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COP27 Climate Change Conference: urgent action needed for Africa and the world: Wealthy nations must step up support for Africa and vulnerable countries in addressing past, present and future impacts of climate change
Lukoye Atwoli, Gregory E Erhabor, Aiah A Gbakima, Abraham Haileamlak, Jean-Marie Kayembe Ntumba, James Kigera, Laurie Laybourn-Langton, Bob Mash, Joy Muhia, Fhumulani Mavis Mulaudzi, David Ofori-Adjei, Friday Okonofua, Arash Rashidian, Maha El-Adawy, Siaka Sidibé, Abdelmadjid Snouber, James Tumwine, Mohammad Sahar Yassien, Paul Yonga, Lilia Zakhama, Chris Zielinski
doi : 10.1093/brain/awac367
Brain, Volume 145, Issue 12, December 2022, Pages 4141–4143
Gabriel Garcia Marquez, the greatest of the amnesia writers
A J Lees
doi : 10.1093/brain/awac303
Brain, Volume 145, Issue 12, December 2022, Pages 4144–4147
Predictive precision medicine efforts for voltage-gated sodium channel genetic variants
Massimo Mantegazza, Sandrine Cestèle
doi : 10.1093/brain/awac397
Brain, Volume 145, Issue 12, December 2022, Pages 4148–4150
Distinct mechanisms of oligodendrocyte injury inform therapeutic interventions in multiple sclerosis
Thomas Garton, Alexander J Gill, Peter A Calabresi
doi : 10.1093/brain/awac406
Brain, Volume 145, Issue 12, December 2022, Pages 4151–4153
Strengthening the link between mitophagy and Parkinson’s disease
Ian G Ganley
doi : 10.1093/brain/awac405
Brain, Volume 145, Issue 12, December 2022, Pages 4154–4156
The impact of integrated brain molecular PET measures on DLB cognitive phenotype and clinical course
Daniela Perani
doi : 10.1093/brain/awac432
Brain, Volume 145, Issue 12, December 2022, Pages 4157–4159
The use of optical coherence tomography in neurology: a review
Jim S Xie, Laura Donaldson, Edward Margolin
doi : 10.1093/brain/awac317
Brain, Volume 145, Issue 12, December 2022, Pages 4160–4177
Optical coherence tomography is a non-invasive, cost-efficient technique that provides high-resolution in vivo imaging of retinal tissue.
Oligodendrocyte progenitor cell recruitment and remyelination in multiple sclerosis: the more, the merrier?
Vanja Tepav�ević, Catherine Lubetzki
doi : 10.1093/brain/awac307
Brain, Volume 145, Issue 12, December 2022, Pages 4178–4192
Promoting remyelination to prevent/reduce neurodegeneration in patients with multiple sclerosis (MS) is a major therapeutic goal. The longstanding view that the block of oligodendrocyte progenitor cell (OPC) differentiation in MS lesions is the leading cause of remyelination failure has inspired the scientific community to focus primarily on OPC differentiation-promoting compounds as pro-remyelinating agents.
COVID-19 induces CNS cytokine expression and loss of hippocampal neurogenesis
Allison L Soung, Abigail Vanderheiden, Anna S Nordvig, Cheick A Sissoko, Peter Canoll, Madeline B Mariani, Xiaoping Jiang, Traci Bricker, Gorazd B Rosoklija, Victoria Arango, Mark Underwood, J John Mann, Andrew J Dwork, James E Goldman, Adrianus C M Boon, Maura Boldrini, Robyn S Klein
doi : 10.1093/brain/awac270
Brain, Volume 145, Issue 12, December 2022, Pages 4193–4201
Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with acute and postacute cognitive and neuropsychiatric symptoms including impaired memory, concentration, attention, sleep and affect.
Variants in the zinc transporter TMEM163 cause a hypomyelinating leukodystrophy
Michelle C do Rosario, Guillermo Rodriguez Bey, Bruce Nmezi, Fang Liu, Talia Oranburg, Ana S A Cohen, Keith A Coffman, Maya R Brown, Kirill Kiselyov, Quinten Waisfisz, Myrthe T Flohil, Shahyan Siddiqui, Jill A Rosenfeld, Alejandro Iglesias, Katta Mohan Girisha, Nicole I Wolf, Quasar Saleem Padiath, Anju Shukla
doi : 10.1093/brain/awac295
Brain, Volume 145, Issue 12, December 2022, Pages 4202–4209
Hypomyelinating leukodystrophies comprise a subclass of genetic disorders with deficient myelination of the CNS white matter. Here we report four unrelated families with a hypomyelinating leukodystrophy phenotype harbouring variants in TMEM163 (NM_030923.5).
Emotional bias modification weakens game-related compulsivity and reshapes frontostriatal pathways
Lulu Wu, Jiahua Xu, Kunru Song, Lei Zhu, Nan Zhou, Linxuan Xu, Guanqun Liu, Ziliang Wang, Rui Wang, Shaozheng Qin, Xiaoyi Fang, Jintao Zhang, Marc N Potenza
doi : 10.1093/brain/awac267
Brain, Volume 145, Issue 12, December 2022, Pages 4210–4221
Addiction is characterized by compulsive engagement despite adverse consequences. Psychobehavioural interventions targeting compulsivity in addictions are relatively rare, particularly for behavioural addictions like internet gaming disorder (IGD).
Dual-site transcranial direct current stimulation to treat tinnitus: a randomized controlled trial
Emilie Cardon, Laure Jacquemin, Hanne Vermeersch, Iris Joossen, Julie Moyaert, Griet Mertens, Olivier M Vanderveken, Marc J W Lammers, Paul Van de Heyning, Vincent Van Rompaey, Annick Gilles
doi : 10.1093/brain/awac263
Brain, Volume 145, Issue 12, December 2022, Pages 4222–4231
Transcranial direct current stimulation (tDCS) has been proposed as a potential intervention for subjective tinnitus, but supporting evidence remains limited. We aimed to investigate the effect of anodal high-definition tDCS of the left temporal area and right dorsolateral prefrontal cortex on tinnitus severity.
Activating RAC1 variants in the switch II region cause a developmental syndrome and alter neuronal morphology
Siddharth Banka, Abigail Bennington, Martin J Baker, Ellen Rijckmans, Giuliana D Clemente, Nurhuda Mohamad Ansor, Hilary Sito, Pritha Prasad, Kwame Anyane-Yeboa, Lauren Badalato, Boyan Dimitrov, David Fitzpatrick, Anna C E Hurst, Anna C Jansen, Melissa A Kelly, Ian Krantz, Claudine Rieubland, Meredith Ross, Natasha L Rudy, Javier Sanz, Katrien Stouffs, Zhuo Luan Xu, Angeliki Malliri, Marcelo G Kazanietz, Tom H Millard
doi : 10.1093/brain/awac049
Brain, Volume 145, Issue 12, December 2022, Pages 4232–4245
RAC1 is a highly conserved Rho GTPase critical for many cellular and developmental processes. De novo missense RAC1 variants cause a highly variable neurodevelopmental disorder.
Continuous manipulation of mental representations is compromised in cerebellar degeneration
Samuel D McDougle, Jonathan S Tsay, Benjamin Pitt, Maedbh King, William Saban, Jordan A Taylor, Richard B Ivry
doi : 10.1093/brain/awac072
Brain, Volume 145, Issue 12, December 2022, Pages 4246–4263
We introduce a novel perspective on how the cerebellum might contribute to cognition, hypothesizing that this structure supports dynamic transformations of mental representations.
Gene therapy targeting the blood–brain barrier improves neurological symptoms in a model of genetic MCT8 deficiency
Sivaraj M Sundaram, Adriana Arrulo Pereira, Helge Müller-Fielitz, Hannes Köpke, Meri De Angelis, Timo D Müller, Heike Heuer, Jakob Körbelin, Markus Krohn, Jens Mittag, Ruben Nogueiras, Vincent Prevot, Markus Schwaninger
doi : 10.1093/brain/awac243
Brain, Volume 145, Issue 12, December 2022, Pages 4264–4274
A genetic deficiency of the solute carrier monocarboxylate transporter 8 (MCT8), termed Allan–Herndon–Dudley syndrome, is an important cause of X-linked intellectual and motor disability.
Gene variant effects across sodium channelopathies predict function and guide precision therapy
Andreas Brunklaus, Tony Feng, Tobias Brünger, Eduardo Perez-Palma, Henrike Heyne, Emma Matthews, Christopher Semsarian, Joseph D Symonds, Sameer M Zuberi, Dennis Lal, Stephanie Schorge
doi : 10.1093/brain/awac006
Brain, Volume 145, Issue 12, December 2022, Pages 4275–4286
Pathogenic variants in the voltage-gated sodium channel gene family lead to early onset epilepsies, neurodevelopmental disorders, skeletal muscle channelopathies, peripheral neuropathies and cardiac arrhythmias.
Lymphotoxin-alpha expression in the meninges causes lymphoid tissue formation and neurodegeneration
Rachel E James Bates, Eleanor Browne, Renee Schalks, Heather Jacobs, Li Tan, Puja Parekh, Roberta Magliozzi, Massimiliano Calabrese, Nicholas D Mazarakis, Richard Reynolds
doi : 10.1093/brain/awac232
Brain, Volume 145, Issue 12, December 2022, Pages 4287–4307,
Organized meningeal immune cell infiltrates are suggested to play an important role in cortical grey matter pathology in the multiple sclerosis brain, but the mechanisms involved are as yet unresolved.
Anterior optic pathway pathology in CNS demyelinating diseases
Marco Pisa, Jonathan Pansieri, Sydney Yee, Jennifer Ruiz, M Isabel Leite, Jacqueline Palace, Giancarlo Comi, Margaret M Esiri, Letizia Leocani, Gabriele C DeLuca
doi : 10.1093/brain/awac030
Brain, Volume 145, Issue 12, December 2022, Pages 4308–4319
The anterior optic pathway is one of the preferential sites of involvement in CNS inflammatory demyelinating diseases, such as multiple sclerosis and neuromyelitis optica, with optic neuritis being a common presenting symptom.
Diverse injury responses of human oligodendrocyte to mediators implicated in multiple sclerosis
Florian Pernin, Julia Xiao Xuan Luo, Qiao-Ling Cui, Manon Blain, Milton G F Fernandes, Moein Yaqubi, Myriam Srour, Jeff Hall, Roy Dudley, Hélène Jamann, Catherine Larochelle, Stephanie E J Zandee, Alexandre Prat, Jo Anne Stratton, Timothy E Kennedy, Jack P Antel
doi : 10.1093/brain/awac075
Brain, Volume 145, Issue 12, December 2022, Pages 4320–4333
Early multiple sclerosis lesions feature relative preservation of oligodendrocyte cell bodies with dying back retraction of their myelinating processes. Cell loss occurs with disease progression.
Intrinsic blood–brain barrier dysfunction contributes to multiple sclerosis pathogenesis
Hideaki Nishihara, Sylvain Perriot, Benjamin D Gastfriend, Marel Steinfort, Celine Cibien, Sasha Soldati, Kinya Matsuo, Sarah Guimbal, Amandine Mathias, Sean P Palecek, Eric V Shusta, Renaud Du Pasquier, Britta Engelhardt
doi : 10.1093/brain/awac019
Brain, Volume 145, Issue 12, December 2022, Pages 4334–4348
Blood–brain barrier (BBB) breakdown and immune cell infiltration into the CNS are early hallmarks of multiple sclerosis (MS). The mechanisms leading to BBB dysfunction are incompletely understood and generally thought to be a consequence of neuroinflammation.
Regulation of mitophagy by the NSL complex underlies genetic risk for Parkinson’s disease at 16q11.2 and MAPT H1 loci
Marc P M Soutar, Daniela Melandri, Benjamin O’Callaghan, Emily Annuario, Amy E Monaghan, Natalie J Welsh, Karishma D’Sa, Sebastian Guelfi, David Zhang, Alan Pittman, Daniah Trabzuni, Anouk H A Verboven, Kylie S Pan, Demis A Kia, Magda Bictash, Sonia Gandhi, Henry Houlden, Mark R Cookson, Nael Nadif Kasri, Nicholas W Wood, Andrew B Singleton, John Hardy, Paul J Whiting, Cornelis Blauwendraat, Alexander J Whitworth, Claudia Manzoni, Mina Ryten, Patrick A Lewis, Hélène Plun-Favreau
doi : 10.1093/brain/awac325
Brain, Volume 145, Issue 12, December 2022, Pages 4349–4367
Parkinson’s disease is a common incurable neurodegenerative disease. The identification of genetic variants via genome-wide association studies has considerably advanced our understanding of the Parkinson’s disease genetic risk.
DJ-1 is an essential downstream mediator in PINK1/parkin-dependent mitophagy
Dorien Imberechts, Inge Kinnart, Fieke Wauters, Joanne Terbeek, Liselot Manders, Keimpe Wierda, Kristel Eggermont, Rodrigo Furtado Madeiro, Carolyn Sue, Catherine Verfaillie, Wim Vandenberghe
doi : 10.1093/brain/awac313
Brain, Volume 145, Issue 12, December 2022, Pages 4368–4384
Loss-of-function mutations in the PRKN, PINK1 and PARK7 genes (encoding parkin, PINK1 and DJ-1, respectively) cause autosomal recessive forms of Parkinson’s disease.
A neural network for tics: insights from causal brain lesions and deep brain stimulation
Christos Ganos, Bassam Al-Fatly, Jan-Frederik Fischer, Juan-Carlos Baldermann, Christina Hennen, Veerle Visser-Vandewalle, Clemens Neudorfer, Davide Martino, Jing Li, Tim Bouwens, Linda Ackermanns, Albert F G Leentjens, Nadya Pyatigorskaya, Yulia Worbe, Michael D Fox, Andrea A Kühn, Andreas Horn
doi : 10.1093/brain/awac009
Brain, Volume 145, Issue 12, December 2022, Pages 4385–4397
Brain lesions are a rare cause of tic disorders. However, they can provide uniquely causal insights into tic pathophysiology and can also inform on possible neuromodulatory therapeutic targets.
Neurofilament light levels predict clinical progression and death in multiple system atrophy
Viorica Chelban, Elham Nikram, Alexandra Perez-Soriano, Carlo Wilke, Alexandra Foubert-Samier, Nirosen Vijiaratnam, Tong Guo, Edwin Jabbari, Simisola Olufodun, Mariel Gonzalez, Konstantin Senkevich, Brice Laurens, Patrice Péran, Olivier Rascol, Anne Pavy Le Traon, Emily G Todd, Alyssa A Costantini, Sondos Alikhwan, Ambreen Tariq, Bai Lin Ng, Esteban Muñoz, Celia Painous, Yaroslau Compta, Carme Junque, Barbara Segura, Kristina Zhelcheska, Henny Wellington, Ludger Schöls, Zane Jaunmuktane, Christopher Kobylecki, Alistair Church, Michele T M Hu, James B Rowe, P Nigel Leigh, Luke Massey, David J Burn, Nicola Pavese, Tom Foltynie, Sofya Pchelina, Nicholas Wood, Amanda J Heslegrave, Henrik Zetterberg, Martina Bocchetta, Jonathan D Rohrer, Maria J Marti, Matthis Synofzik, Huw R Morris, Wassilios G Meissner, Henry Houlden
doi : 10.1093/brain/awac253
Brain, Volume 145, Issue 12, December 2022, Pages 4398–4408
Disease-modifying treatments are currently being trialled in multiple system atrophy.
Alternative processing of human HTT mRNA with implications for Huntington’s disease therapeutics
Sandra Fienko, Christian Landles, Kirupa Sathasivam, Sean J McAteer, Rebecca E Milton, Georgina F Osborne, Edward J Smith, Samuel T Jones, Marie K Bondulich, Emily C E Danby, Jemima Phillips, Bridget A Taxy, Holly B Kordasiewicz, Gillian P Bates
doi : 10.1093/brain/awac241
Brain, Volume 145, Issue 12, December 2022, Pages 4409–4424
Huntington disease is caused by a CAG repeat expansion in exon 1 of the huntingtin gene (HTT) that is translated into a polyglutamine stretch in the huntingtin protein (HTT).
Metabolomics identifies shared lipid pathways in independent amyotrophic lateral sclerosis cohorts
Stephen A Goutman, Kai Guo, Masha G Savelieff, Adam Patterson, Stacey A Sakowski, Hani Habra, Alla Karnovsky, Junguk Hur, Eva L Feldman
doi : 10.1093/brain/awac025
Brain, Volume 145, Issue 12, December 2022, Pages 4425–4439,
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease lacking effective treatments. This is due, in part, to a complex and incompletely understood pathophysiology.
The impact of age on genetic testing decisions in amyotrophic lateral sclerosis
Puja R Mehta, Alfredo Iacoangeli, Sarah Opie-Martin, Joke J F A van Vugt, Ahmad Al Khleifat, Andrea Bredin, Lynn Ossher, Peter M Andersen, Orla Hardiman, Arpan R Mehta, Pietro Fratta, Kevin Talbot, Project MinE ALS Sequencing Consortium , Ammar Al-Chalabi
doi : 10.1093/brain/awac279
Brain, Volume 145, Issue 12, December 2022, Pages 4440–4447
Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative syndrome.
Interrelation of striatal dopamine, brain metabolism and cognition in dementia with Lewy bodies
Han Soo Yoo, Seong Ho Jeong, Kyeong Taek Oh, Sangwon Lee, Young H Sohn, Byoung Seok Ye, Mijin Yun, Phil Hyu Lee
doi : 10.1093/brain/awac084
Brain, Volume 145, Issue 12, December 2022, Pages 4448–4458
Dementia with Lewy bodies (DLB), the second most common neurodegenerative dementia, is characterized by cognitive decline, fluctuation of cognition and alertness, visual hallucinations, rapid eye movement sleep behaviour disorder and parkinsonism.
Accelerated longitudinal changes and ordering of Alzheimer disease biomarkers across the adult lifespan
Jingqin Luo, Folasade Agboola, Elizabeth Grant, John C Morris, Colin L Masters, Marilyn S Albert, Sterling C Johnson, Eric M McDade, Anne M Fagan, Tammie L S Benzinger, Jason Hassenstab, Randall J Bateman, Richard J Perrin, Guoqiao Wang, Yan Li, Brian Gordon, Carlos Cruchaga, Gregory S Day, Johannes Levin, Jonathan Vöglein, Takeshi Ikeuchi, Kazushi Suzuki, Ricardo F Allegri, Chengjie Xiong, Dominantly Inherited Alzheimer Network (DIAN)
doi : 10.1093/brain/awac238
Brain, Volume 145, Issue 12, December 2022, Pages 4459–4473
The temporal evolutions and relative orderings of Alzheimer disease biomarkers, including CSF amyloid-β42 (Aβ42), Aβ40, total tau (Tau) and phosphorylated tau181 (pTau181), standardized uptake value ratio (SUVR) from the molecular imaging of cerebral fibrillar amyloid-β with PET using the 11C-Pittsburgh Compound-B (PiB), MRI-based hippocampal volume and cortical thickness and cognition have been hypothesized but not yet fully tested with longitudinal data for all major biomarker modalities among cognitively normal individuals across the adult lifespan starting from 18 years. By leveraging a large harmonized database from 8 biomarker studies with longitudinal data from 2609 participants in cognition, 873 in MRI biomarkers, 519 in PET PiB imaging and 475 in CSF biomarkers for a median follow-up of 5–6 years, we estimated the longitudinal trajectories of all major Alzheimer disease biomarkers as functions of baseline age that spanned from 18 to 103 years, located the baseline age window at which the longitudinal rates of change accelerated and further examined possible modifying effects of apolipoprotein E (APOE) genotype.
Activation of Wnt/β-catenin pathway mitigates blood–brain barrier dysfunction in Alzheimer’s disease
Qi Wang, Xiaomin Huang, Yixun Su, Guowei Yin, Shouyu Wang, Bin Yu, Hui Li, Junhua Qi, Hui Chen, Wen Zeng, Kai Zhang, Alexei Verkhratsky, Jianqin Niu, Chenju Yi
doi : 10.1093/brain/awac236
Brain, Volume 145, Issue 12, December 2022, Pages 4474–4488
Alzheimer’s disease is a neurodegenerative disorder that causes age-dependent neurological and cognitive declines. The treatments for Alzheimer’s disease pose a significant challenge, because the mechanisms of disease are not being fully understood.
Amyloid, tau and metabolic PET correlates of cognition in early and late-onset Alzheimer’s disease
Jeremy A Tanner, Leonardo Iaccarino, Lauren Edwards, Breton M Asken, Maria L Gorno-Tempini, Joel H Kramer, Julie Pham, David C Perry, Katherine Possin, Maura Malpetti, Taylor Mellinger, Bruce L Miller, Zachary Miller, Nidhi S Mundada, Howard J Rosen, David N Soleimani-Meigooni, Amelia Strom, Renaud La Joie, Gil D Rabinovici
doi : 10.1093/brain/awac229
Brain, Volume 145, Issue 12, December 2022, Pages 4489–4505
Early-onset (age < 65) Alzheimer’s disease is associated with greater non-amnestic cognitive symptoms and neuropathological burden than late-onset disease. It is not fully understood whether these groups also differ in the associations between molecular pathology, neurodegeneration and cognitive performance.
Preclinical Alzheimer’s disease biomarkers accurately predict cognitive and neuropathological outcomes
Justin M Long, Dean W Coble, Chengjie Xiong, Suzanne E Schindler, Richard J Perrin, Brian A Gordon, Tammie L S Benzinger, Elizabeth Grant, Anne M Fagan, Oscar Harari, Carlos Cruchaga, David M Holtzman, John C Morris
doi : 10.1093/brain/awac250
Brain, Volume 145, Issue 12, December 2022, Pages 4506–4518
Alzheimer’s disease biomarkers are widely accepted as surrogate markers of underlying neuropathological changes. However, few studies have evaluated whether preclinical Alzheimer’s disease biomarkers predict Alzheimer’s neuropathology at autopsy.
Association between ultrasonography foetal anomalies and autism spectrum disorder
Ohad Regev, Amnon Hadar, Gal Meiri, Hagit Flusser, Analya Michaelovski, Ilan Dinstein, Reli Hershkovitz, Idan Menashe
doi : 10.1093/brain/awac008
Brain, Volume 145, Issue 12, December 2022, Pages 4519–4530
Multiple pieces of evidence support the prenatal predisposition of autism spectrum disorder (ASD). Nevertheless, robust data about abnormalities in foetuses later developing into children diagnosed with ASD are lacking.
Spinal cord associative plasticity improves forelimb sensorimotor function after cervical injury
Ajay Pal, HongGeun Park, Aditya Ramamurthy, Ahmet S Asan, Thelma Bethea, Meenu Johnkutty, Jason B Carmel
doi : 10.1093/brain/awac235
Brain, Volume 145, Issue 12, December 2022, Pages 4531–4544
Associative plasticity occurs when two stimuli converge on a common neural target. Previous efforts to promote associative plasticity have targeted cortex, with variable and moderate effects.
An ode to his mistress: ‘Lady Neurology’
Anthony E Lang, MD, FRCPC
doi : 10.1093/brain/awac283
Brain, Volume 145, Issue 12, December 2022, Pages 4545–4546
Droplet digital PCR as a first-tier molecular diagnostic tool for focal cortical dysplasia type II
Wei Shern Lee, Richard J Leventer, Paul J Lockhart
doi : 10.1093/brain/awac320
Brain, Volume 145, Issue 12, December 2022, Pages e119–e121
The recurrent mutation in RNF220 also causes hypomyelination in China and is a CpG hot spot
Huifang Yan, Thomas Kubisiak, Kai Gao, Jiangxi Xiao, Junyu Wang, Yu Zhang, Ye Wu, Yuwu Jiang, Margit Burmeister, Jingmin Wang
doi : 10.1093/brain/awac314
Brain, Volume 145, Issue 12, December 2022, Pages e122–e124
The phenotypic spectrum of COX20-associated mitochondrial disorder
Rui Ban, Robert Kopajtich, Junlan Lv, Sarah L Stenton, Masaru Shimura, Zhaoxia Wang, Yun Yuan, Junling Wang, Xiaodi Han, Zhimei Liu, Qiang Shi, Chuanqiang Pu, Holger Prokisch, Fang Fang, Matthias Elstner
doi : 10.1093/brain/awac344
Brain, Volume 145, Issue 12, December 2022, Pages e125–e127
