bluuebunny/crossref_metadata_2025_split huggingface dataset:
Habitat percolation transition undermines sustainability in social‐ecological agricultural systems
Authors: Bengochea Paz Diego , Henderson Kirsten , Loreau Michel 
Published: November 2021

AbstractSteady increases in human population size and resource consumption are driving rampant agricultural expansion and intensification. Habitat loss caused by agriculture puts the integrity of ecosystems at risk and threatens the persistence of human societies that rely on ecosystem services. We develop a spatially explicit model describing the coupled dynamics of an agricultural landscape and human population size to assess the effect of different land‐use management strategies, defined by agricultural clustering and intensification, on the sustainability of the social‐ecological system. We show how agricultural expansion can cause natural habitats to undergo a percolation transition leading to abrupt habitat fragmentation that feedbacks on human's decision making, aggravating landscape degradation. We found that agricultural intensification to spare land from conversion is a successful strategy only in highly natural landscapes, and that clustering agricultural land is the most effective measure to preserve large connected natural fragments, prevent severe fragmentation and thus, enhance sustainability.
Efficacy and safety of ocrelizumab in patients with relapsing‐remitting multiple sclerosis with suboptimal response to prior disease‐modifying therapies: A primary analysis from the phase 3b CASTING single‐arm, open‐label trial
Authors: Vermersch Patrick , Oreja‐Guevara Celia , Siva Aksel , Van Wijmeersch Bart , Wiendl Heinz , Wuerfel Jens , Buffels Regine , Kadner Karen , Kuenzel Thomas , Comi Giancarlo ,   the CASTING Investigators
Published: November 2021

AbstractBackground and purposeUsing the treatment goal of “no evidence of disease activity” (NEDA) incorporating magnetic resonance imaging (MRI) re‐baselining, we aimed to assess the efficacy of ocrelizumab in patients with relapsing‐remitting multiple sclerosis with a prior suboptimal response, defined by MRI or relapse criteria, to one or two disease‐modifying therapies (DMTs).MethodsCASTING was a prospective, international, multicenter, single‐arm, open‐label phase 3 trial (NCT02861014). Patients (Expanded Disability Status Scale [EDSS] score ≤ 4.0, with discontinued prior DMT of ≥6 months duration due to suboptimal disease control) received intravenous ocrelizumab 600 mg every 24 weeks for 96 weeks. The primary endpoint was NEDA (defined as absence of relapses, disability progression, and inflammatory MRI measures, with prespecified MRI re‐baselining at Week 8) over 96 weeks.ResultsA total of 680 patients were enrolled, 167 (24.6%) based on MRI activity only. At Week 96, 74.8% (95% confidence interval [CI] 71.3–78.0, n/N = 492/658) of patients had NEDA. NEDA was highest among patients enrolled due to MRI activity alone (80.6% [95% CI 68.6–89.6], n/N = 50/62) versus those enrolled for relapse (75.1% [95% CI 69.0–80.6], n/N = 172/229) or for relapse with MRI (70.5% [95% CI 60.0–79.0], n/N = 74/105). NEDA across subgroups was highest in patients with a baseline EDSS score <2.5 (77.2% [95% CI 72.8–81.2], n/N = 315/408). NEDA was higher in patients receiving one prior DMT (77.6% [95% CI 73.2–81.6], n/N = 312/402) versus two prior DMTs (70.3% [95% CI 64.3–75.8], n/N = 180/256).ConclusionsIn patients switching therapy due to suboptimal disease control, treatment with ocrelizumab led to an overall high NEDA rate across a wide range of disease‐related and demographic subgroups, regardless of prior treatment background, with no new safety signals detected.
Epidemiology and survival trends of motor neurone disease in Northern Ireland from 2015 to 2019
Authors: McCluskey Gavin , Duddy William , Haffey Stephen , Morrison Karen , Donaghy Colette , Duguez Stephanie 
Published: November 2021

AbstractBackground and purposeThis study evaluates the incidence, prevalence and survival trends of motor neurone disease (MND) in Northern Ireland from 2015 to 2019.MethodsA capture–recapture analysis was performed using five independent data sources. Incidence and prevalence rates were standardized to the European Standard Population. Survival outcomes were analysed using Kaplan–Meier curves and Cox regression analysis.ResultsAmongst 254 total cases of MND, capture–recapture analysis estimated three missing cases (case ascertainment 98.8%). Age standardized incidence of captured cases was 3.12 per 100,000 (2.73, 3.50) and standardized prevalence ranged from 9.45 to 6.49 per 100,000 from 2015 to 2019. Standardized incidence and prevalence rates in 2006 were 1.4 and 3.3 per 100,000 respectively. Of identified cases, 133 (52.4%) were male; 94.5% had amyotrophic lateral sclerosis; median age of onset was 67 years; median time to diagnosis was 12 months (95% confidence interval 11.2, 12.8); survival from diagnosis was 12 months (95% confidence interval 10.6, 15.4); 25 (9.8%) reported a family history of MND or frontotemporal dementia; and a known MND‐associated genetic mutation was identified in 7.9% of total cases, of which the most common was C9orf72 (5.7% of all patients). Factors associated with improved survival were younger age at onset, longer time to diagnosis, attendance at regional MND clinic, and initial neurology presentation as outpatient (all p < 0.001).ConclusionThe incidence and prevalence of MND in Northern Ireland has increased over the last 10 years, in line with increasing rates reported from other European countries. Improved survival was associated with younger age at onset, longer time to diagnosis, attendance at a regional MND clinic and outpatient presentation to a Neurology Department.
Congenital myasthenic syndrome: Correlation between clinical features and molecular diagnosis
Authors: Estephan Eduardo P. , Zambon Antonio A. , Thompson Rachel , Polavarapu Kiran , Jomaa Danny , Töpf Ana , Helito Paulo V. P. , Heise Carlos O. , Moreno Cristiane A. M. , Silva André M. S. , Kouyoumdjian Joao A. , Morita Maria da Penha , Reed Umbertina C. , Lochmüller Hanns , Zanoteli Edmar 
Published: November 2021

AbstractObjectivesTo present phenotype features of a large cohort of congenital myasthenic syndromes (CMS) and correlate them with their molecular diagnosis.MethodsSuspected CMS patients were divided into three groups: group A (limb, bulbar or axial weakness, with or without ocular impairment, and all the following: clinical fatigability, electrophysiology compatible with neuromuscular junction involvement and anticholinesterase agents response), group B (limb, bulbar or axial weakness, with or without ocular impairment, and at least one of additional characteristics noted in group A) and group C (pure ocular syndrome). Individual clinical findings and the clinical groups were compared between the group with a confirmed molecular diagnosis of CMS and the group without molecular diagnosis or with a non‐CMS molecular diagnosis.ResultsSeventy‐nine patients (68 families) were included in the cohort: 48 in group A, 23 in group B and 8 in group C. Fifty‐one were considered confirmed CMS (30 CHRNE, 5 RAPSN, 4 COL13A1, 3 DOK7, 3 COLQ, 2 GFPT1, 1 CHAT, 1 SCN4A, 1 GMPPB, 1 CHRNA1), 7 probable CMS, 5 non‐CMS and 16 unsolved. The chance of a confirmed molecular diagnosis of CMS was significantly higher for group A and lower for group C. Some individual clinical features, alterations on biopsy and electrophysiology enhanced specificity for CMS. Muscle imaging showed at least mild alterations in the majority of confirmed cases, with preferential involvement of soleus, especially in CHRNE CMS.ConclusionsStricter clinical criteria increase the chance of confirming a CMS diagnosis, but may lose sensitivity, especially for some specific genes.
Paroxysmal slow wave events predict epilepsy following a first seizure
Authors: Zelig Daniel , Goldberg Ilan , Shor Oded , Ben Dor Shira , Yaniv‐Rosenfeld Amit , Milikovsky Dan Z. , Ofer Jonathan , Imtiaz Hamza , Friedman Alon , Benninger Felix 
Published: November 2021

AbstractObjectiveManagement of a patient presenting with a first seizure depends on the risk of additional seizures. In clinical practice, the recurrence risk is estimated by the treating physician using the neurological examination, brain imaging, a thorough history for risk factors, and routine scalp electroencephalogram (EEG) to detect abnormal epileptiform activity. The decision to use antiseizure medication can be challenging when objective findings are missing. There is a need for new biomarkers to better diagnose epilepsy following a first seizure. Recently, an EEG‐based novel analytical method was reported to detect paroxysmal slowing in the cortical network of patients with epilepsy. The aim of our study is to test this method's sensitivity and specificity to predict epilepsy following a first seizure.MethodsWe analyzed interictal EEGs of 70 patients admitted to the emergency department of a tertiary referral center after a first seizure. Clinical data from a follow‐up period of at least 18 months were available. EEGs of 30 healthy controls were also analyzed and included. For each EEG, we applied an automated algorithm to detect paroxysmal slow wave events (PSWEs).ResultsOf patients presenting with a first seizure, 40% had at least one additional recurring seizure and were diagnosed with epilepsy. Sixty percent did not report additional seizures. A significantly higher occurrence of PSWEs was detected in the first interictal EEG test of those patients who were eventually diagnosed with epilepsy. Conducting the EEG test within 72 h after the first seizure significantly increased the likelihood of detecting PSWEs and the predictive value for epilepsy up to 82%.SignificanceThe quantification of PSWEs by an automated algorithm can predict epilepsy and help the neurologist in evaluating a patient with a first seizure.
Antiseizure medications and thyroid hormone homeostasis: Literature review and practical recommendations
Authors: Rochtus Anne Maria , Herijgers Dorien , Jansen Katrien , Decallonne Brigitte 
Published: November 2021

AbstractThyroid hormones play an essential role in central nervous system development, normal physiological brain function, and repair mechanisms. On one hand, thyroid hormone alterations influence cortical excitability, and on the other hand antiseizure medications (ASMs) are associated with alterations in thyroid hormone metabolism. Although this interaction has long been described, and epilepsy is a common and chronic neurological disease, studies describing the interplay are often small and retrospective. We performed a systematic review of the current literature on epilepsy, ASMs, and thyroid hormone metabolism according to PRISMA guidelines. Forty‐seven studies were included. Most studies were retrospective cross‐sectional studies (n = 25) and investigated thyroid function alterations in patients on older ASMs such as phenobarbital, phenytoin, carbamazepine, and valproate. Overall, almost one third of patients with epilepsy had thyroid hormone alterations, especially patients on valproate (25%) and carbamazepine (10%–25%). Studies with patients receiving polytherapy are scarce, but reported a higher risk for hypothyroidism in patients with older age (p = .004), female sex (p = .014), longer duration of epilepsy (p = .001), intractable epilepsy (p = .009), and polytherapy. Studies on newer ASMs are also limited, and further studies on an interplay with thyroid hormone homeostasis are essential to improve the care for epilepsy patients. ASMs are associated with alterations in thyroid hormone metabolism. Thyroid function monitoring is indicated in patients on ASMs, especially those with refractory epilepsy and those on polytherapy. We provide a practical guidance for thyroid function monitoring for the clinician taking care of patients on ASMs.
Referral practices for epilepsy surgery in pediatric patients: A North American Study
Authors: Buttle Sarah Grace , Muir Katherine , Dehnoei Sajjad , Webster Richard , Tu Albert 
Published: November 2021

AbstractObjectivePatients with epilepsy who do not respond to two trials of appropriate antiepileptic drugs are considered to have drug‐resistant epilepsy (DRE). The International League Against Epilepsy recommends patients with DRE be referred for surgical evaluation; however, prior literature suggests this is an underutilized intervention, especially in the pediatric setting. This study captures practices of North American pediatric neurologists regarding the management of DRE and factors that may promote or limit referrals for epilepsy surgical evaluation.MethodsA REDCap survey was distributed via the Child Neurology Society mailing list to pediatric neurologists practicing in North America. Ethics approval from the Children's Hospital of Eastern Ontario Research Ethics Board was granted prior to the start of data collection.ResultsNinety‐eight responses were included in the analysis; 77% of participants currently practice in the United States; 73.5% of respondents reported they would refer a patient for surgical consultation after two failed medications. Of all potential predictors tested in a binary logistic regression model, only annual referral volume predicted whether participants refer patients after three or more failed medications. Centers with high referral volume were 37% more likely to adhere to the guideline of referral after two failed medications.SignificancePediatric neurologists demonstrate fair knowledge of formal recommendations to refer patients for surgical evaluation after two failed medication trials, although referral rates remain unacceptably low. Participants continue to report that they would not refer patients with generalized electroencephalographic findings for surgical evaluation; this should continue to be addressed. Other modifiable factors reported, especially family perceptions of epilepsy surgery, should be prioritized when developing tools to enhance effective referrals and increase utilization of epilepsy surgery in the management of pediatric DRE.
Large‐scale mitogenome sequencing reveals consecutive expansions of domestic taurine cattle and supports sporadic aurochs introgression
Authors: Cubric‐Curik Vlatka , Novosel Dinko , Brajkovic Vladimir , Rota Stabelli Omar , Krebs Stefan , Sölkner Johann , Šalamon Dragica , Ristov Strahil , Berger Beate , Trivizaki Stamatina , Bizelis Iosif , Ferenčaković Maja , Rothammer Sophie , Kunz Elisabeth , Simčič Mojca , Dovč Peter , Bunevski Gojko , Bytyqi Hysen , Marković Božidarka , Brka Muhamed , Kume Kristaq , Stojanović Srđan , Nikolov Vasil , Zinovieva Natalia , Schönherz Anna Amanda , Guldbrandtsen Bernt , Čačić Mato , Radović Siniša , Miracle Preston , Vernesi Cristiano , Curik Ino , Medugorac Ivica 
Published: November 2021

AbstractThe contribution of domestic cattle in human societies is enormous, making cattle, along with other essential benefits, the economically most important domestic animal in the world today. To expand existing knowledge on cattle domestication and mitogenome diversity, we performed a comprehensive complete mitogenome analysis of the species (802 sequences, 114 breeds). A large sample was collected in South‐east Europe, an important agricultural gateway to Europe during Neolithization and a region rich in cattle biodiversity. We found 1725 polymorphic sites (810 singletons, 853 parsimony‐informative sites and 57 indels), 701 unique haplotypes, a haplotype diversity of 0.9995 and a nucleotide diversity of 0.0015. In addition to the dominant T3 and several rare haplogroups (Q, T5, T4, T2 and T1), we have identified maternal line in Austrian Murbodner cattle that possess surviving aurochs’ mitochondria haplotype P1 that diverged prior to the Neolithization process. This is convincing evidence for rare female‐mediated adaptive introgression of wild aurochs into domesticated cattle in Europe. We revalidated the existing haplogroup classification and provided Bayesian phylogenetic inference with a more precise estimated divergence time than previously available. Occasionally, classification based on partial mitogenomes was not reliable; for example, some individuals with haplogroups P and T5 were not recognized based on D‐loop information. Bayesian skyline plot estimates (median) show that the earliest population growth began before domestication in cattle with haplogroup T2, followed by Q (~10.0–9.5 kyBP), whereas cattle with T3 (~7.5 kyBP) and T1 (~3.0–2.5 kyBP) expanded later. Overall, our results support the existence of interactions between aurochs and cattle during domestication and dispersal of cattle in the past, contribute to the conservation of maternal cattle diversity and enable functional analyses of the surviving aurochs P1 mitogenome.
Accounting for variability when resurrecting dormant propagules substantiates their use in eco‐evolutionary studies
Authors: Vahsen Megan L. , Gentile Rachel M. , Summers Jennifer L. , Kleiner Helena S. , Foster Benjamin , McCormack Regina M. , James Evan W. , Koch Rachel A. , Metts Dailee L. , Saunders Colin , Megonigal James Patrick , Blum Michael J. , McLachlan Jason S. 
Published: November 2021

AbstractThere has been a steady rise in the use of dormant propagules to study biotic responses to environmental change over time. This is particularly important for organisms that strongly mediate ecosystem processes, as changes in their traits over time can provide a unique snapshot into the structure and function of ecosystems from decades to millennia in the past. Understanding sources of bias and variation is a challenge in the field of resurrection ecology, including those that arise because often‐used measurements like seed germination success are imperfect indicators of propagule viability. Using a Bayesian statistical framework, we evaluated sources of variability and tested for zero‐inflation and overdispersion in data from 13 germination trials of soil‐stored seeds of Schoenoplectus americanus, an ecosystem engineer in coastal salt marshes in the Chesapeake Bay. We hypothesized that these two model structures align with an ecological understanding of dormancy and revival: zero‐inflation could arise due to failed germinations resulting from inviability or failed attempts to break dormancy, and overdispersion could arise by failing to measure important seed traits. A model that accounted for overdispersion, but not zero‐inflation, was the best fit to our data. Tetrazolium viability tests corroborated this result: most seeds that failed to germinate did so because they were inviable, not because experimental methods failed to break their dormancy. Seed viability declined exponentially with seed age and was mediated by seed provenance and experimental conditions. Our results provide a framework for accounting for and explaining variability when estimating propagule viability from soil‐stored natural archives which is a key aspect of using dormant propagules in eco‐evolutionary studies.
MicroRNA profiling of psoriatic skin identifies 11 miRNAs associated with disease severity
Authors: Solvin Åshild Ø. , Chawla Konika , Olsen Lene C. , Hegre Siv Anita , Danielsen Kjersti , Jenssen Marita , Furberg Anne‐Sofie , Saunes Marit , Hveem Kristian , Sætrom Pål , Løset Mari 
Published: November 2021

AbstractMicroRNAs (miRNAs) are small non‐coding RNAs that have emerged as central regulators of gene expression and powerful biomarkers of disease. Much is yet unknown about their role in psoriasis pathology. To globally characterize the miRNAome of psoriatic skin, skin biopsies were collected from psoriatic cases (n = 75) and non‐psoriatic controls (n = 46) and RNA sequenced. Count data were meta‐analysed with a previously published dataset (cases,n = 24, controls,n = 20), increasing the number of psoriatic cases fourfold from previously published studies. Differential gene expression analyses were performed comparing lesional psoriatic (PP), non‐lesional psoriatic (PN) and control (NN) skin. Further, functional enrichment and cell‐specific analyses were performed. Across all contrasts, we identified 439 significantly differentially expressed miRNAs (DEMs), of which 85 were novel for psoriasis and 11 were related to disease severity. Meta‐analyses identified 20 DEMs between PN and NN, suggesting an inherent change in the constitution of all skin in psoriasis. By integrating the miRNA transcriptome with mRNA target interactions, we identified several functionally enriched terms, including “thyroid hormone signalling,” “insulin resistance” and various infectious diseases. Cell‐specific expression analyses revealed that the upregulated DEMs were enriched in epithelial and immune cells. This study provides the most comprehensive overview of the miRNAome in psoriatic skin to date and identifies a miRNA signature related to psoriasis severity. Our results may represent molecular links between psoriasis and related comorbidities and have outlined potential directions for future functional studies to identify biomarkers and treatment targets.
Temperature impact on the influence of penguin‐derived nutrients and mosses on non‐native grass in a simulated polar ecosystem
Authors: Bokhorst Stef , Convey Peter , van Logtestijn Richard , Aerts Rien 
Published: November 2021

AbstractHuman activity and climate change are increasing the spread of species across the planet, threatening biodiversity and ecosystem functions. Invasion engineers, such as birds, facilitate plant growth through manuring of soil, while native vegetation influences plant germination by creating suitable microhabitats which are especially valuable in cold and dry polar regions. Here we tested how penguin‐derived nitrogen, several common Antarctic moss species and warming affect seed germination and growth of the non‐native grass Agrostis capillaris under laboratory conditions. Experimental settings included a simulation of contemporary season‐specific Antarctic light and temperature (2°C) conditions and a +5°C warming scenario. Mosses (Andreaea depressinervis, A. regularis, Sanionia uncinata and Chorisodontium aciphyllum) incorporated a range of nitrogen content and isotopic nitrogen signatures (δ15N) due to variation in sampling proximity to penguin colonies. Moss species greatly affected time to germination with consequences for further growth under the simulated Antarctic conditions. Grass seeds germinated 10 days earlier among A. regularis compared to S. uncinata and C. aciphyllum and 26 days earlier compared to A. depressinervis. Moss‐specific effects are likely related to microclimatic differences within the moss canopy. Warming reduced this moss influence. Grass emerged on average 20 days earlier under warming, leading to increased leaf count (88%), plant height (112%) and biomass (145%). Positive correlations were identified between moss and grass nitrogen content (r = 0.377), grass biomass (r = 0.332) and height (r = 0.742) with stronger effects under the warming scenario. Transfer of nitrogen from moss to grass was confirmed by δ15N (r = 0.803). Overall, the results suggest a shift from temperature‐limited to N‐limited growth of invasive plants under increased warming in the maritime Antarctic.