-induced calcification by regulating the miR-126/Klotho/SIRT1 axis, thereby inhibiting the Wnt/β-catenin signaling pathway. It provides new potential target genes for the clinical treatment of vascular calcification.