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Strategies for translating proteomics discoveries into drug discovery for dementia

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Neural Regeneration Research 2024年第1期19卷 132-139页

作者： Aditi Halder Eleanor Drummond School of Medical Sciences and Brain&Mind Center University of SydneyNSWSydneyAustralia department of Aged Care Prince of Wales HospitalSydneyNSWAustralia

Tauopathies,diseases characterized by neuropathological aggregates of tau including Alzheimer's disease and subtypes of fro ntotemporal dementia,make up the vast majority of dementia *** there have been recent developments in tauopathy biomarkers and disease-modifying treatments,ongoing progress is required to ensure these are effective,economical,and accessible for the globally ageing *** such,continued identification of new potential drug targets and biomarkers is critical."Big data"studies,such as proteomics,can generate information on thousands of possible new targets for dementia diagnostics and therapeutics,but currently remain underutilized due to the lack of a clear process by which targets are selected for future drug *** this review,we discuss current tauopathy biomarkers and therapeutics,and highlight areas in need of improvement,particularly when addressing the needs of frail,comorbid and cognitively impaired *** highlight biomarkers which have been developed from proteomic data,and outline possible future directions in this *** propose new criteria by which potential targets in proteomics studies can be objectively ranked as favorable for drug development,and demonstrate its application to our group's recent tau interactome dataset as an example.

关键词： Alzheimer's disease biomarkers drug development drug discovery druggability frontotemporal dementia interactome proteomics tau tauopathies therapeutics

Congenital absence of the lateral meniscus:A case report

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World Journal of Orthopedics 2024年第5期15卷 477-482页

作者： Hamad Ali Alkhunayfir Abdulaziz Ali AlQahtani Abdulrahman Jalwi Korkoman department of Orthopedic surgery Prince Muhammed bin Abdulaziz HospitalRiyadh 61422Saudi Arabia department of Orthopedic surgery Prince Sultan Military Medical CityRiyadh 12233Saudi Arabia department of Orthopedic surgery University of BishaBisha 67714Saudi Arabia

BACKGROUND Congenital absence of the menisci is a rare anatomical variation characterized by the absence or underdevelopment of one or both menisci in the knee *** menisci are crucial in load distribution,joint stability,and shock *** the clinical presentation,diagnosis,and management of this condition is important for optimal patient *** SUMMARY A 27-year-old male with a long-standing history of knee pain underwent diagnostic arthroscopy,revealing a congenital absence of the *** patient's clinical findings,imaging results,surgical procedures,and pertinent images are *** case presents a unique aspect with the congenital absence of the meniscus,contributing valuable insights to the literature on rare anatomical *** This case of congenital absence of the menisci highlights the diagnostic challenges posed by rare *** diagnostic arthroscopy played a crucial role in identifying the absence of the meniscus and providing an explanation for the patient's persistent knee *** case underscores the importance of individualized treatment approaches,including physical therapy,for optimal management of rare meniscal *** research is warranted to explore effective management strategies for the aforementioned cases and to expand our knowledge of these rare conditions.

关键词： Lateral meniscus Arthroscopy Knee joint Menisci reformation Magnetic resonance imaging Case report

Construction of a novel six-gene signature to predict tumour response to induction chemotherapy and overall survival in locoregionally advanced laryngeal and hypopharyngeal carcinoma

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Genes & Diseases 2024年第3期11卷 148-150页

作者： Chen Tan Lingwa Wang Yifan Yang Shizhi He George G.Chen Jason YK.Chan Michael CF.Tong C.A.van Hasselt Wenbin Xu Ling Feng Ru Wang Jugao Fang department of Otolaryngology Head and Neck surgery Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Key Laboratory of Otolaryngology Head and Neck surgery(Ministry of Education of China) Beijing Institute of OtolaryngologyBeijing 100730China department of Otorhinolaryngology Head and Neck SurgeryThe Chinese University of Hong KongPrince of Wales HospitalHongKong SAR999077China department of Medical Genetics Institute of Basic Medical ScienceChinese Academy of Medical Science&Peking Union Medical CollageBeijing 100730China

Locoregionally advanced laryngeal and hypopharyngeal cancers(LA-LHCs)are traditionally treated with surgery followed by postoperative radiotherapy,which impairs speech and swallowing functions and reduces the quality of life.^(1,2)The use of induction chemotherapy(IC)as a larynxpreserving approach for LA-LHCs has been verified and refined.^(3)However,the short-term tumor response to IC varies,non-responders usually show poor survival and little benefit.

关键词： chemotherapy laryngeal surgery

Loss to Specialized Cardiology Follow-Up in Adults Living with Congenital Heart Disease

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Congenital Heart Disease 2024年第1期19卷 49-63页

作者： Cheryl Dickson Danielle Osborn David Baker Judith Fethney David S.Celermajer Rachael Cordina department of Cardiology Royal Prince Alfred HospitalSydneyAustralia department of Cardiothoracic surgery Westmead HospitalSydneyAustralia Susan Wakil School of Nursing and Midwifery The University of SydneySydneyAustralia Sydney Medical School The University of SydneySydneyAustralia

Background:Much has been written about the loss to follow-up in the transition between pediatric and adult Congenital Heart Disease(CHD)care *** less is understood about the loss to follow-up(LTF)after a successful *** is critical too,as patients lost to specialised care are more likely to experience mor-bidity and premature ***:To understand the prevalence and reasons for loss to follow-up(LTF)at a large Australian Adult Congenital Heart Disease(ACHD)***:Patients with moderate or highly complex CHD and gaps in care of>3 years(deﬁned as LTF)were identiﬁed from a comprehensive ACHD *** telephone interviews examined current care and barriers to clinic ***:Overall,407(22%)of ACHD patients(n=1842)were *** mean age at LTF was 31(SD 11.5)years and 54%were male;311(76%)were *** to adults seen regularly,lost patients were younger,with a greater socio-economic disadvantage,and had less complex CHD(p<0.05 for all).We interviewed 59 patients(14%).The top 3 responses for care absences were“feeling well”(61%),losing track of time(36%),and not needing fol-low-up care(25%).Conclusions:A large proportion of the ACHD population becomes lost to specialised cardiac care,even after a successful *** Australian study reports younger age,moderate complexity defects,and socio-economic disadvantage as predictive of loss to *** study highlights the need for novel approaches to patient-centered service delivery even beyond the age of transition and resources to maintain patient engagement within the ACHD service.

关键词： Loss to follow-up follow-up adult congenital heart disease lapse in care gaps in care care gaps care continuity ACHD predictors

Results of selective decontamination with oral neomycin and metronidazole for major colorectal surgery in Australia:A cohort study

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Laparoscopic, Endoscopic and Robotic surgery 2024年第2期7卷 72-78页

作者： James Wei Tatt Toh Devansh Shah Henry Wang Charlotte Kwik Joseph Do Woong Choi Chelsie Leonie Beinke Paul Morris Eleni Baird-Gunning Geoffrey Peter Collins Fiona Gavegan Karen Shedden Toufic El-Khoury Nimalan Pathma-Nathan Kerry Hitos department of Colorectal surgery Westmead HospitalWestmeadNew South WalesAustralia The University of Sydney Westmead HospitalWestmeadNew South WalesAustralia Western Sydney University New South WalesAustralia University of Notre Dame New South WalesAustralia Westmead Research Centre for Evaluation of Surgical Outcomes Westmead HospitalSydneyAustralia

Objective The role of selective decontamination with oral antibiotics(OABs)and mechanical bowel preparation(MBP)prior to elective colorectal surgery is still widely *** objective of this study was to compare the outcomes of selective decontamination with neomycin,metronidazole and MBP compared to those of decontamination with MBP alone or with no *** Selective decontamination with neomycin and metronidazole combined with bowel preparation was introduced prior to elective colorectal surgery as part of an enhanced recovery after surgery program at Westmead hospital,a major Australian tertiary referral hospital,between June 2017 and January *** between short-term outcomes of OAB+MBP and MBP/no preparation were made using prospectively collected data on length of stay(LOS),readmission,mortality within 30 days,anastomotic leakage(AL),surgical site infection(SSI),urinary tract infection,deep venous thrombosis and/or pulmonary embolism,pneumonia,and ***-up was limited to hospital stays and subsequent presentations within the health district within thirty days of *** Mann-Whitney U test was used to analyse continuous data,and the chi-square test was used for categorical *** and multivariate regression modelling was performed to identify risk factors associated with an increased likelihood of SSI and *** Patients with oral neomycin and metronidazole combined with bowel preparation had reduced superficial SSI(2.7%vs.7.6%,p=0.043)and overall complications(32.7%vs.44.6%,p=0.020),particularly Clavien-Dindo 1 complications(7.3%vs.16.5%,p=0.009).However,the differences in AL(2.7%vs.4.5%,p=0.369)and organ/space SSI(1.3%vs.3.7%,p=0.327)were not statistically *** median LOS(6 d vs.6 d,p=0.370)was not different between the *** Selective decontamination with neomycin and metronidazole reduces the risk of SSIs and overall *** was a trend to toward a lower AL,but this differ

关键词： Neomycin Metronidazole Colorectal surgery Anastomotic leakage Surgical site infection

Smooth muscle cell-specific genetic targeting by Myh11-driven Cre(ER)knockin mice

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Science China(Life Sciences) 2024年第10期67卷 2280-2282页

作者： Enci Wang Ximeng Han Haixiao Wang Kathy O.Lui Bin Zhou Lixin Wang department of Vascular surgery Zhongshan HospitalFudan UniversityShanghai 200032China department of Cardiology Shanghai Chest HospitalShanghai Jiao Tong University School of MedicineShanghai 200030China Pediatric Research Institute The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou 325027China department of Chemical Pathology and Li Ka Shing Institute of Health SciencesPrince of Wales HospitalThe Chinese University of Hong KongHong Kong 999077China New Cornerstone Investigator Institute State Key Laboratory of Cell BiologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai 200031China department of Vascular surgery(Xiamen) Zhongshan hospitalFudan UniversityXiamen 361015China

Dear editor,Site specific recombinases have been widely used for genome engineering in cardiovascular research(Fu et al.,2024;Huang et al.,2023;Xue et al.,2022).In particular,Cre is the most broadly used recombinase for cell type-specific lineage tracing and gene manipulation in *** smooth muscle cell(SMC)-specific targeting,several SMC promoters including Myh11(smooth muscle myosin heavy chain),Acta2(smooth muscle a-2 actin),and SM22a(Tagln)have been used to drive Cre or CreER.

关键词： cardiovascular manipulation

Defining minimal invasive surgical therapy for benign prostatic obstruction surgery: Perspectives from a global knowledge, attitude, and practice survey

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Asian Journal of Urology 2024年第1期11卷 55-64页

作者： Bryan Kwun-Chung Cheng Steffi Kar-Kei Yuen Daniele Castellani Marcelo Langer Wroclawski Hongda Zhao Mallikarjuna Chiruvella Wei-Jin Chua Ho-Yee Tiong Yiloren Tanidir Jean de la Rosette Enrique Rijo Vincent Misrai Amy Krambeck Dean S.Elterman Bhaskar K.Somani Jeremy Yuen-Chun Teoh Vineet Gauhar department of surgery United Christian HospitalHong KongChina S.H.Ho Urology Centre Department of SurgeryPrince of Wales HospitalThe Chinese University of Hong KongHong KongChina department of Urology University Hospital“Ospedali Riuniti”and Polytechnic University of Marche RegionAnconaItaly hospital Israelita Albert Einstein Sao PauloSPBrazil BP—A Beneficencia Portuguesa de Sao Paulo Sao PauloSPBrazil Faculdade de Medicina do ABC Santo AndreSPBrazil department of Urology Asian Institute of Nephrology and UrologyHyderabadTGIndia department of Urology National University HospitalSingapore department of Urology Marmara University School of MedicineIstanbulTurkey department of Urology Medipol Mega University HospitalIstanbul Medipol UniversityIstanbulTurkey department of Urology Hospital Quiron BarcelonaBarcelonaSpain department of Urology Clinique PasteurToulouseFrance department of Urology Indiana University School of MedicineIndianapolisINUSA Division of Urology Department of SurgeryUniversity Health NetworkUniversity of TorontoTorontoCanada department of Urology University Hospital Southampton NHS TrustSouthamptonUK department of Urology Ng Teng Fong General HospitalNUHSSingapore

Objective:To scrutinize the definitions of minimal invasive surgical therapy(MIST)and to investigate urologists’knowledge,attitudes,and practices for benign prostatic obstruction ***:A 36-item survey was developed with a Delphi *** on definitions of MIST and attitudes and practices of benign prostatic obstruction surgeries were *** were invited globally to complete the online *** was achieved when more than or equal to 70%responses were“agree or strongly agree”and less than or equal to 15%responses were“disagree or strongly disagree”(consensus agree),or when more than or equal to 70%responses were“disagree or strongly disagree”and less than or equal to 15%responses were“agree or strongly agree”(consensus disagree).Results:The top three qualities for defining MIST were minimal blood loss(n=466,80.3%),fast post-operative recovery(n=431,74.3%),and short hospital stay(n=425,73.3%).The top three surgeries that were regarded as MIST were Urolift®(n=361,62.2%),Rezum®(n=351,60.5%),and endoscopic enucleation of the prostate(EEP)(n=332,57.2%).Consensus in the knowledge section was achieved for the superiority of Urolift®,Rezum®,and iTIND®over transurethral resection of the prostate with regard to blood loss,recovery,day surgery feasibility,and post-operative *** in the attitudes section was achieved for the superiority of Urolift®,Rezum®,and iTIND®over transurethral resection of the prostate with regard to blood loss,recovery,and day surgery *** on both sections was achieved for EEP as the option with the better symptoms and flow improvement,lower retreatment rate,and better suitable for prostate more than 80 ***:Minimal blood loss,fast post-operative recovery,and short hospital stay were the most important qualities for defining ***®,Rezum®,and EEP were regarded as MIST by most urologists.

关键词： Benignprostate hyperplasia Minimalinvasive surgical therapy surgery Bladderoutlet obstruction

Cold-Induced Reprogramming of Subcutaneous White Adipose Tissue Assessed by Single-Cell and Single-Nucleus RNA Sequencing

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Research 2024年第1期2023卷 763-778页

作者： Qing Liu Qiaoyun Long Jiayu Zhao Wenjie Wu Zexin Lin Wei Sun Ping Gu Tuo Deng Kerry Martin Loomes Donghai Wu Alice P.S.Kong Jingying Zhou Alfred S.Cheng Hannah Xiaoyan Hui School of Biomedical Sciences The Chinese University of Hong KongHong KongChina department of Pharmacology and Pharmacy The University of Hong KongHong KongChina Guangzhou Institute of Biomedicine and Health Chinese Academy of SciencesGuangzhouChina China-New Zealand Joint Laboratory on Biomedicine and Health Chinese Academy of SciencesGuangzhouChina department of Endocrinology Jinling HospitalNanjing UniversitySchool of MedicineNanjingChina National Clinical Research Center for Metabolic Diseases and Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaChina Key Laboratory of Diabetes Immunology Ministry of Educationand Metabolic Syndrome Research CenterThe Second Xiangya Hospital of Central South UniversityChangshaChina Clinical Immunology Center The Second Xiangya Hospital of Central South UniversityChangshaChina School of Biological Sciences and Maurice Wilkins Centre University of AucklandAucklandNew Zealand department of Medicine and Therapeutics The Chinese University of Hong KongHong KongChina Hong Kong Institute of Diabetes and Obesity The Chinese University of Hong KongPrince of Wales HospitalShatinHong KongChina Li Ka Shing Institute of Health Sciences The Chinese University of Hong KongPrince of Wales HospitalShatinHong KongChina

Adipose browning has demonstrated therapeutic potentials in several ***,by conducting transcriptomic profiling at the single-cell and single-nucleus resolution,we reconstituted the cellular atlas in mouse inguinal subcutaneous white adipose tissue(iWAT)at thermoneutrality or chronic cold *** major nonimmune cells within the iWAT,including adipose stem and progenitor cells(ASPCs),mature adipocytes,endothelial cells,Schwann cells,and smooth muscle cells,were recovered,allowing us to uncover an overall and detailed blueprint for transcriptomes and intercellular cross-talks and the dynamics during white adipose tissue brown *** findings also unravel the existence of subpopulations in mature adipocytes,ASPCs,and endothelial cells,as well as new insights on their interconversion and reprogramming in response to *** adipocyte subpopulation competent of major histocompatibility complex class Ⅱ(MHCⅡ)antigen presentation is ***,a subcluster of ASPC with CD74 expression was identified as the precursor of this MHCⅡ^(+)*** adipocytes are transdifferented from preexisting lipid generating adipocytes,which exhibit developmental trajectory from de novo differentiation of amphiregulin cells(Aregs).Two distinct immune-like endothelial subpopulations are present in iWAT and are responsive to *** data reveal fundamental changes during cold-evoked adipose browning.

关键词： evoked programming generating

Surgical intervention combined with weight-bearing walking training promotes recovery in patients with chronic spinal cord injury:a randomized controlled study

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Neural Regeneration Research 2024年第12期19卷 2773-2784页

作者： Hui Zhu James D.Guest Sarah Dunlop Jia-Xin Xie Sujuan Gao Zhuojing Luo Joe E.Springer Wutian Wu Wise Young Wai Sang Poon Song Liu Hongkun Gao Tao Yu Dianchun Wang Libing Zhou Shengping Wu Lei Zhong Fang Niu Xiaomei Wang Yansheng Liu Kwok-Fai So Xiao-Ming Xu Kunming Tongren hospital KunmingYunnan ProvinceChina Neurological surgery and the Miami Project to Cure ParalysisMiller School of MedicineUniversity of MiamiMiamiFLUSA School of Biological Sciences The University of Western AustraliaPerthWAAustralia Minderoo Foundation PerthWAAustralia Clinical Center for Spinal Cord Injury Kunming General Hospital of Chengdu Military CommandKunmingYunnan ProvinceChina department of Biostatistics and Health Data Science Indiana University School of MedicineIndianapolisINUSA department of Orthopedic Spinal surgery Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina Spinal Cord and Brain Injury Research Center Department of Physical Medicine and RehabilitationUniversity of Kentucky College of MedicineLexingtonKYUSA Guangdong-HongKong-Macao Institute of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina W.M.Keck Center for Collaborative Neuroscience Rutgers UniversityPiscatawayNJUSA Neurosurgery department Chinese University of Hong KongPrince of Wales HospitalHong Kong Special Administration RegionChina Spinal Cord and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA

For patients with chronic spinal cord injury,the co nventional treatment is rehabilitation and treatment of spinal cord injury complications such as urinary tract infection,pressure sores,osteoporosis,and deep vein *** is rarely perfo rmed on spinal co rd injury in the chronic phase,and few treatments have been proven effective in chronic spinal cord injury *** of effective therapies fo r chronic spinal co rd injury patients is *** conducted a randomized controlled clinical trial in patients with chronic complete thoracic spinal co rd injury to compare intensive rehabilitation(weight-bearing walking training)alone with surgical intervention plus intensive *** clinical trial was registered at ***(NCT02663310).The goal of surgical intervention was spinal cord detethering,restoration of cerebrospinal fluid flow,and elimination of residual spinal cord *** found that surgical intervention plus weight-bearing walking training was associated with a higher incidence of American Spinal Injury Association Impairment Scale improvement,reduced spasticity,and more rapid bowel and bladder functional recovery than weight-bearing walking training ***,the surgical procedures and intensive rehabilitation were *** Spinal Injury Association Impairment Scale improvement was more common in T7-T11 injuries than in T2-T6 *** combined with rehabilitation appears to have a role in treatment of chronic spinal cord injury patients.

关键词： chronic spinal cord injury intensive rehabilitation locomotor training neurological recovery surgical intervention weightbearing walking training