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Long-term olfactory loss post-COVID-19:Pathobiology and potential therapeutic strategies

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 148-155页

作者： Sarah Kim John B.Finlay tiffany Ko Bradley J.Goldstein Department of Head and Neck Surgery&Communication Sciences Duke UniversityDurhamNorth CarolinaUSA Medical Scientist Training Program Duke UniversityDurhamNorth CarolinaUSA Department of Neurobiology Duke UniversityDurhamNorth CarolinaUSA

An acute loss of smell emerged as a striking symptom present in roughly half of the people infected with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus in the early phases of the COVID-19 pandemic.In most COVID-19 patients,olfaction recovers over the course of a few weeks.However,a lasting partial or complete loss of smell,often associated with distorted olfactory perceptions termed parosmia,has emerged as a widespread problem impacting at least 5%-10%of those who experience anosmia due to COVID-19.Our inability to offer effective therapies to this hyposmic or anosmic population,comprising millions of patients,highlights an enormous unmet need for the medical system.Here,we summarize the current understanding of the pathobiology causing acute olfactory loss due to SARS-CoV-2 infection,focusing on how the virus interacts with the peripheral olfactory system,a major site of viral infection.We also explore the problem of long-COVID olfactory dysfunction,which may accompany other persistent systemic disorders collectively termed postacute sequelae of COVID-19.Specifically,we discuss an emerging model focused on unresolved immune cell activity driving ongoing dysfunction.Finally,we review current and future therapeutic approaches aimed at restoring olfactory function.

关键词： hyposmia inflammation long-COVID parosmia

A cross-sectional study of breastfed infants referred for tongue tie assessment and frenotomy in one Canadian health region

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儿科学研究(英文) 2024年第1期8卷 53-60页

作者： Lee tiffany A. Bishop Jessica Drover Anne Midodzi William K. Twells Laurie K. School of Pharmacy Memorial University of Newfoundland (MUN) St. John’s Canada Faculty of Medicine Memorial University of Newfoundland (MUN) St. John’s Canada

Importance: Tongue tie (TT) is a condition that can cause infant feeding difficulties due to restricted tongue movement. When TT presents as a significant barrier to breastfeeding, a frenotomy may be recommended. Universally accepted diagnostic criteria for TT are lacking and wide prevalence estimates are reported. New referral processes and a Frenotomy Assessment Tool were implemented in one Canadian health region to connect breastfeeding dyads with a provider for TT evaluation and frenotomy.Objective: To determine the proportion of babies with TT as well as the frequency of frenotomy.Methods: This cross-sectional study included infants who initiated breastfeeding at birth and were referred for TT evaluation over a 14-month period. Data were collected retrospectively by chart review and analyzed using SPSS. Factors associated with frenotomy were examined using logistic regression.Results: Two hundred and forty-one babies were referred. Ninety-two percent (n = 222) were diagnosed with TT and 66.0% (n = 159) underwent frenotomy. In the multivariate model, nipple pain/trauma, inability to latch, inability to elevate tongue, and dimpling of tongue on extension were associated with frenotomy (P < 0.05). Most referrals in our region resulted in a diagnosis of TT; however, the number of referrals was lower than expected, and of these two-thirds underwent frenotomy.Interpretation: TT is a relatively common finding among breastfed infants. Future research should examine whether a simplified assessment tool containing the four items associated with frenotomy in our multivariate model can identify breastfed infants with TT who require frenotomy.

关键词： Breastfeeding Nutrition Community health services Pediatrics

Comparison of trigeminal lateralization with differing stimulants

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第1期10卷 66-69页

作者： tiffany Chen Nicolas S.Poupore Michael C.Shih Thomas S.Edwards Shaun A.Nguyen Zachary M.Soler Rodney J.Schlosser Department of Otolaryngology‐Head and Neck Surgery Medical University of South CarolinaCharlestonSouth CarolinaUSA

Trigeminal-specific stimulants have been shown to activate different receptors preferentially and this likely accounts for variation in sensory perception.It is unclear whether trigeminal sensitivity is similar across different transient receptor potential(TRP)receptors or if dysfunction of different receptors results in differing patient symptoms.Therefore,a prospective cohort study was conducted,consisting of trigeminal lateralization testing with three different stimulants(eucalyptol,isothiocyanate,acetic acid),olfaction testing with Sniffin'Sticks,and measurement of various patient‐reported outcome measures(PROMs).A total of 50 participants were enrolled across the olfactory spectrum.Mean TDI score was 27.1±8.3(range 7.0–39.5)with 38%normosmic and 62%dysosmic.Mean trigeminal lateralization scores out of 20 in the overall cohort were 16.18(2.78)for eucalyptol,14.94(3.49)for mustard oil,and 15.28(3.68)for vinegar.Eucalyptol showed a significant correlation with threshold scores of Sniffin'Sticks.A significant correlation was found between acetic acid and various PROMs.None of the lateralization scores of the trigeminal stimulants correlated to each other significantly and there was no correlation to age.The lack of correlation suggests that the measured sensitivity of one type of TRP receptor may not translate to similar sensitivity of the other receptors.Additional investigations with TRPV1 and TRPA1 agonists are needed to corroborate our findings.

关键词： chemosensory olfaction trigeminal TRP receptor

COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

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Journal of Sport and Health Science 2024年第1期13卷 99-107页

作者： Kyle A.Smith tiffany M.Zúñiga Forrest L.Baker Helena Batatinha Charles R.Pedlar Shane C.Burgess Michael P.Gustafson Emmanuel Katsanis Richard J.Simpson School of Nutritional Sciences and Wellness The University of ArizonaTucsonAZ 85721USA Department of Pediatrics The University of ArizonaTucsonAZ 85724USA Faculty of Sport Allied Health and Performance ScienceSt.Mary's UniversityTwickenham TW14SXUK Institute of Sport Exercise and Health University College LondonLondon WC1E 7HUUK Department of Animal and Comparative Biomedical Sciences The University of ArizonaTucsonAZ 85721USA The University of Arizona Cancer Center The University of ArizonaTucsonAZ 85719USA Laboratory Medicine and Pathology Mayo Clinic ArizonaPhoenixAZ 85054USA Department of Immunobiology The University of ArizonaTucsonAZ 85724USA Department of Medicine The University of ArizonaTucsonAZ 85724USA Department of Pathology The University of ArizonaTucsonAZ 85724USA

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

关键词： Anti-viral COVID-19 Exercise immunology SARS-CoV-2 T-Cells Vaccine

CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of PKM supports antitumor immunity

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Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand P.Sharda Mackenzie M.Lieberman Caitlin M.James Shivana M.Lightman Jason H.Tong Guanxi Qiao tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew M.Intlekofer Richard M.Higashi Teresa W.M.Fan Andrew N.Lane Kevin H.Eng Brahm H.Segal Elizabeth A.Repasky Kelvin P.Lee Scott H.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Present address:University of Colorado Boulder BoulderCO 80309USA Present address:Dana Farber Cancer Institute BostonMA 02215USA Present address:Massachusetts Institute of Technology BostonMA 02139USA Present address:Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been determined.In this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T cells.In doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose catabolism.ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events.Among these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector function.Importantly,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 PKM2

蒂芙尼“2024 Blue Book高级珠宝”之“苍穹万象”系列春季作品——再现传奇设计师让·史隆伯杰的宇宙秘境

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中国宝石 2024年第3期 40-47页

作者：蒂芙尼唐贺蒂芙尼(tiffany&Co.)

近日,蒂芙尼(tiffany&Co.)发布的全新“2024 Blue Book高级珠宝”之“苍穹万象”主题系列作品,以超凡出众的设计致敬品牌传奇设计师让·史隆伯杰(Jean Schlumberger)的无限想象力及其对神秘宇宙的热爱。作为蒂芙尼珠宝与高级珠宝首席艺... 详细信息

近日,蒂芙尼(tiffany&Co.)发布的全新“2024 Blue Book高级珠宝”之“苍穹万象”主题系列作品,以超凡出众的设计致敬品牌传奇设计师让·史隆伯杰(Jean Schlumberger)的无限想象力及其对神秘宇宙的热爱。作为蒂芙尼珠宝与高级珠宝首席艺术官娜塔莉·韦代耶(Nathalie Verdeille)加入品牌后设计的第2个“Blue Book高级珠宝”系列,新作以独特视角创新演绎让·史隆伯杰对太阳、月亮、繁星及奇幻宇宙的经典创作。

关键词：高级珠宝 Schlumberger 秘境

The potential of plant proteins as antifungal agents for agricultural applications

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Synthetic and Systems Biotechnology 2022年第4期7卷 1075-1083页

作者： tiffany Chiu Theo Poucet Yanran Li Graduate Program in Genetics GenomicsAnd Bioinformatics1140 Batchelor HallUniversity of California RiversideCalifornia92521USA Department of Chemical and Environmental Engineering University of CaliforniaRiversideCA92521USA

Fungal pathogens induce a variety of diseases in both plants and post-harvest food crops,resulting in significant crop losses for the agricultural industry.Although the usage of chemical-based fungicides is the most common way to control these diseases,they damage the environment,have the potential to harm human and animal life,and may lead to resistant fungal strains.Accordingly,there is an urgent need for diverse and effective agricultural fungicides that are environmentally-and eco-friendly.Plants have evolved various mechanisms in their innate immune system to defend against fungal pathogens,including soluble proteins secreted from plants with antifungal activities.These proteins can inhibit fungal growth and infection through a variety of mechanisms while exhibiting diverse functionality in addition to antifungal activity.In this mini review,we summarize and discuss the potential of using plant antifungal proteins for future agricultural applications from the perspective of bioengineering and biotechnology.

关键词： antifungal potential crops

System Dynamics Forecasting on Taiwan Power Supply Chain

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Computer Systems Science & Engineering 2022年第6期41卷 1191-1205页

作者： Zhiqiu Yu Shuo-Yan Chou Phan Nguyen Ky Phuc tiffany Hui-Kuang Yu Department of Industrial Management National Taiwan University of Science and TechnologyTaipei10607Taiwan Industrial Engineering and Management Department International UniversityHo Chi Minh City70000Vietnam Department of Public Finance Feng Chia UniversityTaichungTaiwan

This research aims to study the sustainability of Taiwan power supplychain based on system dynamics forecasting. The paper tries to investigate electricity shortage effects not only on the industrial side, but also from the standpointof society. In our model, different forecasting methods such as linear regression,time series analysis, and gray forecasting are also considered to predict the parameters. Further tests such as the structure, dimension, historical fit, and sensitivityof the model are also conducted in this paper. Through analysis forecasting result,we believe that the demand for electricity in Taiwan will continue to increase to acertain level for a period of time in the future. This phenomenon is closely relatedto Taiwan’s economic development, especially industrial development. We alsopoint out that electricity prices in Taiwan do not match with high industrialdemand, and that prices are still slightly low. Finally, the future growth trend ofTaiwan’s electricity demand has not changed, and ensuring adequate supply tomeet electricity demand to prevent potential power shortages will pose somedifficulty.

关键词： System dynamics taiwan power supply chain electricity demand

A metabolic conspiracy drives anti-tumorigenic macrophages

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Life Metabolism 2023年第2期2卷 8-9页

作者： Na Li tiffany Horng School of Life Sciences and Technology ShanghaiTech UniversityShanghai 201210China

In the tumor microenvironment,activation of macrophages through CD40 ligation promotes tumor restriction and is being considered clinically.The underpinning metabolic basis is not known and was addressed in a new study by Ho and colleagues.Macrophage activation(or polarization)to distinct cellular states—that are associated with the acquisition of new cellular activities—is fueled by metabolic reprogramming.Intercepting such metabolic reprogramming can disrupt appropriate macrophage activation,thus there is increasing interest in targeting cellular metabolism to alter macrophage activities in a variety of pathophysiological settings[1].

关键词： metabolism tumor activation