bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Deficiency of Flavin-Containing Monooxygenase 3 (
Fmo3
) Protects Against Thrombosis but Has Only a Minor Effect on Plasma Lipid Levels—Brief Report
Authors: Shih Diana M. , Zhu Weifei , Schugar Rebecca C. , Meng Yonghong , Jia Xun , Miikeda Aika , Wang Zeneng , Zieger Marina , Lee Richard , Graham Mark , Allayee Hooman , Cantor Rita M. , Mueller Christian , Brown J. Mark , Hazen Stanley L. , Lusis Aldons J. 
Published: April 2019

Objective—
FMO (flavin-containing monooxygenase) 3 converts bacterial-derived trimethylamine to trimethylamine N-oxide (TMAO), an independent risk factor for cardiovascular disease. We generated FMO3 knockout (FMO3KO) mouse to study its effects on plasma TMAO, lipids, glucose/insulin metabolism, thrombosis, and atherosclerosis.

Approach and Results—
Previous studies with an antisense oligonucleotide (ASO) knockdown strategy targeting FMO3 in LDLRKO (low-density lipoprotein receptor knockout) mice resulted in major reductions in TMAO levels and atherosclerosis, but also showed effects on plasma lipids, insulin, and glucose. Although FMO3KO mice generated via CRISPR/Cas9 technology bred onto the LDLRKO background did exhibit similar effects on TMAO levels, the effects on lipid metabolism were not as pronounced as with the ASO knockdown model. These differences could result from either off-target effects of the ASO or from a developmental adaptation to the FMO3 deficiency. To distinguish these possibilities, we treated wild-type and FMO3KO mice with control or FMO3 ASOs. FMO3-ASO treatment led to the same extent of lipid-lowering effects in the FMO3KO mice as the wild-type mice, indicating off-target effects. The levels of TMAO in LDLRKO mice fed an atherogenic diet are very low in both wild-type and FMO3KO mice, and no significant effect was observed on atherosclerosis. When FMO3KO and wild-type mice were maintained on a 0.5% choline diet, FMO3KO showed a marked reduction in both TMAO and in vivo thrombosis potential.

Conclusions—
FMO3KO markedly reduces systemic TMAO levels and thrombosis potential. However, the previously observed large effects of an FMO3 ASO on plasma lipid levels appear to be due partly to off-target effects.
Secondary Bleeding During Acute Experimental Intracerebral Hemorrhage
Authors: Schlunk Frieder , Böhm Maximilian , Boulouis Gregoire , Qin Tao , Arbel Michal , Tamim Isra , Fischer Paul , Bacskai Brian J. , Frosch Matthew P. , Endres Matthias , Greenberg Steven M. , Ayata Cenk 
Published: April 2019

Background and Purpose—
Mechanisms contributing to acute hematoma growth in intracerebral hemorrhage are not well understood. Neuropathological studies suggest that the initial hematoma may create mass effect that can tear vessels in the vicinity by shearing, causing further bleeding and hematoma growth.

Methods—
To test this in mice, we simulated initial intracerebral hemorrhage by intrastriatal injection of a liquid polymer that coagulates upon contact with tissue and measured the presence and volume of bleeding secondary to the mass effect using Hemoglobin ELISA 15 minutes after injection.

Results—
Secondary hemorrhage occurred in a volume-dependent (4, 7.5, or 15 μL of polymer) and rate-dependent (0.05, 0.5, or 5 μL/s) manner. Anticoagulation (warfarin or dabigatran) exacerbated the secondary hemorrhage volume. In a second model of hematoma expansion, we confirmed that intrastriatal whole blood injection (15 μL, 0.5 μL/s) also caused secondary bleeding, using acute Evans blue extravasation as a surrogate. Anticoagulation once again exacerbated secondary hemorrhage after intrastriatal whole blood injection. Secondary hemorrhage directly and significantly correlated with arterial blood pressures in both nonanticoagulated and anticoagulated mice, when modulated by phenylephrine or labetalol.

Conclusions—
Our study provides the first proof of concept for secondary vessel rupture and bleeding as a potential mechanism for intracerebral hematoma growth.
Air contamination during medical treatment results in deposits of microemboli in the lungs: An autopsy study
Authors: Forsberg Ulf , Jonsson Per , Stegmayr Bernd 
Published: April 2019

Introduction: Microbubbles of air may enter into patients during conventional hemodialysis, infusions of fluids, or by injections. The aim of this study was to investigate whether the air that enters the patient during hemodialysis can be detected in the lungs after death, and if so, whether this may be related to tissue damage. Methods: The material consisted of lung tissue from five chronic hemodialysis patients who died either during (two) or after hemodialysis (range 10 min from start until 3333 min after the last hemodialysis session); as reference group tissue was taken from seven patients who died due to amyotrophic lateral sclerosis. The lung tissue was investigated by microscopy after autopsy using a fluorescein-marked polyclonal antibody against fibrinogen as a marker for clots preformed before death. Results: All five hemodialysis patients had microbubbles of air in the lung tissue, whereas two of seven amyotrophic lateral sclerosis patients had such findings (Fisher’s test p = 0.0278, relative risk = 3.5, confidence interval: 1.08–11.3). There were more microbubbles of air/10 randomly investigated microscopic fields of tissue in the hemodialysis patients than the amyotrophic lateral sclerosis patients (Student’s test, p < 0.05). All hemodialysis patients had a medium graded extent of pulmonary fibrosis that was not found in any of the ALS patients. The microbubbles of air were surrounded by fibrin as a sign of development of clots around the air bubbles while the patients were still alive. Conclusion: Exposure to microbubbles of air during various treatments such as hemodialysis may result in microemboli. Future studies should clarify whether microbubbles of air contribute to tissue scarring. We suggest preventive measures against the exposure to microbubbles of air during especially repeated exposures such as hemodialysis.
Bystander, ‘mitläufer’, collaborator—a personal reflection on crossing borders between politics and psychotherapy
Authors: Gölz Angelika 
Published: April 2019

This article explores the tension between our political, ethical, moral and clinical responsibilities as group analysts working with large groups, in the context of facing issues of wrong-doing. It seems clear that when working with small groups or individuals that we are aware of our responsibility concerning safeguarding. But what if we are faced with political violence, wars and atrocities committed and present in the matrix of our large groups? This article draws on an experience of conducting a group raising questions about our responsibility as group psychotherapists. Do we become bystanders, collaborators or ‘mitläufer’? The article also draws on the author’s personal history growing up in post-war Germany to engage with these and other questions.
Comparison of Intermediate-Term Outcomes of Total Ankle Arthroplasty in Patients Younger and Older Than 55 Years
Authors: Lee Gun-Woo , Seon Jong‑Keun , Kim Nack-Sung , Lee Keun-Bae 
Published: April 2019

Background: Total ankle arthroplasty is often not recommended to younger patients with ankle arthritis because of their high functional demands. The purpose of this study was to compare intermediate-term clinical and radiographic outcomes and survivorship rates of total ankle arthroplasty between patients younger and older than 55 years. Methods: A total of 117 consecutive patients (123 ankles) who underwent primary total ankle arthroplasty using Hintegra prosthesis with a mean follow-up of 78 months were enrolled and divided into 2 age groups: under 55 years (38 ankles; mean age 45 years) and over 55 years (85 ankles; mean age 65 years). Results: Clinical scores of Ankle Osteoarthritis Scale pain and disability, American Orthopaedic Foot & Ankle Society ankle-hindfoot, Short Form–36 Physical Component Summary and Mental Component Summary, and visual analog scale were not significantly different between the 2 age groups at the final follow-up ( P > .05). There were no significant differences in complications and survivorship rates between the two at a mean follow-up of 78 months ( P > .05). Conclusions: Clinical and radiographic outcomes and survival rates of total ankle arthroplasty in patients under age of 55 years were satisfactory and comparable to those in patients older than 55 years in the intermediate-term follow-up. Therefore, total ankle arthroplasty may be considered as a viable treatment option in young patients with end-stage ankle arthritis. Level of Evidence: Level III, comparative series, therapeutic.
Influence of venipuncture point and port chamber site on the risk of catheter fracture in right internal jugular port placements
Authors: Matsunari Kazuya , Watanabe Kota , Hishizume Norihiro , Fujisawa Hidefumi 
Published: April 2019

Background: For subcutaneously implanted central venous ports, some complications due to prolonged placement have been reported. We investigated the appropriate puncture points and port placement sites to prevent catheter fracture in right internal jugular port placement. Methods: This retrospective study included 709 patients who underwent right internal jugular vein puncture and port implantation in the right precordium between 1 May 2012 and 31 March 2018. The cases were divided into undamaged catheter group and damaged catheter group comprising normal and fracture cases, respectively. The catheter angle, distance from the clavicle, tip position, and curvature radius were measured from fluoroscopic images obtained at the time of implantation. The t-test was used in statistical analysis. Results: Median angles were 91.6° in the undamaged catheter group and 58.0° in the damaged catheter group. Median distances were 26.0 mm in the undamaged catheter group and 36.6 mm in the damaged catheter group. Median tip positions were 51.6 mm in the undamaged catheter group and 37.5 mm in the damaged catheter group. Median curvature radii were 9.2 R in the undamaged catheter group and 7.1 R in the damaged catheter group. Significant differences were found in the angle, height, and curvature radius between the two groups. Conclusion: Our results indicate that a venipuncture as close to the clavicle as possible (less than 3 cm) and a gentle catheter curve (close to 90° angle) are associated with a lower risk of catheter fracture.
A Comparative Single-Blind Randomized Controlled Trial With Language Training in People With Mild Cognitive Impairment
Authors: Poptsi Eleni , Lazarou Ioulietta , Markou Nefeli , Vassiloglou Maria , Nikolaidou Evdokia , Diamantidou Alexandra , Siatra Vassiliki , Karathanassi Elina , Karakostas Anastasios , Zafeiropoulou Fotini Kounti , Tsiatsos Thrasyvoulos , Tsolaki Magda 
Published: April 2019

Background: Although cognitive training is effective for people with mild cognitive impairment (MCI), it is not clear which format is more effective. Objective: To compare the effectiveness of the same language programs when carried out via computer, paper/pencil and orally in people with MCI. Methods: Seventy-one participants with MCI were randomly classified in 3 experimental and 2 control groups. The experimental groups attended 48 sessions of language training for 6 months. The control groups attended either unstructured sessions or they were on waiting list. Results: Mixed measures analysis of variance, at the follow-up, showed a significant cognitive abilities improvement among the experimental versus control groups. At the end of the language training, the 3 groups presented improvement in cognitive abilities and daily function, while the control groups remained at the same performance level. Conclusion: All 3 cognitive language training methods were equally significantly effective.
Development of a Novel Emergency Department Mapping Tool
Authors: Grzywinski Matthew , Carlisle Stephanie , Coleman James , Cook Connor , Hayden Geoffrey , Pugliese Robert , Faircloth Billie , Ku Bon 
Published: April 2019

Objectives: Develop a built environment mapping workflow. Implement the workflow in the emergency department (ED). Demonstrate the actionable representations of the data that can be collected using this workflow. Background: The design of the healthcare built environment impacts the delivery of patient care and operational efficiency. Studying this environment presents a series of challenges due to the limitations associated with existing technology such as radio-frequency identification. The authors designed a customized mapping workflow to collect high-resolution spatial, temporal, and activity data to improve healthcare environments, with emphasis on patient safety and operational efficiency. Method: A large, urban, academic medical center ED collaborated with an architecture firm to create a data collection, and mapping workflow using ArcGIS tools and data collectors. The authors developed tools to collect data on the entire ED, as well as individual patients, physicians, and nurses. Advanced visual representations were created from the master data set. Results: In 48 consecutive hourly snapshots, 5,113 data points were collected on patients, physicians, nurses, and other staff reflecting the operations of the ED. Separately, 84 patients, 10 attending physicians, 10 resident physicians, and 17 nurses were tracked. Conclusions: The data obtained from this pilot study were used to create advanced visual representations of the ED environment. This cost-effective ED mapping workflow may be applied to other healthcare settings. Further investigation to evaluate the benefits of this high-resolution data is required.
Compositional MRI of the Hip: Reproducibility, Effect of Joint Unloading, and Comparison of T2 Relaxometry with Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage
Authors: Fernquest Scott , Palmer Antony , Gammer Bonnie , Hirons Emma , Kendrick Benjamin , Taylor Adrian , De Berker Henry , Bangerter Neal , Carr Andrew , Glyn-Jones Sion 
Published: April 2019

Objective Our aim was to compare T2 with delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) in the hip and assess the reproducibility and effect of joint unloading on T2 mapping. Design Ten individuals at high risk of developing hip osteoarthritis (SibKids) underwent contemporaneous T2 mapping and dGEMRIC in the hip (10 hips). Twelve healthy volunteers underwent T2 mapping of both hips (24 hips) at time points 25, 35, 45, and 55 minutes post offloading. Acetabular and femoral cartilage was manually segmented into regions of interest. The relationship between T2 and dGEMRIC values from anatomically corresponding regions of interests was quantified using Pearson’s correlation. The reproducibility of image analysis for T2 and dGEMRIC, and reproducibility of image acquisition for T2, was quantified using the intraclass correlation coefficient (ICC), root mean square coefficient of variance (RMSCoV), smallest detectable difference (SDD), and Bland-Altman plots. The paired t test was used to determine if difference existed in T2 values at different unloading times. Results T2 values correlated most strongly with dGEMRIC values in diseased cartilage ( r = −0.61, P = <0.001). T2 image analysis (segmentation) reproducibility was ICC = 0.96 to 0.98, RMSCoV = 3.5% to 5.2%, and SDD = 2.2 to 3.5 ms. T2 values at 25 minutes unloading were not significantly different to longer unloading times ( P = 0.132). SDD for T2 image acquisition reproducibility was 7.1 to 7.4 ms. Conclusions T2 values in the hip correlate well with dGEMRIC in areas of cartilage damage. T2 shows high reproducibility and values do not change beyond 25 minutes of joint unloading.
Optimization of post-label delay in single-phase arterial spin labeling (ASL) using multi-phase ASL in four-dimensional magnetic resonance angiography
Authors: Oshita Tsuyoshi , Yabuuchi Hidetake , Osame Masanobu 
Published: April 2019

Purpose To optimize the post-label delay in single-phase arterial spin labeling (SP-ASL) using multi-phase ASL in 4-dimensional magnetic resonance angiography (4D-MRA). Methods Ten healthy volunteers (six men, four women; age range, 24–37 years; mean, 29.1) were enrolled. 4D-MRA and SP-ASL were performed on a 3T magnetic resonance imaging (MRI) scanner. Signal intensities in four cerebral arterial territories (anterior cerebral artery, middle cerebral artery, posterior cerebral artery, and whole area) were measured using both 4D-MRA and SP-ASL, and peak time of maximum intensity through each technique was recorded. Regression analysis was used to determine the correlation between the peak times using 4D-MRA and those using SP-ASL, and the regression function obtained was used to estimate the peak time for SP-ASL (optimum post-label delay) from that obtained for 4D-MRA. Results The peak time in anterior cerebral artery territory for SP-ASL was expressed as 1.19 + 0.30 × (peak time of 4D-MRA) s, ( p = 0.017, r2 = 0.14). The peak time in middle cerebral artery territory for SP-ASL was 0.96 + 0.58 × (peak time of 4D-MRA) s, ( p < 0.001, r2 = 0.32). The peak time in posterior cerebral artery territory for SP-ASL was expressed as 0.92 + 0.58 × (peak time of 4D-MRA) s, ( p < 0.001, r2 = 0.33). The peak time in whole brain for SP-ASL was expressed as 1.04 + 0.46 × (peak time of 4D-MRA) s, ( p < 0.001, r2 = 0.25). Conclusion The peak time values at 4D-MRA showed potential for use in predicting the optimum post-label delay of SP-ASL.
Return to work and associations with psychosocial well-being and health-related quality of life in coronary heart disease patients: Results from EUROASPIRE IV
Authors: Cauter Joy Van de , Bacquer Dirk De , Clays Els , Smedt Delphine De , Kotseva Kornelia , Braeckman Lutgart 
Published: April 2019

Background Coronary heart disease (CHD) can lead to loss of workability and early retirement. We aimed to investigate return to work (RTW) and its relationship towards psychosocial well-being and health-related quality of life (HRQoL). Design Secondary analyses were applied to cross-sectional data from the EUROASPIRE IV survey (European Action on Secondary and Primary prevention through Intervention to Reduce Events). Methods Participants were examined and interviewed at 6–36 months following the recruiting event. Psychosocial well-being and HRQoL were evaluated by completing the ‘Hospital Anxiety and Depression Scale’ and ‘HeartQoL’ questionnaire. Using generalised mixed models, we calculated the odds ratios for RTW. Depression, anxiety and adjusted means of HeartQoL were estimated accounting for RTW. Results Out of 3291 employed patients, the majority (76.0%) returned to work, of which 85.6% were men, but there was a general underrepresentation of women. Young ( p < 0.001), high-educated ( p < 0.001) patients without prior cardiovascular events ( p < 0.05) were better off regarding RTW. No significant associations with CHD risk factors and cardiac rehabilitation were established. Those that rejoined the workforce were less susceptible to psychosocial distress (anxiety/depression, p < 0.001) and experienced a better quality of life ( p < 0.001). Conclusion These findings provide evidence that non-modifiable factors (sociodemographic factors, cardiovascular history), more than classical risk factors, are associated with RTW, and that patients who resume work display better psychosocial well-being and HRQoL. Our results illustrate a need for tailored cardiac rehabilitation with a focus on work-related aspects, mental health and HRQoL indicators to reach sustainable RTW, especially in vulnerable groups like less educated and elderly patients.
CRISPR/Cas9-mediated in vivo gene targeting corrects hemostasis in newborn and adult factor IX–knockout mice
Authors: Wang Lili , Yang Yang , Breton Camilo Ayala , White John , Zhang Jia , Che Yan , Saveliev Alexei , McMenamin Deirdre , He Zhenning , Latshaw Caitlin , Li Mingyao , Wilson James M. 
Published: April 2019

Abstract
Many genetic diseases, including hemophilia, require long-term therapeutic effects. Despite the initial success of liver-directed adeno-associated virus (AAV) gene therapy for hemophilia in clinical trials, long-term sustained therapeutic effects have yet to be seen. One explanation for the gradual decline of efficacy over time is that the nonintegrating AAV vector genome could be lost during cell division during hepatocyte turnover, albeit at a slow pace in adults. Readministering the same vector is challenging as a result of the AAV-neutralizing antibodies elicited by the initial treatment. Here, we investigated the use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated homology-directed gene targeting for sustained treatment of hemophilia B. We developed a donor vector containing a promoterless partial human factor IX (FIX) complementary DNA carrying the hyperactive FIX Padua mutation. A single injection of dual AAV vectors in newborn and adult FIX-knockout (FIX-KO) mice led to stable expression of FIX at or above the normal levels for 8 months. Eight weeks after the vector treatment, we subjected a subgroup of newborn and adult treated FIX-KO mice to a two-thirds partial hepatectomy; all of these animals survived the procedure without any complications or interventions. FIX levels persisted at similar levels for 24 weeks after partial hepatectomy, indicating stable genomic targeting. Our results lend support for the use of a CRISPR/Cas9 approach to achieve lifelong expression of therapeutic proteins.
Comparison of different techniques to identify cardiac involvement in immunoglobulin light chain (AL) amyloidosis
Authors: Aljama Mohammed A. , Sidiqi M. Hasib , Dispenzieri Angela , Gertz Morie A. , Lacy Martha Q. , Buadi Francis K. , Dingli David , Muchtar Eli , Fonder Amie L. , Hayman Suzanne R. , Hobbs Miriam A. , Gonsalves Wilson I. , Warsame Rahma M. , Kourelis Taxiarchis , Hwa Yi Lisa , Kapoor Prashant , Leung Nelson , Go Ronald S. , Kyle Robert A. , Rajkumar S. Vincent , Kumar Shaji K. 
Published: April 2019

Abstract
We retrospectively reviewed the utility of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and transthoracic echocardiogram (TTE) in diagnosing cardiac involvement in patients with biopsy-proven systemic immunoglobulin light chain amyloidosis seen at the Mayo Clinic between 1 January 2006 and 30 December 2015. We analyzed 2 cohorts: patients undergoing endomyocardial biopsy for suspicion of cardiac involvement (cohort 1) and patients who had serum NT-proBNP and comprehensive echocardiographic evaluation at diagnosis (cohort 2). Of 179 patients undergoing endomyocardial biopsy (cohort 1), 173 (97%) had evidence of amyloid deposition, with 159 having NT-proBNP performed at the time of the procedure. The NT-proBNP was elevated (&gt;300 pg/mL) in all 159 patients (sensitivity, 100%; median NT-proBNP, 4917 pg/mL; range, 355-69 541). The left ventricular ejection fraction, interventricular septal thickness, and strain rate were abnormal in 89/168 (53%), 102/64 (61%) and 92/95 (97%), respectively. Among cohort 2 (n = 342), 259 (76%) had an elevated NT-proBNP, of whom 237 (92%) had an abnormality detected on TTE. Of 83 patients with normal NT-proBNP &lt;300 pg/mL, 27 (33%) had an abnormality on TTE (all with borderline strain rate −18% to −15%). Only 5/27 patients were considered to have possible early cardiac involvement and none had any other diagnostic or classical features of amyloidosis on TTE. The combination of NT-proBNP and comprehensive echocardiographic evaluation can diagnose cardiac amyloidosis negating the need for endomyocardial biopsy. A negative NT-proBNP rules out clinically meaningful cardiac involvement and may obviate the routine use of TTE in patients with a low clinical suspicion of cardiac amyloidosis.