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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal j.Goldschmidt-Clermont Aisha Khan George jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander j.P.Goldschmidt damien d.Pearse W.dalton dietrich Allan d.Levi james d.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem Cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to Cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLC MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FdA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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A dIRECT SEARCH FRAME-BASEd CONjUGATE GRAdIENTS METHOd

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journal of Computational Mathematics 2004年第4期22卷 489-500页

作者： I.d.Coope C.j.price departmentofMathematicsandStatistics UniversityofCanterburyPrivateBag4800ChristchurchNewZealand

A derivative-free frame-based conjugate gradients algorithm is presented. Convergence is shown for C^1 functions, and this is verified in numerical trials. The algorithm is tested on a variety of low dimensional problems, some of which are ill-conditioned, and is also tested on problems of high dimension. Numerical results show that the algorithm is effective on both classes of problems. The results are compared with those from a discrete quasiNewton method, showing that the conjugate gradients algorithm is competitive. The algorithm exhibits the conjugate gradients speed-up on problems for which the Hessian at the solution has repeated or clustered eigenvalues. The algorithm is easily parallelizable.

关键词： Conjugate gradients derivative-free Frame-based methods Numerical results

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Study of the production of Λ_b^0 band ~0 hadrons in pp collisions and first measurement of the Λ_b^0→j/ψpK^- branching fraction

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Chinese Physics C 2016年第1期40卷 1-16页

作者： O.Kochebina M.Kolpin I.Komarov R.F.Koopman P.Koppenburg M.Kozeiha L.Kravchuk K.Kreplin M.Kreps G.Krocker P.Krokovny F.Kruse W.Krzemien W.Kucewicz M.Kucharczyk V.Kudryavtsev A.K.Kuonen K.Kurek T.Kvaratskheliya d.Lacarrere G.Lafferty A.Lai d.Lambert G.Lanffanchi C.Langenbruch B.Langhans T.Latham C.Lazzeroni R.Le Gac j.van Leerdam j.-P.Lees R.Lefevre A.Leflat j.Lefrancois E.Lemos Cid O.Leroy T.Lesiak B.Leverington Y.Li T.Likhomanenko M.Liles R.Lindner C.Linn F.Lionetto B.Liu X.Liu d.Loh I.Longstaff j.H.Lopes d.Lucchesi M.Lucio Martinez H.Luo A.Lupato E.Luppi O.Lupton A.Lusiani F.Machefert F.Maciuc O.Maev K.Maguire S.Malde A.Malinin G.Manca G.Mancinelli P.Manning A.Mapelli j.Maratas j.F.Marchand U.Marconi C.Marin Benito P.Marino j.Marks G.Martellottil M.Martin M.Martinelli d.Martinez Santos F.Martinez Vidal d.Martins Tostes A.Massafferri R.Matev A.Mathad Z.Mathe C.Matteuzzi A.Mauri B.Maurin A.Mazurov M.McCann j.McCarthy A.McNab R.McNulty B.Meadows F.Meier M.Meissner d.Melnychuk M.Merk E Michielin d.A.Milanes M.-N.Minard d.S.Mitzel j.Molina Rodrigue I.A.Monroy S.Monteil M.Morandin P.Morawski A.Morda M.j.Morello j.Moron A.B.Morris R.Mountain F.Muheim d.Miiller j.Muller K.Muller V.Muller M.Mussini B.Muster P.Naik T.Nakada R.Nandakumar A.Nandi I.Nasteva M.Needham N.Neri S.Neubert N.Neufeld M.Neuner A.d.Nguyen T.d.Nguyen C.Nguyen-Mau V.Niess R.Niet N.Nikitin T.Nikodem d.Ninci A.Novoselov d.P.O'Hanlon A.Oblakowska-Mucha V.Obraztsov S.Ogilvy O.Okhrimenko R.Oldeman C.j.G.Onderwater B.Osorio Rodrigues j.M.Otalora Goicochea A.Otto P.Owen A.Oyanguren A.Palano F.Palombo M.Palutan j.Panman A.Papanestis M.Pappagallo L.L.Pappalardo C.Pappenheimer C.Parkes G.Passaleva G.d.Patel M.Patel C.Patrignani A.Pearce A.Pellegrino G.Penso M.Pepe Altarelli S.Perazzini P.Perret L.Pescatore K.Petridis A.Petrolini M.Petruzzo E.Picatoste Olloqui B.Pietrzyk T:.Pilar d.Pinci A.Pistone A.Piucci S.Playfer M.Plo Casasus T.Poikela F.Polci A.Poluektov I.Polyakov E.Polycarpo A.Popov d.Popov B.Popovici C.Potterat E.price j.d.price j.Prisciandaro A.Pritchard Centro Brasileiro de Pesquisas Ffsicas(CBPF) Rio de JaneiroBrazil Universidade Federal do Rio de janeiro(UFRj) Rio de JaneiroBrazil Center for High Energy Physics Tsinghua UniversityBeijingChina LAPP Universite Savoie Mont-BlancCNRS/IN2P3Annecy-Le-VieuxFrance Clermont Universite Universite Blaise PascalCNRS/IN2P3LPCclermont-FerrandFrance CPPM Aix-Marseille UniversitYCNRS/IN2P3MarseilleFrance LAL Universite Paris-SudCNRS/IN2P3OrsayFrance LPNHE Universite Pierre et Marie CurieUniversite Paris DiderotCNRS/IN2P3ParisFrance Fakultat Physik Technische Universitat DortmundDortmundGermany Max-Planck-lnstitut fur Kernphysik(MPIK) HeidelbergGermany Physikalisches Institut Ruprecht-Karls-Universitat HeidelbergHeidelbergGermany School of Physics University College DublinDublinIreland Sezione INFN di Bari BariItaly Sezione INFN di Bologna BolognaItaly Sezione INFN di Cagliari CagliariItaly Sezione INFN di Ferrara FerraraItaly Sezione INFN di Firenze FirenzeItaly Laboratori Nazionali dell'INFN di Prascati FrascatiItaly Sezione INFN di Genova GenovaItaly Sezione INFN di Milnno Bicocca MilunoItaly Sezione INFN di Milano MilanoItaly Sezione INFN di Padova PadovaItaly Sezione INFN di Pisa PisaItaly Sezione INFN di Roma Tor Vergata RomaItaly Sezione INFN di Roma La Sapienza RomaItaly Henryk Niewodniczanski Institute of Nuclear Physics Polish Academy of Sciences Krak6wPoland AGH-University of Science and Technology Faculty of Physics and Applied Computer ScienceKrakowPoland National Center for Nuclear Research(NCBj) WarsawPoland Horia Hulubei National Institute of Physics and Nuclear Engineering Bucharest-MagureleRomania Petersburg Nuclear Physics Institute(PNPI) GatchinaRussia Institute of Theoretical and Experimental Physics(ITEP) MoscowRussia Institute of Nuclear Physics Moscow State University(SINP MSU)MoscowRussia Institute for Nuclear Research of the Russian Academy of Sciences(INR RAN) MoscowRussia Budker Institute of Nuclear Physics(SB RAS)and Novosibirsk State University No

The product of the ∧0/b （-B/0） differential production cross-section and the branching fraction of the decay ∧0/b→ j/ψ pK-（-B/0→ j/ψ-K＊（892）0）is measured as a function of the beauty hadron transverse momentum, PT, and rapidity, y. The kinematic region of the measurements is pT〈20 GeV/c and 2.0 〈g〈*** measurements use a data sample corresponding to an integrated luminosity of 3fb-1 collected by the LHCb detector in pp collisions at centre-of-mass energies √s=7 TeV in 2011 and √s=8 TeV in 2012. Based on previous LHCb results of the fragmentation fraction ratio,f∧0/b/fd,the branching fraction of the decay ∧0/b→ j/ψ pK-is measured to be B（∧0/b→ j/ψ pK-）=（3.17±0.04±0.07±0.34＋0.45/-0.28）×10-4,where the first uncertainty is statistical, the second is systematic, the third is due to the uncertainty on the branching fraction of the decay -B/0 →j/ψ-K＊（892）0,and the fourth is due to the knowledge of f∧0/b/*** sum of the asymmetries in the production and decay between ∧0/b and ∧0/bis also measured as a function of PT and *** previously published branching fraction of ∧0/b→ j/ψ pπ-,relative to that of ∧0/b→ j/ψ pK-,is updated. The branching fractions of ∧0/b→P＋c（→ j/ψp）K-are determined.

关键词： production cross-section branching fraction b hadrons proton-proton collisions

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Ampullary cancer of intestinal origin and duodenal cancer-A logical clinical and therapeutic subgroup in periampullary cancer

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World journal of Gastrointestinal Oncology 2017年第10期9卷 407-415页

作者： Manju d Chandrasegaram Anthony j Gill jas Samra Tim price john Chen jonathan Fawcett Neil d Merrett the Prince Charles Hospital School of Medicine University of Queensland Sydney Medical School University of Sydney Cancer diagnosis and Pathology Group Kolling Institute of Medical Research Royal North Shore Hospital department of Surgery Royal North Shore Hospital Queen Elizabeth Hospital University of Adelaide Flinders Medical Centre Royal Adelaide Hospital Princess Alexandra Hospital department of Upper GI Surgery Bankstown Hospital discipline of Surgery Western Sydney University

Periampullary cancers include pancreatic, ampullary, biliary and duodenal cancers. At presentation, the majority of periampullary tumours have grown to involve the pancreas, bile duct, ampulla and duodenum. This can result in difficulty in defining the primary site of origin in all but the smallest tumors due to anatomical proximity and architectural distortion. This has led to variation in the reported proportions of resected periampullary cancers. Pancreatic cancer is the most common cancer resected with a pancreaticoduodenectomy followed by ampullary(16%-50%), bile duct(5%-39%), and duodenal cancer(3%-17%). Patients with resected duodenal and ampullary cancers have a better reported median survival(29-47 mo and 22-54 mo) compared to pancreatic cancer(13-19 mo). The poorer survival with pancreatic cancer relates to differences in tumour characteristics such as a higher incidence of nodal, neural and vascular invasion. While small ampullary cancers can present early with biliary obstruction, pancreatic cancers need to reach a certain size before biliary obstruction ensues. This larger size at presentation contributes to a higher incidence of resection margin involvement in pancreatic cancer. Ampullary cancers can be subdivided into intestinal or pancreatobiliary subtype cancers with histomolecular staining. This avoids relying on histomorphology alone, as even some poorly differentiated cancers preserve the histomolecular profile of their mucosa of origin. Histomolecular profiling is superior to anatomic location in prognosticating survival. Ampullary cancers of intestinal subtype and duodenal cancers are similar in their intestinal origin and form a logical clinical and therapeutic subgroup of periampullary cancers. They respond to 5-FU based chemotherapeutic regimens such as capecitabine-oxaliplatin. Unlike pancreatic cancers, KRAS mutation occurs in only approximately a third of ampullary and duodenal cancers. Future clinical trials should group ampullary cancer

关键词： Periampullary cancer Pancreatobiliary subtype Intestinal subtype Ampullary cancer duodenal cancer Epidermal growth factor receptor Pancreatic cancer Chemotherapy Pancreaticoduodenectomy KRAS

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Perturbations in the earthworm metabolite profile during a two-week exposure to metformin

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Emerging Contaminants 2024年第3期10卷 221-229页

作者： j.d.Gillis G.W.price S.O.Prasher department of Bioresource Engineering McGill UniversityFaculty of Agricultural and Environmental SciencesMacdonald-Stewart Building MS1-02721111 Lakeshore RoadSainte-Anne-de-BellevueQuebecH9X 3V9Canada department of Engineering Dalhousie UniversityFaculty of Agriculture39 Cox RoadPO Box 550TruroNova ScotiaB2N 5E3Canada

Metformin is among the most prescribed pharmaceuticals in many countries,and as a result has shown up in biosolids derived from municipal wastewater treatment that are destined for land *** humans taking metformin,the effects include reduced glucose uptake in the intestine,a reduction in gluconeogenesis,increased oxidation of fatty acids,and reduced fatty acid *** effects of metformin on soil-dwelling organisms are not well *** study tested the effects of metformin exposure(0,10,40,160,640μg g^(-1))on the earthworm(***)at four time points(6 h,2 d,7 d,and 14 d)using GC-MS to reveal sub-lethal effects and elucidate potential modes of action for *** were no mortalities observed,and earthworms exposed to the highest concentrations(160 and 640μg g^(-1))gained weight relative to the control on days 7 and *** reductions on day 7 were observed for glucose and malic acid(consistent with a reduction in gluconeogenesis),and for palmitic and margaric acid(consistent with increased oxidation and reduced synthesis of fatty acids).Lactic acid ranked first and second among canonicals 1 and 2 respectively and led to significant differences in discriminant scores across concentration and *** levels increased to equal or greater than the control on day 14,likely caused by reduced exposure as metformin is reported to be readily transformed by microorganisms under aerobic *** observations were consistent with the known effects of metformin in humans,and suggests that a similar mode of action exists in earthworms.

关键词： Metabolites Toxicity Earthworms Metformin GC-MS

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Effects of Root Growth of deep and Shallow Rooting Rice Cultivars in Compacted Paddy Soils on Subsequent Rice Growth

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Rice science 2023年第5期30卷 459-472,I0022-I0024页

作者： Md.dhin ISLAM Adam H.price Paul d.HALLETT School of Biological Sciences University of AberdeenSt Machar DrAberdeen AB243UUthe United Kingdom Faculty of Agriculture Bangabandhu Sheikh Mujibur Rahman Agricultural UniversityGazipur-1706Bangladesh

Rice is often grown as multiple seasons in one year,alternating between flooded and upland systems.A major constraint,introduced from the flooded system,is a plough pan that may decrease rooting depth and productivity of follow-on upland *** penetrating the plough pan under flooded rice system can leave a legacy of weaker root growth *** rooting rice cultivars could have a bigger impact,but no direct evidence is *** explore whether a deep rather than a shallow rooting rice cultivar grown in a flooded cropping cycle benefited deeper root growth of follow-on rice in an upland,reduced tillage cropping cycle,a simulated flooded paddy in greenhouse was planted with deep(Black Gora) and shallow(IR64) rooting cultivars and a plant-free *** plough pans were made in between the topsoil and subsoil to form different treatments with no plough pan(0.35 MPa),soft plough pan(1.03 MPa) and hard plough pan(1.70 MPa).After harvest of this ‘first season’ rice,the soil was drained and undisturbed to simulate zero-tillage upland and planted rice cultivar BRRI dhan *** overall root length density(RLd),root surface area,the numbers of root tips and branching of BRRI dhan 28 did not vary between plough pan and no plough pan *** with the shallow rooting rice genotype,the deep rooting rice genotype as ‘first season’ crop produced 19% greater RLd,34% greater surface area and 29% more branching of BRRI dhan 28 in the *** the topsoil,however,BRRI dhan 28 had 28% greater RLd,35% greater surface area and 43% more branching for the shallow rather than deep rooting genotype planted in the ‘first season’.The results suggested that rice cultivar selection for a paddy cycle affects root growth of a follow-on rice crop grown under no-till,with benefits to subsoil access from deep rooting cultivars and topsoil proliferation for shallow rooting cultivars.

关键词： plough pan root growth biopores crop rotation Oryza sativa preceding crop zero-tillage

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Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher j.O’Connell Matthew j.Robson department of Genetics College of MedicineHarvard UniversityBostonMAUSA james L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

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Colorectal cancer:Metastases to a single organ

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World journal of Gastroenterology 2015年第41期21卷 11767-11776页

作者： Sina Vatandoust Timothy j price Christos S Karapetis department of Medical Oncology Flinders Medical Centre Flinders Centre for Innovation in Cancer Flinders University department of Medical Oncology The Queen Elizabeth Hospital The University of Adelaide

Colorectal cancer(CRC) is a common malignancy worldwide. In CRC patients, metastases are the main cause of cancer-related mortality. In a group of metastatic CRC patients, the metastases are limited to a single site(solitary organ); the liver and lungs are the most commonly involved sites. When metastatic disease is limited to the liver and/or lungs, the resectability of the metastatic lesions will dictate the management approach and the outcome. Less commonly, the site of solitary organ CRC metastasis is the peritoneum. In these patients, cytoreduction followed by hyperthermic intraperitoneal chemotherapy may improve the outcome. Rarely, CRC involves other organs, such as the brain, bone, adrenals and spleen, as the only site of metastatic disease. There are limited data to guide clinical practice in these cases. Here, we have reviewed the disease characteristics, management approaches and prognosis based on the metastatic disease site in patients with CRC with metastases to a single organ.

关键词： Colorectal cancer Metastasis Prognosis disease man

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Secondary steady-state and time-periodic flows from a basic flow with square array of odd number of vortices

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Applied Mathematics and Mechanics(English Edition) 2023年第3期44卷 447-458页

作者： Zhimin CHEN W.G.price School of Mathematics and Statistics Shenzhen UniversityShenzhen 518060Guangdong ProvinceChina Ship Science University of SouthamptonSouthampton SO171BJU.K.

In a magnetohydrodynamic(MHd)driven fluid cell,a plane non-parallel flow in a square domain satisfying a free-slip boundary condition is *** energy dissipation of the flow is controlled by the viscosity and linear *** latter arises from the influence of the Hartmann bottom boundary layer in a three-dimensional(3d)MHd experiment in a square bottomed *** basic flow in this fluid system is a square eddy flow exhibiting a network of N~2 vortices rotating alternately in clockwise and anticlockwise *** N is odd,the instability of the flow gives rise to secondary steady-state flows and secondary time-periodic flows,exhibiting similar characteristics to those observed when N=*** this reason,this study focuses on the instability of the square eddy flow of nine *** is shown that there exist eight bi-critical values corresponding to the existence of eight neutral eigenfunction ***,there exist non-real neutral eigenfunctions,which produce secondary time-periodic flows exhibiting vortices merging in an oscillatory *** Hopf bifurcation phenomenon has not been observed in earlier investigations.

关键词： two-dimensional(2d)Navier-Stokes equation non-parallel square vortex flow primary bifurcation secondary steady-state flow secondary time-periodic flow

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A MOdIFIEd BFGS FORMULA MAINTAINING POSITIVE dEFINITENESS WITH ARMIjO-GOLdSTEIN STEPLENGTHS

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journal of Computational Mathematics 1995年第2期13卷 156-160页

作者： I. d. Coope C. j. price University of Canterbury 新西兰 defence Scientific Establishment 新西兰

The line search subproblem in unconstrained optimization is concerned with finding an acceptable steplength satisfying certain standard conditions. The con-ditions proposed in the early work of Armijo and Goldstein are sometimes replaced by those recommended by Wolf e because these latter conditions automatically allow positive definiteness of some popular quasi-Newton updates to be *** is shown that a slightly modified form of quasi-Newton update allows positive definiteness to be maintained even if line searches based on the Armijo-Goldsteinconditions are used.

关键词： definiteness Quadratic functions

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