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Macrophage-specific inhibition of the histone demethylase JMJD3 decreases STING and pathologic inflammation in diabetic wound repair

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cellular & Molecular Immunology 2022年第11期19卷 1251-1262页

作者： christopher O.Audu William J.Melvin Amrita D.Joshi Sonya J.Wolf Jadie Y.Moon Frank M.Davis emily c.barrett Kevin D.Mangum Hongping Deng Xianying Xing Rachel Wasikowski Lam c.Tsoi Sriganesh B.Sharma Tyler M.Bauer James Shadiow Matthew A.corriere Andrea TObi Steven LKunkel Benjamin Levi Bethany BMoore Johann EGudjonsson Andrew MSmith Katherine A.Gallagher Department of Surgery Section of Vascular SurgeryUniversity of MichiganAnn ArborMIUSA Department of Microbiology and Immunology University of MichiganAnn ArborMIUSA Department of Medicinal chemistry University of MichiganAnn ArborMIUSA Department of Surgery Section of General SurgeryUniversity of MichiganAnn ArborMIUSA Department of Bioengineering University of IllinoisUrbana-ChampaignChampaignILUSA Department of Dermatology University of MichiganAnn ArborMIUSA Department of Pathology University of MichiganAnn ArborMIUSA Department of Surgery University of Texas Southwestern Medical CenterDallasTXUSA

Macrophage plasticity is critical for normal tissue repair following injury.In pathologic states such as diabetes,macrophage plasticity is impaired,and macrophages remain in a persistent proinflammatory state;however,the reasons for this are unknown.Here,using single-cell RNA sequencing of human diabetic wounds,we identified increased JMJD3 in diabetic wound macrophages,resulting in increased inflammatory gene expression.Mechanistically,we report that in wound healing,JMJD3 directs early macrophage-mediated inflammation via JAK1,3/STAT3 signaling.However,in the diabetic state,we found that IL-6,a cytokine increased in diabetic wound tissue at later time points post-injury,regulates JMJD3 expression in diabetic wound macrophages via the JAK1,3/STAT3 pathway and that this late increase in JMJD3 induces NFκB-mediated inflammatory gene transcription in wound macrophages via an H3K27me3 mechanism.Interestingly,RNA sequencing of wound macrophages isolated from mice with JMJD3-deficient myeloid cells(Jmjd3f/fLyz2cre+)identified that the STING gene(Tmem173)is regulated by JMJD3 in wound macrophages.STING limits inflammatory cytokine production by wound macrophages during healing.However,in diabetic mice,its role changes to limit wound repair and enhance inflammation.This finding is important since STING is associated with chronic inflammation,and we found STING to be elevated in human and murine diabetic wound macrophages at late time points.Finally,we demonstrate that macrophage-specific,nanoparticle inhibition of JMJD3 in diabetic wounds significantly improves diabetic wound repair by decreasing inflammatory cytokines and STING.Taken together,this work highlights the central role of JMJD3 in tissue repair and identifies cell-specific targeting as a viable therapeutic strategy for nonhealing diabetic wounds.

关键词： wound healing epigenetics diabetes JMJD3 STING

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A review of public health guidelines for postpartum physical activity and sedentary behavior from around the world

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Journal of Sport and Health Science 2024年第4期13卷 472-483,F0003页

作者： Kelly R.Evenson Wendy J.Brown Alison K.Brinson emily Budzynski-Seymour Melanie Hayman Department of Epidemiology Gillings School of Global Public HealthUniversity of North Carolina at Chapel HillChapel HillNC 27599-8050USA Faculty of Health Sciences and Medicine Bond UniversityGold CoastQLD 4226Australia School of Human Movement and Nutrition Sciences The University of QueenslandBrisbaneQLD 4072Australia Department of Anthropology University of North Carolina at Chapel HillChapel HillNC 27599-3115USA carolina Population center University of North Carolina at Chapel HillChapel HillNC 27599-8120USA Faculty of Sport Health and Social SciencesSolent UniversitySouthamptonSO140YNUK Appleton Institute School of HealthMedical and Applied SciencesCentral Queensland UniversityRockhamptonQLD 4701Australia

Background:The period following pregnancy is a critical time window when future habits with respect to physical activity(PA)and sedentary behavior(SB)are established;therefore,it warrants guidance.The purpose of this scoping review was to summarize public health-oriented country-speciﬁc postpartum PA and SB guidelines worldwide.Methods:To identify guidelines published since 2010,we performed a(a)systematic search of 4 databases(cINAHL,Global Health,PubMed,and SPORTDiscus),(b)structured repeatable web-based search separately for 194 countries,and(c)separate web-based search.Only the most recent guideline was included for each country.Results:We identiﬁed 22 countries with public health-oriented postpartum guidelines for PA and 11 countries with SB guidelines.The continents with guidelines included Europe(n=12),Asia(n=5),Oceania(n=2),Africa(n=1),North America(n=1),and South America(n=1).The most common beneﬁts recorded for PA included weight control/management(n=10),reducing the risk of postpartum depression or depres-sive symptoms(n=9),and improving mood/well-being(n=8).Postpartum guidelines speciﬁed exercises to engage in,including pelvicﬂoor exercises(n=17);muscle strengthening,weight training,or resistance exercises(n=13);aerobics/general aerobic activity(n=13);walking(n=11);cycling(n=9);and swimming(n=9).Eleven guidelines remarked on the interaction between PA and breastfeeding;several guidelines stated that PA did not impact breast milk quantity(n=7),breast milk quality(n=6),or infant growth(n=3).For SB,suggestions included limiting long-term sitting and interrupting sitting with PA.conclusion:country-speciﬁc postpartum guidelines for PA and SB can help promote healthy behaviors using a culturally appropriate context while providing speciﬁc guidance to public health practitioners.

关键词： Breastfeeding caesarean section Guidelines Postnatal Recommendations

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Artificial cavernosa-like tissue based on multibubble Matrigel and a human corpus cavernous fibroblast scaffold

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Asian Journal of Andrology 2024年第3期26卷 260-267页

作者： Yu-Zhuo chen Yi-Hong Zhou Min-Bo Yan Ming Xiao Biao Liu Ying-Hao Yin Xiao-Li Tan Yong-Quan Huang Yu-Hong Lin Ting Xie Jia-Li Tian Qi Wang Jian-Ying Li Zi-Zhou Meng Zheng Li emily Xing Yu-Xin Tang Ya-Wei Li Zhong-Zhen Su Liang-Yu Zhao Department of Ultrasound The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhai 519000China Department of Interventional Medicine Guangdong ProvincialKey Laboratory of Biomedical ImagingThe Fifth Affiliated HospitalSun Yat-sen UniversityZhuhai 519000China Department of Urology The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhai 519000China Department of Andrology the Center for Men’s HealthUrologic Medical CenterShanghai Key Laboratory of ReproductiveMedicineShanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China cedars-Sinai Medical center Los AngelesCA 90024USA

Ex vivo tissue culture of the human corpus cavernosum(cc)can be used to explore the tissue structural changes and complex signaling networks.At present,artificial cc-like tissues based on acellular or three-dimensional(3D)-printed scaffolds are used to solve the scarcity of primary penis tissue samples.However,inconvenience and high costs limit the wide application of such methods.Here,we describe a simple,fast,and economical method of constructing artificial cc-like tissue.Human cc fibroblasts(FBs),endothelial cells(Ecs),and smooth muscle cells(SMcs)were expanded in vitro and mixed with Matrigel in specific proportions.A large number of bubbles were formed in the mixture by vortexing combined with pipette blowing,creating a porous,spongy,and spatial structure.The cc FBs produced a variety of signaling factors,showed multidirectional differentiation potential,and grew in a 3D grid in Matrigel,which is necessary for cc-like tissue to maintain a porous structure as a cell scaffold.Within the c-like tissue,Ecs covered the surface of the lumen,and SMcs were located inside the trabeculae,similar to the structure of the primary cc.Various cell components remained stable for 3 days in vitro,but the Ec content decreased on the 7th day.Wingless/integrated(WNT)signaling activation led to lumen atrophy and increased tissue fibrosis in cc-like tissue,inducing the same changes in characteristics as in the primary cc.This study describes a preparation method for human artificial cc-like tissue that may provide an improved experimental platform for exploring the function and structure of the cc and conducting drug screening for erectile dysfunction therapy.

关键词： artificial tissue corpus cavernosum ex vivo fibroblasts|

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Mortality assessment for pancreas transplants in the United States over the decade 2008-2018

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World Journal of Transplantation 2023年第4期13卷 147-156页

作者： Tambi Jarmi emily Brennan Jacob clendenon Aaron c Spaulding Department of Transplant Mayo Clinic FloridaJacksonvilleFL 32224United States Health Science Research Mayo Clinic FloridaJacksonvilleFL 32224United States

BAcKGROUND Pancreas transplant is the only treatment that establishes normal glucose levels for patients diagnosed with diabetes.However,since 2005,no comprehensive analysis has compared survival outcomes of:(1)Simultaneous pancreas-kidney(SPK)transplant;(2)Pancreas after kidney(PAK)transplant;and(3)Pancreas transplant alone(PTA)to waitlist survival.AIM To explore the outcomes of pancreas transplants in the United States during the decade 2008-2018.METHODS Our study utilized the United Network for Organ Sharing Standard Transplant Analysis and Research file.Pre-and post-transplant recipient and waitlist characteristics and the most recent recipient transplant and mortality status were used.We included all patients with type I diabetes listed for pancreas or kidneypancreas transplant between May 31,2008 and May 31,2018.Patients were grouped into one of three transplant types:SPK,PAK,or PTA.RESULTS The adjusted cox proportional hazards models comparing survival between transplanted and non-transplanted patients in each transplant type group showed that patients who underwent an SPK transplant exhibited a significantly reduced hazard of mortality[hazard ratio(HR)=0.21,95%confidence intervals(cI):0.19-0.25]compared to those not transplanted.Neither PAK transplanted patients(HR=1.68,95%cI:0.99-2.87)nor PTA patients(HR=1.01,95%cI:0.53-1.95)experienced significantly different hazards of mortality compared to patients who did not receive a transplant.cONcLUSION When assessing each of the three transplant types,only SPK transplant offered a survival advantage compared to patients on the waiting list.PKA and PTA transplanted patients demonstrated no significant differences compared to patients who did not receive a transplant.

关键词： Pancreas transplant Simultaneous pancreas-kidney transplant Pancreas after kidney transplant Survival Diabetes mellitus Insulin

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Dietary(poly)phenol intake is associated with cardiometabolic health parameters in adolescents

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Food Science and Human Wellness 2024年

作者： emily P.Laveriano-Santos Sara castro-Barquero camila Arancibia-Riveros Ana María Ruiz-León Rosa casas Ramón Estruch Patricia Bodega Mercedes de Miguel Amaya de cos-Gandoy Jesús Martínez-Gómez Gloria Santos-Beneit Juan M.Fernández-Alvira Rodrigo Fernández-Jiménez Rosa M.Lamuela-Raventós Anna Tresserra-Rimbau The Zena and Michael A.Wiener cardiovascular Institute Icahn School of Medicine at Mount Sinai Department de Nutrició ciències de l'Alimentació I Gastronomia XIA Facultat de Farmàcia i ciències de l'alimentació Institut de Recerca en Nutrició i Seguretat Alimentària (INSA-UB) Universitat de Barcelona Department of Internal Medicine Hospital clínic Institutd'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS) University of Barcelona consorcio cIBER M.P.Fisiopatología de la Obesidad y Nutrición (cIBERObn) Instituto de Salud carlos III (IScIII) Mediterranean Diet Foundation 5. Foundation for Science Health and Education (SHE) 6. centro Nacional de Investigaciones cardiovasculares (cNIc) cIBER de Enfermedades cardiovasculares (cIBERcV) 9. Hospital Universitario clínico San carlos

Background: The protective role of (poly)phenols against metabolic disorders has been extensively studied in adults but not in adolescents.Objective: To assess associations of dietary (poly)phenols and their subclasses with cardiometabolic health parameters in adolescents. Methods: A cross-sectional study was conducted in 944 individuals aged 11 to 14 years enrolled in the SI! Program for Secondary Schools trial (NcT03504059). (Poly)phenol intake was assessed using semi-quantitative food frequency questionnaires and the Phenol-Explorer database. The measured cardiometabolic parameters were waist circumference (Wc) age-sex z-score， blood pressure (BP) age-sex z-score， blood glucose (BG)， triglycerides (TG)， and high-density lipoprotein cholesterol (HDL-c). Multilevel mixed-effect linear regression models were applied to examine the association between (poly)phenol quintiles and cardiometabolic health parameters.Results: compared to the lowest quintile， adolescents in the highest quintile of total (poly)phenol intake had lower Wc z-scores (β=-0.09， 95%cI=-0.09;-0.08， P-for trend=0.002)， mean arterial pressure z-scores (β =-0.11， 95%cI=-0.12;-0.09， P-for trend=0.206)， and HDL-c (β=-1.52， 95%cI=-2.90;-0.14， P-for trend=0.108)， after multivariable adjustment. The Wc z-scores (β=-0.11， 95%cI=-0.19;-0.03， P-for trend=0.013) and HDL-c (β=-2.16， 95%cI=-3.78;-0.53， P-for trend=0.046) were lower in the highest quintile of flavonoid intake compared to the lowest quintile. The highest quintile of phenolic acid intake was associated with a lower Wc z-score (β=-0.14， 95%cI=-0.26;-0.02， P-for trend=0.011) and TG levels (β=-8.83， 95%cI=-12.37;-5.30， P-for trend cI= -3.103;-0.64， P-for trend cI= -4.95;-1.49， P-for trend=0.034)， and with higher HDL-c (β=2.328， 95%cI= 1.40;3.17， P-for trend=0.466) compared to the lowest quintile. conclusion: A higher intake of (poly)phenols， especially flavonoids， phenolic acids， and stilbenes

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Medical treatments of endometriosis: a review

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Reproductive and Developmental Medicine 2023年第3期7卷 166-179页

作者： Bahi Elbasueny Maya Geets emily c.Yang catherine Allaire Paul J.Yong Mohamed A.Bedaiwy Division of Reproductive Endocrinology and Infertility Department of Obstetrics and GynecologyFaculty of MedicineUniversity of British ColumbiaVancouverBCCanada Department of Obstetrics and Gynecology Faculty of MedicineMenoufia University.MenoufiaEgypt.

Endometriosis is a chronic gynecological disorder that affects approximately 10%of women of reproductive age.Most medical treatments used today for endometriosis pain are hormonal therapies,which are not an option for those trying to conceive and are not tolerated by a subset of patients due to side effects.In this article,we offer a comprehensive review of current and investigational medical therapeutic options used to treat endometriosis pain,as well as a symptom-based systematic approach for patients with painful endometriosis.We have also included recommendations for research to enhance the evolution of novel therapeutic options.A thorough literature search was carried out,and the data were synthesized using a synthesis matrix that classifies and categorizes various arguments.

关键词： Endometriosis Pelvic pain Medical treatment Medical therapy Non-steroidal anti-inflammatory drugs combined oral contraceptives Progesterone GnRH agonist GnRH antagonist Aromatase inhibitors Investigational endometriosis treatments

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Myo-inositol reduces β-catenin activation in colitis

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World Journal of Gastroenterology 2017年第28期23卷 5115-5126页

作者： emily M Bradford corey A Thompson Tatiana Goretsky Guang-Yu Yang Luz M Rodriguez Linheng Li Terrence A barrett Division of Gastroenterology Department of Internal MedicineUniversity of Kentucky Department of Internal Medicine Northwestern University Feinberg School of Medicine Division of cancer Research National Cancer InstituteDCP/GOCRGBethesda Department of Surgery Walter Reed National Military Medical Center Department of Pathology and Laboratory Medicine University of Kansas School of Medicine and Stowers Institute for Medical Research

AIM To assess dietary myo-inositol in reducing stem cell activation in colitis,and validate pβ-cateninS^(552) as a biomarker of recurrent dysplasia.METHODS We examined the effects of dietary myo-inositol treatment on inflammation,pβ-cateninS^(552) and p Akt levels by histology and western blot in IL-10-/-and dextran sodium sulfate-treated colitic mice. Additionally,we assessed nuclear pβ-cateninS^(552) in patients treated with myo-inositol in a clinical trial,and in patients with and without a history of colitis-induced dysplasia.RESULTS In mice,pβ-cateninS^(552) staining faithfully reported the effects of myo-inositol in reducing inflammation and intestinal stem cell activation. In a pilot clinical trial of myo-inositol administration in patients with a history of low grade dysplasia(LGD),two patients had reduced numbers of intestinal stem cell activation compared to the placebo control patient. In humans,pβ-cateninS^(552) staining discriminated ulcerative colitis patients with a history of LGD from those with benign disease.cONcLUSION Enumerating crypts with increased numbers of pβ-cateninS^(552)-positive cells can be utilized as a biomarker in colitis-associated cancer chemoprevention trials.

关键词： chemoprevention 发育异常 Biomarker 干细胞联系大肠炎的癌症

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Disturbance cue communication is shaped by emitter diet and receiver background risk in Trinidadian guppies

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current Zoology 2022年第4期68卷 433-440页

作者： Jack A Goldman Adam L crane Laurence E A Feyten emily collins Grant E Brown Department of Biology Concordia University7141 Sherbrooke Street WestMontrealQCCanada H4B 1R6

In animal communication systems,individuals that detect a cue(i.e.,“receivers”)are often influenced by characteristics of the cue emitter.For instance,in many species,receivers avoid chemical cues that are released by emitters experiencing disturbance.These chemical“disturbance cues”appear to benefit receivers by warning them about nearby danger,such as a predator’s approach.While the active ingredients in disturbance cues have been largely unexplored,by-products of metabolized protein are thought to play a role for some species.If so,the content(quality)and volume(quantity)of the emitter’s diet should affect their disturbance cues,thus altering how receivers perceive the cues and respond.Guppies Poecilia reticulata are a species known to discriminate among disturbance cues from different types of donors,but dietary variation has yet to be explored.In this study,we found evidence that diet quality and quantity can affect disturbance cues released by guppy emitters(i.e.,experimental“donors”).Receivers discriminated between donor cue treatments,responding more strongly to cues from donors fed a protein-rich bloodworm diet(Experiment 1),as well as an overall larger diet(Experiment 2).We also found that receivers exposed to higher background risk were more sensitive to disturbance cue variation,with the strongest avoidance responses displayed by high-risk receivers toward disturbance cues from donors fed the high-quality diet.Therefore,diet,and perhaps protein specifically,affects either the concentration or composition of disturbance cues released by guppies.Such variation may be important in information signaling in social species like the guppy.

关键词： alarm cues chemical cues diet quality diet quantity protein

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A scoping review of randomized clinical trials for pain management in pediatric tonsillectomy and adenotonsillectomy

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2023年第1期9卷 9-26页

作者： Michael c.Shih Barry D.Long Phayvanh P.Pecha David R.White Yi-chun c.Liu Brennan emily Mariam I.Nguyen clarice S.clemmens Department of Otolaryngology-Head and Neck Surgery Medical University of South CarolinaCharlestonSouth CarolinaUSA Baylor college of Medicine HoustonTexasUSA Department of Otolaryngology-Head and Neck Surgery Virginia Commonwealth University School of MedicineRichmondVirginiaUSA Department of Otolaryngology-Head and Neck Surgery Baylor College of MedicineHoustonTexasUSA Department of Surgery-Division of Pediatric Otolaryngology Texas Children's HospitalHoustonTexasUSA Department of Research and Education Services Medical University of South Carolina LibraryCharlestonSouth CarolinaUSA charleston county School of the Arts North CharlestonSouth CarolinaUSA

Objectives:To examine the volume,topics,and reporting trends in the published literature of randomized clinical trials for pharmacologic pain management of pediatric tonsillectomy and adenotonsillectomy and to identify areas requiring further research.Data Sources:PubMed(National Library of Medicine and National Institutes of Health),Scopus(Elsevier),cINAHL(EBScO),and cochrane Library(Wiley).Methods:A systematic search of four databases was conducted.Only randomized controlled or comparison trials examining pain improvement with a pharmacologic intervention in pediatric tonsillectomy or adenotonsillectomy were included.Data collected included demographics,pain-related outcomes,sedation scores,nausea/vomiting,postoperative bleeding,types of drug comparisons,modes of administration,timing of administration,and identities of the investigated drugs.Results:One hundred and eighty-nine studies were included for analysis.Most studies included validated pain scales,with the majority using visual-assisted scales(49.21%).Fewer studies examined pain beyond 24 h postoperation(24.87%),and few studies included a validated sedation scale(12.17%).Studies have compared several different dimensions of pharmacologic treatment,including different drugs,timing of administration,modes of administration,and dosages.Only 23(12.17%)studies examined medications administered postoperatively,and only 29(15.34%)studies examined oral medications.Acetaminophen only had four self-comparisons.conclusion:Our work provides the first scoping review of pain and pediatric tonsillectomy.With drug safety profiles considered,the literature does not have enough data to determine which treatment regimen provides superior pain control in pediatric tonsillectomy.Even common drugs like acetaminophen and ibuprofen require further research for optimizing the treatment of posttonsillectomy pain.The heterogeneity in study design and comparisons weakens the conclusions of potential systematic reviews and meta-analyses.Future directions include more noninferiority

关键词： adenotonsillectomy child evidence-based medicine pain pediatrics tonsillectomy

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Incorporation of near-real-time hospital occupancy data to improve hospitalization forecast accuracy during the cOVID19 pandemic

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Infectious Disease Modelling 2022年第1期7卷 277-285页

作者： Alexander Preiss emily Hadley Kasey Jones Marie c.D.Stoner caroline Kery Peter Baumgartner Georgiy Bobashev Jessica Tenenbaum charles carter Kimberly clement Sarah Rhea RTI International Research Triangle ParkNCUSA Explosion BerlinGermany North carolina Department of Health and Human Services RaleighNCUSA North carolina State University Department of Population Health and PathobiologyRaleighNCUSA

Public health decision makers rely on hospitalization forecasts to inform cOVID-19 pandemic planning and resource allocation.Hospitalization forecasts are most relevant when they are accurate,made available quickly,and updated frequently.We rapidly adapted an agent-based model(ABM)to provide weekly 30-day hospitalization forecasts(i.e.,demand for intensive care unit[IcU]beds and non-IcU beds)by state and region in North carolina for public health decision makers.The ABM was based on a synthetic population of North carolina residents and included movement of agents(i.e.,patients)among North carolina hospitals,nursing homes,and the community.We assigned SARScoV-2 infection to agents using county-level compartmental models and determined agents’cOVID-19 severity and probability of hospitalization using synthetic population characteristics(e.g.,age,comorbidities).We generated weekly 30-day hospitalization forecasts during MayeDecember 2020 and evaluated the impact of major model updates on statewide forecast accuracy under a SARS-coV-2 effective reproduction number range of 1.0e1.2.Of the 21 forecasts included in the assessment,the average mean absolute percentage error(MAPE)was 7.8%for non-IcU beds and 23.6%for IcU beds.Among the major model updates,integration of near-real-time hospital occupancy data into the model had the largest impact on improving forecast accuracy,reducing the average MAPE for non-IcU beds from 6.6%to 3.9%and for IcU beds from 33.4%to 6.5%.Our results suggest that future pandemic hospitalization forecasting efforts should prioritize early inclusion of hospital occupancy data to maximize accuracy.

关键词： forecast hospital adapted

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