bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring Heterogeneity in Histology-Independent Technologies and the Implications for Cost-Effectiveness
Authors: Murphy Peter , Claxton Lindsay , Hodgson Robert , Glynn David , Beresford Lucy , Walton Matthew , Llewellyn Alexis , Palmer Stephen , Dias Sofia 
Published: January 2021

Background The National Institute for Health and Care Excellence and a number of international health technology assessment agencies have recently undertaken appraisals of histology-independent technologies (HITs). A strong and untested assumption inherent in the submissions included identical clinical response across all tumour histologies, including new histologies unrepresented in the trial. Challenging this assumption and exploring the potential for heterogeneity has the potential to impact upon cost-effectiveness. Method Using published response data for a HIT, a Bayesian hierarchical model (BHM) was used to identify heterogeneity in response and to estimate the probability of response for each histology included in single-arm studies, which informed the submission for the HIT, larotrectinib. The probability of response for a new histology was estimated. Results were inputted into a simplified response-based economic model using hypothetical parameters. Histology-independent and histology-specific incremental cost-effectiveness ratios accounting for heterogeneity were generated. Results The results of the BHM show considerable heterogeneity in response rates across histologies. The predicted probability of response estimated by the BHM is 60.9% (95% credible interval 16.0; 91.8%), lower than the naively pooled probability of 74.5%. A mean response probability of 56.9% (0.2; 99.9%) is predicted for an unrepresented histology. Based on the economic analysis, the probability of the hypothetical HIT being cost-effective under the assumption of identical response is 78%. Allowing for heterogeneity, the probability of various approval decisions being cost-effective ranges from 93% to 11%. Conclusions Central to the challenge of reimbursement of HITs is the potential for heterogeneity. This study illustrates how heterogeneity in clinical effectiveness can result in highly variable and uncertain estimates of cost-effectiveness. This analysis can help improve understanding of the consequences of histology-independent versus histology-specific decisions.
Measuring functional connectivity in patients with strabismus using stationary functional magnetic resonance imaging: a resting-state network study
Authors: Yu Kang , Lin Qi , Ge Qian-Min , Yu Chen-Yu , Li Qiu-Yu , Pan Yi-Cong , Shao Yi 
Published: January 2021

Background Strabismus (STR) is a common eye disease characterized by abnormal eye movements and stereo vision. Neuroimaging studies have revealed that STR patients have impaired functional connectivity (FC) in the visual cortex and sensorimotor cortex. Purpose To investigate alterations in FC and connections within and between subnetworks of the visual network (VN), sensorimotor network (SMN), and default mode network (DMN) in patients with STR. Material and Methods A total of 32 patients with STR (24 men, 8 women) and 32 age- and sex-matched healthy controls (HCs) (24 men, 8 women) were recruited. Participants underwent resting-state functional magnetic resonance imaging scans. The resting-state network (RSN) was examined by independent component analysis, and differences in RSN FC between STR and HC groups were evaluated with the t test. Functional network connectivity (FNC) analysis was performed for the three RSNs. Results Compared to the HC group, the STR group showed increased FC in the VN and SMN (voxel-level P < 0.01; two-tailed Gaussian random field correction; cluster-level P < 0.05). There were no significant alterations in DMN FC between the two groups. FNC analysis of connections in the RSN revealed that one of the three connections in the VN was reduced, but no connectivity changes were observed in the SMN or DMN. FNC analysis of the connection between two RSNs showed that two had increased and one had a decreased connection value. Conclusion The VN, SMN, and DMN are reorganized in patients with STR compared to HCs, providing novel insight into the neural substrates of STR.
Tumor necrosis factor-α small interfering RNA alveolar epithelial cell-targeting nanoparticles reduce lung injury in C57BL/6J mice with sepsis
Authors: Qian Like , Yin Xi , Ji Jiahao , Chen Zhengli , Fang He , Li Hu , Zhu Feng , Chang Fei 
Published: January 2021

Background The role of tumor necrosis factor (TNF)-α small interfering (si)RNA alveolar epithelial cell (AEC)-targeting nanoparticles in lung injury is unclear. Methods Sixty C57BL/6J mice with sepsis were divided into normal, control, sham, 25 mg/kg, 50 mg/kg, and 100 mg/kg siRNA AEC-targeting nanoparticles groups (n = 10 per group). The wet:dry lung weight ratio, and hematoxylin and eosin staining, western blotting, and enzyme-linked immunosorbent assays for inflammatory factors were conducted to compare differences among groups. Results The wet:dry ratio was significantly lower in control and sham groups than other groups. TNF-α siRNA AEC-targeting nanoparticles significantly reduced the number of eosinophils, with significantly lower numbers in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. The nanoparticles also significantly reduced the expression of TNF-α, B-cell lymphoma-2, caspase 3, interleukin (IL)-1β, and IL-6, with TNF-α expression being significantly lower in the 50 mg/kg group than in 25 mg/kg and 100 mg/kg groups. Conclusion TNF-α siRNA AEC-targeting nanoparticles appear to be effective at improving lung injury-related sepsis, and 50 mg/kg may be a preferred dose option for administration.
Preliminary report of modified expansive laminoplasty in the treatment of thoracic ossification of the ligamentum flavum
Authors: Xue You-Di , Zhang Zhao-Chuan , Ma Chao , Dai Wei-Xiang 
Published: January 2021

Objective This study was performed to evaluate the role of posterior suspension of the laminae–ossification of the ligamentum flavum complex combined with miniplate fixation (modified expansive thoracic laminoplasty) in treating thoracic ossification of the ligamentum flavum (TOLF). Methods Eight patients with TOLF treated by modified expansive thoracic laminoplasty were retrospectively analyzed. Their general information, operative time, intraoperative blood loss, and postoperative complications were recorded. Neurological functional recovery was evaluated by the modified Japanese Orthopaedic Association (mJOA) score and Hirabayashi recovery rate preoperatively, postoperatively, and at the final follow-up. Preoperative and postoperative imaging was performed, and the decompression range and internal fixation positioning were evaluated. Results The mJOA score significantly improved from 4.63 points preoperatively to 9.0 points at the final follow-up (Hirabayashi recovery rate of 77.75%). Postoperative computed tomography and magnetic resonance imaging revealed sufficient decompression of the surgical segment. At the final follow-up, the internal implants were well-placed, the lamina–ligamentum flavum complex showed no significant displacement, and neurological functional recovery was satisfactory. Conclusion Surgical treatment of TOLF is complicated and high-risk. Characterized by simplicity and sufficient decompression, modified expansive thoracic laminoplasty can reduce the risk of cerebrospinal fluid leakage and nerve injury with satisfactory neurological functional recovery.
Impact of a sensory activity schedule intervention on cognitive strategy use in autistic students: A school-based pilot study
Authors: Mills Caroline J , Chapparo Christine , Hinitt Joanne 
Published: January 2021

Introduction Autistic students may experience difficulty performing classroom tasks due to atypical sensory processing and inefficient use of higher-order cognitive strategies. Limited research has investigated the influence of in-class sensory activities to enhance the thinking strategies required for task performance. This study evaluated a classroom-based sensory activity schedule and its impact on cognitive strategy use. Methods A quasi-experimental, non-equivalent groups design was used. Students ( n = 30, mean age 7.4 years) with atypical sensory processing negatively impacting classroom performance, and their teachers ( n = 23), from six autism-specific schools were grouped into intervention (Sensory Activity Schedule and usual teaching) and control (usual teaching only) groups. Students’ cognitive strategy use during the performance of classroom tasks was evaluated at baseline and post-intervention using Perceive, Recall, Plan, Perform Stage Two Cognitive Task Analysis. Results Statistical analysis (Mann–Whitney U test) indicated that students who received the Sensory Activity Schedule intervention improved significantly more than control group students in overall cognitive strategy use ( Z = –2.32, p = 0.02), and with strategy items involving attention and sensory perception (perceive, Z = –2.26, p = 0.02), and planning and organisation (Plan, Z = –.254, p = 0.01). Conclusion The Sensory Activity Schedule may enhance autistic students’ capacity to apply cognitive strategies more effectively during performance of classroom tasks.
Quantitative 3-T Magnetic Resonance Imaging After Matrix-Associated Autologous Chondrocyte Implantation With Autologous Bone Grafting of the Knee: The Importance of Subchondral Bone Parameters
Authors: Jung Matthias , Karampinos Dimitrios C. , Holwein Christian , Suchowierski Joachim , Diallo Thierno D. , Gersing Alexandra S. , Bamberg Fabian , Baumann Frederic A. , Ruschke Stefan , Jungmann Pia M. 
Published: January 2021

Background: Matrix-associated autologous chondrocyte implantation (MACI) with autologous bone grafting (ABG) is an effective surgical treatment for osteochondral defects. Quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as noninvasive biomarkers to assess the biochemical composition of cartilage repair tissue. Purpose: To evaluate the association of quantitative MRI parameters of cartilage repair tissue and subchondral bone marrow with magnetic resonance morphologic and clinical outcomes after MACI with ABG of the knee. Study Design: Case series; Level of evidence, 4. Methods: Qualitative and quantitative 3 T MRI of the knee was performed in 21 patients (16 male) at 2.5 years after MACI with ABG at the medial (18/21) or lateral (3/21) femoral condyle for the treatment of osteochondral defects. Morphologic MRI sequences were assessed using MOCART (magnetic resonance observation of cartilage repair tissue) 2.0 scores. T2 relaxation time measurements for the assessment of cartilage repair tissue (CRT2) were obtained. Single-voxel magnetic resonance spectroscopy was performed in underlying subchondral bone marrow (BM) and at both central femoral condyles. The presence of pain and Tegner scores were noted. Statistical analyses included Student t tests, correlation analyses, and multivariate regression models. Results: The mean defect size was 4.9 ± 1.9 cm2. At a follow-up of 2.5 ± 0.3 years, 9 of 21 patients were asymptomatic. Perfect defect filling was achieved in 66.7% (14/21) of patients. MOCART 2.0 scores (74.1 ± 18.4) did not indicate pain (68.3 ± 19.0 [pain] vs 81.7 ± 15.4 [no pain]; P = .102). However, knee pain was present in 85.7% (6/7) of patients with deep bony defects (odds ratio, 8.0; P = .078). Relative CRT2 was higher in hypertrophic cartilage repair tissue than in repair tissue with normal filling (1.54 ± 0.42 vs 1.13 ± 0.21, respectively; P = .022). The underlying BM edema–like lesion (BMEL) volume was larger in patients with underfilling compared with patients with perfect defect filling (1.87 ± 1.32 vs 0.31 ± 0.51 cm3, respectively; P = .002). Patients with severe pain showed a higher BMEL volume (1.2 ± 1.3 vs 0.2 ± 0.4 cm3, respectively; P = .046) and had a higher BM water fraction (26.0% ± 12.3% vs 8.6% ± 8.1%, respectively; P = .026) than did patients without pain. Conclusion: Qualitative and quantitative MRI parameters including the presence of subchondral defects, CRT2, BMEL volume, and BM water fraction were correlated with cartilage repair tissue quality and clinical symptoms. Therefore, the integrity of subchondral bone was associated with outcomes after osteochondral transplantation.
Management of Osteoarthritis Using 1 Intra-articular Platelet Concentrate Administration in a Canine Osteoarthritis Model
Authors: Alves João Carlos Agostinho , Santos Ana Margarida Moniz Pereira dos , Jorge Patrícia Isabel Figueiredo , Lavrador Catarina Falcão Trigoso Vieira Branco , Carreira Luis Miguel Alves 
Published: January 2021

Background: Osteoarthritis (OA) represents a significant burden to societies, as it affects quality of life and performance and implies a large cost in terms of health care. Autologous platelets are a regenerative treatment modality for OA that are thought to be a potential stimulation of the natural healing cascade. Purpose: To describe the effect of the platelet concentrate V-PET in the management of OA in a naturally occurring canine model, using several outcome assessment modalities. Study Design: Controlled laboratory study. Methods: A total of 40 joints of active working police dogs with hip OA were randomly assigned to a control group (CG) and a platelet concentrate group (PCG; treatment) and evaluated. At treatment day (T0) and 8, 15, 30, 90, and 180 days after treatment, weight distribution, joint range of motion at flexion and extension, thigh girth, digital thermography, radiographic signs, 4 clinical metrology instruments, and synovial fluid interleukin 1 and C-reactive protein levels were recorded. Results were compared using repeated-measures analysis of variance with a Huynh-Feldt correction, paired-samples t test, or Wilcoxon signed rank test, with P < .05. Results: Dogs were 6.5 ± 2.4 years old (mean ± SD) and had a body weight of 26.7 ± 5.2 kg. At T0, 32 (80%) joints were graded as having mild OA, 6 (15%) as moderate, and 2 (5%) as severe. No differences were found between groups at T0. Between the PCG and CG, the symmetry index showed significant improvements in the PCG from 8 days ( P = .01) to 180 days ( P = .01). Joint flexion also improved in the PCG up to 90 days ( P < .05) and extension improved up to 180 days ( P < .01). Several clinical metrology instrument scores also improved up to 90 to 180 days after treatment. In the CG, radiographic signs progressed, while the PCG showed some improved signs. In both groups, increasing body weight and age corresponded with worse clinical and laboratory findings. Conclusion: A single injection of platelet concentrate had a positive effect, lasting up to 6 months, on several clinical, imaging, and laboratory signs in a naturally occurring canine OA model. Clinical Relevance: We characterized the effects of this platelet concentrate in dogs, considered the gold standard of the study of OA, with a group of working animals with similar high demands as athletes.
The DOOR to Antibiotic Stewardship: Refining Assessments of Interventions With Desirability of Outcome Ranking
Authors: Smoke Steven M. , Patel Vishal V. , Leonida Nicole I. 
Published: January 2021

Background: Limited sample size and disparate outcome measures can hinder the ability of antimicrobial stewardship programs to assess the utility of their quality improvement interventions. Desirability of outcome ranking (DOOR) is a novel methodology that incorporates multiple outcomes into a single value to more comprehensively compare therapeutic strategies. The objective of this study was to apply DOOR to a single center antibiotic stewardship intervention. Methods: A pre- and post-interventional study was conducted evaluating the impact of prospective pharmacist review of rapid molecular diagnostic testing (RDT) of blood cultures on antibiotic optimization. Outcomes included the percentage of patients who were switched to appropriate therapy, the time to appropriate therapy, and the percentage of patients who had missed de-escalation opportunities. Results: A total of 19 and 29 patients were included in the final analysis. The percentage of patients reaching appropriate therapy was 84% (16/19) and 97% ([28/29], p = 0.16) in the pre-intervention and post-intervention groups respectively. Median time to appropriate therapy was 26 hours and 36 minutes (IQR 13:05-50:45) and 22:40 (IQR 3:42-48:23, p = 0.32), respectively. One missed de-escalation opportunity was identified in the post-intervention group (0% vs 3%, p = 1.00). DOOR analysis indicated that the probability of a better outcome for the post-intervention group than the pre-intervention group was 58% (95% CI 54-62). Conclusion: In this analysis, DOOR revealed a benefit that would not have been apparent with traditional outcomes assessments. Antimicrobial stewardship programs conducting quality improvement studies should consider incorporating DOOR into their methodology.
Vulnerability: An integrative bioethics review and a proposed taxonomy
Authors: Mergen Merve , Akpınar Aslıhan 
Published: January 2021

Background: Vulnerability is a concept frequently encountered in the bioethical literature, particularly in the context of research ethics. It can be said that the usage of the concept expanded in the 2000s and started to be used in many new contexts in the literature. However, there appears to be no systematic review that examines the definition of the concept of vulnerability. Objectives: The rationale for this study constitutes the questions regarding how vulnerability is defined and which components are used to define the concept of vulnerability in the bioethics literature. Research design: The integrative review method was conducted to reach various definitions of the concept of vulnerability in bioethics. Whittemore and Knafl’s revised framework for integrative reviews guided the analysis. ‘Vulnerability’ and ‘vulnerable’ keywords, intercrossing with the words ‘bioethics’ and ‘medical ethics’, were searched in three different databases (PubMed, Web of Science and Scopus). Collected data were analysed thematically and a taxonomy was developed. Findings: A total of 1287 studies obtained through search were reduced to 123 that kept the definition of vulnerability. As a result of the review, a comprehensive taxonomy of vulnerability has been proposed. The proposed taxonomy of vulnerability has two categories, ontological and circumstantial, with three subcategories each, which might provide a multidimensional perspective. Discussion: Publication dates, origins and contexts of included publications were discussed. Specifications of the term vulnerability and components of its definition and factors that constitute these components provided from the view were evaluated and also discussed. Conclusion: The proposed taxonomy provides a useful classification for assessing vulnerability in bioethics. It is hoped that the taxonomy we put forward as a result of the review will increase awareness on the issue and also take into account the factors that create vulnerability in the context of research, healthcare and nursing care policies. Ethical considerations: The review was conducted in accord with ethical and scientific standards.
Validation of the Dutch-language version of Nurses’ Moral Courage Scale
Authors: Numminen Olivia , Konings Kasper , Claerhout Roelant , Gastmans Chris , Katajisto Jouko , Leino-Kilpi Helena , de Casterlé Bernadette Dierckx 
Published: January 2021

Background: Moral courage as a part of nurses’ moral competence has gained increasing interest as a means to strengthen nurses acting on their moral decisions and offering alleviation to their moral distress. To measure and assess nurses’ moral courage, the development of culturally and internationally validated instruments is needed. Objective: The objective of this study was to validate the Dutch-language version of the four-component Nurses’ Moral Courage Scale originally developed and validated in Finnish data. Research design: This methodological study used non-experimental, cross-sectional exploratory design. Participants and research context: A total of 559 nurses from two hospitals in Flanders, Belgium, completed the Dutch-language version of the Nurses’ Moral Courage Scale. Ethical considerations: Good scientific inquiry guidelines were followed throughout the study. Permission to translate the Nurses’ Moral Courage Scale was obtained from the copyright holder, and the ethical approval and permissions to conduct the study were obtained from the participating university and hospitals, respectively. Findings: The four-component 21-item, Dutch-language version of the Nurses’ Moral Courage Scale proved to be valid and reliable as the original Finnish Nurses’ Moral Courage Scale. The scale’s internal consistency reliability was high (0.91) corresponding with the original Nurses’ Moral Courage Scale validation study (0.93). The principal component analysis confirmed the four-component structure of the original Nurses’ Moral Courage Scale to be valid also in the Belgian data explaining 58.1% of the variance. Confirmatory factor analysis based on goodness-of-fit indices provided evidence of the scale’s construct validity. The use of a comparable sample of Belgian nurses working in speciality care settings as in the Finnish study supported the stability of the structure. Discussion and conclusion: The Dutch-language version of the Nurses’ Moral Courage Scale is a reliable and valid instrument to measure nurses’ self-assessed moral courage in speciality care nursing environments. Further validation studies in other countries, languages and nurse samples representing different healthcare environments would provide additional evidence of the scale’s validity and initiatives for its further development.
A Systematic Review of Blinatumomab in the Treatment of Acute Lymphoblastic Leukemia: Engaging an Old Problem With New Solutions
Authors: Halford Zachery , Coalter Carli , Gresham Vanessa , Brown Tabitha 
Published: January 2021

Objective: To assess the current literature for blinatumomab in the treatment of adult and pediatric B-cell acute lymphoblastic leukemia (ALL). Data Sources: We conducted a PubMed (inception to December 11, 2020) and ClinicalTrials.gov systematic literature search using the following terms: blinatumomab, Blincyto, lymphoblastic leukemia, and bispecific T-cell engager. Study Selection and Data Extraction: All relevant published articles, package inserts, and meeting abstracts evaluating the use of blinatumomab in ALL were considered for inclusion. Data Synthesis: Blinatumomab, a first-in-class bispecific T-cell engager monoclonal antibody, facilitates cytotoxic T-cell activation and subsequent eradication of CD19-positive B cells. The confirmatory phase III TOWER trial demonstrated superior overall survival (OS) with blinatumomab compared with standard chemotherapy (7.7 months vs 4.0 months) in relapsed and refractory (R/R) B-cell ALL. In the phase II BLAST trial, blinatumomab achieved a complete measurable residual disease (MRD) response in 78% of evaluable patients, with a median OS of 36.5 months. Potentially life-threatening cytokine release syndrome and neurotoxicity occurred in approximately 15% and 65% of patients, respectively. Relevance to Patient Care and Clinical Practice: Following initial Food and Drug Administration approval in 2014, blinatumomab gained expanded approval in pediatric patients and in Philadelphia chromosome-positive R/R ALL. In 2018, blinatumomab became the first and only drug approved for the treatment of persistent MRD in any hematologic malignancy. Emerging data demonstrate promising efficacy with blinatumomab in specific ALL settings, including frontline therapy, as a bridge to transplantation, and in “chemotherapy-free” combination regimens. Conclusions: Blinatumomab provides a paradigm-shifting treatment option; however, many questions surrounding optimal patient selection, sequencing, and cost-effectiveness remain.