bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-specific recognition of human myeloma cells by idiotype-induced CD8+ T cells
Authors: Li Yiwen , Bendandi Maurizio , Deng Yuping , Dunbar Cynthia , Munshi Nikhil , Jagannath Sundar , Kwak Larry W. , Lyerly H. Kim 
Published: October 2019

AbstractImmunoglobulin secreted by myeloma cells contains a unique antigenic determinant (idiotype [Id]) that may serve as a tumor-specific antigen. Although Id-protein–specific T-cell responses have been reported in patients with myeloma, it is not known whether primary myeloma tumor cells can present naturally processed Id peptides on their surface as a target. We immunized 2 healthy human stem-cell donors with Id proteins from their recipients. T cells from the immunized donors released high levels of T-helper 1–type cytokines in response to stimulation with myeloma cells from their recipients. The T-cell–mediated cytokine response to tumor cells was blocked by a major histocompatibility complex (MHC) class I monoclonal antibody, whereas the response to soluble Id protein was dependent on MHC class II. To investigate whether Id-specific CD8+ T cells can recognize and kill autologous myeloma cells, we generated T cells from peripheral blood mononuclear cells from a third patient with myeloma by means of in vitro stimulation with autologous dendritic cells pulsed with Id protein. Tumor-specific lysis of myeloma cells was demonstrated by the lack of killing of autologous nonmalignant B cells or natural killer–sensitive K562 cells. Lysis of autologous myeloma targets was restricted by MHC class I molecules. These data represent the first report of class I–restricted T-cell recognition of fresh autologous myeloma targets and formally demonstrate that human myeloma cells can serve as targets of an Id-specific T-cell response.
Down-regulation of the chemokine receptor CCR5 by activation of chemotactic formyl peptide receptor in human monocytes
Authors: Shen Weiping , Li Baoqun , Wetzel Michele A. , Rogers Thomas J. , Henderson Earl E. , Su Shao Bo , Gong Wanghua , Le Yingying , Sargeant Robert , Dimitrov Dimiter S. , Oppenheim Joost J. , Wang Ji Ming 
Published: October 2019

AbstractInteractions between cell surface receptors are important regulatory elements in the complex host responses to infections. In this study, it is shown that a classic chemotactic factor, the bacterial chemotactic peptide N-formyl-methionyl-leucylphenyl-alanine (fMLF), rapidly induced a protein-kinase-C–mediated serine phosphorylation and down-regulation of the chemokine receptor CCR5, which serves as a major human immunodeficiency virus (HIV)-1 coreceptor. The fMLF binding to its receptor, formyl peptide receptor (FPR), resulted in significant attenuation of cell responses to CCR5 ligands and in inhibition of HIV-1-envelope-glycoprotein–mediated fusion and infection of cells expressing CD4, CCR5, and FPR. The finding that the expression and function of CCR5 can be regulated by peptides that use an unrelated receptor may provide a novel approach to the design of anti-inflamatory and antiretroviral agents.
A minimal c-fes cassette directs myeloid-specific expression in transgenic mice
Authors: Heydemann Ahlke , Warming Soren , Clendenin Cynthia , Sigrist Kirsten , Hjorth J. Peter , Simon M. Celeste 
Published: October 2019

AbstractThe c-fes proto-oncogene encodes a 92-kd protein tyrosine kinase whose expression is restricted largely to myeloid and endothelial cells in adult mammals. A 13.2-kilobase (kb) humanc-fes genomic fragment was previously shown to containcis-acting element(s) sufficient for a locus control function in bone marrow macrophages. Locus control regions (LCRs) confer transgene expression in mice that is integration site independent, copy number dependent, and similar to endogenous murine messenger RNA levels. To identify sequences required for this LCR,c-fes transgenes were analyzed in mice. Myeloid-cell–specific, deoxyribonuclease-I–hypersensitive sites localized to the 3′ boundary of exon 1 and intron 3 are required to confer high-level transgene expression comparable to endogenous c-fes, independent of integration site. We define a minimal LCR element as DNA sequences (nucleotides +28 to +2523 relative to the transcription start site) located within intron 1 to intron 3 of the human locus. When this 2.5-kb DNA fragment was linked to a c-fes complementary DNA regulated by its own 446–base-pair promoter, integration-site–independent, copy-number–dependent transcription was observed in myeloid cells in transgenic mice. Furthermore, this 2.5-kb cassette directed expression of a heterologous gene (enhanced green fluorescent protein) exclusively in myeloid cells. The c-fes regulatory unit represents a novel reagent for targeting gene expression to macrophages and neutrophils in transgenic mice.
Role of SCL/Tal-1, GATA, and Ets transcription factor binding sites for the regulation of Flk-1 expression during murine vascular development
Authors: Kappel Andreas , Schlaeger Thorsten M. , Flamme Ingo , Orkin Stuart H. , Risau Werner , Breier Georg 
Published: October 2019

AbstractThe receptor tyrosine kinase Flk-1 is essential for embryonic blood vessel development and for tumor angiogenesis. To identify upstream transcriptional regulators of Flk-1, the gene regulatory elements that mediate endothelium-specific expression in mouse embryos were characterized. By mutational analysis, binding sites for SCL/Tal-1, GATA, and Ets transcription factors located in theFlk-1 enhancer were identified as critical elements for the endothelium-specific Flk-1 gene expression in transgenic mice. c-Ets1, a transcription factor that is coexpressed withFlk-1 during embryonic development and tumor angiogenesis, activated the Flk-1 promoter via 2 binding sites. One of these sites was required for Flk-1 promoter function in the embryonic vasculature. These results provide the first evidence that SCL/Tal-1, GATA, and Ets transcription factors act upstream ofFlk-1 in a combinatorial fashion to determine embryonic blood vessel formation and are key regulators not only of the hematopoietic program, but also of vascular development.
Kaposi sarcoma is a therapeutic target for vitamin D3receptor agonist
Authors: Masood Rizwan , Nagpal Sunil , Zheng Tong , Cai Jie , Tulpule Anil , Smith D. Lynne , Gill Parkash S. 
Published: October 2019

AbstractKaposi sarcoma (KS) is responsive to a number of different steroid hormones, such as glucocorticoids and retinoids. An active metabolite of vitamin D, 1α,25 dihydroxyvitamin D3, was used to study the effect of this steroid hormone in KS. Steroid hormones exert their effect through their cognate nuclear receptors, which for vitamin D metabolites is the vitamin D receptor (VDR). It was first shown that KS cell lines and primary tumor tissue express high levels of VDR, whereas endothelial cells had minimal expression and fibroblasts had no expression. Second, KS cell growth was inhibited by VDR agonist 1α,25 dihydroxyvitamin D3 with a 50% inhibitory concentration of 5 × 10 −8 mol/L, whereas endothelial cells and fibroblast cells showed no response. Studies on the mechanism of KS tumor growth inhibition by 1α,25 dihydroxyvitamin D3 showed that production of autocrine growth factors interleukin (IL)-6 and IL-8 was reduced in a dose-dependent manner, whereas no effect was observed on vascular endothelial growth factor and basic fibroblast growth factor. Transcription initiated at the IL-6 promoter was repressed by VDR agonist. The DNA sequences required to mediate this repression were localized to nucleotides −225/−110 in the 5′-flanking region. The antitumor activity of VDR agonists was also confirmed in KS tumor xenograft and after topical application in patients with KS. 1α,25 Dihydroxyvitamin D3 and its analogs may thus be candidates for clinical development in KS.
Altered ligand binding and transcriptional regulation by mutations in the PML/RARα ligand-binding domain arising in retinoic acid–resistant patients with acute promyelocytic leukemia
Authors: Côté Sylvie , Zhou Dacheng , Bianchini Andrea , Nervi Clara , Gallagher Robert E. , Miller Wilson H. 
Published: October 2019

AbstractAcute promyelocytic leukemia (APL) is characterized by a specific translocation, t(15;17), that fuses the promyelocytic leukemia (PML) gene with the RA receptor RARα. Pharmacologic doses of retinoic acid (RA) induce differentiation in human APL cells and complete clinical remissions. Unfortunately, APL cells develop resistance to RA in vitro and in vivo. Recently, mutations in PML/RARα have been described in APL cells from patients clinically resistant to RA therapy. The mutations cluster in 2 regions that are involved in forming the binding pocket for RA. These mutant PML/RARα proteins have been expressed in vitro, which shows that they cause a diversity of alterations in binding to ligand and to nuclear coregulators of transcription, leading to varying degrees of inhibition of retinoid-induced transcription. This contrasts with the nearly complete dominant negative activity of mutations in PML/RARα previously characterized in cell lines developing RA resistance in vitro. Current data from this study provide additional insight into the molecular mechanisms of resistance to RA and suggest that alterations in the ability of mutants to interact with coregulators can be determinant in the molecular mechanism of resistance to RA. In particular, ligand-induced binding to the coactivator ACTR correlated better with transcriptional activation of RA response elements than the ligand-induced release of the corepressor SMRT. The diversity of effects that are seen in patient-derived mutations may help explain the partial success to date of attempts to overcome this mechanism of resistance in patients by the clinical use of histone deacetylase inhibitors.
Acute systemic inflammatory response to lipopolysaccharide stimulation in pigs divergently selected for residual feed intake
Authors: Liu Haibo , Feye Kristina M. , Nguyen Yet T. , Rakhshandeh Anoosh , Loving Crystal L. , Dekkers Jack C. M. , Gabler Nicholas K. , Tuggle Christopher K. 
Published: October 2019

AbstractBackgroundIt is unclear whether improving feed efficiency by selection for low residual feed intake (RFI) compromises pigs’ immunocompetence. Here, we aimed at investigating whether pig lines divergently selected for RFI had different inflammatory responses to lipopolysaccharide (LPS) exposure, regarding to clinical presentations and transcriptomic changes in peripheral blood cells.ResultsLPS injection induced acute systemic inflammation in both the low-RFI and high-RFI line (n = 8 per line). At 4 h post injection (hpi), the low-RFI line had a significantly lower (p = 0.0075) mean rectal temperature compared to the high-RFI line. However, no significant differences in complete blood count or levels of several plasma cytokines were detected between the two lines. Profiling blood transcriptomes at 0, 2, 6, and 24 hpi by RNA-sequencing revealed that LPS induced dramatic transcriptional changes, with 6296 genes differentially expressed at at least one time point post injection relative to baseline in at least one line (n = 4 per line) (|log2(fold change)| ≥ log2(1.2);q < 0.05). Furthermore, applying the same cutoffs, we detected 334 genes differentially expressed between the two lines at at least one time point, including 33 genes differentially expressed between the two lines at baseline. But no significant line-by-time interaction effects were detected. Genes involved in protein translation, defense response, immune response, and signaling were enriched in different co-expression clusters of genes responsive to LPS stimulation. The two lines were largely similar in their peripheral blood transcriptomic responses to LPS stimulation at the pathway level, although the low-RFI line had a slightly lower level of inflammatory response than the high-RFI line from 2 to 6 hpi and a slightly higher level of inflammatory response than the high-RFI line at 24 hpi.ConclusionsThe pig lines divergently selected for RFI had a largely similar response to LPS stimulation. However, the low-RFI line had a relatively lower-level, but longer-lasting, inflammatory response compared to the high-RFI line. Our results suggest selection for feed efficient pigs does not significantly compromise a pig’s acute systemic inflammatory response to LPS, although slight differences in intensity and duration may occur.
Recurrent post-partum rhombencephalitis associated with anti-centromere antibody: a case report
Authors: Jin Andy , Mamelona Jean , Harper Byrne , Marrero Alier 
Published: October 2019

Abstract

Background
Rhombencephalitis (RE) is a serious condition of the brain with multiple etiologies. We report a unique case of recurrent, postpartum RE that is associated with positive anti-centromere antibody (ACA). A discussion of the case, current literature on autoimmune RE and related autoantibodies are reviewed.

Case presentation
A healthy 33-year-old Caucasian patient (gravida 2, para 2) had two episodes of progressive focal neurological deficits during postpartum periods. Signs and symptoms included right-sided dysmetria, adiadochokinesia, weakness, ataxia, and photophobia. MRI revealed rhombencephalitis involving the mesencephalon of the brainstem. Extensive and comprehensive investigations using blood and cerebrospinal fluid (CSF) were consistently positive only for ACA. The first episode was successfully treated with empiric antimicrobial agents and steroid. Given the negative infectious work up with the prior episode and the nearly identical clinical presentations, the second episode was treated with corticosteroid only. This led to complete resolution of her symptoms and reversal of the brain magnetic resonance imaging (MRI) lesions.

Conclusion
To the author's knowledge, this is the first report of a primary autoimmune RE during postpartum period that is associated with ACA. Immunologic causes should be considered early with any encephalitis. Given the risk of recurrence, relapse, and neurologic deterioration, regular monitoring is recommended, especially for female patients of child-bearing age. Consistent with the current literature on autoimmune RE, steroid seems to be an effective treatment for ACA-associated RE.
A mixed methods evaluation of an integrated adult mental health service model
Authors: Beere Diana , Page Imogen S. , Diminic Sandra , Harris Meredith 
Published: October 2019

Abstract

Background
The Floresco integrated service model was designed to address the fragmentation of community mental health treatment and support services. Floresco was established in Queensland, Australia, by a consortium of non-government organisations that sought to partner with general practitioners (GPs), private mental health providers and public mental health services to operate a ‘one-stop’ mental health service hub.

Methods
We conducted an independent mixed-methods evaluation of client outcomes following engagement with Floresco (outcome evaluation) and factors influencing service integration (process evaluation). The main data sources were: (1) routinely-collected Recovery Assessment Scale — Domains and Stages (RAS–DS) scores at intake and review (n = 108); (2) RAS–DS scores, mental health inpatient admissions and emergency department (ED) presentations among clients prospectively assessed at intake and six-month follow-up (n = 37); (3) semi-structured interviews with staff from Floresco, consortium partners, private practitioners and the local public mental health service (n = 20); and (4) program documentation.

Results
Interviews identified staff commitment, co-location of services, flexibility in problem-solving, and anecdotal evidence of positive client outcomes as important enablers of service integration. Barriers to integration included different organisational practices, difficulties in information-sharing and in attracting and retaining GPs and private practitioners, and systemic constraints on integration with public mental health services. Of 1129 client records, 108 (9.6%) included two RAS–DS measurements, averaging 5 months apart. RAS–DS ‘total recovery’ scores improved significantly (M = 63.3%, SD = 15.6 vs. M = 69.2%, SD = 16.1; p < 0.001), as did scores on three of the four RAS–DS domains (‘Looking forward’, p < 0.001; ‘Mastering my illness’, p < 0.001; and ‘Connecting and belonging’, p = 0.001). Corresponding improvements, except in ‘Connecting and belonging’, were seen in the 37 follow-up study participants. Decreases in inpatient admissions (20.9% vs. 7.0%), median length of inpatient stay (8 vs. 3 days), ED presentations (34.8% vs. 6.3%) and median duration of ED visits (187 vs. 147 min) were not statistically significant.

Conclusions
Despite the lack of a control group and small follow-up sample size, Floresco’s integrated service model showed potential to improve client outcomes and reduce burden on the public mental health system. Horizontal integration of non-government and private services was achieved, and meaningful progress made towards integration with public mental health services.
Intentions to leave and associated factors among laboratory professionals working at Amhara National Regional State public hospitals, Ethiopia: an institution-based cross-sectional study
Authors: Dellie Endalkachew , Andargie Biks Gashaw , Asrade Geta , Gebremedhin Tsegaye 
Published: October 2019

Abstract

Objective
Laboratory professionals play a vital role in the detection, diagnosis, and treatment of diseases. Knowledge of workplace variables that either motivates staff to keep working or quit their jobs is important for decision making. Thus, this study aimed to assess intentions to leave workplace and associated factors among laboratory professionals working at public hospitals of the Amhara National Regional State, Ethiopia.

Results
An institution-based cross-sectional study was conducted from February 16 to March 14, 2016, among 336 randomly selected laboratory professionals. The study revealed that 65.5% (95% CI 60–70) of professionals had intentions to leave their hospitals. Dissatisfaction with the provision of educational opportunities (AOR: 3.59, 95% CI 1.61–7.99), poor pays and benefits (AOR: 3.89, 95% CI 1.53–9.89), lack of recognition (AOR: 2.69, 95% CI 1.35–5.38), poor working environments (AOR: 2.77, 95% CI 1.45–3.30), high workload (AOR: 1.94, 95% CI 1.04–3.63), low affective commitment (AOR: 2.05, 95% CI 1.10–3.82), and being unmarried (AOR: 2.46, 95% CI 1.32–4.58) were factors significantly associated with intentions to leave. Magnitude of laboratory professionals’ intention to leave was so high. Healthcare policymakers and hospital managers need to develop and institutionalize evidence-based retention strategies to reduce the intention of laboratory professionals to leave their workplace.
Local anaesthesia in dentistry – achieving effective painless injections
Authors: Madadian Matin Ali , Renton Tara 
Published: October 2019

A feared aspect of dental care for patients is their expectation of pain and injections. Local anaesthesia in dentistry is an important means of reducing procedural pain and increasing patient comfort during treatment. However, it can be a source of pain in itself. Fear of needles and painful injections is a significant contributing factor to dental anxiety and is a commonly reported concern among patients. This review aims to discuss modes by which the painless and effective injection can be achieved, exploring the causative factors of discomfort and how they can be modulated. Although a wide array of techniques and technologies exist within the field of local anaesthesia (which are outlined in this paper), there is no definitive method for delivering the perfect injection for each and every patient. By being more mindful of current research and understanding with regards to local anaesthesia, however, clinicians may become more confident in their ability to provide a more atraumatic experience. CPD/Clinical Relevance: The aim of this review is to make clinicians aware of evidence-based suggestions for reducing the discomfort associated with delivering conventional local anaesthesia in routine dental practice, as well as to inform clinicians about alternative modes of administration of local anaesthesia which may serve as adjuncts in the management of anxious patients.
Orthodontic retention: a clinical guide for the GDP
Authors: Alkadhimi Aslam , Sharif Mohammad Owaise 
Published: October 2019

Retention is normally required after active orthodontic tooth movement in order to maintain tooth position and minimize the effects of age-related changes to the dentition. The aim of this article is to define stability, retention and relapse with reference to the literature and to review the evidence with regards to clinical effectiveness of different types of fixed and removable retainers and wear regimens, with emphasis on systematic reviews and Randomized Controlled Trials (RCTs). Furthermore, to discuss the general dental practitioner's role and responsibility in managing patients after active orthodontic treatment. CPD/Clinical Relevance: It is common practice for orthodontists to review patients for one year after active orthodontic treatment. Beyond this period, monitoring of the patient's long-term retention is often carried out in general dental practice. This paper provides an overview of orthodontic retention, including retainer types, wear regimens and a discussion of the common problems associated with retainers and advice on management.
A case of granular cell ameloblastoma presenting as a non-healing socket
Authors: Ahmadi-Lari Nazanin , Wilson Mark , Hughes Ceri , Thomas Steven 
Published: October 2019

This case involves a 46-year-old female who was referred to the Bristol Dental Hospital Oral and Maxillofacial Surgery department with a non-healing socket. Investigations were carried out and biopsy confirmed diagnosis of granular cell ameloblastoma. She was subsequently treated with a segmental resection and a bone graft to reconstruct the defect of her mandible. CPD/Clinical Relevance: This report highlights the significance of taking a full history and carrying out a thorough clinical examination to ensure significant diagnoses are not missed.
Routine exodontia: preventing failed extractions
Authors: Bhargava Vijay , Renton Tara 
Published: October 2019

Dental extractions are potentially an unpleasant experience that patients have to undergo. Not only are they losing a tooth that they may have invested significant costs in retaining, but fear and expectation of pain makes the encounter stressful and terrifying for most.Dental extractions are the most common surgery undertaken worldwide, and usually on conscious patients, unlike other branches of surgery. Patients' most common fear of the dentist is the pain during and after surgery and the experience of injections, both guaranteed when undergoing extractions at the dentist.Despite universities aiming to make undergraduate dentists able to undertake routine exodontia, ability remains limited. This may be due to foundation training limiting access to routine exodontia practice or a reluctance on behalf of dentists in general to undertake surgical interventions due to their high risk, patient sequelae or risk of complications, which are perceived as poor practice builders.CPD/Clinical Relevance: This paper aims to provide some clinical tips and information that will assist practitioners in undertaking dental extractions.
Colonic Ischemia After Vaginal Delivery
Authors: Kim Brian , Tayel Hesham , Chaput Kimberly Jegel 
Published: October 2019

ABSTRACT
Ischemic colitis is a common form of bowel ischemia typically associated with vasculopathy in advanced age. Although some predisposing factors can increase the risk of developing ischemic colitis, the disease is relatively uncommon in young adults. Furthermore, cases of ischemic colitis associated with pregnancy are exceedingly rare. We present a young woman with severe ischemic colitis after vaginal delivery that ultimately led to sigmoid resection due to persistent stricturing.