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Superior antibody and membrane protein‑specific T‑cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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World Journal of Pediatrics 2024年第4期20卷 353-370页

作者： Jaime S.Rosa Duque Samuel M.S.Cheng Carolyn A.Cohen Daniel Leung Xiwei Wang Xiaofeng Mu yuet Chung Tsun Ming Lau Manni Wang Wenyue Zhang yanmei Zhang howard h.W.Wong Leo C.h.Tsang Sara Chaothai Tsz Chun Kwan John K.C.Li Karl C.K.Chan Leo L.h.Luk Jenson C.h.ho Wing yan Li Amos M.T.Lee jennifer h.y.lam Sau Man Chan Wilfred h.S.Wong Issan y.S.Tam Masashi Mori Sophie A.Valkenburg Malik Peiris Wenwei Tu yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina School of Public health The University of Hong KongHong KongChina hKU‑Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina Research Institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Microbiology and Immunology Peter Doherty Institute for Infectionand ImmunityUniversity of MelbourneMelbourneVICAustralia Center for Immunology and Infection C2i Hong KongChina

Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary.Fractional dosing by intradermal(ID)administration has been shown to be equally immunogenic as intramuscular(IM)administration for several vaccines,but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)at the full dose is unknown.This study(NCT04800133)investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents.Methods Participants aged 11–17 years received two doses of IM or ID vaccine,followed by the 3rd dose 13–42 days later.humoral and cellular immunogenicity outcomes were measured post-dose 2(IM-CC versus ID-CC)and post-dose 3(IMCCC versus ID-CCC).Doses 2 and 3 were administered to 173 and 104 adolescents,respectively.Results Spike protein(S)immunoglobulin G(IgG),S-receptor-binding domain(RBD)IgG,S IgG Fcγreceptor IIIa(FcγRIIIa)-binding,SNM[sum of individual(S),nucleocapsid protein(N),and membrane protein(M)peptide pool]-specific interleukin-2(IL-2)+CD4+,SNM-specific IL-2+CD8+,S-specific IL-2+CD8+,N-specific IL-2+CD4+,N-specific IL-2+CD8+and M-specific IL-2+CD4+responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC,whereas IgG avidity was inferior.For ID-CCC,S-RBD IgG,surrogate virus neutralisation test,90%plaque reduction neutralisation titre(PRNT90),PRNT50,S IgG avidity,S IgG FcγRIIIa-binding,M-specific IL-2+CD4+,interferon-γ+CD8+and IL-2+CD8+responses were superior and non-inferior to IM-CCC.The estimated vaccine efficacies were 49%,52%,66%and 79%for IM-CC,ID-CC,IM-CCC and ID-CCC,respectively.The ID groups reported more local,mild adverse reactions.Conclusion This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARSCoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines.

关键词： CoronaVac Coronavirus disease 2019 Immunity Intradermal Vaccine

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Antibody and T cell responses against wild-type and Omicron SARS-CoV-2 after third-dose BNT162b2 in adolescents

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Signal Transduction and Targeted Therapy 2023年第1期8卷 266-275页

作者： Xiaofeng Mu Carolyn A.Cohen Daniel Leung Jaime S.Rosa Duque Samuel M.S.Cheng yuet Chung howard h.W.Wong Amos M.T.Lee Wing yan Li Issan y.S.Tam jennifer h.y.lam Derek h.L.Lee Sau Man Chan Leo C.h.Tsang Karl C.K.Chan John K.C.Li Leo L.h.Luk Sara Chaothai Kelvin K.h.Kwan Nym Coco Chu Masashi Mori Trushar Jeevan Ahmed Kandeil Richard JWebby Wenwei Tu Sophie A.Valkenburg Malik Peiris yu Lung Lau Department of Paediatrics and Adolescent Medicine The University of Hong KongHong KongChina hKU-Pasteur Research Pole School of Public HealthThe University of Hong KongHong KongChina School of Public health The University of Hong KongHong KongChina Research Institute for Bioresources and Biotechnology Ishikawa Prefectural UniversityNonoichiJapan Department of Infectious Diseases St Jude Children’s Research HospitalMemphisTNUSA Department of Microbiology and Immunology Peter Doherty Institute for Infection and ImmunityUniversity of MelbourneMelbourneVICAustralia Centre for Immunology&Infection C2i Hong KongChina

The high effectiveness of the third dose of BNT162b2 in healthy adolescents against Omicron BA.1 has been reported in some studies,but immune responses conferring this protection are not yet elucidated.In this analysis,our study(NCT04800133)aims to evaluate the humoral and cellular responses against wild-type and Omicron(BA.1,BA.2 and/or BA.5)SARS-CoV-2 before and after a third dose of BNT162b2 in healthy adolescents.At 5 months after 2 doses,S IgG,S IgG Fc receptor-binding,and neutralising antibody responses waned significantly,yet neutralising antibodies remained detectable in all tested adolescents and S IgG avidity increased from 1 month after 2 doses.The antibody responses and S-specific IFN-γ^(+)and IL-2^(+)CD8^(+)T cell responses were significantly boosted in healthy adolescents after a homologous third dose of BNT162b2.Compared to adults,humoral responses for the third dose were non-inferior or superior in adolescents.The S-specific IFN-γ^(+)and IL-2^(+)CD4^(+)and CD8^(+)T cell responses in adolescents and adults were comparable or non-inferior.Interestingly,after 3 doses,adolescents had preserved S IgG,S IgG avidity,S IgG FcγRIIIa-binding,against Omicron BA.2,as well as preserved cellular responses against BA.1 S and moderate neutralisation levels against BA.1,BA.2 and BA.5.Sera from 100 and 96%of adolescents tested at 1 and 5 months after two doses could also neutralise BA.1.Our study found high antibody and T cell responses,including potent cross-variant reactivity,after three doses of BNT162b2 vaccine in adolescents in its current formulation,suggesting that current vaccines can be protective against symptomatic Omicron disease.

关键词： doses neutral protective

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Working toward an integrated plasticity/network framework for repetitive transcranial magnetic stimulation to inform tailored treatments

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Neural Regeneration Research 2024年第7期19卷 1423-1424页

作者： Jessica Moretti jennifer Rodger Experimental and Regenerative Neurosciences School of Biological SciencesUniversity of Western AustraliaCrawleyWAAustralia Brain Plasticity Lab Perron Institute for Neurological and Translational ScienceNedlandsWAAustralia

Non-invasive brain stimulation techniques(NIBS),including repetitive transcranial magnetic stimulation(rTMS) and transcranial electric stim ulation(tES),are increasingly being adopted clinically for treatment of neuropsychiatric and neurological disorders,albeit with varying success.The rationale behind the use of NIBS has historically been that stim ulation techniques modulate neuronal activity in the targeted region and consequently induce plasticity which can lead to therapeutic outcomes.

关键词： stimulation transcranial treatment

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Germline Gene-Editing Creates Enhanced Livestock-Technical and Especially Ethical Issues Challenge Its Use in humans

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Engineering 2024年第2期33卷 3-5页

作者： jennifer Welsh Senior Technology Writer

Using clustered regularly interspaced short palindromic repeats(CRISPR)-based molecular tools,scientists are engineering-as they are also doing with plants.-animals with advantageous traits,like disease resistance and improved food yield.While these innovative techniques could one day be applied in humans,technical hurdles and ethical concerns likely place this possibility far in the future,The enhancements rely on germline gene editing,which alters the genes in a way that passes the changes on to offspring.Ger m-line gene editing differs from the somatic cell gene editing used in the highly promising new treatment recently approved for the human disease sickle cell anemia.

关键词： likely Create editing

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Implications of regional identity for neural stem and progenitor cell transplantation in the injured or diseased nervous system

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Neural Regeneration Research 2024年第4期19卷 715-716页

作者： Prakruthi Amar Kumar jennifer N.Dulin Department of Biology Texas A&M UniversityCollege Station Texas A&M Institute for Neuroscience Texas A&M UniversityCollege Station

Neural stem and progenitor cell(NSPC)transpla ntation has emerged as a promising therapeutic strategy for replacing lost neuronal populations and repairing damaged neural circuits following nervous system injury and disease.A great deal of experimental work has investigated the biology of NSPC grafting in preclinical animal models;more recently.

关键词： neural system injured

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Optimizing artificial intelligence in sepsis management: Opportunities in the present and looking closely to the future

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Journal of Intensive Medicine 2024年第1期4卷 34-45页

作者： Darragh O’Reilly jennifer McGrath Ignacio Martin-Loeches Department of Intensive Care Medicine Multidisciplinary Intensive Care Research Organization(MICRO)St James’HospitalDublinIreland Department of Respiratory Intensive care Hospital ClinicUniversitat de BarcelonaIDIBAPSCIBERESBarcelonaSpain

Sepsis remains a major challenge internationally for healthcare systems.Its incidence is rising due to poor public awareness and delays in its recognition and subsequent management.In sepsis,mortality increases with every hour left untreated.Artificial intelligence(AI)is transforming worldwide healthcare delivery at present.This review has outlined how AI can augment strategies to address this global disease burden.AI and machine learning(ML)algorithms can analyze vast quantities of increasingly complex clinical datasets from electronic medical records to assist clinicians in diagnosing and treating sepsis earlier than traditional methods.Our review highlights how these models can predict the risk of sepsis and organ failure even before it occurs.This gives providers additional time to plan and execute treatment plans,thereby avoiding increasing complications associated with delayed diagnosis of sepsis.The potential for cost savings with AI implementation is also discussed,including improving workflow efficiencies,reducing administrative costs,and improving healthcare outcomes.Despite these advantages,clinicians have been slow to adopt AI into clinical practice.Some of the limitations posed by AI solutions include the lack of diverse data sets for model building so that they are widely applicable for routine clinical use.Furthermore,the subsequent algorithms are often based on complex mathematics leading to clinician hesitancy to embrace such technologies.Finally,we highlight the need for robust political and regulatory frameworks in this area to achieve the trust and approval of clinicians and patients to implement this transformational technology。

关键词： Artificial intelligence Data science Machine learning Intensive care unit(ICU) Critical care Sepsis

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Classifying moisture sources associated with snowfall in the mountains of Lesotho

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Journal of Mountain Science 2024年第6期21卷 1941-1953页

作者： Alexi M.MARINAKI jennifer M.FITChETT School of Geography Archaeology and Environmental StudiesUniversity of the WitwatersrandPrivate Bag X3Wits 2050South Africa

An average of eight snowfall events occur each year in the eastern Lesotho highlands.These snowfall events are typically associated with cut-off low(CoLs)systems and mid-latitude cyclones.however,the moisture sources of the snowfall are unclassified and unclear.The hybrid Single-Particle Lagrangian Integrated Trajectory(hySPLIT)model,an air mass back trajectory model,has been used to evaluate moisture source waters locally in southern Africa and internationally in China and Europe.This study uses hySPLIT to determine the source moisture of snow in Lesotho.A list of all 82 snowfall events in Lesotho spanning 2017 to 2022 was compiled using the Snow Report SA Instagram page,including the date and location of snowfall.A 72-hour back trajectory for each snowfall event was initiated for both Afriski and the whole of Lesotho.This amounts to models of moisture source trajectories for 28 and 82 snowfall days,respectively.These air mass pathways are classified according to their frequency per snowfall event,per month in the snow season,per year and for the full period.From this,associated moisture source regions and dominant air mass trajectories were identified.This study reports that the air mass trajectories associated with Afriski and Lesotho as a whole are very similar.The most common pathway of air mass trajectories transporting snow-bearing moisture to Lesotho was an inland trajectory from the northern regions of southern Africa.This pathway makes up 16.6%of all trajectories reported and is associated with the Angola Low,the Congo Air Boundary and the St.helena high Pressure.

关键词： Eastern Lesotho highlands Afriski Snow Cut-off Lows hySPLIT Synoptic Climatology

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Increasing polymer scission rate by tying an overhand knot

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Science China Chemistry 2024年

作者： yuheng hu jennifer T.Ou Jim y.huang yuanning Feng Department of Chemistry and Biochemistry The University of Oklahoma

Similar to the phenomenon of knotted ropes in life, knotted climbing ropes will reduce their strength due to knots. Although computer simulations [1], theoretical speculation[2,3], and intuition [3] suggest that similar processes may occur at the nanoscale, this hypothesis has not been experimentally proven before. With the increasing maturity of molecular recognition and self-assembly, a research communication by Leigh et al. [4]

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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 pancreatitis.The centralisation of pancreatic surgery services,with the development of designated large-volume centres,has contribu-ted to significantly improved outcomes.In 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 services.Type 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 outcome.Adequate 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 period.The 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 pancreatitis.Early involvement of a specialist diabetes team is essential to ensure a holistic management.In 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 outcomes.While 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 improvement.The need for perioperative support of diabetic patients by specialist diabetes teams is uniform

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

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Exercise and exerkine upregulation:Brain-derived neurotrophic factor as a potential non-pharmacological therapeutic strategy for Parkinson’s disease

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BIOCELL 2024年第5期48卷 693-706页

作者： VIRAAJ VIShNU PRASAD jennifer SALLy SAMSON VENKATAChAlam DEEPA PARVAThI Department of Biomedical Sciences Sri Ramachandra Institute of Higher Education and ResearchChennai600116India

Physical activity and exercise have several beneficial roles in enhancing both physiological and psychological well-being of an individual.In addition to aiding the regulation of aerobic and anaerobic metabolism,exercise can stimulate the synthesis of exerkine hormones in the circulatory system.Among several exerkines that have been investigated for their therapeutic potential,Brain-derived neurotrophic factor(BDNF)is considered the most promising candidate,especially in the management of neurodegenerative diseases.Owing to the ability of physical activity to enhance BDNF synthesis,several experimental studies conducted so far have validated this hypothesis and produced satisfactory results at the pre-clinical level.This review highlights some of the recent animal model studies that have evaluated the efficiency of exercise in enhancing BDNF synthesis and promoting neuroprotective effects.Further,this review focuses on understanding the therapeutic benefits of exercise-induced exerkine synthesis as a non-pharmacological strategy in Parkinson’s disease(PD).Regarding physical activity and exerkine induction,the neuromuscular electrical stimulation(NMES)strategy could be considered as an alternate treatment modality for patients affected with PD.

关键词： Exercise therapy Dopaminergic neurons Parkinson’s disease Brain-derived neurotrophic factor Electrical stimulation

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