bluuebunny/crossref_metadata_2025_split huggingface dataset:
TSPO2 translocates 5‐aminolevulinic acid into human erythroleukemia cells
Authors: Manceau Hana , Lefevre Sophie D , Mirmiran Arienne , Hattab Claude , Sugier Hugo R , Schmitt Caroline , Peoc'h Katell , Puy Hervé , Ostuni Mariano A , Gouya Laurent , Lacapere Jean‐Jacques 
Published: January 2020

Background5‐Aminolevulinic acid (ALA) is the first precursor of heme biosynthesis pathway. The exogenous addition of ALA to cells leads to protoporphyrin IX (PPIX) accumulation that has been exploited in photodynamic diagnostic and photodynamic therapy. Several types of ALA transporters have been described depending on the cell type, but there was no clear entry pathway for erythroid cells. The 18 kDa translocator protein (TSPO) has been proposed to be involved in the transport of porphyrins and heme analogs.ResultsALA‐induced PPIX accumulation in erythroleukemia cells (UT‐7 and K562) was impaired by PK 11195, a competitive inhibitor of both transmembrane proteins TSPO (1 and 2). PK 11195 did not modify the activity of the enzymes of heme biosynthesis, suggesting that ALA entry at the plasma membrane was the limiting factor. In contrast, porphobilinogen (PBG)‐induced PPIX accumulation was not affected by PK 11195, suggesting that plasma membrane TSPO2 is a selective transporter of ALA. Overexpression of TSPO2 at the plasma membrane of erythroleukemia cells increased ALA‐induced PPIX accumulation, confirming the role of TSPO2 in the import of ALA into the cells.ConclusionsALA‐induced PPIX accumulation in erythroid cells involves TSPO2 as a selective translocator through the plasma membrane.SignificanceThis is the first characterisation of molecular mechanisms involving a new actor in ALA transport in ALA‐induced PPIX accumulation in erythroleukemia cells, which could be inhibited by specific drug ligands.
Discovery of inner centromere protein‐derived small peptides for cancer imaging and treatment targeting survivin
Authors: Fuchigami Takeshi , Ishikawa Natsumi , Nozaki Iori , Miyanari Yusuke , Yoshida Sakura , Yamauchi Motohiro , Soejima Ayumi , Haratake Mamoru , Nakayama Morio 
Published: January 2020

AbstractSurvivin belongs to the inhibitor of apoptosis protein family, which is consistently overexpressed in most cancer cells but rarely expressed in normal adult tissues. Therefore, the detection and inhibition of survivin are regarded as attractive strategies for cancer‐specific treatment. In this study, we designed and synthesized 7‐19 residues of inner centromere protein (INCENP)‐derived small peptides (INC peptides) as novel survivin‐targeting agents. The INC peptides showed binding affinity for the human survivin protein (Kd = 91.4‐255 nmol L−1); INC16‐22, which contains residues 16‐22 of INCENP, showed the highest affinity (91.4 nmol L−1). Confocal fluorescence imaging showed consistent colocalization of FITC‐INC16‐22 and survivin in cell lines. Nona‐arginine‐linked INC16‐22 (r9‐INC16‐22) rendered INC16‐22 cells penetrable and strongly inhibited cell growth of MIA PaCa‐2 cells (52% inhibition at 1.0 µmol L−1) and MDA‐MB‐231 cells (60% inhibition at 10 µmol L−1) as determined by MTT assays. The exposure of MIA PaCa‐2 cells to 40 µmol L−1 r9‐INC16‐22 apparently reduced the intracellular protein expression levels of survivin. However, cleaved caspase‐3 was significantly increased in cells treated with r9‐INC16‐22, even at 10 µmol L−1, compared to untreated cells. Flow cytometry revealed that r9‐INC16‐22 strongly induced apoptosis in MIA PaCa‐2 cells. These results indicate that the cytotoxic effects of r9‐INC16‐22 could be mediated mainly through the disruption of survivin‐dependent antiapoptotic functions and partly because of the direct degradation of the survivin protein. Our findings suggest that INC peptides can act as useful scaffolds for novel cancer imaging and anticancer agents.
The Effect of Birth weight on Child Development Prior to School Entry
Authors: Hines Caitlin T. , Padilla Christina M. , Ryan Rebecca M. 
Published: January 2020

The present study examines variation in the effect of birth weight on children’s early cognitive and socioemotional outcomes by family socioeconomic status (SES). It is hypothesized that not only will lower birth weight children display worse cognitive and socioemotional outcomes prior to school entry, as prior research has found, but that effects will be stronger for lower‐SES children. Using data from the Early Childhood Longitudinal Study–Birth Cohort, the study compares the age 4 outcomes of twins discordant for birth weight (N ~ 1,400). Twin fixed‐effects models are run on the full twin sample and separately for low‐ and high‐SES children. Results support the study’s hypotheses, suggesting that socioeconomic risk accentuates the effects of birth weight on early development.
Comparison of elapegademase and pegademase in ADA-deficient patients and mice
Authors: Murguia-Favela L , Min W , Loves R , Leon-Ponte M , Grunebaum E 
Published: January 2020

Summary
The absence of adenosine deaminase (ADA) causes severe combined immune deficiency (SCID), which has been treated with PEGylated bovine-extracted ADA (ADAGEN). ADAGEN was recently replaced by a PEGylated recombinant bovine ADA, expressed in Escherichia coli (elapegademase, ELA–ADA). Limited information on ELA–ADA is available. ADA enzymatic activity of ELA–ADA and ADAGEN was assessed in vitro at diverse dilutions. ADA activity and immune reconstitution in an ADA–SCID patient treated with ELA–ADA were compared with age-matched patients previously treated with ADAGEN. ADA activity and thymus reconstitution were evaluated in ADA-deficient mice following ELA–ADA or ADAGEN administered from 7 days postpartum. In vitro, ADA activity of ELA–ADA and ADAGEN were similar at all dilutions. In an ADA–SCID patient, ELA–ADA treatment led to a marked increase in trough plasma ADA activity, which was 20% higher than in a patient previously treated with ADAGEN. A marked increase in T cell numbers and generation of naive T cells was evident following 3 months of ELA–ADA treatment, while T cell numbers increased following 4 months in 3 patients previously treated with ADAGEN. T cell proliferations stimulation normalized and thymus shadow became evident following ELA–ADA treatment. ADA activity was significantly increased in the blood of ADA-deficient mice following ELA–ADA compared to ADAGEN, while both treatments improved the mice weights, the weight, number of cells in their thymus and thymocyte subpopulations. ELA–ADA has similar in- vitro and possibly better in-vivo activity than ADAGEN. Future studies will determine whether ELA–ADA results in improved long-term immune reconstitution.
Mechanisms of checkpoint inhibition-induced adverse events
Authors: Urwyler P , Earnshaw I , Bermudez M , Perucha E , Wu W , Ryan S , Mcdonald L , Karagiannis S N , Taams L S , Powell N , Cope A , Papa S 
Published: January 2020

SummaryImmune checkpoint inhibition has revolutionized the treatment of several solid cancers, most notably melanoma and non-small-cell lung cancer (NSCLC). Drugs targeting cytotoxic T lymphocyte antigen (CTLA)-4 and programmed cell death 1 (PD-1) have made their way into routine clinical use; however, this has not been without difficulties. Stimulation of the immune system to target cancer has been found to result in a reduction of self-tolerance, leading to the development of adverse effects that resemble autoimmunity. These adverse effects are erratic in their onset and severity and can theoretically affect any organ type. Several mechanisms for immune-related toxicity have been investigated over recent years; however, no consensus on the cause or prediction of toxicity has been reached. This review seeks to examine reported evidence for possible mechanisms of toxicity, methods for prediction of those at risk and a discussion of future prospects within the field.
Charcot–Marie–Tooth disease and neuroinflammation
Authors: Kokubun Norito 
Published: January 2020

AbstractPatients with the misdiagnosis or co‐occurrence of Charcot–Marie–Tooth disease (CMT) and inflammatory neuropathies have been reported previously. Both CMT and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have similar clinical features, including flaccid weakness in four limbs with areflexia, demyelinating neurophysiological features and pathological demyelination. However, the symptoms of CIDP progress for several weeks or months, and typical CIDP shows proximal and distal muscle weakness. In contrast, CMT progresses for several decades and presents distal‐dominant muscle weakness, which is called length‐dependent neuropathy. On neurophysiological evaluation, CMT had been considered to show “uniform conduction slowing.” However, a recent study showed that CMT could show non‐uniform conduction abnormalities, which resemble inflammatory neuropathies. Furthermore, the incidence of inflammatory neuropathy in CMT is estimated to be higher than that in the general population. CMT1A with CIDP was the most common, followed by CMTX1 with CIDP and CMT1A with Guillain–Barré syndrome. Some patients showed macrophage‐associated demyelination or mononuclear cell infiltrations in their nerves. Most patients responded to immune therapies at least partly. The pathophysiology in such patients has not yet been elucidated. However, the involvement of the immune system in the development of demyelination in CMT was established by experimental animal studies, and vulnerability to immune abnormalities is suggested in abnormal myelin.
Facial alveolar bone alterations and gray value changes based on cone beam computed tomography around maxillary anterior implants: A clinical retrospective study of 1–3 years
Authors: Zhou Yi , Gao Jiayu , Sheng Min , Qi Wenting , Jin Jiali , He Fuming 
Published: January 2020

AbstractObjectivesThe purpose of this cone beam computed tomography (CBCT) study was to describe facial alveolar bone alterations and gray value (GV) changes around implants in aesthetic anterior maxilla with simultaneous guided bone regeneration (GBR) and to investigate potential influence of factors related to vertical alveolar bone stability, such as particle sizes of the deproteinized bovine bone mineral (DBBM) used.Materials and MethodsA retrospective study design was adopted. Four facio‐palatal cross‐sectional CBCT images of 166 implants from 124 patients who had maxillary anterior implants were obtained. Measurements of the vertical facial alveolar bone level (VFBL), horizontal facial alveolar bone thickness (HFBT), and GV were identified of 1–3 years. Then, correlation coefficients for those parameters were calculated. Finally, linear mixed models were established to investigate potential factors influencing vertical alveolar bone resorption.ResultsFacial alveolar bone underwent fast bone modeling and remodeling during the first 6 months, with decreases of 1.00 ± 1.19 and 0.74 ± 0.86 mm in VFBL and HFBT in implant shoulder, respectively, and there was positive and significant correlation between the alterations in VFBL and HFBT1 (rs = .516, p = .000). Linear mixed models identified particle size of DBBM as a critical factor associated with vertical bone resorption (p = .000). The GV gradually increased during the follow‐up period.ConclusionsRapid and unavoidable peri‐implant bone resorption usually happened during the first 6 months after implant placement. GBR is a predictable treatment for maxillary anterior implants, since GV has an increasing trend. Large bone particles of DBBM help maintain vertical alveolar bone stability.
Freshwater fish diversity hotspots for conservation priorities in the Amazon Basin
Authors: Jézéquel Céline , Tedesco Pablo A. , Darwall William , Dias Murilo S. , Frederico Renata G. , Hidalgo Max , Hugueny Bernard , Maldonado‐Ocampo Javier , Martens Koen , Ortega Hernan , Torrente‐Vilara Gislene , Zuanon Jansen , Oberdorff Thierry 
Published: January 2020

AbstractConserving freshwater habitats and their biodiversity in the Amazon Basin is a growing challenge in the face of rapid anthropogenic changes. We used the most comprehensive fish‐occurrence database available (2355 valid species; 21,248 sampling points) and 3 ecological criteria (irreplaceability, representativeness, and vulnerability) to identify biodiversity hotspots based on 6 conservation templates (3 proactive, 1 reactive, 1 representative, and 1 balanced) to provide a set of alternative planning solutions for freshwater fish protection in the Amazon Basin. We identified empirically for each template the 17% of sub‐basins that should be conserved and performed a prioritization analysis by identifying current and future (2050) threats (i.e., degree of deforestation and habitat fragmentation by dams). Two of our 3 proactive templates had around 65% of their surface covered by protected areas; high levels of irreplaceability (60% of endemics) and representativeness (71% of the Amazonian fish fauna); and low current and future vulnerability. These 2 templates, then, seemed more robust for conservation prioritization. The future of the selected sub‐basins in these 2 proactive templates is not immediately threatened by human activities, and these sub‐basins host the largest part of Amazonian biodiversity. They could easily be conserved if no additional threats occur between now and 2050.
Using preoperative three‐dimensional endoanal ultrasound to determine operative procedure in patients with perianal fistulas
Authors: Mantoo S. , Mandovra P. , Goh S. 
Published: January 2020

AbstractAimAccurate preoperative identification of perianal fistula tracts and internal openings can facilitate the choice of surgical procedure and may lead to improved healing rates. Our aim was to explore the effectiveness of three‐dimensional endoanal ultrasound (3D‐EAUS) in determining the type of perianal fistula and planning operative management.MethodThis was a cohort longitudinal study. Patients with perianal fistulas from January 2017 to January 2018 who underwent 3D‐EAUS and subsequent surgery were included. Intra‐operative findings were considered as standard for comparison with clinical examination and 3D‐EAUS findings. The primary outcome measure was to evaluate the concordance between 3D‐EAUS and intra‐operative findings and the secondary outcome measure was healing rates.ResultsSixty‐eight patients with a mean age of 43.1 ± 14.1 years were included. Twenty‐eight patients had inter‐sphincteric (41.2%) and 40 (14 high and 26 low) trans‐sphincteric fistulas (58.8%). 3D‐EAUS, clinical examination and intra‐operative exploration could predict the location of internal openings in 62/68 (91.2%), 48/68 (70.5%) and 56/68 (82.4%) patients, respectively. Hydrogen peroxide (H₂O₂)‐enhanced 3D‐EAUS accurately predicted the location of internal openings when compared with 3D‐EAUS without H₂O₂ (concordance K = 0.963, P = 0.05). High concordance rates were seen between intra‐operative and 3D‐EAUS findings on the type of perianal fistula. No significant difference was seen between the suggested surgical treatment based on 3D‐EAUS and the eventual surgical treatment (P > 0.05). Study limitations were the small sample size and lack of randomization.Conclusion3D‐EAUS may be considered as a first‐line investigation for patients with perianal fistulas because of high concordance with intra‐operative assessment and facilitation of surgical planning.
Revealing migration and reproductive habitat of invasive fish under an active population suppression program
Authors: Gutowsky Lee F.G. , Romine Jason G. , Heredia Nicholas A. , Bigelow Patricia E. , Parsley Michael J. , Sandstrom Philip T. , Suski Cory D. , Danylchuk Andy J. , Cooke Steven J. , Gresswell Robert E. 
Published: January 2020

AbstractEndemic species face a variety of threats including predation from non‐native invaders. In some cases, however, invasive species can be managed by directly suppressing populations, and tracking technologies that allow researchers to identify movement patterns and aggregations representative of the population can facilitate suppression activities. In Yellowstone Lake (Yellowstone National Park, Wyoming), invasive lake trout (Salvelinus namaycush) have been the target of a population suppression program for over two decades. For this form of management, the reproductive period is particularly important because fish migrate to and from spawning grounds. From 2011 to 2014, adult lake trout (n = 317) in Yellowstone Lake were tracked using acoustic biotelemetry. After controlling for spatial and temporal dependency in the data, total abundance of unique individuals was estimated where migratory trajectories occurred at confirmed spawning sites. Aggregations and migratory trajectories were further estimated at locations where spawning had not previously been observed. Across years, the greatest number of individuals was observed along a migration corridor in the southwestern area of the lake. Novel strategies for analyzing acoustic telemetry data provided insights into the behavior of an invasive fish species. By betraying the positions of conspecifics, tagged fish revealed potentially important reproductive habitats and migration corridors that warranted further investigation as possible sites for population suppression.
Regional‐scale patterns of deep seafloor biodiversity for conservation assessment
Authors: O'Hara Timothy D. , Williams Alan , Althaus Franziska , Ross Andrew S. , Bax Nicholas J. 
Published: January 2020

AbstractAimMining and petroleum industries are exploring for resources in deep seafloor environments. Lease areas are often spatially aggregated and continuous over hundreds to thousands of kilometres. Sustainable development of these resources requires an understanding of the patterns of biodiversity at similar scales, yet these data are rarely available for the deep sea. Here, we compare biodiversity metrics and assemblage composition of epibenthic megafaunal samples from deep‐sea benthic habitats from the Great Australian Bight (GAB), a petroleum exploration zone off southern Australia, to similar environments off eastern Australia.LocationThe Great Australian Bight (34–36°S, 129–134°E) and south‐eastern (SE) and north‐eastern (NE) Australian continental margins (23–42°S, 149–155°E) in depths of 1,900–5,000 m.MethodsA species–sample matrix was constructed from invertebrate and fish megafauna collected from beam trawl samples across regions at lower bathyal (1,900–3,200 m) and abyssal (>3,200 m) depths, and analysed using multivariate, rarefaction and model‐based statistics. We modelled rank abundance distributions (RAD) against environmental factors to identify drivers of abundance, richness and evenness.ResultsMultivariate analyses showed regional and bathymetric assemblage structure across the region. There was an almost complete turnover of sponge fauna between the GAB and SE. SE samples had the highest total faunal abundance and species richness. RAD models linked total abundance and species richness to levels of carbon flux. Evenness was associated with seasonality of net primary production.ConclusionsSignificant assemblage structure at regional scales is reported for the first time at lower bathyal and abyssal depths in the southern Indo‐Pacific region along latitudinal and longitudinal gradients. The GAB fauna was distinct from other studied areas. Relatively high species richness, previously reported from the GAB continental shelf, did not occur at lower bathyal or abyssal depths. Instead, the abundance, richness and evenness of the benthic fauna are linked to surface primary production, which is elevated off SE Australia.
Do you understand what I want to tell you? Early sensitivity in bilinguals' iconic gesture perception and production
Authors: Wermelinger Stephanie , Gampe Anja , Helbling Natascha , Daum Moritz M. 
Published: January 2020

AbstractPrevious research has shown differences in monolingual and bilingual communication. We explored whether monolingual and bilingual pre‐schoolers (N = 80) differ in their ability to understand others' iconic gestures (gesture perception) and produce intelligible iconic gestures themselves (gesture production) and how these two abilities are related to differences in parental iconic gesture frequency. In a gesture perception task, the experimenter replaced the last word of every sentence with an iconic gesture. The child was then asked to choose one of four pictures that matched the gesture as well as the sentence. In a gesture production task, children were asked to indicate ‘with their hands’ to a deaf puppet which objects to select. Finally, parental gesture frequency was measured while parents answered three different questions. In the iconic gesture perception task, monolingual and bilingual children did not differ. In contrast, bilinguals produced more intelligible gestures than their monolingual peers. Finally, bilingual children's parents gestured more while they spoke than monolingual children's parents. We suggest that bilinguals' heightened sensitivity to their interaction partner supports their ability to produce intelligible gestures and results in a bilingual advantage in iconic gesture production.
Health professionals' views about who would benefit from using a closed‐loop system: a qualitative study
Authors: Lawton J. , Kimbell B. , Rankin D. , Ashcroft N. L. , Varghese L. , Allen J. M. , Boughton C. K. , Campbell F. , Randell T. , Besser R. E. J. , Trevelyan N. , Hovorka R. ,   the CLOuD Consortium
Published: January 2020

AbstractAimTo explore health professionals' views about who would benefit from using a closed‐loop system and who should be prioritized for access to the technology in routine clinical care.MethodsHealth professionals (n = 22) delivering the Closed Loop from Onset in type 1 Diabetes (CLOuD) trial were interviewed after they had ≥ 6 months' experience supporting participants using a closed‐loop system. Data were analysed thematically.ResultsInterviewees described holding strong assumptions about the types of people who would use the technology effectively prior to the trial. Interviewees described changing their views as a result of observing individuals engaging with the closed‐loop system in ways they had not anticipated. This included educated, technologically competent individuals who over‐interacted with the system in ways which could compromise glycaemic control. Other individuals, who health professionals assumed would struggle to understand and use the technology, were reported to have benefitted from it because they stood back and allowed the system to operate without interference. Interviewees concluded that individual, family and psychological attributes cannot be used as pre‐selection criteria and, ideally, all individuals should be given the chance to try the technology. However, it was recognized that clinical guidelines will be needed to inform difficult decisions about treatment allocation (and withdrawal), with young children and infants being considered priority groups.ConclusionsTo ensure fair and equitable access to closed‐loop systems, prejudicial assumptions held by health professionals may need to be addressed. To support their decision‐making, clinical guidelines need to be made available in a timely manner.