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High mortality of patients with severe pneumonia caused by respiratory syncytial virus, August 2021-June 2023, Taiwan

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JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION 2024年第1期57卷 184-188页

作者： Chen, Chieh-Lung Lin, Yu -Chao Tseng, How -Yang Chen, Wei-Cheng Liang, Shinn-Jye Tu, Chih-Yen Hsueh, Po-Ren China Med Univ China Med Univ Hosp Dept Internal Med Div Pulm & Crit Care Med Taichung Taiwan China Med Univ Sch Chinese Med Taichung Taiwan China Med Univ China Med Univ Hosp Dept Lab Med Taichung Taiwan China Med Univ China Med Univ Hosp Dept Internal Med Taichung Taiwan China Med Univ Sch Med PhD Program Aging Taichung Taiwan China Med Univ Sch Med Dept Lab Med Taichung Taiwan China Med Univ China Med Univ Hosp Dept Lab Med 2 Yude Rd Taichung 40447 Taiwan China Med Univ China Med Univ Hosp Dept Internal Med 2 Yude Rd Taichung 40447 Taiwan

Among the 14 patients with respiratory syncytial virus pneumonia, the majority (n = 8, 57.1 %) were older than 65 years and had health care -associated pneumonia (57.1 %). Over 70 % (n = 10) of them exhibited bacterial co -infection, with a high proportion (64.3 %) requiring mechanical ventilation. The hospital mortality rate was 50 %. Copyright (c) 2023, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY -NC -ND license (http://***/licenses/bync-nd/4.0/).

关键词： Respiratory syncytial virus Older adults Pneumonia Bacterial co infection Mortality

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High-efficiency purification of divergent AAV serotypes using AAVX affinity chromatography

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MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT 2023年 28卷 146-159页

作者： Florea, Michael Nicolaou, Fotini Pacouret, Simon Zinn, Eric M. Sanmiguel, Julio Andres-Mateos, Eva Unzu, Carmen Wagers, Amy J. Vandenberghe, Luk H. Schepens Eye Res Inst Grousbeck Gene Therapy Ctr Boston MA 02114 USA Massachusetts Eye & Ear Infirm Boston MA 02114 USA Harvard Univ Harvard PhD Program Biol & Biomed Sci Div Med Sci Boston MA USA Harvard Univ Dept Stem Cell & Regenerat Biol Cambridge MA USA Harvard Med Sch Dept Ophthalmol Ocular Genom Inst Boston MA USA Broad Inst Harvard & MIT Boston MA USA Harvard Univ Harvard Stem Cell Inst Cambridge MA USA Harvard Med Sch Paul F Glenn Ctr Biol Aging Boston MA USA Joslin Diabet Ctr Sect Islet Cell & Regenerat Biol Boston MA 02215 USA

The adeno-associated viral vector (AAV) provides a safe and efficient gene therapy platform with several approved products that have marked therapeutic impact for patients. However, a major bottleneck in the development and commercialization of AAV remains the efficiency, cost, and scalability of AAV production. Chromatographic methods have the potential to allow purification at increased scales and lower cost but often require optimization specific to each serotype. Here, we demonstrate that the POROS CaptureSelect AAVX affinity resin efficiently captures a panel of 15 divergent AAV serotypes, including the commonly used AAV2, AAV8, AAV9, PHP.B, and Anc80. We also find that AAVX resin can be regenerated repeatedly without loss of efficiency or carry-over contamination. While AAV preps purified with AAVX showed a higher fraction of empty capsids than preps purified using iodixanol ultracentrifugation, the potency of the AAVX purified vectors was comparable with that of iodixanol purified vectors both in vitro and in vivo. Finally, optimization of the purification protocol resulted in a process with an overall efficiency of 65%-80% across all scales and AAV serotypes tested. These data establish AAVX affinity chromatography as a versatile and efficient method for purification of a broad range of AAV serotypes.

关键词： AAV gene therapy adeno-associated purification manufacturing downstream affinity chromatography AAVX

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Human gene-engineered calreticulin mutant stem cells recapitulate MPN hallmarks and identify targetable vulnerabilities

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LEUKEMIA 2023年第4期37卷 843-853页

作者： Fosselteder, Johannes Pabst, Gabriel Sconocchia, Tommaso Schlacher, Angelika Auinger, Lisa Kashofer, Karl Beham-Schmid, Christine Trajanoski, Slave Waskow, Claudia Schoell, Wolfgang Sill, Heinz Zebisch, Armin Woelfler, Albert Thomas, Daniel Reinisch, Andreas Med Univ Graz Dept Internal Med Div Hematol Graz Austria Res Inst Mol Pathol IMP Vienna Bioctr VBC Vienna Austria Univ Vienna Vienna Bioctr PhD Program Doctoral Sch Vienna Austria Med Univ Vienna Vienna Bioctr VBC Vienna Austria Med Univ Graz Diagnost & Res Inst Pathol Graz Austria Med Univ Graz Core Facil Computat Bioanalyt Graz Austria Leibniz Inst Aging Fritz Lipmann Inst Jena Germany Friedrich Schiller Univ Inst Biochem & Biophys Fac Biol Sci Jena Germany Med Univ Graz Dept Obstet & Gynecol Graz Austria Med Univ Graz Dept Blood Grp Serol & Transfus Med Div Pharmacol Immunol & Inflammat Graz Austria South Australian Hlth & Med Res Inst SAHMRI Canc Program Precis Med Theme Adelaide Australia Univ Adelaide Adelaide Med Sch Adelaide Australia

Calreticulin (CALR) mutations present the main oncogenic drivers in JAK2 wildtype (WT) myeloproliferative neoplasms (MPN), including essential thrombocythemia and myelofibrosis, where mutant (MUT) CALR is increasingly recognized as a suitable mutation-specific drug target. However, our current understanding of its mechanism-of-action is derived from mouse models or immortalized cell lines, where cross-species differences, ectopic over-expression and lack of disease penetrance are hampering translational research. Here, we describe the first human gene-engineered model of CALR MUT MPN using a CRISPR/Cas9 and adeno-associated viral vector-mediated knock-in strategy in primary human hematopoietic stem and progenitor cells (HSPCs) to establish a reproducible and trackable phenotype in vitro and in xenografted mice. Our humanized model recapitulates many disease hallmarks: thrombopoietin-independent megakaryopoiesis, myeloid-lineage skewing, splenomegaly, bone marrow fibrosis, and expansion of megakaryocyte-primed CD41(+) progenitors. Strikingly, introduction of CALR mutations enforced early reprogramming of human HSPCs and the induction of an endoplasmic reticulum stress response. The observed compensatory upregulation of chaperones revealed novel mutation-specific vulnerabilities with preferential sensitivity of CALR mutant cells to inhibition of the BiP chaperone and the proteasome. Overall, our humanized model improves purely murine models and provides a readily usable basis for testing of novel therapeutic strategies in a human setting.

关键词： Cancer models Haematopoietic stem cells Myeloproliferative disease

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Palliative care for case managers: Building capacity to extend community-based palliative care to underserved older adults

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GERONTOLOGY & GERIATRICS EDUCATION 2022年第2期43卷 269-284页

作者： Gardner, Daniel S. Doherty, Meredith Ghesquiere, Angela Villanueva, Carolina Kenien, Cara Callahan, Jean Reid, M. Cary CUNY Hunter Coll Silberman Sch Social Work 2180 Third AveRoom 805 New York NY 10035 USA CUNY Grad Ctr PhD Program Social Welf New York NY USA CUNY Hunter Coll Brookdale Ctr Hlth Aging New York NY 10021 USA Univ Calif Irvine Sch Publ Hlth Irvine CA USA Weill Cornell Med Coll Div Geriatr & Palliat Med New York NY USA

Palliative care has demonstrated effectiveness in alleviating the biological, emotional, social, and spiritual symptoms that accompany serious illness, and improving quality of life for seriously ill individuals and their family members. Despite increasing availability, there are significant disparities in access to and utilization of palliative care, particularly among diverse, low-income, and community-dwelling older adults with chronic illness. Training frontline service providers is a novel approach to expanding access to palliative care among underserved elders. This article presents a process and outcome evaluation of a palliative care curriculum that was developed and piloted for geriatric case managers in a large urban area. We describe the background, planning, design, implementation, and preliminary outcomes associated with a pilot implementation of the curriculum. We conclude with implications for replicating efforts to enhance frontline providers' knowledge, skills, and self-efficacy in extending palliative care to communities that lack access to critical supports for their burdensome symptoms.

关键词： Palliative care case management geriatrics curriculum development process evaluation

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Planning in advance: exploring end-of-life hopes and fears among healthy young people

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MORTALITY 2021年第3期26卷 316-325页

作者： Dark-Freudeman, Alissa Terry, Christian Fleming, Jason Hollander, John Bensadon, Benjamin Univ North Carolina Wilmington Dept Psychol 601 South Coll Rd Wilmington NC 28403 USA Univ North Carolina Wilmington Clin Psychol Program Wilmington NC 28403 USA Univ Memphis Memphis TN 38152 USA Univ Memphis Expt Psychol PhD Program Memphis TN 38152 USA Univ Florida Dept Aging & Geriatr Res Div Geriatr Med Gainesville FL 32611 USA

Discussions regarding end-of-life (EOL) preferences often occur late in the course of a disease leading to rushed clinical decisions misaligned with patient goals. Thus, the purpose of the current study was to identify EOL goals among a healthy sample of young adults (N = 305) through a possible selves framework. Common EOL hopes included: having loved ones present, closure, and living a full life. Common EOL fears included: pain and suffering, specific types of death, and dying alone. Hopes and fears related to religiosity were rare. Overall, participants felt more confident attaining EOL hopes than avoiding EOL fears. Even in young adulthood, when concerns related to ageing, illness, and dying are not acute, individuals have clear ideas regarding what they do and do not want to experience at their end of life. Conversations regarding EOL preferences should therefore be initiated with adult patients of all ages. Clinically, end-of-life training and care should integrate these psychological insights.

关键词： Possible selves death attitudes end-of-life goals mixed methods

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Pterostilbene and Its Derivative 3′-Hydroxypterostilbene Ameliorated Nonalcoholic Fatty Liver Disease Through Synergistic Modulation of the Gut Microbiota and SIRT1/AMPK Signaling Pathway

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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022年第16期70卷 4966-4980页

作者： Tsai, Hui-Yun Shih, Yu-Yuan Yeh, Yao-Tsung Huang, Cheng-Hsieh Liao, Chorng-An Hu, Chun-Yi Nagabhushanam, Kalyanam Ho, Chi-Tang Chen, Yu-Kuo Fooyin Univ Dept Nutr & Hlth Sci Kaohsiung 83102 Taiwan Fooyin Univ Aging & Dis Prevent Res Ctr Kaohsiung 83102 Taiwan Natl Pingtung Univ Sci & Technol Dept Food Sci Pingtung 91201 Taiwan Fooyin Univ Dept Med Lab Sci & Biotechnol Kaohsiung 83102 Taiwan Fooyin Univ Hosp Biomed Anal Ctr Pingtung 92849 Taiwan Kaohsiung Med Univ PhD Program Environm & Occupat Med Kaohsiung 80708 Taiwan Meiho Univ Dept Food Sci & Nutr Pingtung 912009 Taiwan Sabinsa Corp East Windsor NJ 08520 USA Rutgers State Univ Dept Food Sci New Brunswick NJ 08901 USA

Nonalcoholic fatty liver disease (NAFLD) is a recent chronic liver disease common in many developed countries and is closely associated with metabolic syndrome, such as obesity and insulin resistance. The present study was performed to investigate the effects of pterostilbene (Pt) and its derivative 3'- hydroxypterostilbene (OHPt) on free fatty acids (FFA)-induced lipid accumulation in HepG2 cells and high-fat diet (HFD)-induced NAFLD in C57BL/6J mice. The results showed that Pt and OHPt significantly ameliorated FFA-induced steatosis in HepG2 cells and enhanced lipolysis through the upregulation of SIRT1/AMPK and insulin signaling pathways. In the in vivo study, Pt and OHPt treatment resulted in reduced hepatic lipid droplets accumulation. The data showed that Pt and OHPt upregulated the SIRT1/AMPK pathway and subsequently downregulated the protein expression of SREBP-1 to activate fatty acid (FA) beta-oxidation to inhibit FA synthesis. Pt and OHPt administration activated the insulin signaling pathway and further ameliorated the insulin resistance and liver function in the HFD-fed mice. Furthermore, Pt and OHPt markedly increased the numbers of Oscillospira and decreased the numbers of Allobaculum, Phascolarctobacterium, and Staphylococcus compared with those in the HFD group. These robust results indicate that Pt and OHPt are able to possess potential health benefits in improving insulin resistance and hepatic steatosis by promoting healthy populations or abundances of considered vital microbiota. Besides, OHPt is more effective than Pt, which might have promising chemotherapeutic effects for future clinical application.

关键词： nonalcoholic fatty liver disease pterostilbene 3 '-hydroxypterostilbene HepG2 cells gut dysbiosis

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Rapid detection of gastrointestinal pathogens using a multiplex polymerase chain reaction gastrointestinal panel and its role in antimicrobial stewardship

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JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION 2023年第1期56卷 1273-1283页

作者： Chen, Chih-Hao Low, Yan-Yi Liu, Yu-Hsuan Lin, Hsiu-Hsien Ho, Mao-Wang Hsueh, Po-Ren China Med Univ Hosp Dept Internal Med Div Infect Dis Taichung Taiwan China Med Univ China Med Univ Childrens Hosp Div Pediat Infect Dis Taichung Taiwan China Med Univ Hosp Dept Lab Med Taichung Taiwan China Med Univ China Med Univ Hosp Sch Med Dept Internal Med Taichung Taiwan China Med Univ China Med Univ Hosp Sch Med Dept Lab Med Taichung Taiwan China Med Univ Sch Med PhD Program Aging Taichung Taiwan China Med Univ China Med Univ Hosp Dept Lab Med Taichung Taiwan China Med Univ China Med Univ Hosp Dept Internal Med Taichung Taiwan

Objectives: The FilmArray gastrointestinal panel (FAGIP) is widely used to detect infectious diarrhoea due to its outstanding sensitivity compared to conventional methods, but there is geographic variation, such as in the distribution of pathogens, among populations. Methods: This was a retrospective study that analysed patients with acute diarrhoea who underwent FAGIP tests from all age groups during 2022. We compared positive rates of FAGIP between paediatric (n = 245) and adult patients (n = 242) of different origins. The targeted therapy rate and antimicrobial agent use rate were also analysed. Results: Among the 487 stool samples evaluated, the overall, communityorigin (CO), and nosocomial (NC) positivity rates of paediatric patients were significantly higher than those of adults (73.9 % vs. 43.0 %, p = 0.000;76.2 % vs. 51.7 %, p = 0.000;50.0 % vs. 19.7 %, p = 0.000). Salmonella was the most frequently detected pathogen (35.9 %) in children, while the predominant pathogen in adult patients was toxin A/B-genic Clostridioides difficile (13.2 %). There was a significantly lower antimicrobial agent use rate after FAGIP results were available (79.1 % vs. 64.5 %, p = 0.000) and a higher rate of targeted therapy towards C. difficile infection in adults than in children (84.4 % vs. 69.0 %, p = 0.011). Conclusion: Paediatric diarrhoea patients showed higher positivity rates than adult patients. Application of FAGIP for acute diarrhoea might lower unnecessary antimicrobial use. Copyright 2023, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-nc-nd/4.0/).

关键词： FilmArray gastrointestinal panel Acute diarrhoea Positivity rate Community origin Nosocomial diarrhoea Mixed detections

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Association between aphasia and risk of dementia after stroke

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JOURNAL OF STROKE & CEREBROVASCULAR DISEASES 2022年第12期31卷 106838-106838页

作者： Lin, Hui-Lin Tsai, Chung-Fen Liu, Shih-Ping Muo, Chih-Hsin Chen, Pei-Chun China Med Univ PhD Program Aging Taichung Taiwan Lin Shin Hosp Dept Phys Med & Rehabil Taichung Taiwan Fu Jen Catholic Univ Cardinal Tien Hosp Dept Neurol New Taipei Taiwan China Med Univ Dept Publ Hlth Taichung Taiwan

Background and purpose: Although findings from published studies suggest post-stroke aphasia is associated with an increased risk of dementia, few studies have evaluated its association in a nationally representative cohort with long-term follow-up. No studies have reported data by type of stroke. Therefore, we examined the association between post-stroke aphasia and the risk of developing dementia. Methods: Using claims data from Taiwan's universal health insurance program, a cohort of patients >= 18 years old with an initial hospitalization for stroke in 2002-2005 were identified and followed up until December 31, 2016. Patients with newly diagnosed aphasia during stroke hospitalization or within 6 months of discharge were defined as the aphasia group. Cox proportional hazards models were used to estimate hazard ratios (HRs) for developing overall, vascular, and non-vascular dementia in patients with and without post-stroke aphasia. Results: During a median follow-up period of 7.9 and 8.6 years for the aphasia (n=17063) and non-aphasia groups (n=105940), respectively, overall dementia incidence was similar, whereas vascular dementia incidence was higher in the aphasia group (7.52 vs. 5.52 per 1000 person-years). The adjusted HRs (95% confidence intervals) were 1.11 (1.06-1.17), 1.42 (1.31-1.53), and 0.94 (0.88-1.01) for overall, vascular, and non-vascular dementia, respectively. The association between aphasia and the risk of vascular dementia did not differ by stroke type (P for interaction=0.43). The analysis of 16856 propensity score-matched pairs revealed similar results. Conclusion: Patients with post-stroke aphasia have an increased risk of developing vascular dementia irrespective of the type of stroke.

关键词： Post-stroke aphasia Stroke Dementia Vascular dementia

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Narratives bridge the divide between distant events in episodic memory

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MEMORY & COGNITION 2022年第3期50卷 478-494页

作者： Cohn-Sheehy, Brendan I. Delarazan, Angelique I. Crivelli-Decker, Jordan E. Reagh, Zachariah M. Mundada, Nidhi S. Yonelinas, Andrew P. Zacks, Jeffrey M. Ranganath, Charan Univ Calif Davis MD PhD Program Sacramento CA 95817 USA Univ Calif Davis Neurosci Grad Grp Davis CA 95616 USA Univ Calif Davis Ctr Neurosci Davis CA 95616 USA Washington Univ Dept Psychol & Brain Sci 1 Brookings Dr St Louis MO 63110 USA Univ Calif Davis Dept Psychol Davis CA 95616 USA Univ Calif San Francisco Memory & Aging Ctr San Francisco CA 94143 USA

Many studies suggest that information about past experience, or episodic memory, is divided into discrete units called "events." Yet we can often remember experiences that span multiple events. Events that occur in close succession might simply be linked because of their proximity to one another, but we can also build links between events that occur farther apart in time. Intuitively, some kind of organizing principle should enable temporally distant events to become bridged in memory. We tested the hypothesis that episodic memory exhibits a narrative-level organization, enabling temporally distant events to be better remembered if they form a coherent narrative. Furthermore, we tested whether post-encoding memory consolidation is necessary to integrate temporally distant events. In three experiments, participants learned and subsequently recalled events from fictional stories, in which pairs of temporally distant events involving side characters ("sideplots") either formed one coherent narrative or two unrelated narratives. Across participants, we varied whether recall was assessed immediately after learning, or after a delay: 24 hours, 12 hours between morning and evening ("wake"), or 12 hours between evening and morning ("sleep"). Participants recalled more information about coherent than unrelated narrative events, in most delay conditions, including immediate recall and wake conditions, suggesting that post-encoding consolidation was not necessary to integrate temporally distant events into a larger narrative. Furthermore, post hoc modeling across experiments suggested that narrative coherence facilitated recall over and above any effects of sentence-level semantic similarity. This reliable memory benefit for coherent narrative events supports theoretical accounts which propose that narratives provide a high-level architecture for episodic memory.

关键词： Episodic memory Consolidation Narratives Recall Event cognition

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A Bite of B Cells: The Potential Role of Bispecific T Cell Engager Therapy (BiTE) in Autoimmune Diseases

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INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES 2025年第5期28卷 e70252页

作者： Zheng, Jie-Fu Lee, Yung-Heng Kao, Shih-Wen Wei, James Cheng-Chung Tainan Municipal Hosp Dept Internal Med Div Rheumatol & Immunol Tainan Taiwan Minist Hlth & Welf Feng Yuan Hosp Dept Orthoped Kaohsiung Taiwan Natl Sun Yat Sen Univ Inst Med Sci & Technol Kaohsiung Taiwan Minghsin Univ Sci & Technol Dept Sr Serv Ind Management Hsinchu Taiwan Shu Te Univ Dept Recreat & Sport Management Kaohsiung Taiwan Chung Shan Med Univ Hosp Dept Orthopaed Surg Taichung Taiwan Chung Shan Med Univ Sch Med Taichung Taiwan China Med Univ Coll Med PhD Program Aging Taichung Taiwan Chung Shan Med Univ Hosp Dept Allergy Immunol & Rheumatol Taichung Taiwan Chung Shan Med Univ Inst Med Taichung Taiwan Chung Shan Med Univ Dept Nursing Taichung Taiwan China Med Univ Grad Inst Integrated Med Taichung Taiwan

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