bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of immunosuppressive activity of human mesenchymal stem cells using murine antigen specific CD4 and CD8 T cells in vitro
Authors: Nazarov Cristina , Surdo Jessica Lo , Bauer Steven R , Wei Cheng-Hong 
Published: October 2013

Abstract
Introduction
Mesenchymal stem cells (MSCs) have immunosuppressive activity. They do not induce allospecific T cell responses, making them promising tools for reducing the severity of graft versus host disease (GVHD) as well as treating various immune diseases. Currently, there is a need in the MSC field to develop a robust in vitro bioassay which can characterize the immunosuppressive function of MSCs.

Methods
Murine clonal CD4 and CD8 T cells were stimulated with cognate peptide antigen and antigen presenting cells (APCs) in the absence or presence of human MSCs, different aspects of T cell activation were monitored and analyzed using flow cytometery, real time RT-PCR and cytokine measurement.

Results
Human MSCs (hMSCs) can alter multiple aspects of murine T cell activation induced by stimulation with specific antigen, including: reduced proliferation, inhibited or stimulated cell surface marker expression (CD25, CD69, CD44 and CD62L), inhibited mRNA expression of transcription factors (T-bet and GATA-3) and decreased cytokine expression (interferon-gamma, interleukin-10). Disappearance of activation-induced cluster formation and decreased apoptosis of CD8 T cells were also observed. Moreover, the effects are specific to MSCs; incubating the T cells with non-MSC control cell lines had no effect on T cell proliferation and activation.

Conclusions
Clonal murine T cells can be used to measure, characterize, and quantify the in vitro immunosuppressive activity of human MSCs, representing a promising approach to improve bioassays for immunosuppression.
Progression in Smoldering Myeloma Is Independently Determined by the Chromosomal Abnormalities del(17p), t(4;14), Gain 1q, Hyperdiploidy, and Tumor Load
Authors: Neben Kai , Jauch Anna , Hielscher Thomas , Hillengass Jens , Lehners Nicola , Seckinger Anja , Granzow Martin , Raab Marc S. , Ho Anthony D. , Goldschmidt Hartmut , Hose Dirk 
Published: October 2013

Purpose The aim of this study was to analyze chromosomal aberrations in terms of frequency and impact on time to progression in patients with smoldering multiple myeloma (SMM) on the background of clinical prognostic factors. Patients and Methods The chromosomal abnormalities 1q21, 5p15/5q35, 9q34, 13q14.3, 15q22, 17p13, t(11;14)(q13;q32), and t(4;14)(p16.3;q32) were assessed in CD138-purified myeloma cells by interphase fluorescent in situ hybridization (iFISH) alongside clinical parameters in a consecutive series of 248 patients with SMM. Results The high-risk aberrations in active myeloma (ie, del(17p13), t(4;14), and +1q21) present in 6.1%, 8.9%, and 29.8% of patients significantly confer adverse prognosis in SMM with hazard ratios (HRs) of 2.90 (95% CI, 1.56 to 5.40), 2.28 (95% CI, 1.33 to 3.91), and 1.66 (95% CI, 1.08 to 2.54), respectively. Contrary to the conditions in active myeloma, hyperdiploidy, present in 43.3% of patients, is an adverse prognostic factor (HR, 1.67; 95% CI, 1.10 to 2.54). Percentage of malignant bone marrow plasma cells assessed by iFISH and combination of M-protein and plasma cell infiltration as surrogates of tumor load significantly confer adverse prognosis with HRs of 4.37 (95% CI, 2.79 to 6.85) and 4.27 (95% CI, 2.77 to 6.56), respectively. In multivariate analysis, high-risk aberrations, hyperdiploidy, and surrogates of tumor load are independently prognostic. Conclusion The high-risk chromosomal aberrations del(17p13), t(4;14), and +1q21 are adverse prognostic factors in SMM just as they are in active myeloma, independent of tumor mass. Hyperdiploidy is the first example for an adverse prognostic factor in SMM of opposite predictiveness in active myeloma. Risk association of chromosomal aberrations is not only a priori treatment dependent (predictive) but is also an intrinsic property of myeloma cells (prognostic).
Dose-Limiting Toxicity After Hypofractionated Dose-Escalated Radiotherapy in Non–Small-Cell Lung Cancer
Authors: Cannon Donald M. , Mehta Minesh P. , Adkison Jarrod B. , Khuntia Deepak , Traynor Anne M. , Tomé Wolfgang A. , Chappell Richard J. , Tolakanahalli Ranjini , Mohindra Pranshu , Bentzen Søren M. , Cannon George M. 
Published: October 2013

Purpose Local failure rates after radiation therapy (RT) for locally advanced non–small-cell lung cancer (NSCLC) remain high. Consequently, RT dose intensification strategies continue to be explored, including hypofractionation, which allows for RT acceleration that could potentially improve outcomes. The maximum-tolerated dose (MTD) with dose-escalated hypofractionation has not been adequately defined. Patients and Methods Seventy-nine patients with NSCLC were enrolled on a prospective single-institution phase I trial of dose-escalated hypofractionated RT without concurrent chemotherapy. Escalation of dose per fraction was performed according to patients' stratified risk for radiation pneumonitis with total RT doses ranging from 57 to 85.5 Gy in 25 daily fractions over 5 weeks using intensity-modulated radiotherapy. The MTD was defined as the maximum dose with ≤ 20% risk of severe toxicity. Results No grade 3 pneumonitis was observed and an MTD for acute toxicity was not identified during patient accrual. However, with a longer follow-up period, grade 4 to 5 toxicity occurred in six patients and was correlated with total dose (P = .004). An MTD was identified at 63.25 Gy in 25 fractions. Late grade 4 to 5 toxicities were attributable to damage to central and perihilar structures and correlated with dose to the proximal bronchial tree. Conclusion Although this dose-escalation model limited the rates of clinically significant pneumonitis, dose-limiting toxicity occurred and was dominated by late radiation toxicity involving central and perihilar structures. The identified dose-response for damage to the proximal bronchial tree warrants caution in future dose-intensification protocols, especially when using hypofractionation.
Surgical treatment of severe congenital thoracolumbar kyphosis through a single posterior approach
Authors: Spiro A. S. , Rupprecht M. , Stenger P. , Hoffman M. , Kunkel P. , Kolb J. P. , Rueger J. M. , Stuecker R. 
Published: October 2013

A combined anterior and posterior surgical approach is generally recommended in the treatment of severe congenital kyphosis, despite the fact that the anterior vascular supply of the spine and viscera are at risk during exposure. The aim of this study was to determine whether the surgical treatment of severe congenital thoracolumbar kyphosis through a single posterior approach is feasible, safe and effective. We reviewed the records of ten patients with a mean age of 11.1 years (5.4 to 14.1) who underwent surgery either by pedicle subtraction osteotomy or by vertebral column resection with instrumented fusion through a single posterior approach. The mean kyphotic deformity improved from 59.9° (45° to 110°) pre-operatively to 17.5° (3° to 40°) at a mean follow-up of 47.0 months (29 to 85). Spinal cord monitoring was used in all patients and there were no complications during surgery. These promising results indicate the possible advantages of the described technique over the established procedures. We believe that surgery should be performed in case of documented progression and before structural secondary curves develop. Our current strategy after documented progression is to recommend surgery at the age of five years and when 90% of the diameter of the spinal canal has already developed. Cite this article: Bone Joint J 2013;95-B:1527–32.
Reverse shoulder replacement after resection of the proximal humerus for bone tumours
Authors: Kaa A. K. S. , Jørgensen P. H. , Søjbjerg J. O. , Johannsen H. V. 
Published: October 2013

We investigated the functional outcome in patients who underwent reverse shoulder replacement (RSR) after removal of a tumour of the proximal humerus. A total of 16 patients (ten women and six men) underwent this procedure between 1998 and 2011 in our hospital. Five patients died and one was lost to follow-up. Ten patients were available for review at a mean follow-up of 46 months (12 to 136). Eight patients had a primary and two patients a secondary bone tumour.At final follow up the mean range of active movement was: abduction 78° (30° to 150°); flexion 98° (45° to 180°); external rotation 32° (10° to 60°); internal rotation 51° (10° to 80°). The mean Musculoskeletal Tumor Society score was 77% (60% to 90%) and the mean Toronto Extremity Salvage Score was 70% (30% to 91%). Two patients had a superficial infection and one had a deep infection and underwent a two-stage revision procedure. In two patients there was loosening of the RSR; one dislocated twice. All patients had some degree of atrophy or pseudo-atrophy of the deltoid muscle.Use of a RSR in patients with a tumour of the proximal humerus gives acceptable results.Cite this article: Bone Joint J 2013;95-B:1551–5.
Effect of early administration of alendronate after surgery for distal radial fragility fracture on radiological fracture healing time
Authors: Uchiyama S. , Itsubo T. , Nakamura K. , Fujinaga Y. , Sato N. , Imaeda T. , Kadoya M. , Kato H. 
Published: October 2013

This multicentre prospective clinical trial aimed to determine whether early administration of alendronate (ALN) delays fracture healing after surgical treatment of fractures of the distal radius. The study population comprised 80 patients (four men and 76 women) with a mean age of 70 years (52 to 86) with acute fragility fractures of the distal radius requiring open reduction and internal fixation with a volar locking plate and screws. Two groups of 40 patients each were randomly allocated either to receive once weekly oral ALN administration (35 mg) within a few days after surgery and continued for six months, or oral ALN administration delayed until four months after surgery. Postero-anterior and lateral radiographs of the affected wrist were taken monthly for six months after surgery. No differences between groups was observed with regard to gender (p = 1.0), age (p = 0.916), fracture classification (p = 0.274) or bone mineral density measured at the spine (p = 0.714). The radiographs were assessed by three independent assessors. There were no significant differences in the mean time to complete cortical bridging observed between the ALN group (3.5 months (se 0.16)) and the no-ALN group (3.1 months (se 0.15)) (p = 0.068). All the fractures healed in the both groups by the last follow-up. Improvement of the Quick-Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, grip strength, wrist range of movement, and tenderness over the fracture site did not differ between the groups over the six-month period. Based on our results, early administration of ALN after surgery for distal radius fracture did not appear to delay fracture healing times either radiologically or clinically. Cite this article: Bone Joint J 2013;95-B:1544–50.
Ponseti casting for club foot – above- or below-knee?
Authors: Maripuri S. N. , Gallacher P. D. , Bridgens J. , Kuiper J. H. , Kiely N. T. 
Published: October 2013

We undertook a randomised clinical trial to compare treatment times and failure rates between above- and below-knee Ponseti casting groups. Eligible children with idiopathic clubfoot, treated using the Ponseti method, were randomised to either below- or above-knee plaster of Paris casting. Outcome measures were total treatment time and the occurrence of failure, defined as two slippages or a treatment time above eight weeks. A total of 26 children (33 feet) were entered into the trial. The above-knee group comprised 17 feet in 13 children (ten boys and three girls, median age 13 days (1 to 40)) and the below-knee group comprised 16 feet in 13 children (ten boys and three girls, median age 13 days (5 to 20)). Because of six failures (37.5%) in the below-knee group, the trial was stopped early for ethical reasons. The rate of failure was significantly higher in the below-knee group (p = 0.039). The median treatment times of six weeks in the below-knee and four weeks in the above-knee group differed significantly (p = 0.01). This study demonstrates that the use of a below-knee plaster of Paris cast in conjunction with the Ponseti technique leads to unacceptably high failure rates and significantly longer treatment times. Therefore, this technique is not recommended. Cite this article: Bone Joint J 2013;95-B:1570–4.
A reliable measurement for identifying a lumbosacral transitional vertebra with a solid bony bridge on a single-slice midsagittal MRI or plain lateral radiograph
Authors: Farshad M. , Aichmair A. , Hughes A. P. , Herzog R. J. , Farshad-Amacker N. A. 
Published: October 2013

The purpose of this study was to devise a simple but reliable radiological method of identifying a lumbosacral transitional vertebra (LSTV) with a solid bony bridge on sagittal MRI, which could then be applied to a lateral radiograph. The vertical mid-vertebral angle (VMVA) and the vertical anterior vertebral angle (VAVA) of the three most caudal segments of the lumbar spine were measured on MRI and/or on a lateral radiograph in 92 patients with a LSTV and 94 controls, and the differences per segment (Diff-VMVA and Diff-VAVA) were calculated. The Diff-VMVA of the two most caudal vertebrae was significantly higher in the control group (25° (sd 8) than in patients with a LSTV (type 2a+b: 16° (sd 9), type 3a+b: -9° (sd 10), type 4: -5° (sd 7); p < 0.001). A Diff-VMVA of ≤ +10° identified a LSTV with a solid bony bridge (type 3+4) with a sensitivity of 100% and a specificity of 89% on MRI and a sensitivity of 94% and a specificity of 74% on a lateral radiograph. A sensitivity of 100% could be achieved with a cut-off value of 28° for the Diff-VAVA, but with a lower specificity (76%) on MRI than with Diff-VMVA. Using this simple method (Diff-VMVA ≤ +10°), solid bony bridging of the posterior elements of a LSTV, and therefore the first adjacent mobile segment, can be easily identified without the need for additional imaging. Cite this article: Bone Joint J 2013;95-B:1533–7.
Circulating Proteolytic Products of Carboxypeptidase N for Early Detection of Breast Cancer
Authors: Li Yaojun , Li Yueguo , Chen Tao , Kuklina Anna S , Bernard Paul , Esteva Francisco J , Shen Haifa , Ferrari Mauro , Hu Ye 
Published: October 2013

Abstract

BACKGROUND
Carboxypeptidase N (CPN) is important in regulating vasoactive peptide hormones, growth factors, and cytokines by specifically cleaving their C-terminal basic residues. We investigated whether circulating peptides specifically cleaved by CPN in the tumor microenvironment can be stage-specific indicators of breast cancer.

METHODS
CPN activity was measured using an ex vivo peptide cleavage assay by incubating synthesized C3f peptide (His6-C3f_S1304-R1320-His6) in interstitial fluids of breast tumors and adjacent normal breast tissues in mice with orthotopic implantation of the human cell line MDA-MB-231. The nature and extent of peptide cleavage by CPN was investigated by fragment profiling using nanopore fractionation and mass spectrometry. The fragment profiles in interstitial fluid correlated with concentrations of CPN-catalyzed peptides in blood samples taken from the tumor-bearing mice, healthy women, and breast cancer patients. CPN expression in the same set of samples was further examined by immunohistochemistry and immunoblotting.

RESULTS
We showed that generation of C3f_R1310-L1319 specifically correlated with the CPN expression level. In both the mouse and clinical patient samples, CPN was clearly increased in tumor tissues compared with normal breast tissue, whereas corresponding CPN abundance in blood remained constant. Concentrations of 6 CPN-catalyzed peptides predominantly increased in sera taken from the mice (n = 8) at 2 weeks after orthotopic implantation. Six homologous peptides displayed significantly higher expression in the patients' plasma as early as the first pathologic stage of breast cancer.

CONCLUSIONS
Circulating CPN-catalyzed peptide concentrations reflect the CPN activity in tumors. These biomarkers show strong potential for the noninvasive and early diagnosis of breast cancer.
Extensive study of human insulin immunoassays: promises and pitfalls for insulin analogue detection and quantification
Authors: Heurtault Béatrice , Reix Nathalie , Meyer Nicolas , Gasser Françoise , Wendling Marie-Josée , Ratomponirina Charline , Jeandidier Nathalie , Sapin Rémy , Agin Arnaud 
Published: October 2013

Abstract

Background: Over the last few decades, new synthetic insulin analogues have been developed. Their measurement is of prime importance in the investigation of hypoglycaemia, but their quantification is hampered by variable cross-reactivity with many insulin assays. For clinical analysis, it has now become essential to know the potential cross-reactivity of analogues of interest.

Methods: In this work, we performed an extensive study of insulin analogue cross-reactivity using numerous human insulin immunoassays. We investigated the cross-reactivity of five analogues (lispro, aspart, glulisine, glargine, detemir) and two glargine metabolites (M1 and M2) with 16 commercial human insulin immunoassays as a function of concentration.

Results: The cross-reactivity values for insulin analogues or glargine metabolites ranged from 0% to 264%. Four assays were more specific to human insulin, resulting in negligible cross-reactivity with the analogues. However, none of the 16 assays was completely free of cross-reactivity with analogues or metabolites. The results show that analogue cross-reactivity, which varies to a large degree, is far from negligible, and should not be overlooked in clinical investigations.

Conclusions: This study has established the cross-reactivity of five insulin analogues and two glargine metabolites using 16 immunoassays to facilitate the choice of the immunoassay(s) and to provide sensitive and specific analyses in clinical routine or investigation.
The Evaluation Criteria of Recruiting Local Staffs for Taiwanese Enterprise in China
Authors: Lu Shih-Tong , Lin Cheng-Wei , Dai Yuan-Fung , Shiue Yih-Chearng 
Published: October 2013

Abstract
Taiwanese enterprises are currently facing competitive challenges in both domestic and international markets as well as being under huge pressure from economic change. They must learn to intensely study this environment to find a suitable place for investment to extend their businesses. Usually, the first priority for an investment location is in mainland China, largely because of the closeness of culture and language, which make it easier to integrate resources between the headquarters in Taiwan and subsidiaries in China. The employment of suitable local staff members in China is very important to the success of business operations. This article reviews the literature related to multinational enterprise staffing selection and the factors that should be considered. These are then categorized into four dimensions and 20 sub-factors that can be used for the recruitment of local staff in China. The fuzzy linguistic preference relation (Fuzzy LinPreRa) approach is employed to assess the importance of these factors. The goal is to help managers reduce the risk of employing inappropriate local staff members and to enhance management effectiveness.
Six-year follow-up of a characteristic osteolytic lesion in a patient with tumor-induced osteomalacia
Authors: Piemonte Sara , Romagnoli Elisabetta , Cipriani Cristiana , De Lucia Federica , Pilotto Roberta , Diacinti Daniele , Pepe Jessica , Minisola Salvatore 
Published: October 2013

ObjectiveTumor-induced osteomalacia is a rare paraneoplastic syndrome characterized by hypophosphatemia and inappropriately normal or low 1,25-dihydroxyvitamin D.Clinical caseHere, we report a 6-year postoperative follow-up of a patient with oncogenic osteomalacia with a distinctive skeletal manifestation. The latter was characterized by an almost linear lytic lesion of a few millimeters with irregular borders, mainly involving the trabecular compartment but extending into cortical shell, located in the middle third of the right fibula. Six years after tumor resection, a sclerotic repair with a complete recovery was observed. Furthermore, we monitored a striking increase in bone mineral density throughout the observation period, reaching a peak of 73% over basal values at lumbar spine after 2 years; at total femur and radius, the peak was 47.5 and 4.6% respectively, after 4 years from tumor resection.ConclusionsWe report for the first time that an osteolytic lesion may be part of the skeletal involvement in tumor-induced osteomalacia.
Systematic screening for PRKAR1A gene rearrangement in Carney complex: identification and functional characterization of a new in-frame deletion
Authors: Guillaud Bataille M , Rhayem Y , Sousa S B , Libé R , Dambrun M , Chevalier C , Nigou M , Auzan C , North M O , Sa J , Gomes L , Salpea P , Horvath A , Stratakis C A , Hamzaoui N , Bertherat J , Clauser E 
Published: October 2013

BackgroundPoint mutations of the PRKAR1A gene are a genetic cause of Carney complex (CNC) and primary pigmented nodular adrenocortical disease (PPNAD), but in 30% of the patients no mutation is detected.ObjectiveSet up a routine-based technique for systematic detection of large deletions or duplications of this gene and functionally characterize these mutations.MethodsMultiplex ligation-dependent probe amplification (MLPA) of the 12 exons of the PRKAR1A gene was validated and used to detect large rearrangements in 13 typical CNC and 39 confirmed or putative PPNAD without any mutations of the gene. An in-frame deletion was characterized by western blot and bioluminescence resonant energy transfer technique for its interaction with the catalytic subunit.ResultsMLPA allowed identification of exons 3–6 deletion in three patients of a family with typical CNC. The truncated protein is expressed, but rapidly degraded, and does not interact with the protein kinase A catalytic subunit.ConclusionsMLPA is a powerful technique that may be used following the lack of mutations detected by direct sequencing in patients with bona fide CNC or PPNAD. We report here one such new deletion, as an example. However, these gene defects are not a frequent cause of CNC or PPNAD.
Spanking and Child Development Across the First Decade of Life
Authors: MacKenzie Michael J. , Nicklas Eric , Waldfogel Jane , Brooks-Gunn Jeanne 
Published: October 2013

OBJECTIVE:To examine the prevalence of maternal and paternal spanking of children at 3 and 5 years of age and the associations between spanking and children’s externalizing behavior and receptive vocabulary through age 9.METHODS:The Fragile Families and Child Well-Being Study, a longitudinal birth cohort study of children in 20 medium to large US cities, was used. Parental reports of spanking were assessed at age 3 and 5, along with child externalizing behavior and receptive vocabulary at age 9 (N = 1933). The data set also included an extensive set of child and family controls (including earlier measures of the child outcomes).RESULTS:Overall, 57% of mothers and 40% of fathers engaged in spanking when children were age 3, and 52% of mothers and 33% of fathers engaged in spanking at age 5. Maternal spanking at age 5, even at low levels, was associated with higher levels of child externalizing behavior at age 9, even after an array of risks and earlier child behavior were controlled for. Father’s high-frequency spanking at age 5 was associated with lower child receptive vocabulary scores at age 9.CONCLUSIONS:Spanking remains a typical rearing experience for American children. These results demonstrate negative effects of spanking on child behavioral and cognitive development in a longitudinal sample from birth through 9 years of age.