bluuebunny/crossref_metadata_2025_split huggingface dataset:
Facilitators and barriers for RhD‐immunized women to become and remain anti‐D donors
Authors: Slootweg Yolentha Maria , Koelewijn Johanna Maria , de Kort Wim L. , de Haas Masja , Merz Eva‐Maria 
Published: March 2018

BACKGROUNDThe successful introduction of prophylaxis with anti‐RhD immunoglobulin has resulted in a significant decline of pregnancy‐related RhD immunizations but also has decreased the availability of naturally immunized women as (new) anti‐D donors. An influx of new donors is necessary to maintain a sufficient pool of anti‐D donors. We investigated motivators, barriers, and predictors for anti‐D donorship in RhD‐immunized women.STUDY DESIGN AND METHODSA mixed‐methods design was applied, including focus group discussions and questionnaires. Two focus groups (including 11 women) served as input for the questionnaire.RESULTSIn total, 47.6% of 750 anti‐D donors and potential donors completed the questionnaire (50.4% donors; 38% nondonors; 11.6% former donors). Almost 70% of the nondonors would have become donors if they had known about the possibility. Travel time investment was reported as a disadvantage; one‐half of donors mentioned no disadvantages. Motivators for anti‐D donorship were “doing something in return” (31.2%) and “preventing others having a sick child or losing a child” (33.9%). In multivariable analysis, living single (odds ratio, 5.8; p = 0.02) and living partnered without resident children (odds ratio, 7.9; p = 0.03), compared with living partnered with children, were predictors for anti‐D donorship. Not being registered as an organ donor (odds ratio, 0.25; p < 0.001) predicted that the individual would not be an anti‐D donor.CONCLUSIONThe main barrier for anti‐D donorship was a lack of knowledge. Positive predictors of anti‐D donorship were living without resident children, altruism, and being registered as an organ donor. A blood bank should develop targeted recruitment strategies with a focus on spreading knowledge about anti‐D donorship among RhD‐immunized women.
Clinical‐scale production of cGMP compliant CD3/CD19 cell‐depleted NK cells in the evolution of NK cell immunotherapy at a single institution
Authors: Williams Shelly M. , Sumstad Darin , Kadidlo Diane , Curtsinger Julie , Luo Xianghua , Miller Jeffrey S. , McKenna David H. 
Published: March 2018

BACKGROUNDAllogeneic natural killer (NK) cell adoptive immunotherapy is a growing therapeutic option for patients. Clinical‐scale production of NK cells using immunomagnetic selection complies with current good manufacturing practices (cGMPs) and allows for closed‐system, automated purification. We report our experience with CD3/CD19 cell‐depleted (CD3/CD19dep) NK cell production and compare to previous methods of CD3 cell depletion and CD3 cell depletion/CD56 cell enrichment.STUDY DESIGN AND METHODSNonmobilized mononuclear cells collected by apheresis were incubated with anti‐CD3/anti‐CD19 microbeads and depleted in an automated cell selection system (CliniMACS, Miltenyi). The NK cell–enriched products were incubated overnight in interleukin (IL)‐2 or IL‐15, washed, and resuspended prior to lot release testing and infusion.RESULTSSince 2010, 94 freshly infusible CD3/CD19dep NK cell products were manufactured in support of eight clinical trials. Sixty‐six products were incubated in IL‐2 and 28 products in IL‐15. Processing resulted in a mean NK cell recovery of 74% and viability of 95.8%; NK cells, T cells, B cells, and monocytes accounted for 47%, 0.2%, 0.08%, and 49% of the final products, respectively. Seven products required dose adjustments to meet lot release. The specification for purity changed throughout the evolution of manufacturing. IL‐2 or IL‐15 activation enhanced in vitro cytotoxicity compared to preactivated cells. There was no difference in final product composition or cytotoxicity between cytokine cohorts.CONCLUSIONClinical‐scale/cGMP production of NK cells using CD3/CD19 cell‐depletion effectively minimized T‐cell and B‐cell contamination in a single manipulation without compromise to NK‐cell recovery. Cytokine activation increased in vitro cytotoxicity compared to column‐depleted, preactivated NK cells.
Lymphocyte apheresis for chimeric antigen receptor T‐cell manufacturing in children and young adults with leukemia and neuroblastoma
Authors: Ceppi Francesco , Rivers Julie , Annesley Colleen , Pinto Navin , Park Julie R. , Lindgren Catherine , Mgebroff Stephanie , Linn Naomi , Delaney Meghan , Gardner Rebecca A. 
Published: March 2018

BACKGROUNDThe first step in the production of chimeric antigen receptor T cells is the collection of autologous T cells using apheresis technology. The procedure is technically challenging, because patients often have low leukocyte counts and are heavily pretreated with multiple lines of chemotherapy, marrow transplantation, and/or radiotherapy. Here, we report our experience of collecting T lymphocytes for chimeric antigen receptor T‐cell manufacturing in pediatric and young adult patients with leukemia, non‐Hodgkin lymphoma, or neuroblastoma.STUDY DESIGN AND METHODSApheresis procedures were performed on a COBE Spectra machine using the mononuclear cell program, with a collection target of 1 × 109 total mononuclear cells per kilogram. Data were collected regarding preapheresis and postapheresis blood counts, apheresis parameters, products, and adverse events.RESULTSNinety‐nine patients (ages 1.3‐25.7 years) and 102 apheresis events were available for analysis. Patients underwent apheresis at a variety of absolute lymphocyte cell counts, with a median absolute lymphocyte count of 944 cells/μL (range, 142‐6944 cells/μL). Twenty‐two patients (21.6%) had absolute lymphocyte counts less than 500 cells/μL. The mononuclear cell target was obtained in 100% of all apheresis harvests, and chimeric antigen receptor T‐cell production was possible from the majority of collections (94%). Mononuclear cell collection efficiency was 65.4%, and T‐lymphocyte collection efficiency was 83.4%. Ten patients (9.8%) presented with minor adverse events during the 102 apheresis procedures, with one exception of a severe allergy.CONCLUSIONSMononuclear cell apheresis for chimeric antigen receptor T‐cell therapy is well tolerated and safe, and it is possible to obtain an adequate quantity of CD3+ lymphocytes for chimeric antigen receptor T‐cell manufacturing in heavily pretreated patients who have low lymphocyte counts.
Autologous blood as a source of platelet gel for the effective and safe treatment of oral chronic graft‐versus‐host disease
Authors: Bojanic Ines , Mravak Stipetic Marinka , Pulanic Drazen , Desnica Lana , Mazic Sanja , Golubic Cepulic Branka , Serventi Seiwerth Ranka , Vrhovac Radovan , Nemet Damir , Pavletic Steven Z. 
Published: March 2018

BACKGROUNDOral chronic graft‐versus‐host disease (cGvHD) impairs oral function and patients' quality of life. Some lesions are refractory to local and systemic immunosuppressive therapy, and new therapeutic modalities are required. The aim of the study was to assess the efficacy and safety of topical application of autologous platelet gel (PG) in patients with oral cGvHD.STUDY DESIGN AND METHODSPG was prepared from autologous blood and applied on ulcerous lesions using an automated system. The oral cGvHD was assessed using the 273‐point Oral Mucositis Rating Scale (OMRS) prior and after completion of the PG treatment. The overall response to treatment of particular topography expressed as the total score on OMRS was compared to total score on National Institutes of Health cGvHD Oral Mucosal Score (NIH OMS). The pain intensity was measured by the Numeric Pain Rating Scale (NRS).RESULTSIn five patients, 12 autologous blood collections were performed; median 3 (range 1‐3) per patient, and 26 PG applications were performed; median 6 (range 2‐8) per patient. PG applications reduced lesions in oral cGvHD: median OMRS total score was reduced for 43.2% (range 9.6%‐47.3%), and median NIH OMS total score for 27.3% (range 20.0%‐50.0%) from baseline values. Median of pain intensity reduction on NRS scale was 57.1% (range 50%‐100%). No side effects were observed.CONCLUSIONApplication of autologous PG in oral cGvHD showed as an efficient and safe treatment option for patients who do not respond to standard local treatment.
Influence of radiographic techniques on the measurement of femoral anteversion angles and a conformation score of pelvic limbs inLabrador retrievers
Authors: Mostafa Ayman A. , Cunningham Devin P. , Boudrieau Randy J. , Kowaleski Michael P. , Griffon Dominique J. 
Published: March 2018

AbstractObjectiveTo determine repeatability of and correlation between 2 radiographic measurements of femoral anteversion angles (FAA) and to determine their influence on a score derived from tibial plateau angle (TPA) and FAA to predict the risk of cranial cruciate ligament disease (CCLD).Study DesignProspective clinical study.AnimalsForty‐eight Labrador retrievers with or without CCLD.MethodsFAA and CCLD scores were calculated for each limb from extended pelvic radiographs (t‐FAA) or angled (a‐FAA) projections of the femur by 3 investigators. One investigator repeated measurements twice. Data were analyzed for repeatability, correlation between t‐FAA and a‐FAA, and their influence on CCLD scores.ResultsFAA correlated most strongly with the distance between the femoral head and the femoral axis on mediolateral radiographs, a measurement with excellent repeatability. t‐FAA and a‐FAA correlated with each other (r > 0.79,P < .0001), although t‐FAA were about 1° greater than a‐FAA (P = .01). Intrainvestigator and interinvestigator repeatability of the CCLD score was fair when derived from t‐FAA and good to excellent when derived from a‐FAA. CCLD scores differed between radiographic techniques but led to different predictions in only 9 (10%) limbs, all with lower TPA and CCLD scores than the rest of the population.Conclusiona‐FAA correlated strongly with t‐FAA and improved the repeatability of CCLD scores within and between investigators.Clinical significanceA craniocaudal angled beam projection of the femur is a suitable alternative to a ventrodorsal pelvic radiograph when measuring FAA and may improve the repeatability and positive predictive value of CCLD scores.
Radiographic, computed tomographic, and arthroscopic diagnosis of radioulnar incongruence in dogs with medial coronoid disease
Authors: Griffon Dominique J. , Mostafa Ayman A. , Blond Laurent , Schaeffer David J. 
Published: March 2018

AbstractObjectiveTo characterize radioulnar incongruence (RUI) in large dogs with medial coronoid disease (MCD) and determine the agreement between radiography, computed tomography (CT), and arthroscopy.Study designProspective observational case series.AnimalsTwenty‐four large‐breed dogs under 3 years of age with confirmed MCD.MethodsMCD and incongruence were evaluated by radiographs and CT. RUI was measured along the ulnar commissure, mid‐body, and apex of the medial coronoid process (MCP) by CT and arthroscopy. Joints with RUI ≥ 2 mm were considered incongruent. Variables recorded during arthroscopic treatment included type of MCD, RUI, and modified Outerbridge score. Agreement between the 3 diagnostic imaging techniques was evaluated, and the association between RUI and cartilage damage was analyzed.ResultsSingle fragmentation was the most common MCD according to CT and arthroscopy. RUI was associated with degenerative joint disease according to CT and with cartilage damage according to arthroscopy. RUI was diagnosed in 26% of elbows by radiography, in 35% of elbows by CT, in 78% of elbows according to CT measurements of RUI ≥ 2 mm, and in 57% of joints by arthroscopy. RUI was most commonly detected at the ulnar commissure with CT and at the apex of the MCP with arthroscopy. Imaging modalities were in poor to fair agreement with arthroscopy when evaluating RUI.ConclusionCT and arthroscopy provided similar detection of MCD and cartilage disease but disagreed in the assessment and localization of RUI.Clinical significanceCT does not reliably predict arthroscopic assessment of RUI and associated treatment decisions for MCD.
Development of a Broadly Accessible Venezuelan Equine Encephalitis Virus Replicon Particle Vaccine Platform
Authors: Agnihothram Sudhakar , Menachery Vineet D. , Yount Boyd L. , Lindesmith Lisa C. , Scobey Trevor , Whitmore Alan , Schäfer Alexandra , Heise Mark T. , Baric Ralph S. 
Published: March 2018

ABSTRACT

Zoonotic viruses circulate as swarms in animal reservoirs and can emerge into human populations, causing epidemics that adversely affect public health. Portable, safe, and effective vaccine platforms are needed in the context of these outbreak and emergence situations. In this work, we report the generation and characterization of an alphavirus replicon vaccine platform based on a non-select agent, attenuated Venezuelan equine encephalitis (VEE) virus vaccine, strain 3526 (VRP 3526). Using both noroviruses and coronaviruses as model systems, we demonstrate the utility of the VRP 3526 platform in the generation of recombinant proteins, production of virus-like particles, and
in vivo
efficacy as a vaccine against emergent viruses. Importantly, packaging under biosafety level 2 (BSL2) conditions distinguishes VRP 3526 from previously reported alphavirus platforms and makes this approach accessible to the majority of laboratories around the world. In addition, improved outcomes in the vulnerable aged models as well as against heterologous challenge suggest improved efficacy compared to that of previously attenuated VRP approaches. Taking these results together, the VRP 3526 platform represents a safe and highly portable system that can be rapidly deployed under BSL2 conditions for generation of candidate vaccines against emerging microbial pathogens.

IMPORTANCE
While VEE virus replicon particles provide a robust, established platform for antigen expression and vaccination, its utility has been limited by the requirement for high-containment-level facilities for production and packaging. In this work, we utilize an attenuated vaccine strain capable of use at lower biocontainment level but retaining the capacity of the wild-type replicon particle. Importantly, the new replicon platform provides equal protection for aged mice and following heterologous challenge, which distinguishes it from other attenuated replicon platforms. Together, the new system represents a highly portable, safe system for use in the context of disease emergence.
Efficacy and safety of 0.1% ciclosporin A cationic emulsion in dry eye disease: a pooled analysis of two double-masked, randomised, vehicle-controlled phase III clinical studies
Authors: Leonardi Andrea , Messmer Elisabeth M , Labetoulle Marc , Amrane Mourad , Garrigue Jean-Sébastien , Ismail Dahlia , Sainz-de-la-Maza Maite , Figueiredo Francisco C , Baudouin Christophe 
Published: March 2018

Background/aimTo assess the treatment effect of 0.1% ciclosporin A cationic emulsion (CsA CE) versus vehicle on signs/symptoms of dry eye disease (DED) in various subgroups (moderate-to-severe DED/severe DED/Sjögren’s syndrome (SS)/SS with severe DED).MethodsPooled data were analysed from two similar phase III studies: SICCANOVE (moderate-to-severe DED) and SANSIKA (severe DED with severe keratitis). In both studies, patients aged ≥18 years received CsA CE 0.1% (n=395) or vehicle (n=339) once daily for 6 months. A composite responder efficacy endpoint (corneal fluorescein staining–Ocular Surface Disease Index (CFS–OSDI) at month 6) was used to evaluate the efficacy of CsA CE in alleviating signs/symptoms of DED (response defined as improvement of ≥2 grades in CFS and ≥30% in OSDI (baseline to month 6)). Human leucocyte antigen-DR (HLA-DR) conjunctival expression was used as a biomarker of ocular surface inflammation.ResultsCsA CE–treated patients were significantly more likely to be CFS–OSDI responders than vehicle-treated patients in the overall (OR 1.66, 95% CI 1.11 to 2.50; P=0.015), severe DED (1.80, 1.04 to 3.19; P=0.038) and SS with severe DED (3.37, 1.20 to 11.19; P=0.030) populations. The difference was not significant for CsA CE versus vehicle for the overall Sjögren’s population (OR 1.77, CI 0.89 to 3.66; P=0.109). CsA CE also significantly reduced median HLA-DR expression versus vehicle at 6 months (P=0.002).ConclusionPooled phase III data indicate CsA CE produced significant improvement in signs/symptoms versus vehicle in patients with moderate-to-severe DED (especially in those with severe keratitis), including patients with SS with severe DED.
Can we successfully teach novice junior doctors basic interventional ultrasound in a single focused training session?
Authors: McKay Grace Frances Mary , Weerasinghe Asoka 
Published: March 2018

AbstractBackgroundUltrasonography is recognised as an invaluable imaging modality for assessing critically unwell patients and obtaining vascular access. Senior emergency medicine and anaesthetic clinicians will regularly use ultrasound-guided imaging to establish vascular access for unwell patients; however, junior doctors, who are routinely the first clinicians to review deteriorating patients, are not encouraged or required to develop basic ultrasound interventional skills and are therefore ill equipped to use ultrasonography.AimTo demonstrate that teaching basic interventional ultrasound skills to novice junior doctors in a single focused session is an achievable outcome.MethodWe reviewed the success of the ‘Junior doctor Ultrasound Training’ (JUST) course in teaching basic interventional ultrasound skills to junior clinicians. We collated information from 237 JUST delegates. We surveyed candidates’ prior ultrasound experience and retrospectively analysed their level 2 Kirkpatrick formative assessment outcome following the JUST course.ResultsThe overwhelming majority of doctors had no prior ultrasound experience (&gt;95%). 99% (235) of candidates performed ultrasound to an acceptable standard to pass the formative assessment. 73% (174) achieved the course outcomes independent of faculty prompting. 1% (2) candidates failed the formative assessment.ConclusionBasic ultrasound competency is an achievable educational outcome for the overwhelming majority of novice junior doctors. Our findings add to growing evidence that early ultrasound tuition can be both valuable and economical for training clinicians. By arming junior doctors with a relevant and versatile skill set, we can provide opportunity for clinicians to develop their expertise and prepare for the future challenges of clinical medicine.
Thermodynamic investigation by heat capacity measurements of κ-type dimer-Mott organic compounds with chemical pressure tuning
Authors: Matsumura Y. , Imajo S. , Yamashita S. , Akutsu H. , Nakazawa Y. 
Published: March 2018

Thermodynamic discussion on the physical properties around the Mott boundary of the dimer-Mott system of [Formula: see text]-type (BEDT-TTF)2X system, where BEDT-TTF is bis(ethylenedithio)tetrathiafulvalene and X denotes monovalent counter anions is performed by heat capacity measurements of the [Formula: see text]-(d[n,n] BEDT-TTF)2Cu[N(CN)2]Br of which donor molecules are partially deuterated. We compare temperature dependences of heat capacity of d[2,2], d[3,3] and d[4,4] compounds (defined as shown in Fig. 1) obtained in rapidly cooled and slowly cooled conditions. While the heat capacity of d[2,2] compound shows cooling rate dependence with the slight change of the absolute values Cp between 25 K and 50 K, the temperature dependences of the other compounds do not give drastic change by changing the cooling rate. The compounds of d[2,2] and d[3,3] located very close to the Mott boundary show peculiar hump structure in the C[Formula: see text]T[Formula: see text] that is related to the existence of a kind of lattice instability region around the first-order phase boundary. The temperature and chemical pressure dependences of the anomalous region are discussed in terms of the phase diagram in which the Mott boundary has peculiar rounding at low-temperature region.
Repeatability and reliability of muscle relaxation properties induced by motor cortical stimulation
Authors: Molenaar J. P. , Voermans N. C. , de Jong L. A. , Stegeman D. F. , Doorduin J. , van Engelen B. G. 
Published: March 2018

Impaired muscle relaxation is a feature of many neuromuscular disorders. However, few tests are available to quantify muscle relaxation. Transcranial magnetic stimulation (TMS) of the motor cortex can induce muscle relaxation by abruptly inhibiting corticospinal drive. The aim of our study was to investigate whether repeatability and reliability of TMS-induced relaxation are greater than voluntary relaxation. Furthermore, effects of sex, cooling, and fatigue on muscle relaxation properties were studied. Muscle relaxation of deep finger flexors was assessed in 25 healthy subjects (14 men and 11 women, age 39.1 ± 12.7 and 45.3 ± 8.7 yr, respectively) with handgrip dynamometry. All outcome measures showed greater repeatability and reliability in TMS-induced relaxation compared with voluntary relaxation. The within-subject coefficient of variability of normalized peak relaxation rate was lower in TMS-induced relaxation than in voluntary relaxation (3.0% vs. 19.7% in men and 6.1% vs. 14.3% in women). The repeatability coefficient was lower (1.3 vs. 6.1 s−1in men and 2.3 vs. 3.1 s−1in women) and the intraclass correlation coefficient was higher (0.95 vs. 0.53 in men and 0.78 vs. 0.69 in women) for TMS-induced relaxation compared with voluntary relaxation. TMS enabled demonstration of slowing effects of sex, muscle cooling, and muscle fatigue on relaxation properties that voluntary relaxation could not. In conclusion, repeatability and reliability of TMS-induced muscle relaxation were greater compared with voluntary muscle relaxation. TMS-induced muscle relaxation has the potential to be used in clinical practice for diagnostic purposes and therapy effect monitoring in patients with impaired muscle relaxation.NEW & NOTEWORTHY Transcranial magnetic stimulation (TMS)-induced muscle relaxation demonstrates greater repeatability and reliability compared with voluntary relaxation, represented by the ability to demonstrate typical effects of sex, cooling, and fatigue on muscle relaxation properties that were not seen in voluntary relaxation. In clinical practice, TMS-induced muscle relaxation could be used for diagnostic purposes and therapy effect monitoring. Furthermore, fewer subjects will be needed for future studies when using TMS to demonstrate differences in muscle relaxation properties.