bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inotuzumab ozogamicin in infants and young children with relapsed or refractory acute lymphoblastic leukaemia: a case series
Authors: Brivio Erica , Chantrain Christophe F. , Gruber Tanja A. , Thano Adriana , Rialland Fanny , Contet Audrey , Elitzur Sarah , Dalla‐Pozza Luciano , Kállay Krisztián Miklós , Li Chi‐kong , Kato Motohiro , Markova Inna , Schmiegelow Kjeld , Bodmer Nicole , Breese Erin H. , Hoogendijk Raoull , Pieters Rob , Zwaan Christian Michel 
Published: February 2021

SummaryNo data on inotuzumab ozogamicin (InO) in infant acute lymphoblastic leukaemia (ALL) have been published to date. We collected data internationally on infants/young children (<3 years) with ALL treated with InO. Fifteen patients (median 4.4 months at diagnosis) received InO due to relapsed or refractory (R/R) disease. Median percentage of CD22+ blasts was 72% (range 40–100%, n = 9). The median dose in the first course was 1.74 mg/m2 (fractionated). Seven patients (47%) achieved complete remission; one additional minimal residual disease (MRD)‐positive patient became MRD‐negative. Six‐month overall survival was 47% (95% confidence interval [CI] 27–80%). Two patients developed veno‐occlusive disease after transplant. Further evaluation of InO in this subgroup of ALL is justified.
Characteristics and outcome of patients with acute myeloid leukaemia and t(8;16)(p11;p13): results from an International Collaborative Study*
Authors: Kayser Sabine , Hills Robert K. , Langova Ralitsa , Kramer Michael , Guijarro Francesca , Sustkova Zuzana , Estey Elihu H. , Shaw Carole M. , Ráčil Zdeněk , Mayer Jiri , Zak Pavel , Baer Maria R. , Brunner Andrew M. , Szotkowski Tomas , Cetkovsky Petr , Grimwade David , Walter Roland B. , Burnett Alan K. , Ho Anthony D. , Ehninger Gerhard , Müller‐Tidow Carsten , Platzbecker Uwe , Thiede Christian , Röllig Christoph , Schulz Angela , Warsow Gregor , Brors Benedikt , Esteve Jordi , Russell Nigel H. , Schlenk Richard F. , Levis Mark J. 
Published: February 2021

SummaryIn acute myeloid leukaemia (AML) t(8;16)(p11;p13)/MYST3–CREBBP is a very rare abnormality. Previous small series suggested poor outcome. We report on 59 patients with t(8;16) within an international, collaborative study. Median age was 52 (range: 16–75) years. AML was de novo in 58%, therapy‐related (t‐AML) in 37% and secondary after myelodysplastic syndrome (s‐AML) in 5%. Cytogenetics revealed a complex karyotype in 43%. Besides MYST3–CREBBP, whole‐genome sequencing on a subset of 10 patients revealed recurrent mutations in ASXL1, BRD3, FLT3, MLH1, POLG, TP53, SAMD4B (n = 3, each), EYS, KRTAP9‐1 SPTBN5 (n = 4, each), RUNX1 and TET2 (n = 2, each). Complete remission after intensive chemotherapy was achieved in 84%. Median follow‐up was 5·48 years; five‐year survival rate was 17%. Patients with s‐/t‐AML (P = 0·01) and those with complex karyotype (P = 0·04) had an inferior prognosis. Allogeneic haematopoietic cell transplantation (allo‐HCT) was performed in 21 (36%) patients, including 15 in first complete remission (CR1). Allo‐HCT in CR1 significantly improved survival (P = 0·04); multivariable analysis revealed that allo‐HCT in CR1 was effective in de novo AML but not in patients with s‐AML/t‐AML and less in patients exhibiting a complex karyotype. In summary, outcomes of patients with t(8;16) are dismal with chemotherapy, and may be substantially improved with allo‐HCT performed in CR1.
Shared and unique features of mammalian sleep spindles – insights from new and old animal models
Authors: Iotchev Ivaylo Borislavov , Kubinyi Eniko 
Published: February 2021

ABSTRACTSleep spindles are phasic events observed in mammalian non‐rapid eye movement sleep. They are relevant today in the study of memory consolidation, sleep quality, mental health and ageing. We argue that our advanced understanding of their mechanisms has not exhausted the utility and need for animal model work. This is both because some topics, like cognitive ageing, have not yet been addressed sufficiently in comparative efforts and because the evolutionary history of this oscillation is still poorly understood. Comparisons across species often are either limited to referencing the classical cat and rodent models, or are over‐inclusive, uncritically including reports of sleep spindles in rarely studied animals. In this review, we discuss the emergence of new (dog and sheep) models for sleep spindles and compare the strengths and shortcomings of new and old models based on the three validation criteria for animal models – face, predictive, and construct validity. We conclude that an emphasis on cognitive ageing might dictate the future of comparative sleep spindle studies, a development that is already becoming visible in studies on dogs. Moreover, reconstructing the evolutionary history of sleep spindles will require more stringent criteria for their identification, across more species. In particular, a stronger emphasis on construct and predictive validity can help verify if spindle‐like events in other species are actual sleep spindles. Work in accordance with such stricter validation suggests that sleep spindles display more universally shared features, like defining frequency, than previously thought.
Rhizophora zonation, salinity, and nutrients in the western atlantic
Authors: Cerón‐Souza Ivania , Barreto María Beatriz , Barreto‐Pittol Eduardo , Silva Angie , Feliner Gonzalo N. , Medina Ernesto 
Published: February 2021

AbstractRhizophora is the dominant genus of mangrove forests on the Atlantic coast of northern South America. What determines the zonation frequently observed in sympatric populations of the two neotropical species, R. mangle and R. racemosa, and their hybrids, R. × harrisonii, is an open question. The most widely held hypothesis is that differences in salinity tolerance among the taxonomic groups explain the observed zonation. To address this question, we analyzed the elemental composition of soils and canopy leaves from 60 Rhizophora spp. trees distributed in different intertidal zones of an estuarine site of the Paria Gulf, Venezuela. The low intertidal zone showed lower salinity, organic matter, C, N, S, and Na, and higher bulk density, Al, Fe, and Mn concentrations compared with the higher intertidal zones. Using morphological characters and microsatellite molecular markers, we identified 39 pure R. mangle, 19 hybrids, and only two pure R. racemosa. We found that both intertidal position and taxonomic groups explained most of the differences in leaf variables measured across trees. The ratio Mg/Ca, however, was higher in R. mangle than in R. racemosa and hybrids regardless of intertidal position. Moreover, at some specific intertidal position, R. mangle differed from R. racemosa and hybrids in the values of C, N, K, Mg, Fe, Mn, C/N, K/Ca, S/Ca, and δ13C. We conclude that despite the scarcity of R. racemosa and the absence of a clear species zonation, our results suggest that R. mangle copes with salinity differently than R. racemosa and R. × harrisonii.
LPAR5 promotes thyroid carcinoma cell proliferation and migration by activating class IA PI3K catalytic subunit p110β
Authors: Zhao Wei‐Jun , Zhu Liu‐Lian , Yang Wei‐Qiang , Xu Shuai‐Jun , Chen Jie , Ding Xiao‐Fei , Liang Yong , Chen Guang 
Published: February 2021

AbstractLysophosphatidic acid receptor 5 (LPAR5) is involved in mediating thyroid cancer progression, but the underlying mechanism needs to be further revealed. In this study, we confirmed that LPAR5 is upregulated in papillary thyroid carcinoma (PTC), especially in BRAF‐like PTC, by analyzing The Cancer Genome Atlas (TCGA) database and performing immunohistochemistry assay in human thyroid cancer tissues. LPAR5‐specific antagonist TC LPA5 4 treatment inhibited CGTH‐W3, TPC‐1, B‐CPAP, and BHT‐101 cell proliferation, CGTH‐W3 and TPC‐1 cell migration significantly. In vivo, TC LPA5 4 treatment could delay CGTH‐W3 xenograft growth in nude mice. We also found that LPAR5‐specific antagonist TC LPA5 4, PI3K inhibitor wortmannin, or mTOR inhibitor rapamycin pretreatment abrogated phosphorylation of Akt and p70S6K1 stimulated by LPA in CGTH‐W3 and TPC‐1 cells. Stimulating CGTH‐W3 cells transfected with pEGFPC1‐Grp1‐PH fusion protein with LPA resulted in the generation of phosphatidylinositol (3,4,5)‐triphosphate, which indicates that PI3K was activated by LPA directly. The p110β‐siRNA instead of p110α‐siRNA transfection abrogated the increase of levels of phosphorylated Akt and S6K1 stimulated by LPA. Furthermore, immunoprecipitation assay confirmed an interaction between LPAR5 and p110β. Overall, we provide new insights that the downregulation of LPAR5 decreased the proliferation and migration phenotype via the PI3K/Akt pathway. Inhibition of LPAR5 or the PI3K/Akt signal may be a novel therapeutic strategy for treating thyroid cancer.
The noncanonical role of EZH2 in cancer
Authors: Huang Jinhua , Gou Hongwei , Yao Jia , Yi Kaining , Jin Zhigang , Matsuoka Masao , Zhao Tiejun 
Published: February 2021

AbstractEnhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PRC2). Dysregulation of EZH2 causes alteration of gene expression and functions, thereby promoting cancer development. The regulatory function of EZH2 varies across different tumor types. The canonical role of EZH2 is gene silencing through catalyzing the trimethylation of lysine 27 of histone H3 (H3K27me3) in a PRC2‐dependent manner. Accumulating evidence indicates that EZH2 has an H3K27me3‐independent function as a transcriptional coactivator and plays a critical role in cancer initiation, development, and progression. In this review, we summarize the regulation and function of EZH2 and focus on the current understanding of the noncanonical role of EZH2 in cancer.
Family‐centredness of a provincial autism programme: A quality assurance evaluation using the Measure of Processes of Care
Authors: Williams Uzma , Teplicky Rachel , Rosenbaum Peter , Gorter Jan Willem 
Published: February 2021

AbstractBackgroundUniversity researchers worked with 13 children's service provider agencies to conduct a programme evaluation of parents' perceptions of the family‐centredness of service spanning 3 years (January 2015 to May 2018). Parents of Ontario children with autism spectrum disorder (ASD) receiving applied behaviour analysis (ABA) programming reported outcomes of their experience of family‐centred services (FCS) using the 20‐item Measure of Processes of Care (MPOC‐20). The purpose of this paper is to report the outcomes of the quality assurance evaluation of FCS as measured by MPOC‐20 among parents of children with ASD receiving ABA services.MethodsA total of 11 490 surveys (from 21 571 potential respondents [53.3%]) were completed. Means and proportions were used to describe the demographics, service utilization and MPOC‐20 scores with its 7‐point Likert scales, ranging from 1 (lowest) to 7 (highest).ResultsThe overall provincial MPOC scores were consistent over the 3 years, ranging from very good to excellent, with Respectful and Supportive Care (n = 11 348,
= 6.27, SD = 0.83) reporting the highest scale score and Providing General Information (n = 10 485,
= 5.51, SD = 1.43) the lowest.ConclusionGiven the consistently high MPOC scores found in this and other programme evaluations, it is believed that health service providers have caught up to the FCS quality standards proposed 30 years ago. For this reason, the developers of MPOC are now planning a revision of the measure to address its ceiling effects and to integrate contemporary perspectives on family‐centred practice for children and their families.
The Immigrant Paradox in the Problem Behaviors of Youth in the United States: A Meta‐analysis
Authors: Tilley Jacqueline L. , Huey Stanley J. , Farver JoAnn M. , Lai Mark H.C. , Wang Crystal X. 
Published: February 2021

This meta‐analysis synthesizes the empirical data on problem behaviors among foreign‐ (G1) and U.S‐born (G2+) youth and explores the effects of immigrant status on youth internalizing and externalizing problems. A random effects meta‐regression with robust variance estimates summarized effect sizes for internalizing and externalizing problems across 91 studies (N = 179,315, Mage = 13.98). Results indicated that G1 youth reported significantly more internalizing problems (g = .06), and fewer externalizing problems than G2+ youth (g = −.06). Gender and sample type moderated the effects. The findings provide a first‐step toward reconciling mixed support for the immigrant paradox by identifying for whom and under what conditions the immigrant experience serves as a risk or protective factor for youth.
Peanuts in the air ‐ clinical and experimental studies
Authors: Lovén Björkman Sofia , Sederholm Ulrika , Ballardini Natalia , Beck Olof , Lundahl Joachim , Nopp Anna , Nilsson Caroline 
Published: February 2021

AbstractBackgroundAllergic reactions to food allergens usually occur after ingestion. However, fear of reactions to airborne peanut is a common concern for people with peanut allergy. There are no scientific reports on severe reactions with airborne peanut allergen.ObjectiveTo investigate the occurrence of allergic reactions in peanut‐allergic children undergoing airborne peanut challenge and to determine levels of airborne peanut protein in a separate experimental evaluation.MethodsEighty‐four children with peanut allergy underwent an airborne peanut challenge, 0.5 m from a bowl of peanuts for 30 min under controlled conditions. In a separate experiment, airborne peanut proteins from roasted and dry‐roasted peanuts were collected at varying distances and at varying times with an electret SensAbues filter connected to an air pump. Collected airborne peanut proteins were extracted, dissolved and detected by ELISA. Basophil activation test was used to confirm biological activity.ResultsNo moderate/severe allergic reactions to airborne peanut allergens were observed. Two children (2%) had mild rhino‐conjunctivitis which required no treatment. The IgE‐antibodies to peanut or Ara h 2 did not predict a reaction. In the experimental set‐up, biological active peanut proteins were detected, in a very low amount, in median 166 ng/ml for dry‐roasted and 33 ng/ml for roasted peanuts and decreased dramatically when the collection occurred at a greater distance (0.5–2 m) from the peanut source. Increased exposure time did affect the amount of collected peanut protein at 0 m, and the highest median was obtained after 60 min (p = .012); for time trend p = .0006.Conclusions and Clinical RelevanceAllergic reactions to airborne peanut proteins are rare and cannot be predicted by high levels of IgE‐antibodies to peanut or Ara h 2. Only small amounts of biologically active peanut proteins were detected in the air and seem unlikely to trigger moderate/severe allergic reactions.
Association between plasma aldosterone and markers of tubular and glomerular damage in primary aldosteronism
Authors: Nakamura Yoshihiro , Kobayashi Hiroki , Tanaka Sho , Hatanaka Yoshinari , Fukuda Noboru , Abe Masanori 
Published: February 2021

AbstractObjectiveAlthough renal impairments are observed in patients with primary aldosteronism (PA), the association between plasma aldosterone concentration (PAC) and specific structural kidney damage remains unknown. Thus, we analysed the association between PAC, and markers of glomerular and tubular damage.DesignThis was a retrospective cross‐sectional study of 96 PA patients, in which we analysed the association between PAC and markers of kidney damage, including urinary albumin‐creatinine ratio (ACR) for glomerular damage, and urinary liver fatty acid‐binding protein (L‐FABP), N‐acetyl‐β‐D‐glucosaminidase (NAG) and β2‐microglobulin (β2‐MG) for tubular damage. In addition, we evaluated the association between PAC and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) as a marker for body fluid volume.ResultsUrinary ACR, L‐FABP, NAG, β2‐MG and NT‐proBNP significantly correlated with PAC. PAC (<415 pmol/L, 415‐550, 550‐740, 740 <)‐based quartile analysis revealed that both elevated markers of kidney damage and NT‐proBNP could be observed in PA patients with a PAC over 550 pmol/L. Logistic regression analysis showed that PAC was significantly associated with a risk of both microalbuminuria and lowered eGFR (<60 mL/min/1.73 m2), with its optimal cut‐offs for predicting each, 558 and 594 pmol/L, respectively.ConclusionsIncreased PAC, especially over 550 pmol/L, is associated with excessive damage to the tubule and glomerulus.
Exosomes containing miR‐451a is involved in the protective effect of cerebral ischemic preconditioning against cerebral ischemia and reperfusion injury
Authors: Li He , Luo Yin , Liu Peng , Liu Pei , Hua Weilong , Zhang Yongxin , Zhang Lei , Li Zifu , Xing Pengfei , Zhang Yongwei , Hong Bo , Yang Pengfei , Liu Jianmin 
Published: February 2021

AbstractAimTo study the role of exosomes in the protective effect of cerebral ischemic preconditioning (cerebral‐IPC) against cerebral I/R injury.MethodMouse models of cerebral‐IPC and MCAO/R were established as described previously, and their behavioral, pathological, and proteomic changes were analyzed. Neuro‐2a subjected to OGD/R were treated with exosomes isolated from the plasma of sham‐operated and cerebral‐IPC mice. The differentially expressed miRNAs between exosomes derived from sham‐operated (S‐exosomes) and preconditioned (IPC‐exosomes) mice were identified through miRNA array, and their targets were identified through database search. The control and OGD/R cells were treated with the IPC‐exosomes, miRNA mimic or target protein inhibitor, and their viability, oxidative, stress and apoptosis rates were measured. The activated pathways were identified by analyzing the levels of relevant proteins.ResultsCerebral‐IPC mitigated the cerebral injury following ischemia and reperfusion, and increased the number of plasma exosomes. IPC‐exosomes increased the survival of Neuro‐2a cells after OGD/R. The miR‐451a targeting Rac1 was upregulated in the IPC‐exosomes relative to S‐exosomes. The miR‐451a mimic and the Rac1 inhibitor NSC23766 reversed OGD/R‐mediated activation of Rac1 and its downstream pathways.ConclusionCerebral‐IPC ameliorated cerebral I/R injury by inducing the release of exosomes containing miR‐451a.
Stem cell‐derived mitochondria transplantation: A promising therapy for mitochondrial encephalomyopathy
Authors: Liu Kaiming , Zhou Zhijian , Pan Mengxiong , Zhang Lining 
Published: February 2021

AbstractMitochondrial encephalomyopathies are disorders caused by mitochondrial and nuclear DNA mutations which affect the nervous and muscular systems. Current therapies for mitochondrial encephalomyopathies are inadequate and mostly palliative. However, stem cell‐derived mitochondria transplantation has been demonstrated to play an key part in metabolic rescue, which offers great promise for mitochondrial encephalomyopathies. Here, we summarize the present status of stem cell therapy for mitochondrial encephalomyopathy and discuss mitochondrial transfer routes and the protection mechanisms of stem cells. We also identify and summarize future perspectives and challenges for the treatment of these intractable disorders based on the concept of mitochondrial transfer from stem cells.
Long‐term therapy with botulinum toxin in facial synkinesis: Retrospective data analysis of data from 1998 to 2018
Authors: Alipour Sara , Pick Carina , Jansen Stefanie , Rink Svenja , Klußmann Jens Peter , Grosheva Maria 
Published: February 2021

AbstractObjectivesTreatment with botulinum toxin A (BoNT) is the therapy of choice for many patients with facial synkinesis. Repeated injections relieve hypertonicity and hyperkinesis of reinnervated mimic muscles. Aim of the study was to prove if the injection regime and dosage of BoNT change during long‐time therapy.DesignRetrospective analysis of patients´ data, who were treated for synkinesis with BoNT from 1998 to 2018.SettingTertiary referral facial nerve centre.ParticipantsInjection pattern of BoNT was based on clinical symptoms, observations of the specialist and on previous treatment pattern. Onabotulinumtoxin (OnaBoNT), Incobotulinumtoxin (IncoBoNT) and Abobotulinumtoxin (AboBoNT) were available for treatment. Patients consulted our department for following treatment as soon as the symptoms re‐occurred.Main outcome measuresChange in dosage and injection pattern, the time intervals between treatments over the entire therapy period.ResultsSeventy‐three patients were repeatedly injected. The median number of treatments was 18, the median treatment interval was 3.0 months. During the initial treatment, orbicularis oculi and the mentalis muscles were the most frequently injected muscles (94%). During repeated treatment, the number of injected muscles increased significantly (P < .0001), whereas the dose per muscle remained stable. The initial dose was 24 U (95%‐CI 22‐27 U) for OnaBoNT and IncoBoNT; 69 U for AboBoNT(95%‐CI 44‐94 U). We observed a significant increase in dosage for OnaBoNT and IncoBoNT (P < .0001) during the long‐term therapy. The time intervals between treatments were stable for all three BoNT preparations (P > .05).ConclusionsWe observed significant change in treatment dose and injection pattern of BoNT in patients with facial synkinesis. These results provide an orientation in dose finding and injection regimen of BoNT in the long‐term course of therapy.
Determination of variables for a more accurate diagnostic approach in suspected acute invasive fungal rhinosinusitis: A non‐concurrent cohort study
Authors: Lagos Antonia E. , García‐Huidobro Francisco G. , Sepúlveda Valeria , Cruz Juan Pablo , González Claudia , Callejas Claudio A. 
Published: February 2021

AbstractObjectiveTo describe a group of patients with suspected acute invasive fungal rhinosinusitis (AIFRS) diagnosis, and identify factors associated with a greater risk of presenting this disease.DesignNon‐concurrent cohort study.SettingA single‐centre non‐concurrent follow‐up of patients with suspected AIFRS between August 2015 and July 2018.Participants50 inpatients referred due to suspected AIFRS at Hospital Clínico Universidad Católica based on the association of a predisposing factor (neutropenia/immunodeficiency/poorly controlled diabetes) with fever of unknown origin.Main outcome measureThe primary outcome was AIFRS diagnosis, defined as a concordant tissue biopsy.ResultsAcute invasive fungal rhinosinusitis was confirmed in 18% (9/50) of the evaluated patients. AIFRS was significantly associated with a positive galactomannan (P = .04), and a paranasal sinus MRI with lack of contrast enhancement (LoCE) (P = .04) orbit compromise (P = .03) or global extrasinusal extension (P = .04). LoCE and extrasinusal extension in the paranasal sinus/brain MRI were risk factors for AIFRS (OR 16; CI 1.2‐210.6 and OR 12.75; CI 1.3‐128.8, respectively). Conversely, a nasal endoscopy showing healthy mucosa was identified as a protective factor for AIFRS (OR 0.06; CI 0.007‐0.57).ConclusionsIn patients with suspected AIFRS, we identified laboratory and radiologic variables associated with the disease, which may help for a more accurate diagnostic algorithm and approach in this population.