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mRNA vaccines:a new era in vaccine development

Oncology Research 2024年第10期32卷 1543-1564页

作者： SHUBHRA cHANDRA jennifer c.wilson DAVID GOOD MING Q.WEI School of Pharmacy&Medical Sciences Gold Coast campusGriffith UniversityBrisbaneQLD-4222Australia Menzies Health Institute Queensland(MHIQ) Gold Coast CampusGriffith UniversityBrisbaneQLD-4215Australia School of Allied Health Australian Catholic UniversityBrisbaneQLD-4014Australia

The advent of RNA therapy,particularly through the development of mRNA cancer vaccines,has ushered in a new era in the field of *** article provides a concise overview of the key principles,recent advancements,and potential implications of mRNA cancer vaccines as a groundbreaking modality in cancer *** cancer vaccines represent a revolutionary approach to combatting cancer by leveraging the body’s innate immune *** vaccines are designed to deliver specific mRNA sequences encoding cancer-associated antigens,prompting the immune system to recognize and mount a targeted response against malignant *** personalized and adaptive nature of mRNA vaccines holds immense potential for addressing the heterogeneity of cancer and tailoring treatments to individual *** breakthroughs in the development of mRNA vaccines,exemplified by the success of cOVID-19 vaccines,have accelerated their application in *** mRNA platform’s versatility allows for the rapid adaptation of vaccine candidates to various cancer types,presenting an agile and promising avenue for therapeutic *** trials of mRNA cancer vaccines have demonstrated encouraging results in terms of safety,immunogenicity,and *** candidates,such as BioNTech’s BNT111 and Moderna’s mRNA-4157,have exhibited promising outcomes in targeting melanoma and solid tumors,*** successes underscore the potential of mRNA vaccines to elicit robust and durable anti-cancer immune *** the field holds great promise,challenges such as manufacturing complexities and cost considerations need to be addressed for widespread *** development of scalable and cost-effective manufacturing processes,along with ongoing clinical research,will be pivotal in realizing the full potential of mRNA cancer ***,mRNA cancer vaccines represent a cutting-edge therapeutic approach that holds the promise of transforming cancer treatment.

关键词： cancer immunotherapy Immune checkpoint Preventive&therapeutic vaccine Delivery system mRNA

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Individual and geospatial factors associated with receipt of colorectal cancer screening:a state-wide mixed-level analysis

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Family Medicine and community Health 2024年第S2期12卷 18-25页

作者： jennifer E Bayly Mara A Schonberg Marcia c castro Kenneth J Mukamal Beth Israel Deaconess Medical center BostonMassachusettsUSA Harvard Medical School BostonMassachusettsUSA Department of Global Health and Population Harvard T H Chan School of Public HealthBostonMassachusettsUSA

Background colorectal cancer(cRc)is the second leading cause of cancer death in US adults but can be reduced by *** roles of individual and contextual factors,and especially physician supply,in attaining universal cRc screening remains *** We used data from adults 50-75 years old participating in the 2018 New York(NY)Behavioural Risk Factor Surveillance System linked to county-level covariates,including primary care physician(PcP)density and gastroenterologist(GI)*** were analysed in *** analyses included(1)ecological and geospatial analyses of county-level cRc screening prevalence and(2)individual-level Poisson regression models of receipt of screening,adjusted for socioeconomic and county-level contextual *** Mean prevalence of up-to-date cRc screening was 71%(95%cI 70%to 73%)across NY’s 62 ***-level cRc screening demonstrated significant spatial patterning(Global Moran’s I=0.14,p=0.04),consistent with the existence of county-level contextual *** both county-level and individual-level analyses,lack of health insurance was associated with lower likelihood of up-to-date screening(?−1.09(95%cI−2.00 to-0.19);adjusted prevalence ratio 0.68(95%cI 0.60 to 0.77)),even accounting for age,race/ethnicity and *** contrast,county-level densities of both PcPs and GIs were completely unassociated with screening at either the county or individual *** expected,other determinants at the individual level included education status and *** In this state-wide representative analysis,physician density was completely unassociated with cRc screening,although health insurance status remains strongly *** similar screening environments,broadened insurance coverage for cRc screening is likely to improve screening far more effectively than increased physician supply.

关键词： state screening county

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The trxG protein ULT1 regulates Arabidopsis organ size by interacting with TcP14/15 to antagonize the LIM peptidase DA1 for H3K4me3 on target genes

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Plant communications 2024年第4期5卷 255-274页

作者： Fan Xu Huixue Dong Weijun Guo Liang Le Yexing Jing jennifer c.Fletcher Jiaqiang Sun Li Pu Biotechnology Research Institute Chinese Academy of Agricultural SciencesBeijing 100081China State Key Laboratory of crop Gene Resources and Breeding Institute of Crop SciencesChinese Academy of Agricultural SciencesBeijing 100081China Department of Plant and Microbial Biology University of CaliforniaBerkeleyBerkeleyCA 94720USA Plant Gene Expression center United States Department of Agriculture-Agricultural Research ServiceAlbanyCA 94710USA These authors contributed equally to this article

Plant organ size is an important agronomic trait that makes a significant contribution to plant *** its central importance,the genetic and molecular mechanisms underlying organ size control remain to be fully ***,we report that the trithorax group protein ULTRAPETALA1(ULT1)interacts with the TEOSINTE BRANcHED1/cYcLOIDEA/PcF14/15(TcP14/15)transcription factors by antagonizing the LIN-11,ISL-1,and MEc-3(LIM)peptidase DA1,thereby regulating organ size in *** of ULT1 function significantly increases rosette leaf,petal,silique,and seed size,whereas overexpression of ULT1 results in reduced organ ***1 associates with TcP14 and TcP15 to co-regulate cell size by affecting cellular *** analysis revealed that ULT1 and TcP14/15 regulate common target genes involved in endoreduplication and leaf ***1 can be recruited by TcP14/15 to promote lysine 4 of histone H3 trimethylation at target genes,activating their expression to determinefinal cell ***,we found that ULT1 influences the interaction of DA1 and TcP14/15 and antagonizes the effect of DA1 on TcP14/15 ***,ourfindings reveal a novel epigenetic mechanism underlying the regulation of organ size in Arabidopsis.

关键词： ULT1 TcP DA1 organ size endoreduplication

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Pancreatic surgery and tertiary pancreatitis services warrant provision for support from a specialist diabetes team

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World Journal of Diabetes 2024年第4期15卷 598-605页

作者： Vasileios K Mavroeidis jennifer Knapton Francesca Saffioti Daniel L Morganstein Department of HPB Surgery Bristol Royal InfirmaryUniversity Hospitals Bristol and Weston NHS Foundation TrustBristol BS28HWUnited Kingdom Department of Gastrointestinal Surgery Southmead HospitalNorth Bristol NHS TrustBristol BS105NBUnited Kingdom Department of Academic Surgery Royal Marsden NHS Foundation TrustLondon SW36JJUnited Kingdom Department of Gastroenterology and Hepatology Oxford University Hospitals NHS Foundation TrustOxford OX39DUUnited Kingdom UcL Institute for Liver and Digestive Health University College LondonLondon NW32PFUnited Kingdom Department of Endocrinology Chelsea and Westminster Hospital NHS Foundation TrustLondon SW109NHUnited Kingdom Department of Gastrointestinal Unit Royal Marsden NHS Foundation TrustLondon SW36JJUnited Kingdom

Pancreatic surgery units undertake several complex operations,albeit with consi-derable morbidity and mortality,as is the case for the management of complicated acute pancreatitis or chronic *** centralisation of pancreatic surgery services,with the development of designated large-volume centres,has contribu-ted to significantly improved *** this editorial,we discuss the complex associations between diabetes mellitus(DM)and pancreatic/periampullary disease in the context of pancreatic surgery and overall management of complex pancreatitis,highlighting the consequential needs and the indispensable role of specialist diabetes teams in support of tertiary pancreatic *** 3c pan-creatogenic DM,refers to DM developing in the setting of exocrine pancreatic disease,and its identification and management can be challenging,while the glycaemic control of such patients may affect their course of treatment and *** preoperative diabetes assessment is warranted to aid identification of patients who are likely to need commencement or escalation of glucose lowering therapy in the postoperative *** incidence of new onset diabetes after pancreatic resection is widely variable in the literature,and depends on the type and extent of pancreatic resection,as is the case with pancreatic parenchymal loss in the context of severe *** involvement of a specialist diabetes team is essential to ensure a holistic *** the current era,large volume pancreatic surgery services commonly abide by the principles of enhanced recovery after surgery,with inclusion of provisions for optimisation of the perioperative glycaemic control,to improve *** various guidelines are available to aid perioperative management of DM,auditing and quality improvement platforms have highlighted deficiencies in the perioperative management of diabetic patients and areas of required *** need for perioperative support of diabetic

关键词： Pancreatectomy Pancreatoduodenectomy Whipple’s Pancreatitis Diabetes specialist Type 3c pancreatogenic diabetes mellitus

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Are there sex-based disparities in cataract surgery?

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 137-143页

作者： Matthew D.Geiger Anne M.Lynch Alan G.Palestine Nathan c.Grove Karen L.christopher Richard S.Davidson Michael J.Taravella Naresh Mandava jennifer L.Patnaik Department of Ophthalmology University of Colorado School of MedicineAuroraCO 80045USA

AIM:To investigate sex-based differences in the occurrence of intra-operative and post-operative complications and associated visual outcomes following cataract ***:This was a retrospective study of patients who had phacoemulsification cataract surgery at the University of colorado School of *** collected included the patient’s health history,ocular comorbidities,operative and post-operative complications,and the post-operative best corrected visual acuity(BcVA).The data were analyzed using univariate and multivariable logistic regression with generalized estimating equations to account for the correlation of some patients having two eyes included in the ***:A total of 11977 eyes from 7253 patients were included in the *** comorbidities differed by sex,with males having significantly higher percentages of traumatic cataracts(males 0.7%vs females 0.1%),prior ocular surgery(6.7%vs 5.5%),and mature cataracts(2.8%vs 1.9%).conversely,females had significantly higher rates of pseudoexfoliation(2.0%vs 3.2%).In unadjusted analysis,males had higher rates of posterior capsular rupture(0.8%vs 0.4%)and vitreous loss(1.0%vs 0.6%),but this difference was not significant after adjustment for *** had a significantly increased risk of post-operative retinal detachment,but in multivariable analysis this was no longer *** were significantly less likely to undergo post-operative neodymium-doped yttrium aluminum garnet(Nd:YAG)laser capsulotomy for posterior capsule opacification(OR=0.8,95%cI=0.7-0.9,P=0.0005).The BcVA was slightly worse for males pre-operatively;but post-operatively,both sexes exhibited similar visual acuity of Snellen equivalent 20/***:The study finds that in a cohort of patients presenting for cataract surgery,sex differences exist in pre-operative comorbidities and surgical characteristics that contribute to higher rates of some complications for ***,observed surgical complicatio

关键词： cataract surgery sex-based disparity phacoemulsification outcomes

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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon c.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny cheung jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

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How completely are randomized controlled trials of non-pharmacological interventions following concussion reported? A systematic review

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Journal of Sport and Health Science 2024年第4期13卷 537-547页

作者： Jacqueline Josee van Ierssel Olivia Galea Kirsten Holte caroline Luszawski Elizabeth Jenkins jennifer O’Neil carolyn A Emery Rebekah Mannix Kathryn Schneider Keith Owen Yeates Roger Zemek children’s Hospital of Eastern Ontario Research Institute OttawaON K1H 8L1Canada The centre for Health Activity and Rehabilitation ResearchUniversity of OtagoDunedin 9016New Zealand Sport Injury Prevention Research centre Faculty of KinesiologyUniversity of CalgaryCalgaryAB T2N 1N4Canada Alberta children’s Hospital Research Institute University of calgary CalgaryAB T2N 1N4Canada Hotchkiss Brain Institute University of CalgaryCalgaryAB T2N 4N1Canada Department of Psychology University of CalgaryCalgaryAB T2N 1N4Canada g Faculty of MedicineUniversity of OttawaOttawaON K1H 8M5Canada School of Rehabilitation Sciences University of OttawaOttawaON K1H 8M5Canada Bruyere Research Institute OttawaON K1N 5C8Canada Departments of Pediatrics and Emergency Medicine Harvard Medical SchoolBostonMA 02115USA Departments of Pediatrics and Emergency Medicine University of OttawaOttawaON K1H 8M5Canada

Purpose:The study aimed to examine the reporting completeness of randomized controlled trials(RcTs)of non-pharmacological interventions following ***:We searched MEDLINE,Embase,PsycInfo,cINAHL,and Web of Science up to May *** reviewers independently screened studies and assessed reporting completeness using the Template for Intervention Description and Replication(TIDieR),consensus on Exercise Reporting Template(cERT),and international consensus on Therapeutic Exercise aNd Training(i-cONTENT)*** information was sought my study authors where reporting was *** of bias(ROB)was assessed with the cochrane ROB-2 *** examining non-pharmacological interventions following ***:We included 89 RcTs(n=53 high ROB)examining 11 different interventions for concussion:sub-symptom threshold aerobic exercise,cervicovestibular therapy,physical/cognitive rest,vision therapy,education,psychotherapy,hyperbaric oxygen therapy,transcranial magnetic stimulation,blue light therapy,osteopathic manipulation,and head/neck *** scores were:TIDieR 9/12(75%;interquartile range(IQR)=5;range:5-12),cERT 17/19(89%;IQR=2;range:10-19),and i-cONTENT 6/7(86%;IQR=1;range:5-7).Percentage of studies completely reporting all items was TIDieR 35%(31/89),cERT 24%(5/21),and i-cONTENT 10%(2/21).Studies were more completely reported after publication of TIDieR(t_(87)=2.08;p=0.04)and cERT(t_(19)=2.72;p=0.01).Reporting completeness was not strongly associated with journal impact factor(TIDieR:rs=0.27;p=0.01;cERT:r_(s)=-0.44;p=0.06;i-cONTENT:r_(s)=-0.17;p=0.48)or ROB(TIDieR:rs=0.11;p=0.31;cERT:rs=0.04;p=0.86;i-cONTENT:rs=0.12;p=0.60).conclusion:RcTs of non-pharmacological interventions following concussion demonstrate moderate to good reporting completeness,but are often missing key components,particularly modifications,motivational strategies,and qualified *** completeness improved after TIDieR and cERT publication,but p

关键词： concussion Intervention Randomized controlled trial Systematic review

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Gate-controlled supercurrent effect in dry-etched Dayem bridges of non-centrosymmetric niobium rhenium

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Nano Research 2024年第7期17卷 6575-6581页

作者： jennifer Koch carla cirillo Sebastiano Battisti Leon Ruf Zahra Makhdoumi Kakhaki Alessandro Paghi Armen Gulian Serafim Teknowijoyo Giorgio De Simoni Francesco Giazotto carmine Attanasio Elke Scheer Angelo Di Bernardo Department of Physics University of KonstanzUniversitätsstraße 1078464 KonstanzGermany cNR-Spin c/o Universitàdegli Studi di Salernovia Giovanni Paolo II 13284084 Fisciano(SA)Italy NEST Istituto Nanoscienze-CNR and Scuola Normale SuperiorePiazza San Silvestro 1256127 PisaItaly Dipartimento di Fisica“E.R.caianiello” Universitàdegli Studi di SalernoVia Giovanni Paolo II 13284084 Fisciano(SA)Italy Advanced Physics Laboratory Institute for Quantum StudiesChapman UniversityBurtonsvilleMD 20866USA

The application of a gate voltage to control the superconducting current flowing through a nanoscale superconducting constriction,named as gate-controlled supercurrent(GcS),has raised great interest for fundamental and technological *** gain a deeper understanding of this effect and develop superconducting technologies based on it,the material and physical parameters crucial for the GcS effect must be ***-down fabrication protocols should also be optimized to increase device scalability,although studies suggest that top-down fabricated devices are more resilient to show a ***,we investigate gated superconducting nanobridges made with a top-down fabrication process from thin films of the noncentrosymmetric superconductor niobium rhenium with varying ratios of the constituents(NbRe).Unlike other devices previously reported and made with a top-down approach,our NbRe devices systematically exhibit a GcS effect when they were fabricated from NbRe thin films with small grain size and etched in specific *** observations pave the way for the realization of top-down-made GcS devices with high *** results also imply that physical parameters like structural disorder and surface physical properties of the nanobridges,which can be in turn modified by the fabrication process,are crucial for a GcS observation,providing therefore also important insights into the physics underlying the GcS effect.

关键词： superconductivity non-centrosymmetric superconductors superconducting devices gated devices gate-controlled supercurrent top-down fabrication

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Geospatial Analysis of Urban Heat Island Effects and Tree Equity

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Open Journal of Forestry 2024年第1期14卷 1-18页

作者： Jillian Gorrell Sharon R. Jean-Philippe Paul D. Ries jennifer K. Richards Neelam c. Poudyal Rochelle Butler School of Natural Resources University of Tennessee 203 Third Creek Building Knoxville Tennessee USA

In recent decades, Urban Heat Island Effects have become more pronounced and more widely examined. Despite great technological advances, our current societies still experience great spatial disparity in urban forest access. Urban Heat Island Effects are measurable phenomenon that are being experienced by the world’s most urbanized areas, including increased summer high temperatures and lower evapotranspiration from having impervious surfaces instead of vegetation and trees. Tree canopy cover is our natural mitigation tool that absorbs sunlight for photosynthesis, protects humans from incoming radiation, and releases cooling moisture into the air. Unfortunately, urban areas typically have low levels of vegetation. Vulnerable urban communities are lower-income areas of inner cities with less access to heat protection like air conditioners. This study uses mean evapotranspiration levels to assess the variability of urban heat island effects across the state of Tennessee. Results show that increased developed land surface cover in Tennessee creates measurable changes in atmospheric evapotranspiration. As a result, the mean evapotranspiration levels in areas with less tree vegetation are significantly lower than the surrounding forested areas. central areas of urban cities in Tennessee had lower mean evapotranspiration recordings than surrounding areas with less development. This work demonstrates the need for increased tree canopy coverage.

关键词： Spatial Analysis Land cover Urban Heat Island Effect (UHIE) Evapotranspiration Tree canopy Impervious Surface GIS Prediction Model GIS Machine Learning

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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari jennifer c.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric critical care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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