bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Bone Marrow Endothelial Progenitor Cell Transplantation into Symptomatic ALS Mice Delays Disease Progression and Increases Motor Neuron Survival by Repairing Blood-Spinal Cord Barrier
Authors: Garbuzova-Davis Svitlana , Kurien Crupa , Haller Edward , Eve David J. , Navarro Stephanie , Steiner George , Mahendrasah Ajay , Hailu Surafuale , Khatib Mohammed , Boccio Kayla J. , Borlongan Cesario V. , Van Loveren Harry R. , Appel Stanley H. , Sanberg Paul R. 
Published: March 2019

AbstractConvincing evidence demonstrated impairment of the blood-spinal cord barrier (BSCB) in Amyotrophic Lateral Sclerosis (ALS), mainly by endothelial cell (EC) alterations. Replacing damaged ECs by cell transplantation is a potential barrier repair strategy. Recently, we showed that intravenous (iv) administration of human bone marrow CD34+ (hBM34+) cells into symptomatic ALS mice benefits BSCB restoration and postpones disease progression. However, delayed effect on motor function and some severely damaged capillaries were noted. We hypothesized that hematopoietic cells from a restricted lineage would be more effective. This study aimed to establish the effects of human bone marrow-derived endothelial progenitor cells (hBMEPCs) systemically transplanted into G93A mice at symptomatic disease stage. Results showed that transplanted hBMEPCs significantly improved behavioral disease outcomes, engrafted widely into capillaries of the gray/white matter spinal cord and brain motor cortex/brainstem, substantially restored capillary ultrastructure, significantly decreased EB extravasation into spinal cord parenchyma, meaningfully re-established perivascular astrocyte end-feet, and enhanced spinal cord motor neuron survival. These results provide novel evidence that transplantation of hBMEPCs effectively repairs the BSCB, potentially preventing entry of detrimental peripheral factors, including immune/inflammatory cells, which contribute to motor neuron dysfunction. Transplanting EC progenitor cells may be a promising strategy for barrier repair therapy in this disease.
P4 medicine for epilepsy and intellectual disability: nutritional therapy for inherited metabolic disease
Authors: Tseng Laura A. , Sowerbutt Claire , Lee Jessica J.Y. , van Karnebeek Clara D.M. 
Published: March 2019

AbstractEarly identification and treatment of inherited metabolic diseases (IMDs) are essential to prevent and minimize intellectual disability (ID) and epilepsy. The oldest form of treatment, nutritional modulation, has proved beneficial for many IMDs. These conditions represent a promising model for P4 medicine — predictive, preventive, personalized, and participatory — specifically through the interpretation of individual genetic, pathophysiological, and clinical characteristics. More than 1000 IMDs have been described, and for these different nutritional modulation strategies are applied, varying from substrate reduction, supplementation of vitamins for catalyzation of enzymatic reactions or supplementation of amino acids or other nutrients, to substitution for deficient or inactivated products. This review provides an overview of all IMDs presenting with epilepsy and/or ID amenable to nutritional modulation; these are 85 in number, belonging to 27 categories. Therapeutic strategies include protein-restricted diet, ketogenic diet, fat-restricted diet, lactose-restricted diet; supplementation of amino acids, carbohydrates, or others; and supplementation of vitamins or cofactors as well as a sick-day protocol. Nutritional therapies are generally safe, affordable, and accessible, but compliance is an issue. Three different types of response exist: (1) a positive effect on seizure control and/or psychomotor development; (2) efficacy in prevention of decompensation but ongoing damage occurs; and (3) insufficient insights or evidence to establish the treatment as effective. For the latter category, we describe pyridoxine-dependent epilepsy as a case vignette for P4 medicine, discuss the benefits and challenges of nutritional modulation in IMDs, and outline novel approaches and solutions.
Evaluation of radiated immunity tests using adjusted pulse modulated signals
Authors: Nogueira de São José Artur , Adriano Ricardo , Resende Úrsula do Carmo , Menezes Magno Alves de , Mary de Souza Batalha Rose , Fujioka Mologni Juliano 
Published: March 2019

The main goals of an engineering test are reproducing a real scenario in a controlled environment and monitoring a device under validation when exposed to such condition. In this context, some recent studies have indicated misalignments between the waveforms suggested by the Radiated Immunity standards and the real telecommunication signals. Reproducing an actual signal in an electromagnetic compatibility laboratory might, however, be an expensive task, since it demands more sophisticated hardware. In this study, a simple solution for this problem is proposed based on adjustments applied to the standardised pulse modulated waveform. The objective is to develop an alternative to the traditional procedures, in an attempt to provide the manufacturers a more realistic test environment for their products. Mathematical manipulations indicate that a good agreement between the adjusted waveforms and a digital television signal cannot be simultaneously achieved in both time and frequency domains. Multiple trade‐off solutions are then generated and analysed through electromagnetic simulations. Results show that, in the 210–216 MHz frequency range, the pulse modulated signals model the digital television interference capability better than the classical continuous wave does.
Pull-Type Radiologically Inserted Gastrostomy: An Improvised Technique Using a Frugal Innovation
Authors: Chahal Anurag , Malla Sundeep , Dash Chinmaya , Gupta Deepak , Gamanagatti Shivanand 
Published: March 2019

Abstract
Purpose To describe a new technique for “pull type” radiologically inserted gastrostomy (RIG) and prospectively compare it with conventional (described) technique in terms of technical ease (fluoroscopy time, radiation dose) and safety profile.
Materials and Methods Adult patients with head injury with Glasgow coma scale (GCS) (M score) < 5, one week after decompression or those requiring nutritional support for > 4 weeks, or patients with recurrent aspiration pneumonitis on nasogastric feeding were included. Hemodynamically unstable patients or those with uncorrectable coagulopathy were excluded. Patients underwent pull-type RIG with alternate patient getting allocated to groups A (conventional technique) and B (new technique). The authors compared the technical success, complication rate, fluoroscopy time, radiation dose, and cost of hardware in these two groups.
Results The average fluoroscopy time for group A (9 patients) was 498.7 ± 145.3 seconds, whereas for group B (16 patients), it was 302.8 ± 54.1 seconds with p-value = 0.06. The mean radiation dose of group A was 74.7 ± 15.7 mGy, whereas for group B, it was 56.7 ± 14.1 mGy (p-value = 0.004). The minor complication rates were 11.1% in both the groups.
Conclusion The authors’ innovative technique using a customized snare has the potential to increase the technical ease of pull-type RIG with reduced fluoroscopy time, radiation dose, and cost with a similar safety profile.
Incident Atrial Fibrillation, Dementia and the Role of Anticoagulation: A Population-Based Cohort Study
Authors: Field Thalia S. , Weijs Bob , Curcio Antonio , Giustozzi Michela , Sudikas Saulius , Katholing Anja , Wallenhorst Christopher , Weitz Jeffrey I. , Cohen Alexander T. , Martinez Carlos 
Published: March 2019

Introduction Atrial fibrillation (AF) is associated with dementia. Anticoagulation may modify this relationship, but it is unclear if this is due to stroke reduction alone.
Methods Age- and sex-matched individuals from the U.K. Clinical Practice Research Datalink (2008–2016) with and without an incident diagnosis of AF were followed for a new dementia diagnosis. We estimated adjusted hazard ratios (aHRs) for incident dementia diagnosis in the AF cohort, overall and stratified by anticoagulation status, using the matched non-AF cohorts as reference. We performed a sensitivity analysis excluding individuals with stroke/transient ischaemic attack (TIA) before the observation period.
Results Over 193,082 person-years (mean follow-up 25.7 ± 0.1 months), 347/15,276 AF (2.3%) and 1,085/76,096 non-AF (1.4%) were newly diagnosed with dementia (aHR, 1.31, 95% confidence interval, 1.15–1.49). The AF group had more co-morbidity and higher rates of dementia, both with and without anticoagulation, than non-AF. When those with history of stroke/ TIA before the observation period were excluded and those with incident stroke/TIA during the observation period were censored, AF individuals not on anticoagulation had significantly higher rates of dementia compared with non-AF, aHR 1.30 (1.06–1.58).
Conclusion Our findings support the hypothesis that AF is a distinct risk factor for dementia, independent of stroke/TIA and other vascular risk factors. In those without stroke/TIA, risk of dementia is increased only in those who are not on anticoagulation, suggesting anticoagulation is protective presumably through reduction of sub-clinical embolic events. Further prospective research is needed to better ascertain the role of anticoagulation amongst targeted therapeutic strategies to reduce cognitive decline in AF.
The Disulfide Bond between Cys22 and Cys27 in the Protease Domain Modulate Clotting Activity of Coagulation Factor X
Authors: Li Fang , Chen Changming , Qu Si-Ying , Zhao Ming-Zhu , Xie Xiaoling , Wu Xi , Li Lei , Wang Xuefeng , Ding Qiulan , Xu Qin , Wei Dong-Qing , Wu Wenman 
Published: March 2019

AbstractThe Cys22-Cys27 disulfide bond of factor X (FX) protease domain is not conserved among coagulation factors and its contribution to the physiological haemostasis and implication in the pathogenesis of haemostatic and thrombotic disorders remain to be elucidated. Mutation p.Cys27Ser was identified in a pedigree of congenital FX deficiency and fluorescence labelling study of transiently transfected HEK293 cells showed accumulation of FX p.Cys27Ser within cell, indicating incompetent secretion partially responsible for the FX deficiency. The clotting activity of FX p.Cys27Ser was decreased to about 90% of wild-type, while amidolytic and pro-thrombinase activities (kcat/Km) determined with recombinant FXa mutant were 1.33- and 4.77-fold lower. Molecular dynamic simulations revealed no major change in global structure between FXa p.Cys27Ser and wild-type FXa; however, without the Cys22-Cys27 disulfide bond, the insertion of newly formed N terminal of catalytic domain after the activation cleavage is hindered, perturbing the conformation transition from zymogen to enzyme. The crystal structure of FXa shows that this disulfide bond is solvent accessible, indicating that its stability might be subject to the oxidation/reduction balance. As demonstrated with FX p.Cys27Ser here, Cys22-Cys27 disulfide bond may modulate FX clotting activity, with reduced FX pertaining less pro-coagulant activity.
Neonatal Functional and Structural Connectivity Are Associated with Cerebral Palsy at Two Years of Age
Authors: Merhar Stephanie L. , Gozdas Elveda , Tkach Jean A. , Parikh Nehal A. , Kline-Fath Beth M. , He Lili , Yuan Weihong , Altaye Mekibib , Leach James L. , Holland Scott K. 
Published: March 2019

Objective The accuracy of structural magnetic resonance imaging (MRI) to predict later cerebral palsy (CP) in newborns with perinatal brain injury is variable. Diffusion tensor imaging (DTI) and task-based functional MRI (fMRI) show promise as predictive tools. We hypothesized that infants who later developed CP would have reduced structural and functional connectivity as compared with those without CP.
Study Design We performed DTI and fMRI using a passive motor task at 40 to 48 weeks' postmenstrual age in 12 infants with perinatal brain injury. CP was diagnosed at age 2 using a standardized examination.
Results Five infants had CP at 2 years of age, and seven did not have CP. Tract-based spatial statistics showed a widespread reduction of fractional anisotropy (FA) in almost all white matter tracts in the CP group. Using the median FA value in the corticospinal tracts as a cutoff, FA was 100% sensitive and 86% specific to predict CP compared with a sensitivity of 60 to 80% and a specificity of 71% for structural MRI. During fMRI, the CP group had reduced functional connectivity from the right supplemental motor area as compared with the non-CP group.
Conclusion DTI and fMRI obtained soon after birth are potential biomarkers to predict CP in newborns with perinatal brain injury.
Higher Function Scores and Satisfaction in Patients with Anteromedial Osteoarthritis Compared with Other Wear Patterns of the Knee: 2 Years after Both Total and Unicondylar Knee Arthroplasties
Authors: Witjes Suzanne , Hoorntje Alexander , Koenraadt Koen L. M. , Kerkhoffs Gino M. M. J. , van Geenen Rutger C. I. 
Published: March 2019

AbstractAnteromedial osteoarthritis (AMOA) is a common wear pattern in primary osteoarthritic knees. In patients with bone-on-bone disease, the most appropriate surgical intervention is still a matter of debate. Knee arthroplasty is a well-accepted treatment to relieve symptoms and regain function. Unfortunately, satisfaction is limited, especially related to activities. A cross-sectional study was performed among patients treated with total knee arthroplasty (TKA) and unicondylar arthroplasty (UKA) to determine if the osteoarthritis wear pattern or type of prosthesis affects knee-specific function scores and satisfaction related to activities. All UKA patients (N = 100) were treated for AMOA. Based on radiological assessment of the wear pattern, TKA patients were divided into two groups: TKA for AMOA (N = 68) and true TKA (N = 99). The Knee injury and Osteoarthritis Outcomes Score (KOOS), new Knee Society score (KSS), anterior knee pain scale, visual analog scales (VASs) for satisfaction about activities, and net promoter score were collected. After 2 years' follow-up, the anterior knee pain scale and VAS satisfaction showed significantly better scores for patients treated with TKA for AMOA compared with the true TKA group. Also in the KOOS subscales, some differences were seen in favor of the TKA for AMOA group. The new KSS was not in favor of a specific wear pattern, but patients with AMOA treated with UKA performed better on the symptoms subscale compared with patients treated with TKA. In conclusion, patients treated with TKA for AMOA showed better knee-specific function scores and satisfaction scores compared with patients treated with TKA for other wear patterns, and only slight differences were found between both the AMOA groups (TKA for AMOA and UKA). Thus, the radiologic assessment of wear patterns might be useful to take into account the shared decision-making process, when discussing expectations, timing, and outcomes with knee osteoarthritis patients considering knee arthroplasty. When AMOA is present, it might be beneficial to choose UKA over TKA.
LGR4 is essential for R-spondin1-mediated suppression of food intake via pro-opiomelanocortin
Authors: Otsuka Ayano , Jinguji Ayana , Maejima Yuko , Kasahara Yoshiyuki , Shimomura Kenju , Hidema Shizu , Nishimori Katsuhiko 
Published: March 2019

ABSTRACT
Leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4) suppresses food intake after its activation by binding of its ligands, R-spondins. We investigated the mechanism of food intake suppression by R-spondin1 in a region-specific Lgr4 gene knockout (LGR4 cKO) mouse model, generated by deletion of the Lgr4 gene in arcuate nucleus (ARC) using Lgr4fx/fx mice combined with infection of an AAV-Cre vector. After R-spondin1 administration, LGR4 cKO mice didn’t exhibit a suppressed appetite, compared to that in control mice, which received a vehicle. In ARC of LGR4 cKO mice, Pomc mRNA expression was reduced, leading to suppressed food intake. On the other hand, neurons-specific LGR4 KO mice exhibited no differences in Pomc expression, and no structural differences were observed in the ARC of mutant mice. These results suggest that LGR4 is an essential part of the mechanism, inducing Pomc gene expression with R-spondin1 in ARC neurons in mice, thereby regulating feeding behavior.
Abbreviations: LGR4: Leucine-rich repeat-containing G-protein coupled receptor 4; RSPOs: roof plate-specific spondins; ARC: arcuate nucleus; AAV: adeno associated virus; POMC: pro-opiomelanocortin; CART: cocaine and amphetamine-regulated transcript; NPY: neuropeptide Y; AgRP: agouti-related peptide; Axin2: axis inhibition protein 2; Lef1: lymphoid enhancer binding factor 1; ccnd1: cyclin D1
Identification of the targets of HbEIN3/EILs in genomic wide in Hevea brasiliensis
Authors: Wang Qichao , Xu Gang , Zhai Jinling , Yuan Hongmei , Huang Xi 
Published: March 2019

ABSTRACT
EIN3/EILs are key regulators in ET signaling pathway. In this work, 4 members of EIN3/EILs of Hevea brasiliensis (HbEIN3/EILs) showed interaction with two F box proteins, HbEBF1 and HbEBF2. HbEIN3 located in nucleus and exhibited strong transcriptional activity. HbEIN3 was induced by ET treatment in C-serum, but not in B-serum of latex. HbEIN3/EILs bound to G-box cis-element. To globally search the potential targets of HbEIN3/EILs, genomic sequences of H. brasiliensis was re-annotated and an HCES (Hevea Cis-Elements Scanning) program was developed (www.h-brasiliensis.com). HCES scanning results showed that ET- and JA- responsive cis-elements distribute overlapping in gene promoters. 3146 genes containing G-box in promoters are potential targets of HbEIN3, including 41 genes involved in biosynthesis and drainage of latex, of which 7 rate-limiting genes of latex production were regulated by both ET and JA, suggesting that ET and JA signaling pathways coordinated the latex biosynthesis and drainage in H. brasiliensis.
Abbreviations: ABRE: ABA responsive elements; bHLH: basic helix-loop-helix; COG: Orthologous Groups; DRE: dehydration response element; ERE: ethylene responsive element; ET: Ethylene; GO: Gene Ontology; HCES: Hevea Cis-Elements Scanning; JA: jasmonates; JRE: Jasmonate-responsive element; KEGG: Kyoto Encyclopedia of Genes and Genomes; NR: non-redundant database; PLACE: Plant Cis-acting Regulatory DNA Elements; qRT-PCR: quantitative real-time RT-PCR.
The financialisation of transnational family care: a study of UK-based senders of remittances to Ghana and Nigeria
Authors: Yeates Nicola , Owusu-Sekyere Freda 
Published: March 2019

AbstractTransnational families occupy centre-stage in literatures on transformations in the social organisation and relations of care and welfare because they express how social bonds are sustained despite geographical separation. This paper examines some key themes arising from a research study into remittance-sending practices of UK-based Ghanaians and Nigerians in the light of research literatures on transnational family care and development finance. The data comprises qualitative interviews with 20 UK-based Ghanaian and Nigerian people who regularly send remittances to their families ‘back home’. This paper discusses a social issue that arises from the transnationalisation of family structures and relations, when migrant family members are positioned within family networks as ‘absent providers’, and familial relations eventually become financialised. The findings show the complexities of transnational living, the hardships endured by remittance-senders and the particular strains of remittance-mediated family relationships. The financialisation of family relations affects the social subjectivity and positioning of remittance-senders within the family. Strain and privation are integral to participants’ experiences of transnational family life, while themes of deception, betrayal, and expatriation also feature. The suppression of emotion is a feature of the significant labour inputs participants make in sustaining relationships within transnational families. The paper considers UK social policy implications of the findings.
Assessment of 3D motion modeling performance for dose accumulation mapping on the MR-linac by simultaneous multislice MRI
Authors: Borman P T S , Bos C , Stemkens B , Moonen C T W , Raaymakers B W , Tijssen R H N 
Published: March 2019

Abstract
Hybrid MR-linac systems enable intrafraction motion monitoring during radiation therapy. Since time-resolved 3D MRI is still challenging, various motion models have been developed that rely on time-resolved 2D imaging. Continuous validation of these models is important for accurate dose accumulation mapping. In this study we used 2D simultaneous multislice (SMS) imaging to improve the PCA-based motion modeling method developed previously (Stemkens et al 2016 Phys. Med. Biol. 61 5335–55). From the additional simultaneously acquired slices, several independent motion models could be generated, which allowed for an assessment of the sensitivity of the motion model to the location of the time-resolved 2D slices. Additionally, the best model could be chosen at every time-point, increasing the method’s robustness.
Imaging experiments were performed in six healthy volunteers using three simultaneous slices, which generated three independent models per volunteer. For each model the motion traces of the liver tip and both kidneys were estimated. We found that the location of the 2D slices influenced the model’s error in five volunteers significantly with a p -value  <0.05, and that selecting the best model at every time-point can improve the method. This allows for more accurate and robust motion characterization in MR-guided radiotherapy.
Community-based monitoring of Indigenous food security in a changing climate: global trends and future directions
Authors: Lam Steven , Dodd Warren , Skinner Kelly , Papadopoulos Andrew , Zivot Chloe , Ford James , Garcia Patricia J , Harper Sherilee L 
Published: March 2019

Abstract
Climate change is expected to exacerbate existing food security challenges, especially in Indigenous communities worldwide. Community-based monitoring (CBM) is considered a promising strategy to improve monitoring of, and local adaptation to climatic and environmental change. Yet, it is unclear how this approach can be applied in food security or Indigenous contexts. The objectives of this paper are to: (1) review and synthesize the published literature on CBM of Indigenous food security; and, (2) identify gaps and trends in these monitoring efforts in the context of climate change. Using a systematic search and screening process, we identified 86 published articles. To be included, articles had to be published in a journal, describe a CBM system, describe any aspect of food security, and explicitly mention an Indigenous community. Relevant articles were thematically analyzed to characterize elements of CBM in the context of climate change. Results show that the number of articles published over time was steady and increased more than two-fold within the last five years. The reviewed articles reported on monitoring mainly in North America (37%) and South America (28%). In general, monitoring was either collaborative (51%) or externally-driven (37%), and focused primarily on tracking wildlife (29%), followed by natural resources (16%), environmental change (15%), fisheries (13%), climate change (9%), or some combination of these topics (18%). This review provides an evidence-base on the uses, characteristics, and opportunities of CBM, to guide future food security monitoring efforts in the context of climate change.