bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of TNF-receptor and ligand superfamily molecules in patients with lymphoproliferative disease of granular lymphocytes
Authors: Zambello Renato , Trentin Livio , Facco Monica , Siviero Marta , Galvan Silvia , Piazza Francesco , Perin Alessandra , Agostini Carlo , Semenzato Gianpietro 
Published: October 2019

AbstractIn 21 patients with lymphoproliferative disease of granular lymphocytes (LDGL), we investigated the expression and the function of molecules belonging to TNF-receptor and TNF-ligand superfamilies (CD30/CD30L; CD40/CD40L; CD27/CD70; Fas [CD95]/FasL[CD95L]). Fourteen patients were characterized by a proliferation of granular lymphocytes (GLs) expressing the CD3+CD16+phenotype, whereas 7 cases showed the CD3−CD16+ CD56 ± phenotype. Our data show that both CD3+ and CD3-GLs are preferentially equipped with CD30, CD40, CD40L, CD70, and CD95 antigens; this pattern is usually associated with the lack of CD27 and CD30L antigens expression. CD95L was demonstrated in the cytoplasm in 14 of 21 cases by flow cytometry, but a definite signal was demonstrated in all cases studied using polymerase chain reaction analysis. On functional grounds, a stimulatory activity on rIL-2 mediated redirected-cytotoxicity against Fcγ+ P815 targets was demonstrated with anti-CD30, CD40, CD40L, CD70, CD95, and CD95L mAbs, although resting cells were unable to exhibit significant redirected-cell lysis. The addition of anti-CD30, CD30L, CD40, CD40L, CD95, and CD95L mAbs did not show any significant effect on cell proliferation at resting conditions or after rIL-2 stimulation, whereas anti-CD70 mAb mediated cell proliferation in 6 of 10 cases tested. This figure was not related to an increase in apoptotic cells, as investigated by Annexin-V expression. Our data indicate that both CD3+ and CD3− GLs are equipped with different costimulatory antigens, supporting the concept that these cells are in vivo activated and suggesting that these molecules might play a role in the cytotoxic mechanisms of GLs.
Prolonged CD4 depletion after sequential autologous peripheral blood progenitor cell infusions in children and young adults
Authors: Mackall Crystal L. , Stein Dagmar , Fleisher Thomas A. , Brown Margaret R. , Hakim Frances T. , Bare Catherine V. , Leitman Susan F. , Read Elizabeth J. , Carter Charles S. , Wexler Leonard H. , Gress Ronald E. 
Published: October 2019

AbstractAdministration of mobilized peripheral blood progenitor cells (PBPCs) after high-dose chemotherapy rapidly restores multilineage hematopoiesis, but the ability of such products to restore lymphocyte populations remains unclear. In this report, we evaluated immune reconstitution in a series of patients treated with sequential cycles of high-dose chemotherapy, followed by autologous PBPC infusions (median CD34+ cell dose 7.2 × 106 cells/kg [range 2-29.3]). Although patients experienced rapid reconstitution of B cells and CD8+ T cells, we observed CD4 depletion and diminished immune responsiveness in all patients for several months after completion of therapy. Mature CD4+ T cells contained within the grafts did not appear to contribute substantially to immune reconstitution because CD4 counts did not differ between recipients of unmanipulated T-cell replete infusions versus CD34 selected, T-cell–depleted infusions. Rather, at 12 months after therapy, total CD4 count was inversely proportional to age (ρ = −0.78,P = .04), but showed no relationship to CD34 cell dose (ρ = −0.42, P = .26), suggesting that age-related changes within the host are largely responsible for the limited immune reconstitution observed. These results demonstrate that in the autologous setting, the infusion of large numbers of PBPCs is not sufficient to restore T-cell immune competence and emphasize that specific approaches to enhance immune reconstitution are necessary if immune-based therapy is to be used to eradicate minimal residual disease after autologous PBPC transplantation.
Immunohistochemical staining for megakaryocyte c-mpl may complement morphologic distinction between polycythemia vera and secondary erythrocytosis
Authors: Tefferi Ayalew , Yoon Soo-Young , Li Chin-Yang 
Published: October 2019

Abstract
Recent studies have shown decreased megakaryocyte expression of the thrombopoietin receptor (c-mpl) in patients with polycythemia vera (PV) but not in those with reactive erythrocytosis. We examined the diagnostic utility of this observation in 22 patients with PV, 7 patients with secondary erythrocytosis (SE), and 10 normal controls. Commercial antibodies against c-mpl were used with standard immunoperoxidase methods. Megakaryocyte c-mpl staining intensity was uniformly moderate-to-strong in the healthy controls and in all the patients with SE. In contrast, staining intensity in 9 patients with PV (41%) was uniformly weak. Furthermore, in 12 of the remaining 13 patients with PV, the c-mpl staining pattern in each case was heterogeneous and was associated with weak staining intensity in more than 20% of the megakaryocyte population. These preliminary data suggest that c-mpl immunostains may complement bone marrow histopathology in distinguishing PV from nonclonal causes of erythrocytosis.
Impairment of lymphopoiesis and myelopoiesis in mice reconstituted with bone marrow–hematopoietic progenitor cells expressing SDF-1–intrakine
Authors: Onai Nobuyuki , Zhang Yan-yun , Yoneyama Hiroyuki , Kitamura Toshio , Ishikawa Sho , Matsushima Kouji 
Published: October 2019

Abstract
Both SDF-1 and CXCR4 disruption are lethal to mice at the embryonic stage and cause abnormalities in B lymphopoiesis, myelopoiesis, cardiogenesis, vasculogenesis, and cerebellar development. To investigate the role of SDF-1 and CXCR4 in hematopoiesis during the adult stage, mice reconstituted with bone marrow–derived hematopoietic progenitor cells transduced with either the SDF-1 or a genetically modified SDF-1–intrakine gene using a retroviral expression vector were analyzed. Flow cytometric (FCM) analysis showed a dramatic reduction of CXCR4 expression on the cells of intrakine-transduced mice, whereas CCR7 and CCR1 expression was unchanged or marginally decreased on splenocytes. Migration of splenocytes and bone marrow cells to SDF-1 was markedly suppressed in intrakine-transduced mice. FCM analysis of bone marrow cells of intrakine-transduced mice exhibited decreased numbers of pro-B (B220+ CD43+), pre-B (B220+CD43−), and immature B (B220+IgM+) cells and a decreased number of granulocytes/myeloid (Gr1+ CD11b+) cells. Impaired B lymphopoiesis and myelopoiesis in intrakine-transduced mice were confirmed by an in vitro colony-forming assay of bone marrow cells. In contrast, B lymphopoiesis and myelopoiesis were enhanced in SDF-1–transduced mice. Interestingly, T-cell maturation in the thymus was impaired both in intrakine- and SDF-1–transduced mice, suggesting that SDF-1 and CXCR4 play an important role in T lymphopoiesis as well as in B lymphopoiesis and myelopoiesis in adults. These results demonstrate an essential role of CXCR4 and its ligand SDF-1 in adult hematopoiesis, and they indicate the intrakine method as a powerful tool for functional analysis of chemokines/chemokine receptors in vivo and as a potential therapeutic approach for acquired immunodeficiency syndrome.
Recovery of immune reactivity after T-cell–depleted bone marrow transplantation depends on thymic activity
Authors: Roux Etienne , Dumont-Girard Florence , Starobinski Michel , Siegrist Claire-Anne , Helg Claudine , Chapuis Bernard , Roosnek Eddy 
Published: October 2019

Abstract
To evaluate the importance of the thymus for the reconstitution of immunity in recipients of a T-cell–depleted bone marrow, we measured the appearance of CD4+CD45RA+RO−naive T cells (thymic rebound), restoration of the diversity of the T-cell–receptor (TCR) repertoire and the response to vaccinations with tetanus toxoid (TT). Repopulation by CD4+CD45RA+RO− thymic emigrants varied among patients, starting at approximately 6 months after transplantation. Young patients reconstituted swiftly, whereas in older patients, the recovery of normal numbers of naive CD4+ T cells could take several years. Restoration of TCR diversity was correlated with the number of naive CD4+CD45RA+RO− T cells. Moreover, the extent of the thymic rebound correlated with the patient's capacity to respond to vaccinations. Patients without a significant thymic rebound at the moment of vaccination (CD4+CD45RA+RO− T cells less than 30 μL) did not respond, or responded only marginally even after 3 boosts with TT. We conclude that during the first year after transplantation, the absence of an immune response is due mainly to the loss of an adequate T-cell repertoire. Restoration of the repertoire can come only from a thymic rebound that can be monitored by measuring the increase of CD4+CD45RA+RO−naive T cells. This will allow postponing revaccinations to a moment when the patient will be able to respond more effectively. This may be particularly useful in the elderly patient who, owing to low thymic activity, might not yet be able to respond 1 year after transplant when revaccinations are usually scheduled.
Changes in acquired immunodeficiency syndrome–related lymphoma since the introduction of highly active antiretroviral therapy
Authors: Matthews Gail V. , Bower Mark , Mandalia Sundhiya , Powles Tom , Nelson Mark R. , Gazzard Brian G. 
Published: October 2019

Abstract
Clinical data on 7840 HIV-positive patients, representing 43 745 patient-years of follow-up, has been collected. All patients with ARL since 1986 (n = 150) were assessed at presentation for prognostic factors and outcomes recorded. Comparisons are made between cases in the pre-HAART era (1988-1995), and the HAART era (1996-1999). Statistical models are used to calculate the incidence of ARL and factors predicting its development. The incidence of ARL has not changed over time (3 to 7 of 1000 patients per year,P = .933), but contributes to a greater percentage of first AIDS-defining illnesses (ADI) in the HAART era (P ≤ .0001). Older age, nadir CD4 count, and no prior HAART use, predict the development of ARL. There has been no change in stage at presentation, presence of B symptoms, performance status, or marrow involvement between the 2 time cohorts or between patients with or without prior HAART exposure. Similarly, there is no difference in survival duration between the pre-HAART and HAART era (log rankP = .15) or specifically in patients treated with HAART before ARL diagnosis (log rank P = .12). The use of HAART has not yet been shown to influence the incidence or survival of ARL. However, because nadir CD4 count and use of HAART are independent predictors of ARL development, this may translate into a future fall in new cases.
Secretory phospholipase A2 predicts impending acute chest syndrome in sickle cell disease
Authors: Styles Lori A. , Aarsman Anton J. , Vichinsky Elliott P. , Kuypers Frans A. 
Published: October 2019

Abstract
Acute chest syndrome (ACS) is the leading cause of death in sickle cell disease. Severe ACS often develops in the course of a vaso-occlusive crisis (VOC), but currently there are no predictors for its development. Secretory phospholipase A2(sPLA2), a potent inflammatory mediator, is elevated in ACS, and previous work suggests that sPLA2 predicts impending ACS. We prospectively evaluated sPLA2concentration during 21 admissions for VOC; 6 of these patients went on to develop ACS. Elevation of sPLA2 was detected all 6 patients 24 to 48 hours before ACS was clinically diagnosed. Adding the requirement for fever raised the specificity of sPLA2 to 87% while retaining 100% sensitivity. These data indicate that sPLA2 can be useful in alerting the clinician to patients with impending ACS. In addition, sPLA2 may be useful for instituting early therapies to prevent or reduce the clinical morbidity of ACS.
Drug-resistant human cytomegalovirus infection in children after allogeneic stem cell transplantation may have different clinical outcomes
Authors: Eckle Tobias , Prix Lothar , Jahn Gerhard , Klingebiel Thomas , Handgretinger Rupert , Selle Barbara , Hamprecht Klaus 
Published: October 2019

Abstract
Three seropositive pediatric recipients of allogeneic stem cell transplantation out of a group of 42 patients receiving T-cell–depleted, unrelated transplants and 37 patients receiving T-cell–depleted, haploidentical transplants were monitored longitudinally for human cytomegalovirus (HCMV) infection and the emergence of antiviral drug resistance. Early in the posttransplant course, all 3 patients developed HCMV mutations conferring drug resistance to ganciclovir. One child additionally developed multidrug resistance to foscarnet and cidofovir, with mutations in the viral phosphotransferase gene (UL97) and the DNA-polymerase gene (UL54) being found. These data show that resistant HCMV infection does not necessarily correlate with a severe clinical outcome. The early detection of genotypic resistance up to 129 days before the emergence of phenotypic resistance and the dissociation of resistance patterns among different body sites emphasize the importance of genotypic analyses of different DNA specimens for an efficient antiviral therapy. T-cell–depleted children having transplantation might be at an increased risk for the development of drug resistance.
Infliximab for pediatric patients with ulcerative colitis: a phase 3, open-label, uncontrolled, multicenter trial in Japan
Authors: Tajiri Hitoshi , Arai Katsuhiro , Kagimoto Seiichi , Kunisaki Reiko , Hida Nobuyuki , Sato Noriko , Yamada Hiroshi , Nagano Mieko , Susuta Yutaka , Ozaki Kunihiko , Kondo Kazuoki , Hibi Toshifumi 
Published: October 2019

Abstract

Background
Pediatric ulcerative colitis (UC) is typically more extensive and has a more active disease course than adult UC, and requires early treatment augmentation to achieve and maintain disease remission. The present study aimed to investigate the efficacy, safety, and pharmacokinetic profile of infliximab (IFX) in pediatric patients with moderate-to-severe UC and inadequate response to existing treatment.

Methods
This open-label, uncontrolled, multicenter, Phase 3 trial was conducted at 17 centers in Japan between April 2012 and September 2014. Pediatric patients (aged 6–17 years) diagnosed with moderate-to-severe UC received a treatment protocol comprising 5 mg/kg IFX at Weeks 0, 2, and 6, and Clinical Activity Index (CAI)-based responders at Week 8 also received treatment at 8-week intervals at Weeks 14 and 22, with a final evaluation at Week 30.

Results
A total of 21 patients were treated in this study. IFX therapy rapidly improved clinical symptoms, and this effect was maintained for up to 30 weeks. Overall CAI-based remission rate was 42.9% and overall Pediatric Ulcerative Colitis Activity Index (PUCAI)-based remission rate was 19.0%. Median partial Mayo score was 6.0 at baseline and 4.0 at Week 30 (overall). Among the eight patients who underwent sigmoidoscopy, Mayo response was achieved at Week 30 (overall) in three patients (37.5%). Trough serum IFX concentrations in Week 8 CAI-based responders were maintained throughout the study period. Adverse events and serious adverse events were observed in 95.2 and 14.3% of patients, respectively.

Conclusions
These results support the use of IFX in the treatment of pediatric patients with UC with inadequate response to existing treatment.

Trial registration
ClinicalTrials.gov, registration number: NCT01585155.
What are the information needs of parents caring for a child with Glutaric aciduria type 1?
Authors: Piercy Hilary , Yeo Mildrid , Yap Sufin , Hart Anthony R. 
Published: October 2019

Abstract

Background
Newborn screening has enabled the early diagnosis of Glutaric aciduria type 1, with the possibility of improving neurological outcomes in affected children. Achieving those outcomes requires parents to effectively manage their child’s condition by adherence to a strict dietary regime and responding to situations that may trigger decompensation. The specific information and support needs of this group of parents are unknown.

Methods
A focus group with five parents was conducted to gain insights into the information that parents needed and the ways in which they accessed and used information to manage their child’s condition. A topic guide was used to direct the discussion which was recorded and fully transcribed. All participants gave informed consent. Data were analysed using thematic analysis, a structured approach that contributes to transparency and validity of results while allowing the integration of predetermined and emerging themes. To ensure rigour, two researchers were involved in initial coding of data and key analytic decisions.

Results
Two main themes were identified. ‘Understanding the condition’ explored parent’s needs to understand the scientific complexity of the condition and to be aware of the worst case scenario associated with loss of metabolic control. ‘Managing the condition’ explained how parents co-ordinated and controlled the involvement of other carers and parents’ need to be active partners in medical management to feel in control of the situation.

Conclusions
The study highlights the importance of addressing parents’ initial and ongoing informational needs so they can fulfil their role and protect their child from metabolic harm.
Is there any benefit to adding students to the European council on chiropractic education evaluation teams and general council? An audit of stakeholders
Authors: Peterson Cynthia , Miller Joyce , Humphreys B. Kim , Vall Ken 
Published: October 2019

Abstract

Background
The European Council on Chiropractic Education (ECCE) is currently the only chiropractic specific accrediting body in the world to include students as equal members on Council and accreditation evaluation teams. Therefore, the purpose of this study is to evaluate feedback from four ECCE stakeholder groups regarding the effectiveness of chiropractic students on ECCE General Council and evaluation teams.

Methods
This was a mixed-methods audit using questionnaires including closed statements requesting level of agreement and open-ended statements requesting written responses. The proportion of responses falling into the five categorical options for level of agreement was calculated for each questionnaire using descriptive statistics. The analysis of the two statements per questionnaire requiring written responses used a modified ‘thematic analysis’ approach. Three researchers independently identified themes from the written responses. They then met to agree the final themes for each statement.

Results
The response rates for the four questionnaires ranged from 87 to 100%. Feedback regarding ‘Student members on General Council’ was the least positive with 65% neutral or negative regarding ‘students being prepared for meetings’. Feedback from stakeholders regarding use of students on evaluation teams was universally positive, ranging from 82.4–100% Strongly Agreeing or Agreeing with each closed statement.
Themes were identified for each open statement. The unique contribution students make to evaluation teams was most common. General Council feedback identified ‘lack of student preparation’ and ‘the short time period of student membership’ as important themes.

Conclusions
This study demonstrates the unique and positive contributions chiropractic students make to accreditation evaluation teams. The results were less positive concerning students on ECCE General Council due to the lack of specific training for their roles and the short time-frame of their membership. Therefore, the ECCE has created training workshops and expanded the time period for students on Council in order to address these issues.
A Consensus on the Diagnosis and Treatment of Acromegaly Comorbidities: An Update
Authors: Giustina Andrea , Barkan Ariel , Beckers Albert , Biermasz Nienke , Biller Beverly M K , Boguszewski Cesar , Bolanowski Marek , Bonert Vivien , Bronstein Marcello D , Casanueva Felipe F , Clemmons David , Colao Annamaria , Ferone Diego , Fleseriu Maria , Frara Stefano , Gadelha Monica R , Ghigo Ezio , Gurnell Mark , Heaney Anthony P , Ho Ken , Ioachimescu Adriana , Katznelson Laurence , Kelestimur Fahrettin , Kopchick John , Krsek Michal , Lamberts Steven , Losa Marco , Luger Anton , Maffei Pietro , Marazuela Monica , Mazziotti Gherardo , Mercado Moises , Mortini Pietro , Neggers Sebastian , Pereira Alberto M , Petersenn Stephan , Puig-Domingo Manel , Salvatori Roberto , Shimon Ilan , Strasburger Christian , Tsagarakis Stylianos , van der Lely A J , Wass John , Zatelli Maria Chiara , Melmed Shlomo 
Published: October 2019

AbstractObjectiveThe aim of the Acromegaly Consensus Group was to revise and update the consensus on diagnosis and treatment of acromegaly comorbidities last published in 2013.ParticipantsThe Consensus Group, convened by 11 Steering Committee members, consisted of 45 experts in the medical and surgical management of acromegaly. The authors received no corporate funding or remuneration.EvidenceThis evidence-based consensus was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence following critical discussion of the current literature on the diagnosis and treatment of acromegaly comorbidities.Consensus ProcessAcromegaly Consensus Group participants conducted comprehensive literature searches for English-language papers on selected topics, reviewed brief presentations on each topic, and discussed current practice and recommendations in breakout groups. Consensus recommendations were developed based on all presentations and discussions. Members of the Scientific Committee graded the quality of the supporting evidence and the consensus recommendations using the GRADE system.ConclusionsEvidence-based approach consensus recommendations address important clinical issues regarding multidisciplinary management of acromegaly-related cardiovascular, endocrine, metabolic, and oncologic comorbidities, sleep apnea, and bone and joint disorders and their sequelae, as well as their effects on quality of life and mortality.
The general position problem and strong resolving graphs
Authors: Klavžar Sandi , Yero Ismael G. 
Published: October 2019

Abstract
The general position number gp(G) of a connected graph G is the cardinality of a largest set S of vertices such that no three pairwise distinct vertices from S lie on a common geodesic. It is proved that gp(G) ≥ ω(GSR), where GSR is the strong resolving graph of G, and ω(GSR) is its clique number. That the bound is sharp is demonstrated with numerous constructions including for instance direct products of complete graphs and different families of strong products, of generalized lexicographic products, and of rooted product graphs. For the strong product it is proved that gp(G ⊠ H) ≥ gp(G)gp(H), and asked whether the equality holds for arbitrary connected graphs G and H. It is proved that the answer is in particular positive for strong products with a complete factor, for strong products of complete bipartite graphs, and for certain strong cylinders.
Continuous linear operators on Orlicz-Bochner spaces
Authors: Nowak Marian 
Published: October 2019

Abstract
Let (Ω, Σ, μ) be a complete σ-finite measure space, φ a Young function and X and Y be Banach spaces. Let Lφ(X) denote the corresponding Orlicz-Bochner space and
$\begin{array}{}
\displaystyle
\mathcal T^\wedge_\varphi
\end{array}$ denote the finest Lebesgue topology on Lφ(X). We examine different classes of (
$\begin{array}{}
\displaystyle
\mathcal T^\wedge_\varphi
\end{array}$, ∥ ⋅ ∥Y)-continuous linear operators T : Lφ(X) → Y: weakly compact operators, order-weakly compact operators, weakly completely continuous operators, completely continuous operators and compact operators. The relationships among these classes of operators are established.